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Mouse let-7 miRNA populations exhibit RNA editing that is constrained in the 5′-seed/ cleavage/anchor regions and stabilize predicted mmu-let-7a:mRNA

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Posted on : 10:27 PM | By : Biochemistry Den | In :

Massively parallel sequencing of millions of <30-nt class="search-term-highlight">RNAs expressed in mouse ovary, embryonic pancreas (E14.5), and insulin-secreting beta-cells (βTC-3) reveals that ∼50% of the mature miRNAs representing mostly the mmu-let-7 family display internal insertion/deletions and substitutions when compared to precursor miRNA and the mouse genome reference sequences.

Approximately, 12%–20% of species associated with mmu-let-7 populations exhibit sequence discrepancies that are dramatically reduced in nucleotides 3–7 (5′-seed) and 10–15 (cleavage and anchor sites). This observation is inconsistent with sequencing error and leads us to propose that the changes arise predominantly from post-transcriptional RNA-editing activity operating on miRNA:target mRNA complexes.

Internal nucleotide modifications are most enriched at the ninth nucleotide position. A common ninth base edit of U-to-G results in a significant increase in stability of down-regulated let-7a targets in inhibin-deficient mice (Inha−/−). An excess of U-insertions (14.8%) over U-deletions (1.5%) and the presence of cleaved intermediates suggest that a mammalian TUTase (terminal uridylyl transferase) mediated dUTP-dependent U-insertion/U-deletion cycle may be a possible mechanism.

We speculate that mRNA target site-directed editing of mmu-let-7a duplex-bulges stabilizes “loose” miRNA:mRNA target associations and functions to expand the target repertoire and/or enhance mRNA decay over translational repression. Our results also demonstrate that the systematic study of sequence variation within specific RNA classes in a given cell type from millions of sequences generated by next-generation sequencing (NGS) technologies (“intranomics”) can be used broadly to infer functional constraints on specific parts of completely uncharacterized RNAs.

Source - http://genome.cshlp.org/content/18/10/1571.abstract?sid=40206306-7c2e-4b18-96b3-8319fa594a4b

Genome-wide discovery and verification of novel structured RNAs in Plasmodium falciparum

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Posted on : 10:24 PM | By : Biochemistry Den | In : ,

We undertook a genome-wide search for novel noncoding RNAs (ncRNA) in the malaria parasite Plasmodium falciparum. We used the RNAz program to predict structures in the noncoding regions of the P. falciparum 3D7 genome that were conserved with at least one of seven other Plasmodium spp.

genome sequences. By using Northern blot analysis for 76 high-scoring predictions and microarray analysis for the majority of candidates, we have verified the expression of 33 novel ncRNA transcripts including four members of a ncRNA family in the asexual blood stage. These transcripts represent novel structured ncRNAs in P. falciparumand are not represented in any RNA databases.

We provide supporting evidence for purifying selection acting on the experimentally verified ncRNAs by comparing the nucleotide substitutions in the predicted ncRNA candidate structures in P. falciparum with the closely related chimp malaria parasite P. reichenowi. The high confirmation rate within a single parasite life cycle stage suggests that many more of the predictions may be expressed in other stages of the organism’s life cycle.

Source - http://genome.cshlp.org/content/18/2/281.abstract?sid=40206306-7c2e-4b18-96b3-8319fa594a4b

A survey of RNA editing in human brain

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Posted on : 10:23 PM | By : Biochemistry Den | In : ,

We have conducted a survey of RNA editing in human brain by comparing sequences of clones from a human brain cDNA library to the reference human genome sequence and to genomic DNA from the same individual. In the RNA sample from which the library was constructed, 01:2000 nucleotides were edited out of >3 Mb surveyed. All edits were adenosine to inosine (A→I) and were predominantly in intronic and in intergenic RNAs.

No edits were found in translated exons and few in untranslated exons. Most edits were in high-copy-number repeats, usually Alus. Analysis of the genome in the vicinity of edited sequences strongly supports the idea that formation of intramolecular double-stranded RNAwith an inverted copy underlies most A→I editing.

The likelihood of editing is increased by the presence of two inverted copies of a sequence within the same intron, proximity of the two sequences to each other (preferably within 2 kb), and by a high density of inverted copies in the vicinity. Editing exhibits sequence preferences and is less likely at an adenosine 3′ to a guanosine and more likely at an adenosine 5′ to a guanosine. Simulation by BLAST alignment of the double-stranded RNA molecules that underlie known edits indicates that there is a greater likelihood of A→I editing at A:C mismatches than editing at other mismatches or at A:U matches. However, because A:U matches in double-stranded RNA are more common than all mismatches, overall the likely effect of editing is to increase the number of mismatches in double-stranded RNA.

Source - http://genome.cshlp.org/content/14/12/2379.abstract?sid=4be18750-d5af-4896-b05e-eeb49c944425

One Dose of H1N1 Vaccine May Provide Sufficient Protection for Infants and Children

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Posted on : 10:52 PM | By : Biochemistry Den | In : ,

One dose of vaccine may be effective to protect infants and children and reduce transmission of the H1N1 virus, according to a study in JAMA, just published online because of its public health implications. The study will appear in the January 6 print edition of the journal.

Initial reports of 2009 influenza A(H1N1) infection in many countries have largely involved children, especially those attending school. Reports have also indicated high hospitalization rates of children younger than 5 years of age in the current pandemic, according to background information provided by the authors. "The Advisory Committee on Immunization Practices also currently recommends that infants and children aged 9 years or younger receive two doses of H1N1 influenza vaccine at least 21 days apart, based on existing experience with seasonal trivalent influenza vaccines in this age group."

Terry Nolan, M.B.B.S., Ph.D., from the University of Melbourne, Australia and colleagues assessed the effectiveness and safety of two doses of a 2009 influenza A(H1N1) vaccine in 370 healthy infants and children ages six-months to less than 9 years living in Australia. The children were randomized into groups that received a two-injection regimen 21 days apart in doses of either 15-micrograms or 30-micrograms of the vaccine.

"Following the first dose of vaccine, antibody titers of 1:40 or greater were observed in 161 of 174 infants and children in the 15-microgram group (92.5 percent) and in 168 of 172 infants and children in the 30 microgram group (97.7 percent)," the authors report. "All participants demonstrated antibody titers of 1:40 or greater after the second vaccine dose," [which means that every child achieved an antibody level considered high enough to protect against the H1N1 virus]. The researchers note that the majority of adverse reactions to the vaccine were mild to moderate in severity. The immune responses to the vaccine were strong regardless of age, baseline antibody status, or whether the child had received a seasonal influenza vaccination prior to this study.

"Our findings suggest that a single dose 15-microgram dose vaccine regimen may be effective and well tolerated in children, and may have positive implications for disease protection and reduced transmission of pandemic H1N1 in the wider population," the authors conclude.

Editor's Note: This study was sponsored by CSL Limited with funding from the Australian government's Department of Health and Ageing.

Editorial: 2009 Influenza A(H1N1) Vaccines for Children

"Even though influenza activity has decreased in recent weeks in some states, there remains the possibility of continued activity through the traditional winter influenza season and the prospect of normal winter circulation of seasonal influenza viruses," and the authors of the editorial note that this pandemic has highlighted the fact the children have no measurable immunity against the H1N1 virus.

Anthony E. Fiore, M.D., M.P.H., from the National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, and Kathleen M. Neuzil, M.D., M.P.H., of PATH, Seattle, write that children have been a primary source of illness in community outbreaks of pandemic influenza with more severe complications, hospitalizations and deaths from this virus than what is usually seen for seasonal influenza.

The editorial authors urge caution at interpretation of the results of the study. "The hemagglutinin antigen content administered to six-month-old infants and children younger than 3 years in this study was 15-micrograms, the equivalent of two doses of the 7.5-microgram vaccine currently licensed in the United States for this age group."

"The immunogenicity data presented by Nolan et al suggest that at least some children will be protected after a single 15-microgram dose of the H1N1 vaccine used in this study, but the findings cannot be generalized with confidence to all children, epidemiological circumstances in every country, or different vaccine formulations."

In conclusion, the authors write: "… it remains prudent to continue to follow current recommendations for administering two doses to infants and young children while awaiting definitive vaccine effectiveness data."

The Largest Subunit of Human RNA Polymerase III Is Closely Related to the Largest Subunit of Yeast and Trypanosome RNA Polymerase-III

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Posted on : 10:18 PM | By : Biochemistry Den | In : ,

In both yeast and mammalian systems, considerable progress has been made toward the characterization of the transcription factors required for transcription by RNA polymerase III. However, whereas in yeast all of the RNA polymerase III subunits have been cloned, relatively little is known about the enzyme itself in higher eukaryotes.

For example, no higher eukaryotic sequence corresponding to the largest RNA polymerase III subunit is available. Here we describe the isolation of cDNAs that encode the largest subunit of human RNApolymerase III, as suggested by the observations that

(1) antibodies directed against the cloned protein immunoprecipitate an active enzyme whose sensitivity to different concentrations of α-amanitin is that expected for human RNA polymerase III; and

(2) depletion of transcription extracts with the same antibodies results in inhibition of transcription from an RNA polymerase III, but not from an RNA polymerase II, promoter.

Sequence comparisons reveal that regions conserved in the RNA polymerase I, II, and III largest subunits characterized so far are also conserved in the human RNA polymerase III sequence, and thus probably perform similar functions for the human RNA polymerase III enzyme.

Source - http://genome.cshlp.org/content/7/10/1006.abstract?sid=4be18750-d5af-4896-b05e-eeb49c944425

A Biochemist Explains The Chemistry Of Cooking

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Posted on : 10:47 PM | By : Biochemistry Den | In : ,

A biochemist and cook explains that cooking is all about chemistry and knowing some facts can help chefs understand why recipes go wrong. Because cooking is essentially a series of chemical reactions, it is helpful to know some basics. For example, plunging asparagus into boiling water causes the cells to pop and result in a brighter green. Longer cooking, however, causes the plant's cell walls to shrink and releases an acid. This turns the asparagus an unappetizing shade of grey.

You love to cook, but have you whipped up some disasters? Even the best recipes can sometimes go terribly wrong. A nationally recognized scientist and chef says knowing a little chemistry could help.

Long before she was a cook, Shirley Corriher was a biochemist. She says science is the key to understanding what goes right and wrong in the kitchen.

"Cooking is chemistry," said Corriher. "It's essentially chemical reactions."

This kind of chemistry happens when you put chopped red cabbage into a hot pan. Heat breaks down the red anthocyanine pigment, changing it from an acid to alkaline and causing the color change. Add some vinegar to increase the acidity, and the cabbage is red again. Baking soda will change it back to blue.

Cooking vegetables like asparagus causes a different kind of reaction when tiny air cells on the surface hit boiling water.

"If we plunge them into boiling water, we pop these cells, and they suddenly become much brighter green," Corriher said.

Longer cooking is not so good. It causes the plant's cell walls to shrink and release acid.

"So as it starts gushing out of the cells, and with acid in the water, it turns cooked green vegetables into [a] yucky army drab," Corriher said.

And that pretty fruit bowl on your counter? "Literally, overnight you can go from [a] nice green banana to an overripe banana," Corriher said.

The culprit here is ethylene gas. Given off by apples and even the bananas themselves, it can ruin your perfect fruit bowl -- but put an apple in a paper bag with an unripe avocado, and ethylene gas will work for you overnight.

"We use this as a quick way to ripen," Corriher said. Corriher says understanding a little chemistry can help any cook.

"You may still mess up, but you know why," she said. When it works, this kind of chemistry can be downright delicious.

WHAT ARE ACIDS AND BASES? An acid is defined as a solution with more positive hydrogen ions than negative hydroxyl ions, which are made of one atom of oxygen and one of hydrogen. Acidity and basicity are measured on a scale called the pH scale. The value of freshly distilled water is seven, which indicates a neutral solution. A value of less than seven indicates an acid, and a value of more than seven indicates a base. Common acids include lemon juice and coffee, while common bases include ammonia and bleach.

WHY DOES FOOD SPOIL? Processing and improper storage practices can expose food items to heat or oxygen, which causes deterioration. In ancient times, salt was used to cure meats and fish to preserve them longer, while sugar was added to fruits to prevent spoilage. Certain herbs, spices and vinegar can also be used as preservatives, along with anti-oxidants, most notably Vitamins C and E. In processed foods, certain FDA-approved chemical additives also help extend shelf life.

Genomic localization of RNA binding proteins reveals links between pre-mRNA processing and transcription

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Posted on : 10:16 PM | By : Biochemistry Den | In : ,

Natural antisense transcripts (NATs) have been shown to play important roles in post-transcriptional regulation through the RNA interference pathway. We have combined pyrophosphate-based high-throughput sequencing and computational analysis to identify and analyze, in genome scale, cis-NAT and trans-NAT small RNAs that are derived under normal conditions and in response to drought and salt stresses in the staple plant Oryza sativa.

Computationally, we identified 344 cis-NATs and 7142 trans-NATs that are formed by protein-coding genes. From the deep sequencing data, we found 108 cis-NATs and 7141trans-NATs that gave rise to small RNAs from their overlapping regions. Consistent with early findings, the majority of these 108 cis-NATs seem to be associated with specific conditions or developmental stages. Our analyses also revealed several interesting results.

The overlapping regions of the cis-NATs and trans-NATs appear to be more enriched with smallRNA loci than non-overlapping regions. The small RNAs generated from cis-NATs and trans-NATs have a length bias of 21 nt, even though their lengths spread over a large range. Furthermore, >40% of the small RNAs from cis-NATs and trans-NATs carry an A as their 5′-terminal nucleotides.

A substantial portion of the transcripts are involved in both cis-NATs and trans-NATs, and many trans-NATs can form many-to-many relationships, indicating that NATs may form complex regulatory networks in O. sativa. This study is the first genome-wide investigation of NAT-derived small RNAs in O. sativa. It reveals the importance of NATs in biogenesis of small RNAs and broadens our understanding of the roles of NAT-derived smallRNAs in gene regulation, particularly in response to environmental stimuli.

Source - http://genome.cshlp.org/content/19/1/70.abstract?sid=40206306-7c2e-4b18-96b3-8319fa594a4b

Fish can help improve nervous system function

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Posted on : 10:30 PM | By : Biochemistry Den | In : , , ,

Omega-3 fatty acids, commonly found in fish, appears to play a significant role in improving nervous system function, reveals a new study.

Fish

The researchers insist two omega-3 fatty acids – docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have been found to avoid sensory overload, maybe by maintaining nerve-cell membranes.
The finding connects low omega-3s to the information-processing problems found in people with schizophrenia; bipolar, obsessive-compulsive, and attention-deficit hyperactivity disorders; Huntington’s disease; and other afflictions of the nervous system.
"It is an uphill battle now to reverse the message that ‘fats are bad,’ and to increase omega-3 fats in our diet," said Norman Salem Jr., PhD, who led this study at the Laboratory of Membrane Biochemistry and Biophysics at the National Institute on Alcohol Abuse and Alcoholism.
The body cannot make these essential nutrients from scratch. It gets them by metabolizing their precursor, á-linolenic acid (LNA), or from foods or dietary supplements with DHA and EPA in a readily usable form.
"Humans can convert less than one percent of the precursor into DHA, making DHA an essential nutrient in the human diet," said Irina Fedorova, PhD, one of the paper’s co-authors.
EPA is already known for its anti-inflammatory and cardiovascular effects, but DHA makes up more than 90 percent of the omega-3s in the brain (which has no EPA), retina and nervous system in general.
During the study, the researchers fed four different diets with no or varying types and amounts of omega-3s to four groups of pregnant mice and then their offspring.
They measured how the offspring, once grown, responded to a classic test of nervous-system function in which healthy animals are exposed to a sudden loud noise. Normally, animals flinch. However, when they hear a softer tone in advance, they flinch much less.
It appears that normal nervous systems use that gentle warning to prepare instinctively for future stimuli, an adaptive process called sensorimotor gating.
The mice raised on DHA and EPA showed normal, adaptive sensorimotor gating by responding in a significantly calmer way to the loud noises that followed soft tones.
The research is published in journal Behavioural Neuroscience .

Source: http://timesofindia.indiatimes.com/life/health-fitness/health/Fish-can-help-improve-nervous-system-function/articleshow/5347748.cms

Genome-wide mapping of alternative splicing

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Posted on : 4:54 PM | By : Biochemistry Den | In : ,

Alternative splicing can enhance transcriptome plasticity and proteome diversity. In plants, alternative splicing can be manifested at different developmental stages, and is frequently associated with specific tissue types or environmental conditions such as abiotic stress. We mapped the Arabidopsis transcriptome at single-base resolution using the Illumina platform for ultrahigh-throughput RNA sequencing (RNA-seq).

Deep transcriptome sequencing confirmed a majority of annotated introns and identified thousands of novel alternatively spliced mRNA isoforms. Our analysis suggests that at least ∼42% of intron-containing genes in Arabidopsisare alternatively spliced; this is significantly higher than previous estimates based on cDNA/expressed sequence tag sequencing.

Random validation confirmed that novel splice isoforms empirically predicted by RNA-seq can be detected in vivo. Novel introns detected by RNA-seq were substantially enriched in nonconsensus terminal dinucleotide splice signals. Alternative isoforms with premature termination codons (PTCs) comprised the majority of alternatively spliced transcripts.

Using an example of an essential circadian clock gene, we show that intron retention can generate relatively abundant PTC+ isoforms and that this specific event is highly conserved among diverse plant species. Alternatively spliced PTC+isoforms can be potentially targeted for degradation by the nonsense mediated mRNA decay (NMD) surveillance machinery or regulate the level of functional transcripts by the mechanism of regulated unproductive splicing and translation (RUST).

We demonstrate that the relative ratios of the PTC+ and reference isoforms for several key regulatory genes can be considerably shifted under abiotic stress treatments. Taken together, our results suggest that like in animals, NMD and RUST may be widespread in plants and may play important roles in regulating gene expression.

Source - http://genome.cshlp.org/content/early/2009/11/18/gr.093302.109.abstract

Genome-wide identification and analysis of small RNAs originated from natural antisense transcripts in Oryza sativa

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Posted on : 4:49 PM | By : Biochemistry Den | In : , ,

Natural antisense transcripts (NATs) have been shown to play important roles in post-transcriptional regulation through the RNA interference pathway. We have combined pyrophosphate-based high-throughput sequencing and computational analysis to identify and analyze, in genome scale, cis-NAT and trans-NAT small RNAs that are derived under normal conditions and in response to drought and salt stresses in the staple plant Oryza sativa. Computationally, we identified 344 cis-NATs and 7142 trans-NATs that are formed by protein-coding genes. From the deep sequencing data, we found 108 cis-NATs and 7141trans-NATs that gave rise to small RNAs from their overlapping regions. Consistent with early findings, the majority of these 108 cis-NATs seem to be associated with specific conditions or developmental stages. Our analyses also revealed several interesting results. The overlapping regions of the cis-NATs and trans-NATs appear to be more enriched with smallRNA loci than non-overlapping regions. The small RNAs generated from cis-NATs and trans-NATs have a length bias of 21 nt, even though their lengths spread over a large range. Furthermore, >40% of the small RNAs from cis-NATs and trans-NATs carry an A as their 5′-terminal nucleotides. A substantial portion of the transcripts are involved in both cis-NATs and trans-NATs, and many trans-NATs can form many-to-many relationships, indicating that NATs may form complex regulatory networks in O. sativa. This study is the first genome-wide investigation of NAT-derived small RNAs in O. sativa. It reveals the importance of NATs in biogenesis of small RNAs and broadens our understanding of the roles of NAT-derived smallRNAs in gene regulation, particularly in response to environmental stimuli.

Source - http://genome.cshlp.org/content/19/1/70.abstract?sid=40206306-7c2e-4b18-96b3-8319fa594a4b

CSIR NET JRF: Key points to know for Paper-I- Part 1

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Posted on : 5:45 AM | By : Biochemistry Den | In : ,

Which metal is always found in free state in nature-Gold.
Bauxite is an ore of-Aluminum.
• Material used for bleaching pulp is-Sodium Hypo -chlori
• Which gas is leaked in Bhopal gas tragedy-Methyl Isocyanides.
Which element is common in all organic compounds is -Chlorine.
• What is the function of Green leaves in plants –Photosynthesis.
• Which is largest Gland in human body- Liver
• Which is largest Organ in human body –Skin
• Which is longest Bone in human body –Femur
• Malaraia is a disease which effect the –Spleen
• Leukemia is a disease of the –Blood.
Rickets is a disease of the –Bones.
• ECG is used for the diagnosis of ailments of –Heart.
• Food is normally digested in the –Small intestines.
• The main function of the kidney is –To remove waste product from body
The human cells contains –46 Chromosomes
• Centigrade and Fahrenheit scales resemble at ( –40C).
• Study of insects is called – Entomology.
• The inner layer of the skin is called – Dermis
• Nucleus of an atom has – Neutrons and Protons
• Marsh gas is – Methane
• In fireworks the green flame is produced because of – Barium
• Nuclear fission is caused by the impact –Neutron
• Atom Bomb is based on principal of – Nuclear Fission.
• Glass is made from the mixture of – Sand and Salt.
• Permanent hardness of water may be removed by the addition of – Sodium Carbonate.
• P.V.C is obtained by the polymerization of – Vinylchtoride
• The pursuit form of iron is – Cast Iron
• The element found on the surface of the moon is –Titanium
• One joule is equivalent to-10 ergs
• The most efficient engine is –Electric
• Wisdom teeth normally grow during the age of- 17- 30 years
• The yellow colures of urine is due to the presence of –Urochrome.
• Life of RBC in human blood is of –120 days.
• How many teeth are known as milk teeth in human beings – 20.
• Colure of the skin due to presence of -Melanin
• Bile juice secreted by -Lactro meter
• The smallest cell in the human body are –Blood cells.
• Food is mainly digested in –small intestine.
• The number of ribs in human body is –24

• A nuclear reactor uses as fuel –Uranium.
• The Velocity of light was first measured by –Roemer.
• The purity of milk is checked by –Lacto meter.
• The hottest part of the flame lies in its –Non luminous Zone.
• The first life came on this earth –In Water
• An object weights maximum in –Vacuum
• Which is the semiconductor –Silicon
• Ic Chips for Computers are usually made of –Silicon
• A device used for converting AC into DC is called-Rectifier.
• The volume Urine produced in an adult human every 24 hours is-1.5Liters.
• The average Gestation period of Sheep is –150 days.
• The Smallest possible unit of a comical compounds is –Molecule
• The Vitamin which contains Cobalt is –B12
• The first metal to used by man was Copper
• All acid essentially contain the element –Hydrogen
• The main active continent of tea and coffee is –Caffeine.
• Pencil lead is made up of –Graphite.
• The human body contains the maximum amount of –water.

• The smallest bone in the human body is – Stirrup
• Total number of bones in human skill are- 30
• The hitting element in an electric iron is made of –Tungsten.
• Acquired immune-deficiency syndrome(AIDS)is caused by –Virus
• The light with the longest wave length in the visible spectrum is – Red.
• In the electric bulb, the gas used is – Inert.

• Which Gland is called the master Gland –Pituitary
• How many Bones in adult human body –206
• How many Bones in child’s body –300
• What is the temperature of normal human body –36.9C.
• Which is the helps in clotting in blood –Vitamin K.
• Total volume of blood in normal adult human body 5-6iiters.
• Red blood corpuscles(RBC)are formed in the bone marrow
• The largest part of the human brain is the –cerebrum
• What is main component of the bone and teeth –Calcium Phosphate
• The main constituent of hemoglobin is –Transport Oxygen
• The main function of Hemoglobin is - Transport Oxygen.
• The chemical name of table salt is-Sodium Chloride.
• Chemical name of Vitamin C is –Ascorbic Acid.
• Bone is used as fertilizer because it contains the plant nutrient-Phosphorus.
• Baking soda is-Sodium Bicarbonat.
• Plaster of Paris is made from-Gypsum.
• Which element is common in all acids-Hydrogen.

CSIR Study materials

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Posted on : 5:44 AM | By : Biochemistry Den | In : ,

We collecting the question models from various source for your practice. Download the question model question papers for CSIR exam which is given below if you have any problem in downloading . write us your problem in the comment section. All our best wishes for your preparation


Accumulating Experiences Through Clinical Research Jobs

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Posted on : 9:53 PM | By : Biochemistry Den | In :

Scientists and researchers who want high-level clinical research jobs need to take the right approach to jobs early in their careers. The pressures of clinical research along with international competition for these jobs make deliberate career planning necessary for any professional. There are a few steps that can help clinical research aspirants of all ages find their dream jobs in a timely manner.


A clinical researcher should not shy away from non-profit work early in her career to gain appreciation for private and government jobs. Advocacy groups who conduct clinical research offer jobs to young scientists with commitments to public service and sound science. The sacrifice of lucrative salaries in favour of assisting an independent research group find methods of fighting cancer will help you develop an ethical compass during your career.


Every researcher should work with an established scientist in the first few years of a career to learn the subtleties of clinical research jobs. The earnest and often frank advice of a veteran scientist who has worked multiple jobs in the past will inform your approach to clinical research jobs. It is important to select a senior scientist in your early career with a personality and teaching style that match your approach to clinical research. The value of a mentor/protégée relationship rests on sober expectations and ground rules that make both sides feel comfortable.


The time spent on journal articles should be considered an investment in career advancement as well as intellectual enlightenment. Some of the greatest feats in clinical research have arisen from obscure journal articles that build on years of hard work. You can collaborate with other scientists to promote a series of findings that extend beyond your clinical research experiences. Every clinical researcher needs to publish individual articles to break away from “group think” and develop a written voice that will impress experienced scientists.


One of the best ways to show off clinical research skills is attendance at national and international conferences. The presentation of your findings in front of an audience of your peers can bring life to raw data and dense pages of information. Your career as a clinical researcher can take off quickly in a few months by networking at national and international conferences. These conferences also give clinical researchers an opportunity to learn about government initiatives, college programmes and private investments in research that lead to new jobs.

Clinical Research Associate Training - the Key to Becoming a Certified Professional

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Posted on : 9:52 PM | By : Biochemistry Den | In :

An ideal option for people who wish to build a solid career in the medical field, the clinical research associate profession brings many financial benefits and also a set of personal satisfactions, allowing practitioners to sustain their professional activity for the benefits of the community. Apart from the main function of monitoring clinical trials, the clinical research associate profession involves a wide variety of roles, such as verifying clinical site activities, making regular on site visits, reviewing and checking the accuracy of case report forms, as well as permanently interacting with clinical research investigators, all activities having to respect the imposed clinical protocols and good clinical practice guidelines.

It is important to note that the clinical research associate profession involves a lot of responsibility and dedication, rendering a long-term career in the branch quite demanding. However, clinical research associates have the opportunity to work in a clean and structured environment, to permanently interact with people and to ensure the protection of the rights, safety, health and well-being of human study subjects that participate in clinical trials.

The basic role of a clinical research associate, also referred to as a monitor, is to supervise the entire progress of clinical trials, initiated and conducted by physicians at hospitals, clinics, physician's offices and other medical establishments. Apart from being responsible for the health and well-being of clinical study participants, clinical research associates have to ensure the accuracy, quality and integrity of the scientific data collected during trials. The extensive set of roles and duties characteristic to practicing clinical research associates include ensuring that the physicians respect good clinical practices and study protocols, checking the required documentation for each study participant, ensuring that all side-effects and adverse physical responses are appropriately reported and filed and ensuring the proper filing of various regulatory documents.

Clinical research associates are generally employed by pharmaceutical companies, medical research organizations and other institutions in the medical field. The profession involves a lot of field work, practitioners having to visit various sites and to maintain permanent connection with clinical study coordinators and investigators.

Persons who wish to follow the career of clinical research associate attend rigorous training programs to show good practical, decisional and communicational skills in the process. All persons who possess the skills and abilities required by the clinical research associate profession can easily obtain the proper training by attending clinical research associate training programs, regardless of their previous level of experience in the medical field.

Official clinical research training programs allow attending trainees to rapidly familiarize with the theoretical curriculum, and polish their practical skills and abilities required in their future profession. Instructor-led clinical research associate training programs are well-structured in a comprehensive manner, facilitating the process of learning and allowing graduates to leave with a complete baggage of knowledge and practical experience. A set of course examinations, self study and evaluations further prepare students for their final exams. The keys to becoming a well-trained, clinical research associate are attending to a proper clinical research training program and rigorously preparing for the final exams.

Mesothelioma

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Posted on : 10:12 PM | By : Biochemistry Den | In : , , , ,

What is it?



Malignant mesothelioma is a rare type of cancer that occurs in the thin layer of cells lining the body's internal organs, known as the mesothelium. There are three recognized types of mesothelioma. Pleural mesothelioma is the most common form of the disease, accounting for roughly 70% of cases, and occurs in the lining of the lung known as the pleura.



Peritoneal mesothelioma occurs in the lining of the abdominal cavity, known as the peritoneum and pericardial mesothelioma originates in the pericardium, which lines the heart.

Who is at risk for Mesothelioma?

The only recognized cause of mesothelioma is exposure to asbestos, though other factors such as smoking can make the disease more or less likely in some individuals. Industrial laborers were widely subjected to asbestos exposure on the job, as the material was widely used throughout the 20th century. Few of these workers knew they were being exposed to asbestos, however, despite the fact that many manufacturers were aware the material was hazardous.

In most cases, mesothelioma symptoms will not appear in an individual exposed to asbestos until many years after the exposure has occurred. Those who believe they may have been exposed to asbestos should fill out our form to receive a free mesothelioma information packet, detailing treatment options, emerging therapies, and jobsite exposure information.

3 Reasons Why You Should Use a Cord Blood Bank

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Posted on : 3:23 AM | By : Biochemistry Den | In : , , , , , ,

When you find you are pregnant, whether it is the first time or the fourth time it can seem like the whole world has new information for you to digest and make decisions on.

One of the things you are sure to hear about is banking your baby's umbilical cord blood, this idea is relatively new so there is a good chance that you don't really know why you would want to bank the cord blood.

1- Protection against future ill health

You are expecting a baby and the last thing you want to think about is that there is even the faintest possibility that your baby will ever be sick. As horrible as it is to think about any of our kids getting ill, it does happens and any insurance you can have to protect them is worthwhile.

2- Advancing Medical Knowledge

While the benefits that you will gain at the moment from the blood you store may not seem worth the time or effort, no one really knows what the future holds. This is especially true for medicine, illnesses that had high mortality rates 30 years ago are now treatable and in many cases completely curable.

3- Help Others

As well as helping your child, or one of their siblings at some time in the future, your choice to save the umbilical cord could well save another child or another member of your family.

While it may not seem like something that would have happened in our parents day that is no reason to just throw this simple method of having some sort of insurance against possible future illness.

Bone Marrow Stem Cell Transplant & Congestive Heart Failure (CHF)

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Posted on : 5:23 PM | By : Biochemistry Den | In : , , ,

Congestive heart failure (CHF) is a serious and life-threatening illness that is associated with premature death. If one thinks of the heart as a pump, progressive damage to this pump's muscle fibers results in decreased "pump efficiency," which causes blood to, essentially, back-up within the vascular system under increased pressure. This increased back-pressure causes swelling of the entire body (edema), and particularly the lower extremities, the lungs, the liver, as well as within the heart itself. In more severe cases, CHF is associated with generalized weakness and profound shortness of breath.

The American Heart Association estimates that there are already more than 5 million Americans living with CHF, and that more than 550,000 new cases of CHF are diagnosed each year. Although mortality rates associated with CHF have improved dramatically over the past 30 years, the 5-year death rate associated with clinically significant CHF still approaches 50 percent.

As our population continues to grow older, on average, the incidence of CHF is expected to continue to rise. Although precise estimates are difficult to arrive at, the cost of caring for CHF is thought to be at least $33 billion per year in the United States alone.

There are several known major risk factors for CHF, including coronary artery disease and heart attack (myocardial infarction), uncontrolled high blood pressure (hypertension), diabetes, obesity, diseased heart valves, elevated cholesterol, and smoking. In most countries, coronary artery disease and myocardial infarction are the leading causes of CHF, and these two related risk factors account for approximately two-thirds of all CHF cases in the United States.

In adults, heart muscle fibers (cardiac myocytes) that have become damaged by chronic oxygen deprivation (myocardial ischemia) or oxygen loss (myocardial infarction) are essentially unable to regenerate themselves, and are gradually replaced by scar tissue that interferes with the heart's pumping action. At the present time, the standard clinical management of heart injury due to ischemia or infarction includes the use of medications such as aspirin, ACE inhibitors, aldosterone antagonists, beta-blockers and nitrates. So-called "reperfusion strategies," including coronary artery stent placement and coronary artery bypass graft (CABG) surgery may also be required in some patients. However, once the heart's blood-pumping muscle fibers have become extensively replaced with non-contractile scar tissue (fibrosis), irreversible CHF develops, and only symptomatic management is possible at this point.

Recent animal studies, and limited clinical research studies in humans, have looked at the use of stem cell auto-transplantation into damaged hearts afflicted with CHF. Although mature cardiac myocytes cannot regenerate or reproduce following severe ischemia or infarction, primitive "pluropotential" stem cells in the bone marrow are thought to be potentially capable, under certain conditions, of metamorphosing, or differentiating, themselves into almost any type of specialized cell of the body, including cardiac myocytes. However, this transformation, from undifferentiated bone marrow stem cell into a highly differentiated and specialized cardiac muscle cell, does not occur naturally in the human body, at least not to any clinically significant degree. Therefore, as is also the case in other areas of stem cell research, the greatest challenge in this type of clinical research is in coaxing undifferentiated stem cells to morph into functional cardiac myocytes and to find a way to incorporate these new heart muscle cells into the damaged heart in such a way that they actually improve the damaged heart's compromised pumping function. (These two challenges continue to vex clinical research into stem cell therapy, and particularly research into the use of adult patients' own stem cells.)

Now, newly published clinical research in the Journal of the American College of Cardiology appears to have pushed the existing boundaries of so-called autologous stem cell transplantation in the treatment of CHF, and may represent a major advancement towards finding an enduring treatment, if not an eventual cure, for this increasingly common and disabling disease.

In this prospective interventional clinical study, 124 patients who had just experienced an acute myocardial infarction were evaluated with coronary angiograms, treadmill EKGs, 24-hour EKGs, and echocardiograms, among other cardiac studies. Half of this cohort of patient volunteers also underwent collection of their own (autologous) bone marrow cells, and injection of these bone marrow cells into the blocked coronary arteries that had caused these patients' heart attacks.

Both groups of patients were matched with each other in terms of baseline cardiac function and the extent of their myocardial infarctions. All 124 patients were then closely followed, at regular intervals, for 5 years. The results of this study were rather dramatic.

Within 3 months of bone marrow cell injection, significant improvement was noted in cardiac pumping efficiency (ejection fraction) of the bone marrow cell transplant patients, when compared to the patients who did not receive autologous intracardiac bone marrow cell transfusions.

Moreover, on average, the total area of heart muscle death (infarction) following heart attack was 8 percent smaller in the patients who received the bone marrow cell transplants, when compared to the "control group" patients.

In the area of the "infarction zone" of the heart, a very significant 31 percent increase in cardiac contractility was observed in the patients who had undergone bone marrow cell transplant, suggesting that the infused bone marrow stem cells had actually incorporated themselves into the infarcted heart muscle, and had successfully transformed themselves into functional cardiac myocytes. When compared to the control group patients, the patients who had undergone autologous intracardiac bone marrow cell transplantation also experienced significantly improved exercise tolerance and a decreased risk of death throughout the 5-year observation period within this study.

Furthermore, these highly significant improvements in cardiac function continued to remain stable and durable throughout the 5-year period of post-transplant observation of these patients. As the "treatment group" patients were infused with their own bone marrow cells, there were no episodes of rejection, and no major complications were reported with this novel treatment.

This small prospective pilot study strongly suggests that autotransplantation with stem cells contained in the bone marrow can significantly reduce the risk and extent of CHF following acute myocardial infarction. Not only does this therapy appear to be clinically effective, but it appears to be associated with a very low risk of complications, and it also side-steps the ongoing ethical debate that surrounds the use of more versatile, but more controversial, fetal stem cells.

Based upon the rather remarkable findings of this small clinical study, much larger multi-institution, prospective, randomized, controlled studies of autologous intracardiac bone marrow cell transplantation, following acute myocardial infarction, need to be performed. Fortunately, several such studies are already underway in the United States and Europe.

I look forward to the long-term results of such studies, as I believe that they may have the potential to radically transform the management of coronary artery disease and acute myocardial infarction, and offer the best and most practical hope of reducing both the incidence of CHF and the mortality rate associated with CHF.

The information in this column is intended for informational purposes only, and does not constitute medical advice or recommendations by the author. Please consult with your physician before making any lifestyle or medication changes, or if you have any other concerns regarding your health.

Disclaimer: As always, my advice to readers is to seek the advice of your physician before making any significant changes in medications, diet, or level of physical activity.

Dr. Wascher is an oncologic surgeon, a professor of surgery, a widely published author, and a Surgical Oncologist at the Kaiser Permanente healthcare system in Orange County, California. Send your feedback to Dr. Wascher at: rwascher@doctorwascher.net
http://doctorwascher.com

Swine flu - everything you need to know

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Posted on : 10:46 PM | By : Biochemistry Den | In : , , , , , ,

The number of cases of swine flu in England continued to fall last week (week ending 9 August). The Health Protection Agency (HPA) estimates there were 25,000 new cases of swine flu in England last week, compared with 30,000 the week before and 100,000 the week before that. Cases of swine flu have fallen in all regions and among all age groups.

The disease is generally mild in most people so far, but is proving severe in a small minority of cases. So far 371 people have been hospitalised in England, while 44 people have died.

Swine flu vaccine

The government has announced that priority for the swine flu vaccine will be given to at-risk groups. These include pregnant women and people with serious underlying health conditions.

Vaccinations for these groups are expected to begin in the autumn. Steps are being taken to extend the vaccination programme to other people once this stage has been completed.

Swine flu - treatment and prevention

If you are in England, you can get antivirals to treat swine flu from a local collection point without seeing your GP. If you are in Scotland, Wales or Northern Ireland, contact your GP or specific helpline. Reduce your risk of catching swine flu by following good hand hygiene – CATCH IT, BIN IT, KILL IT. Antiviral drugs - Tamiflu and Relenza

Swine flu is being treated with antiviral drugs such as Tamiflu and Relenza. Antiviral drugs work by preventing the flu virus from reproducing - to be effective you need to take them within 48 hours of the symptoms beginning. This can reduce the risk of complications and possibly shorten the illness by a day.

If the National Pandemic Flu Service or your GP confirm you have swine flu, you will be told where your nearest antiviral collection point is so your 'flu friend' - a friend or relative who does not have swine flu - can pick up antiviral drugs for you

Revised Guidelines for testing of persons with flu like symptoms reporting at hospitals notified for influenza H1N1

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Posted on : 6:02 PM | By : Biochemistry Den

So far, the present guidelines stipulate that a person suspected of influenza A H1N1 need to be referred to an identified govt. health facility. He/she needs to be kept in an isolation facility in that hospital and if found positive, is treated accordingly.

In order to make the testing facility for H1N1 more accessible at large and due to the onset of the Influenza season in the country, it has been decided to revise the existing guidelines.

Under the new guidelines, any person with flu like symptoms such as fever, cough, sore throat, cold, running nose etc. should go to a designated Government facility for giving his/her sample for testing for the H1N1 virus. After clinical assessment, the designated medical officer would decide on the need for testing. Except for cases that are severe, the patient would be allowed to go home (This was not allowed under the existing guidelines).

The sample of the suspect case would be collected and sent to the notified laboratory for testing. If tested as positive for H1N1 and in case the symptoms are mild, the patient would be informed and given the option of admission into the hospital or isolation and treatment at his own home.

In case the patient opts for home isolation and treatment, he/she would be provided with detailed guidelines / safety measures to be strictly adhered to by the entire household of the patient. He/ she would have to provide full contact details of his entire household. The house hold and social contacts would be provided with the preventive treatment.

Notwithstanding the above guidelines, the decision of the doctor of the notified hospital about admitting the patient would be final.

In case the test is negative, the patient will accordingly be informed.

These guidelines have been issued by the Government in public interest and shall be reviewed from time to time depending on the spread of the pandemic and its severity in the country. These guidelines would however not apply to passengers who are identified through screening at the points of entry. The existing policy of isolating passengers with flu like symptoms would continue.

What Is Swine Flu? How Is Swine Flu Treated?

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Posted on : 2:10 AM | By : Biochemistry Den | In : , , , , , ,

Swine flu (swine influenza) is a disease of pigs. It is a highly contagious respiratory disease caused by one of many Influenza A viruses. Approximately 1% to 4% of pigs that get swine flu die from it. It is spread among pigs by direct and indirect contact, aerosols, and from pigs that are infected but do not have symptoms. In many parts of the world pigs are vaccinated against swine flu.
Most commonly, swine flu is of the H1N1 influenza subtype. However, they can sometimes come from the other types, such as H1N2, H3N1, and H3N2.
The current outbreak of swine flu that has infected humans is of the H1N1 type - this type is not as dangerous as some others.

Avian Influenza (Bird Flu) can also infect pigs

Avian flu and human seasonal flu viruses can infect pigs, as well as swine influenza. The H3N2 influenza virus subtype, a virulent one, is thought to have come from pigs - it went on to infect humans.
It is possible for pigs to be infected with more than one flu virus subtype simultaneously. When this happens the genes of the viruses have the opportunity to mingle. When different flu subtypes mix they can create a new virus which contains the genes from several sources - a reassortant virus.

Although swine influenza tends to just infect pigs, they can, and sometimes do, jump the species barrier and infect humans.

What is the risk for human health?

Outbreaks of human infection from a virus which came from pigs (swine influenza) do happen and are sometimes reported. Symptoms will generally be similar to seasonal human influenzas - this can range from mild or no symptoms at all, to severe and possibly fatal pneumonia.
As swine flu symptoms are similar to typical human seasonal flu symptoms, and other upper respiratory tract infections, detection of swine flu in humans often does not happen, and when it does it is usually purely by chance through seasonal influenza surveillance. If symptoms are mild it is extremely unlikely that any connection to swine influenza is found - even if it is there. In other words, unless the doctors and experts are specifically looking for swine flu, it is rarely detected. Because of this, we really do not know what the true human infection rate is.

Examples of known swine flu infecting humans

Since the World Health Organization's (WHO's) implementation of IHR (2005) in 2007, they have been notified of swine influenza cases from the USA and Spain.
In March/April 2009 human cases of influenza A swine fever (H1N1) were first reported in California and Texas. Later other states also reported cases. A significant number of human cases during the same period have also been reported in Mexico - starting just in Mexico City, but now throughout various parts of the country. More cases are being reported in Canada, Europe, and New Zealand - mainly from people who have been in Mexico.

How does a human catch swine influenza?

  • From contact with infected pigs (most common way)
  • From contact with infected humans (much less common way)

In cases when humans have infected other humans close contact was necessary with the infected person, and they nearly always occurred in closed groups of people.

Can I eat pork meat and pork products?

If the pork meat and pork food products have been handled properly transmission of swine influenza to humans is not possible. Cooking pork meats to a temperature of 70C (160F) kills the virus. So the answer is YES, pork meat and pork food products are safe to eat.

Where have pigs been infected?

As swine influenza infection among pigs is not an internationally notifiable disease we cannot be completely sure. Swine influenza infection among pigs is known to be endemic in the USA. Outbreaks have also occurred in other parts of North America, South American, Europe, Africa, China, Japan, and other parts of Asia.

Is there a pandemic risk?

People who are not in close contact with pigs generally have no immunity to the swine influenza viruses - they are less likely to be able to prevent a virus infection. If the virus infects enough people in a given area, the risk of an influenza pandemic is significantly greater. Experts say it is very hard to predict what impact a flu pandemic caused by a swine influenza virus would have on the global human population. This would depend on how virulent the virus is, what existing immunity among humans there already is, plus several other factors.

Do we have a specific swine flu vaccine?

No - not for humans.

Will current human flu vaccines help protect people from swine influenza infection?

We really don't know. Influenza viruses are adapting and changing all the time. If a vaccine was made, it would have to be specifically for a current strain that is circulating for it to be effective. The WHO says it needs access to as many viruses as possible so that it can isolate the most appropriate candidate vaccine.

What are the signs and symptoms of swine influenza in humans?

They are similar to those of regular flu, and include:

  • Body aches
  • Chills
  • Cough
  • Diarrhea (less common)
  • Headache
  • Sore throat
  • Temperature (fever)
  • Tiredness (fatigue)
  • Vomiting (less common)

What medications are there?

There are some drugs around that can effectively treat swine flu infection in humans - and many types of flu infections in humans. There are two main types:

  • adamantanes (amantadine and remantadine)
  • inhibitors of influenza neuraminidase (oseltamivir and zanamivir)

Most previous swine influenza human cases recovered completely without the need for medical attention.

What can I do to protect myself?

  • Wash your hands regularly with soap
  • Try to stay healthy
  • Get plenty of sleep
  • Do plenty of exercise
  • Try to manage your stress
  • Drink plenty of liquids
  • Eat a well balanced diet
  • Refrain from touching surfaces which may have the virus
  • Do not get close to people who are sick
  • Stay away from crowded areas if there is a swine flu outbreak in your area

If I am infected, how can I stop others from becoming infected?

  • Limit your contact with other people
  • Do not go to work or school
  • When you cough or sneeze cover your mouth with a tissue. If you do not have a tissue, cover your mouth and nose.
  • Put your used tissues in a waste basket
  • Wash your hands and face regularly
  • Keep all surfaces you have touched clean
  • Follow your doctor's instructions

Mexico City - Some good news

In Mexico City, where a sizeable number of people have become infected with H1N1 swine flu, authorities are urging people with flu symptoms to go straight to their doctors or a local hospital. They insist that the flu is completely treatable if the patient comes in straight away.

What is Swine Flu - Video

The Centers for Disease Control and Prevention (CDC) Influenza Division has produced a video all about swine flu.
This video includes information on the signs and symptoms of swine flu, how swine flu is transmitted, what medicines are available to treat it and steps that people can take to help protect themselves from it. There are also some tips on what to do if you become ill with swine flu.

Map of Swine Flu Outbreaks

If you would like to keep up-to-date with the locations of the latest outbreaks of H1N1, see the map of swine flu outbreaks.

Scientists develop 'nanospears' that could lead to more efficient solar cells

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Posted on : 7:08 AM | By : Biochemistry Den | In : , , ,

Researchers at Missouri University of Science and Technology (S and T), US, have developed microscopic, spear-shaped zinc oxide crystals on a surface of single-crystal silicon, which may be used to make more efficient solar cells.

According to Dr. Jay A. Switzer and his colleagues at Missouri S and T, their simple, inexpensive process could also lead to new materials for ultraviolet lasers, solid-state lighting and piezoelectric devices.

"It's kind of like growing rock candy crystals on a string," said Switzer, the Donald L. Castleman/Foundation for Chemical Research Professor of Discovery at Missouri S and T.

But instead of using sugar water and string, Switzer's team grows the zinc oxide "nanospears" on the single-crystal silicon placed in a beaker filled with an alkaline solution saturated with zinc ions.

The process yields tilted, single-crystal, spear-shaped rods that grow out of the silicon surface, like tiny spikes.

The spears are about 100-200 nanometers in diameter - hundreds of times smaller than the width of a human hair - and about 1 micrometer in length.

Zinc oxide is a semiconductor that possesses some unusual physical properties, according to Switzer.

The material both absorbs and emits light, so it could be used in solar cells to absorb sunshine as well as in lasers or solid-state lighting as an emitter of light.

Silicon is also a semiconductor, but it absorbs light at a different part of the spectrum than zinc oxide.

By growing zinc oxide on top of the silicon, "you're putting two semiconductors on top of each other," thereby widening the spectrum from which a solar cell could draw light, Switzer said.

"You can absorb more light and possibly get more power out" with a zinc oxide-silicon solar cell, he added.

Previous efforts to grow zinc oxide on silicon have been limited to expensive ultra-high-vacuum methods, and because of silicon's high reactivity, it's been impossible to deposit the zinc oxide directly, without the use of a third material as a buffer.

In addition, previous attempts to align the two materials epitaxially - or perfectly one on top of the other - have been unsuccessful until now.

By tilting the nanospears 51 degrees, Switzer and his team have reduced the mismatch from 40 percent to just 0.2 percent, a near-perfect alignment.

"Epitaxially aligning the zinc oxide and silicon is important to ensure higher efficiency," Switzer said. (ANI)

Glucose Intolerance In Animals Reversed By Carnitine Supplements

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Posted on : 2:00 AM | By : Biochemistry Den | In : , , , , , , , , ,

Supplementing obese rats with the nutrient carnitine helps the animals to clear the extra sugar in their blood, something they had trouble doing on their own, researchers at Duke University Medical Center report.

A team led by Deborah Muoio (Moo-ee-oo), Ph.D., of the Duke Sarah W. Stedman Nutrition and Metabolism Center, also performed tests on human muscle cells that showed supplementing with carnitine might help older people with prediabetes, diabetes, and other disorders that make glucose (sugar) metabolism difficult.

Carnitine is made in the liver and recycled by the kidney, but in some cases when this is insufficient, dietary carnitine from red meat and other animal foods can compensate for the shortfall.

After just eight weeks of supplementation with carnitine, the obese rats restored their cells' fuel- burning capacity (which was shut down by a lack of natural carnitine) and improved their glucose tolerance, a health outcome that indicates a lower risk of diabetes.

These results offer hope for a new therapeutic option for people with glucose intolerance, older people, people with kidney disease, and those with type 2 diabetes (what used to be called adult-onset diabetes).

Muoio said that soon her team of researchers will begin a small clinical trial of carnitine supplementation in people who fit the profile of those who might benefit from additional carnitine - older people (60 to 80 years) with glucose intolerance.

The study is published in the Aug. 21 issue of the Journal of Biological Chemistry.
The Duke researchers began studying carnitine more closely when abnormalities in the nutrient emerged from blood chemistry profiles of obese and old animals. These chemical profiles report on hundreds of byproducts of cell metabolism called metabolites and give scientists an opportunity to identify markers of disease states.

Carnitine is a natural compound known for helping fatty acids enter the mitochondria, the powerhouses of cells, where fatty acids are "burned" to give cells energy for their various tasks. Carnitine also helps move excess fuel from cells into the circulating blood, which then redistributes this energy source to needier organs or to the kidneys for removal. These processes occur through the formation of acylcarnitine molecules, energy molecules that can cross membrane barriers that encase all cells.

Researchers at Duke had observed that skeletal muscle of obese rats produced high amounts of the acylcarnitines, which requires free carnitine. As these molecules started to accumulate, the availability of free, unprocessed carnitine decreased. This imbalance was linked to fuel-burning problems, that is, impairments in the cells' combustion of both fat and glucose fuel.

"We suspected that persistent increases in acylcarnitines in the rats were causing problems, and we could also see that the availability of free carnitine was decreasing with weight gain and aging," said Muoio. "It appeared that carnitine could no longer do its job when chronic metabolic disruptions were stressing the system. That's when we designed an experiment to add extra carnitine to the rats' diet."

Muoio is also a professor in the departments of medicine, pharmacology and cancer biology.
Other study authors included Robert C. Noland, Sarah E. Seiler, Helen Lum, Olga Ilkayeva, Robert Stevens, and Timothy R. Koves of the Sarah W. Stedman Nutrition and Metabolism Center. Koves is also with the Duke Department of Medicine. Robert M. Lust is with the Department of Physiology at East Carolina University in Greenville, N.C., and Fausto G. Hegardt is with the CIBER division Fisiopatología de la Obesidad y la Nutrición of the Instituto de Salud Carlos III in Spain.

The work was supported by grants from the National Institutes of Health, and the American Diabetes Association, and a John A. Hartford Duke Center for Excellence Award.

Source:
Mary Jane Gore
Duke University Medical Center

The Sperm Cell – Reproductive cell

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Posted on : 6:11 PM | By : Biochemistry Den | In : , , , , , ,

Contrary to belief babies really don’t come from storks. I think we all pretty much know where babies come from. But do we really? To put it in perspective you need a sperm cell and an egg to make a baby.

During sexual intercourse, a mans sperm, which is produced by the testicles travels to the woman’s cervix, it then travels to the fallopian tubes. There are millions of sperm cells swimming to the fallopian tubes but it only takes one to penetrate an egg which is called fertilization. At this point a single life begins.

The question now is where does the sperm come from? Millions of sperm are produced daily by the testicles. Sperm cells undergo natural cell division which leads to its maturation. Half of the sperm cells carry the Y and X chromosome. Y comes from your dad and X comes from your mom. If a Y fertilizes an egg there will be a baby girl and X would be a baby boy.

During ejaculation, sperm goes into the mans vas deferens where fructose, seminal fluids, and other chemicals are secreted. Your sperm and other seminal fluids rush past the bladder through the urethra and out the penis.

Three things are needed for the sperm to enter the woman’s cervix. You need to have an erection, orgasm and ejaculation. Erections take place when the penis is stimulated or when erotic thoughts come into your mind. There is a sudden rush of blood to the erectile tissue chambers in the penis. With all this the penis engorges, making the penis hard, enlarged and elevated.

You need continued stimulation to achieve orgasm and ejaculation. Orgasm is the sexual climax. It is a pleasurable emotional or psychological response that accompanies ejaculation. In a man there are two stages to an orgasm. The first one is ejaculatory inevitability. This take place just second before you ejaculate. You know that you are about to ejaculate and at this point there is no turning back. Your seminal vesicles and your prostate gland begin to throb. The second stage of orgasm is when you involuntarily ejaculate semen in convulsive surges. On average a teaspoon of sperm contains any where between 40 to 150 million sperm.

Now that you have achieved orgasm as a man you have to go through a recovery period. Through out this recovery period you cannot experience another orgasm. This recovery period varies for different men. It can range anywhere from minutes to hours.

Dale has been married for 20 years and studies topics of this sort. You can check out some of his ever growing blogs at http://relationshiptidbits.blogspot.com/ or http://stcajo-readshortstories.blogspot.com/ and http://fishingtutor.blogspot.com/

Cellular maturity and apoptosis in human sperm: creatine kinase, caspase-3 and Bcl-XL leve

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Posted on : 6:08 PM | By : Biochemistry Den | In : , , , , , , , ,

The relationship between human sperm maturity and apoptosis is of interest because of the persistence of immature sperm in ejaculates in spite of various apoptotic processes during spermatogenesis. We assessed sperm maturity by HspA2 chaperone levels, and plasma membrane maturity by sperm binding to immobilized hyaluronic acid (HA). We also utilized objective morphometry.

Sperm were stained with three antibody combinations: active caspase-3/creatine kinase (CK, a marker of cytoplasmic retention), caspase-3/the antiapoptotic Bcl-(XL), and CK/Bcl-(XL). In semen, 13% of sperm stained with CK, caspase-3 or Bcl-(XL), and 28% had stained with two markers.

In the mature HA-bound sperm fraction, <4% were single- or double-stained. Regarding sperm regions, CK staining, whether alone or as double staining, occurred in the head and midpiece (15-20%), whereas caspase-3 and Bcl-(XL) were primarily (>80% of sperm) in the midpiece.

Morphometrical attributes of clear, single- and double-stained sperm, in line with their more pronounced maturation arrest, showed an incremental increase in head size (due to cytoplasmic retention) and shorter tail length. We hypothesize that during faulty sperm development, three alternatives may occur: (i) elimination of aberrant germ cells by apoptosis; (ii) in surviving immature cells, caspase-3 is activated, and in response the antiapoptotic Bcl-(XL), and perhaps HspA2, provide protection; (iii) in a third type of immature sperm, in addition to the CK, caspase-3 and Bcl-(XL) expression, there are related manifestations of increased head size and shorter tail length.

Thus, immature sperm may vary in the type of developmental arrest and in protection mechanisms for apoptosis. These variations are likely to explain the persistence of immature sperm in the ejaculate.

Sperm Cell Development and Motility Linked To The Presence of Protein MIF

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Posted on : 6:07 PM | By : Biochemistry Den | In : , , , , , , ,

New evidence is helping to confirm what many fertility doctors already knew; That the health and quality of a man's sperm cells are one of the biggest components to successfully conceiving.

The health of a man's sperm is so important because it truly is survival of the fittest. You have thousands of sperm cells competing for the chance to penetrate and fertilize the female egg. Compound this fact with the numerous variables that stand in the sperm cells way and you have an extremely difficult mission. The factors that dictate your success as well as your fertility rate are outlined in greater detail in the next section.

Factors of Importance-The Battle of Conception

First the environment of the female reproductive system is very acidic, and in order for the sperm cells to survive in this environment long enough to find the female egg they need a protective barrier. This protective barrier is the seminal fluid which contains the sperm cells. It not only acts as a barrier but also acts as a fuel on which the sperm cells feed off of. So in order to have strong and healthy sperm cells you also need a healthy dose of semen.

Next the sperm cells themselves must be of high quality with key traits like motility and mobility. What this means is that the sperm cells should show signs of being strong swimmers and the ability to swim in a forward motion. There should also be few signs of sperm abnormalities including: low sperm count low semen volume, poor swimming ability, crooked tails and malformed sperm cells and the presence of a large number of dead sperm cells.

What researchers have recently found is a correlation between the health and quality of a man's sperm cell and the presence of a particular protein that is found in the immune system. This protein was crucial to the continued strength and health of the sperm cells because it helped increase the sperms motility. Again what this confirms is the importance of a healthy body and the role that key amino acids (the building blocks of protein), nutrients, vitamins and minerals have in the health of the male sexual health system.

If you ensure that your body is receiving enough of these key elements as part of your diet then you are on your way to maintaining a healthy fertility level with healthy sperm cells. If you are unsure as to whether you are receiving the adequate nutrients adding a specially formulated supplement will help.

To read more about the latest on the protein MIF and the role it plays in the male reproductive system or to learn more about all natural supplements designed just for the male reproductive system please visit Sperm Cell Development Based on Protein MIF

Bacteria Pack Their Own Demise

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Posted on : 2:38 AM | By : Biochemistry Den | In : , , ,

Numerous pathogens contain an 'internal time bomb', a deadly mechanism that can be used against them. After years of work, VIB researchers at the Vrije Universiteit Brussel (VUB) were able to determine the structure and operating mechanism of the proteins involved. This clears the road for finding ways to set the clock on this internal time bomb and, hopefully, in the process developing a new class of antibiotics. The research was accepted for publication by journal Molecular Cell.

It's in the genes

For years, Nathalie De Jonge, Remy Loris and their colleagues of the VIB Department of Molecular and Cellular Interactions at VUB, have applied their relentless dedication to the study of the precise structure and function of the toxin-antitoxin complex, a system that had not been the focus of much interest in the past. Only in the last couple of years the rest of the scientific world come to realize its importance and as a result the number of papers in this field has exploded.

All living creatures, people as well as bacteria, store their genetic information in the same way, i.e. in the DNA. Every human cell contains 46 neatly folded DNA strands that together measure two meters, while bacteria have to make do with around one millimetre of DNA. A piece of DNA containing the recipe for one characteristic, such as "how to make citric acid" or "how to make hair curl," is called a gene. Humans have several tens of thousands of genes.

Toxin and antitoxin

If your genetic information becomes damaged, you have a good chance of becoming ill or even dying. This is also true for bacteria, which over time developed a handy way of providing extra protection to important genes – the toxin-antitoxin (T-A) system. These T-A genes are tucked in near the genes to be protected. T-A genes contain instructions for both a toxin and its antitoxin. As long as the cell is producing both, all is well. However, if for some reason the piece of DNA where the T-A gene is located gets damaged or lost, the production of toxin and antitoxin comes to a halt and a time bomb starts ticking. Because the toxin is more stable than the antitoxin, it is broken down more slowly by the cell's clean-up mechanisms. Once the antitoxin is all gone, there is still enough toxin left to kill the bacterium. The upshot for the species is that bacteria that loses their T-A gene – and probably have sustained damage to the important genes just next to it – can no longer reproduce.

Our best-known intestinal residents, Escherichia coli bacteria, more commonly known as E.coli, have such a T-A system in five different locations in their DNA, while Mycobacterium tuberculosis bacteria even have them in 60 locations.

A difficult feat

The T-A mechanism has been known for a while, but nobody clearly understood the workings of the proteins carrying out the instructions of the T-A gene. The VIB researchers clarified in detail both the appearance of the toxin and antitoxin, the mechanism of their interaction and the forms they take while in action – a difficult feat to pull off, requiring the simultaneous use of a whole range of different technologies. One of the difficulties for instance lay in the fact that part of the antitoxin lacks a fixed structure. This formlessness keeps it from being brought into view.

Future

Now that we finally know how the time bomb functions (or more exactly, one of the time bombs, as there are several closely related T-A systems), biomedical scientists can start looking for substances to start the time bomb of pathogens ticking, i.e. substances that imitate the toxin protein, block the antitoxin protein, or disrupt the interaction between the toxin and antitoxin. In time, a new class of antibiotics might come out of it – though Nature mostly has a countermove up its sleeve against any move scientists do.

Virus Linked To Some Cases Of Common Skin Cancer

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Posted on : 2:37 AM | By : Biochemistry Den | In : , , , , ,

A virus discovered last year in a rare form of skin cancer has also been found in people with the second most common form of skin cancer among Americans, according to researchers at the Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute.

The researchers examined tissue samples from 58 people with squamous cell carcinoma (SCC), a highly curable form of skin cancer that is expected to affect more than 200,000 Americans this year.

They identified the virus in more than a third of the patients and in 15 percent of the tumors tested. In addition, all of the virus found in tumor cells had a mutation that could enable the viral DNA to integrate into the DNA of the host cell.

“This is indirect evidence that the virus might play a role in causing some cases of squamous cell carcinoma,” says principal investigator Amanda E. Toland, assistant professor of molecular virology, immunology and medical genetics and a researcher with the Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute.

The findings are published in a recent issue of the Journal of Investigative Dermatology.

The virus was first discovered in patients with Merkel cell carcinoma, a rare, aggressive skin cancer that occurs mainly in the elderly and people with a suppressed immune system. The people in the new study all had a healthy immune system.

“Originally it was thought that this virus caused only this rare skin cancer, but our findings indicate that it is a lot more prevalent than we initially thought.”

To learn if people with SCC harbored the virus, Toland, working closely with first author and graduate research associate Amy Dworkin and Ohio State pathologists O. Hans Iwenofu and Sara B. Peters, examined DNA samples from SCC tumors, from normal-appearing skin adjacent to the tumor, when available; from white blood cells, and from cells washed from the mouth.

The investigators detected the virus in 26 of 177 SCC samples, 11 of 63 adjacent-skin samples, and one sample from a mouthwash. They found no viral DNA in any of the blood samples from 57 patients. In all, 21 of 58 SCC patients, or 36 percent, tested positive for the virus.

By sequencing the viral DNA from 31 normal and tumor samples, the researchers showed that the same mutation was present in all the viruses tested from tumors, and in 60 percent of the viruses tested from adjacent healthy-looking tissue.

“That suggests that the virus may develop a mutation that causes it to integrate into host-cell DNA, and, therefore, may play a role in causing the cancer,” Toland says.

Next, Toland wants to test normal skin in healthy individuals to learn how common this virus is in people generally and to learn whether the virus actually integrates with the host DNA.

“If it proves to be a cancer-causing virus, and if it proves to be common in the general population, it might be something we should begin screening people for,” she says.

Funding from the American Cancer Society supported this research. Ohio State researchers Stephanie Y. Tseng and Dawn C. Allain were also involved in this study.


New Drug Target For Kaposi's Sarcoma

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Posted on : 2:34 AM | By : Biochemistry Den | In : , , , ,

UCSF researchers have identified a new potential drug target for the herpes virus that causes Kaposi’s sarcoma, re-opening the possibility of using the class of drugs called protease inhibitors against the full herpes family of viruses, which for 20 years has been deemed too difficult to attain.

The new drug target, which is known as a protease dimer, could serve as a model for developing new therapeutics for diseases ranging from cancer to Alzheimer’s, the researchers say. Findings are reported in the Advance Online Publication section of the Nature Chemical Biology web site.

Most current antiviral drugs target the active sites of viral proteins, where enzymes and receptors work in a lock-and-key approach to either activate or deactivate that particular protein, the researchers explained. Traditionally, drug development has focused on inhibiting that lock-and-key action to prevent the enzyme, or receptor from being effective.

Some viral enzymes known as proteases, however, including those for HIV and the herpes virus family, take the form of a dimer, or two identical halves – much like a fully opened clamshell – in their most stable state. Those proteases play an essential role in making the virus infectious, but require the two clamshell halves to bind together to be activated, according to the paper.

The HIV protease was successfully targeted for drug development in the 1980s, by blocking the active site on the surface of the dimer, but the herpes virus protease dimer has consistently eluded efforts to disrupt it at its active site, the researchers said.

The UCSF team set out to find ways to instead prevent the two halves of the dimer from connecting at that clamshell joint, to prevent it from activating. What they found was a new target on the unstable, monomer form of the protease, which responded well to a chemical inhibitor.

“If you disrupt the protein-protein interactions, you don’t need the key to a specific lock,” said Charles S. Craik, PhD, senior author on the paper and a professor of pharmaceutical chemistry in the UCSF School of Pharmacy. “Instead, we’re essentially preventing the lock from being made in the first place.”

Craik, who also led a team that identified HIV protease inhibitors in the late 1980s, said the “Nature Chemical Biology” paper validates this new site as a viable option for small-molecule drugs to treat Kaposi’s, as well as other members of this viral family.

“All known herpes virus proteases are structurally similar,” Craik explained. “The inhibitor we found knocks out not only KS, but also the cytomegalovirus protease, so the site we’ve identified here could be a target for a broad-acting inhibitor against the entire viral family.”

To their knowledge, the researchers said, this is the first small-molecule inhibitor of a herpes virus protease to not only act outside the active site, but also to select for the partially unfolded protein to keep it from forming the dimer interface.

Herpes viruses make up one of the most prevalent viral families, including eight human viruses that cause a variety of devastating illnesses, the researchers said. Those include mononucleosis (Epstein-Barr virus), shingles (Varicella zoster virus), genital herpes (herpes simplex), retinitis (cytomegalovirus) and cancer (Kaposi’s sarcoma). While therapies exist for these viruses, they often have negative side effects and are facing rising viral resistance.

In addition to validating herpes virus proteases as suitable targets, Craik said this research was also among the first to use computational design to identify and create a potential drug to target that protease interface.

Using high-throughput screening, the team screened a library of 182 compounds that it had specifically and rationally designed to mimic the protease interface. The work identified six molecules that inhibited the Kaposi’s sarcoma virus protease activity by at least 50 percent, including one that was highly potent.

That discovery potentially opens myriad opportunities for drug discovery, Craik said, by making target receptors that were biologically validated, but then deemed undruggable, more attractive. Protein-protein interactions have been researched as drug targets against a range of diseases, from certain cancers to neurodegenerative diseases. This advance could enable researchers to reconsider those targets, he said.

The lead investigator on the paper was Tina Shahian, with the Graduate Group in Biochemistry and Molecular Biology at UCSF. Co-authors were Gregory M. Lee and Ana Lazic, both in the UCSF Department of Pharmaceutical Chemistry; and Leggy A. Arnold, Priya Velusamy, Christina M. Roels and R. Kiplin Guy, all with the Department of Chemical Biology and Therapeutics at St. Jude Children’s Research Hospital, Memphis, TN.

The CMV protease expression plasmid for this work was provided by Wade Gibson, a professor in the Department of Pharmacology and Molecular Sciences at Johns Hopkins School of Medicine. The work was funded by grants from the National Institutes of Health, the American Lebanese and Syrian Associated Charities and St. Jude Children’s Research Hospital.