Candida Albicans- A Friend Or Foe?

Candida’s ability to cause infection has been identified.

Almost everyone has this fungus in their gut-Candida albicans! Though it lives in almost 80% of the human population, its quantities are kept under control by friendly gut bacterias. Affected are generally those people who have a relatively weak immune system, like HIV-infected patients, cancer chemotherapy recipients, or that are suffering from other severe illnesses. A study published in TheJournal of Biological Chemistry reported that it is now to target the fungal component, which is responsible for causing the dreaded disease.

The major roadblock has always been finding drug targets to control the fungal infection, because fungi are quite closely related to us. This means that if we consume an anti-fungal drug in order to kill the fungus, it might also adversely affect us. Keeping this in mind, research groups at John Hopkins University and Harvard Medical School have identified vacuoles as cellular organelles that play an important role in this process.

Vacuoles are meant to destroy cellular waste due to their acidic nature. The researchers discovered that acidification of vacuoles was important for fungal virulence. The research team focused on V-ATPase, an enzyme responsible for making many compartments of the cell, including the vacuoles, acidic.

Instead of taking whole enzymes into consideration, they homed in on just one of the enzymes components, known as subunit, which comes in many versions due to gene duplication. After inactivating many versions of subunit, they confirmed one subunit involved in imparting acidity as well as virulence to the vacuoles. Now unable to acidify the vacuole, the fungus could no longer form the tentacle-like filaments that characterize its deadly form.

This new discovery has opened many paths in the area of drug discovery. The study reveals a vulnerability that could be exploited using drugs known to alter the pH of the vacuole, rendering Candida harmless, posing little risk to infected patients.

Photo: Flickr, zabozrut
Source :

Patenaude C, Zhang Y, Cormack B, Köhler J, & Rao R (2013). Essential Role for Vacuolar Acidification in Candida albicans Virulence. The Journal of biological chemistry, 288 (36), 26256-64 PMID: 23884420

Human Gut Micro Flora Gives an Index of Obesity

Research shows that less intestinal bacteria is associated with susceptibility to obesity.

With easy access to energy-rich junk food and modern living with a sedentary lifestyle, more and more people are becoming slaves to excessive fat consumption. Yet being a couch potato is dangerous for our health. Studies on the human genome variation show there are significant differences in the genome of bacteria that live in our intestine. The latest research published in Nature reveals that the bacterial population in the intestine varies significantly from obese to thin bodies. This indicates that people with fewer bacterial species in their intestine are more likely to develop complications, such as cardiovascular diseases and diabetes.

An international consortium, including the VIB scientists Falk Hildebrand, Gwen Falony and Jeroen Raes in Brussels, examined the intestinal flora of 292 volunteers from the Ethical Committees of the Capital Region of Denmark before participation in the study. All individuals were examined after an overnight fast with blood sampling and physical body parameter measurements like height, weight, skin fold thickness and bodily circumference at the waist, hip, and chest. Faeces samples were collected from all volunteers and frozen immediately; DNA was extracted from it and sequenced to know the arrangement of genes on DNA. Then gene frequency matching was done to match the intestinal genes to those in the gut bacterial catalogue.

The results were interesting. Two groups were distinguished on the basis of their intestinal flora: People having rich intestinal gut micro flora and people with less bacterial species. Clearly the two groups behaved differently in function. The latter was more susceptible to developing obesity-related conditions and chronic inflammation.  Therefore, it can be inferred that it is not only weight gain and dietary habits that play an important role in the development of medical complications in obese people, but different bacterial species that make up the gut microflora as well.

Reference : Emmanuelle Le Chatelier, Trine Nielsen, Junjie Qin, Edi Prifti, Falk Hildebrand, Gwen Falony, Mathieu Almeida, Manimozhiyan Arumugam, Jean-Michel Batto, Sean Kennedy, Pierre Leonard, Junhua Li, Kristoffer Burgdorf, Niels Grarup, Torben Jørgensen, Ivan Br (2013). Richness of human gut microbiome correlates with metabolic markersNature DOI: 10.1038/nature12506

Researchers Discover New Strategy to Prevent Influenza Infection

Research shows microRNA based strategy to fight against viral pathogens.

H5N1, also called “Influenza A virus,” has the potential to cause catastrophic pandemics. This virus circulates in birds as a pathogen of the digestive and respiratory tracts but, on occasion, gains the capacity to jump to other species and establish respiratory infections in mammals. According to a new study published in Nature Biotechnology, scientists have developed a strategy by which healthy molecules in human lung cells catch these bugs and kill them before they get a chance to infect the human host.

Researchers at Icahn School of Medicine at Mount Sinai have used a microRNA based mechanism to help the body fight against these invading viral pathogens. MicroRNAs are small non-coding RNA molecules that help regulate gene expression. This process involves recognizing a foreign viral particle, creation of small inhibitory RNA (siRNA) molecules and cleavage of virus by siRNAs.  Generally, humans have these small inhibitory siRNA but only to maintain cell health and not for killing such virus. Dr. tenOever and Garcia-Sastre along with scientists from University of Maryland have discovered that altering the viral genome leads to viral genome disruption in the same way as plants do. So, they discovered a unique miR-192 that is found only in human and mouse lung cells but not in ferrets. By addition of multiple binding site of miR-192 onto the H1N5 genome, lung cells completely destroyed the virus in the mice model. Researchers showed that this approach also works well with other influenza A viruses.

This finding is unique in a way that it can be applied to any virus provided humans have a miRNA for the same. Knowledge generated from this study will help resolve concerns that led to a controversy worldwide for research in H1N5 virus.

Reference:
Langlois, RA, Albrecht, RA, Kimble, B, Sutton, T, Shapiro, JS, Finch, C, Angel, M, Chua, MA, Gonzalez-Reiche, AS, Xu, K, Perez, D, García-Sastre, A, & tenOever, BR (2013). MicroRNA-based strategy to mitigate the risk of gain-of-function influenza studies. Nature Biotechnology DOI: 10.1038/nbt.2666

Sensors for Rapid Detection of Proteins Developed

Chemists have developed nano sensors for detecting multiple proteins in tiny samples.

Could you ever imagine that one day testing a protein in your tiny sample would be so easy, just like performing a pregnancy strip test at home. Yes, this is made possible by a group of chemists from Johannes Gutenberg University Mainz (JGU). They have developed a new method for multiple protein analysis that is, in principle, capable of identifying hundreds or even thousands of different proteins. It could be used to detect the presence of viruses and identify their type in tiny samples. The method is quite efficient, quick and cost-effective which means it may find application in medicine, water monitoring, environment technology, food analysis, etc.

The procedure involves taking of a small drop of sample which can be blood, saliva or any body fluid on a small test strip. The test strips consist of glass capillary tubes that basically have gold nano-particles as sensor elements on their internal surfaces. Because the test sample is very small so nano sized sensors are to be used in order to identify many proteins. The nano-particles are prepared using specific DNA strands which have affinity to the foreign proteins. Thus, when a protein locks with one of these special DNA strands, the corresponding nano-particle changes its color. This change is then detected by a spectrometer. This is a very simple method by which multiple proteins can be identified simultaneously in a fluid-flow containing randomly placed nano-rods, reported by researchers from JGU’s Institute of Physical Chemistry.

The study published in Nano Letters can be very useful for detecting various flu viruses that infects people world-wide. Also, it will be used in detection of various kinds of toxin in environment or food, particularly milk or baby food as well as in identifying  doping cases.

Reference:
Rosman C, Prasad J, Neiser A, Henkel A, Edgar J, & Sönnichsen C (2013). Multiplexed Plasmon Sensor for Rapid Label-Free Analyte Detection. Nano letters PMID: 23789876

Gut Microbes Help Rootworms to Adapt

How rootworms can adapt and become resistant to the practice of crop rotation.

You know it’s not only you and me who are constantly evolving by adjusting to our living environment;  There are millions of others too who are doing this job as efficiently as it could be. Researchers from University of Illinois have discovered that gut bacteria facilitate the adaptation of the western corn rootworm, which is basically a beetle, to crop rotation.

Crop rotation is a practice of growing two different types of crop in the same field in sequential seasons. Corn and Soybean are two important crops in the Midwest Corn Belt. They are grown alternately, meaning that after a season of farming corn crop, farmers usually plant soy in the same field. This practice should wipe out corn rootworms (Diabrotica virgifera virgifera) which feed on corn during summer and lay eggs in the fall. The larva feeds essentially on corn roots during spring, which causes severe root injury and yield loss. In order to avoid this, soybean is grown in the subsequent season, so that when larvae emerge, it feeds on potentially toxic soy and dies. This way crop rotation had been effective for several decades until recently.Things have changed, however, and farmers began to find rootworms even in the rotated fields.

A research team led by Chia-Ching Chu now analyzed the microbiota of resistant and non-resistant beetles. They dissected almost 4000 insects and found significant differences in the two types of microbe’s community in their gut. The specialized microbe community helped the resistant rootworms to physiologically adapt to consuming soybeans.

The scientists also found that resistant rootworms had elevated levels of cysteine protease inhibitors when being the soy field. Cystein proteases are group of enzymes that are present in Soybean leaves/foliage. When rootworms feed on them, the proteases degrade important proteins of rootworms and therefore, the worms die. Due to evolution, resistant rootworms produces Cysteine protease inhibitors, which means they degrade those enzymes and hence, the rootworms can now feed on soybean without getting affected.

This is perhaps why resistant rootworms are able to survive in soybean fields after hatching eggs and crop rotation was unsuccessful.

The study published in PNAS Early edition paves way for the need of much deeper understanding of the host-microbe relationship from an evolutionary perspective that may have significant importance in sustainable management.

Reference:Chu CC, Spencer JL, Curzi MJ, Zavala JA, & Seufferheld MJ (2013). Gut bacteria facilitate adaptation to crop rotation in the western corn rootworm. Proceedings of the National Academy of Sciences of the United States of AmericaPMID: 23798396

New Engineered Bacteria becomes a Biofuel Precursor

Research shows using genetic engineering approach, desired products can be produced.

Global population explosion puts us in a very difficult stage where it is very important to have alternatives to modern day fuels like gasoline that fuels million of cars with internal combustion engines as our current biofuels sources are exhaustible. In a recent finding published in PNAS, Scientists at the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Department of Systems Biology at Harvard Medical School have engineered a bacterium which is capable of producing biofuel precursors that is reported to have high-octane fatty acid moieties.

The E. coli uses a natural oil production mechanism to convert sugars into fats which are then used in the bacteria’s cell membrane. By genetically altering E. coli, researchers were able to convert the sugars to the imitation fossil fuel. Pamela Silver and her team are focusing on medium-chain fatty acids (MCFA), those with chains between four and 12 carbons long as they are just the right length to be transformed into an energy-packed liquid fuel for internal-combustion engines. Fatty acids with shorter chains do not store enough energy to be good fuels and they tend to vaporize easily, while those with chains longer than 12 carbons are too waxy. Through genetic engineering approach, a drug was used which blocks the enzyme that extends fatty-acid chain synthesis. This led to the production of eight-carbon fatty acid called octanoate which can be converted into octane. Basically, they stopped the usual pathway where addition of carbon atoms leads to build up of long chain fatty acids in the middle such that it only produces MCFA. This led to the buildup of MCFA pool.

Though gasoline produces more energy than current biofuels when burned in an internal combustion engine, and remains liquid in wide temperature range but burning gasoline itself adds huge amounts of carbon dioxide to the atmosphere which is a global concern. The strategy reported in this study should be widely useful in a range of metabolic engineering applications in which essential enzymes divert flux away from a desired product. It will also help in producing precursors of pharmaceuticals, bioplastics, herbicides, detergents, and more.

Source: J. P. Torella, T. J. Ford, S. N. Kim, A. M. Chen, J. C. Way, P. A. Silver. Tailored fatty acid synthesis via dynamic control of fatty acid elongation. Proceedings of the National Academy of Sciences, 2013; DOI: 10.1073/pnas.1307129110

Super Sugar Keeps Naked Mole Rats Cancer-Free

Researchers have discovered how nature’s oddest creature has given up the secret of its incredible cancer immunity and longevity.

The naked mole rat, a hairless rodent that lives underground has never been known to get cancer, despite its unusually long 30-year lifespan. Researchers at the University of Rochester, New York have achieved a breakthrough by discovering a chemical compound which is a complex sugar, called hyaluronan that exists between cells in body tissues and helps keeps them from clumping and forming tumors.

Known as high molecular weight hyaluronan, HMW-HA is a part of extracellular matrix of many animals but naked mole rats are unusual in producing it about five times the size found in mice, rats and humans. It has an annoying tendency to clog up vacuum pumps and tubing in the laboratory, that’s when it caught attention.

Researchers tested the role of HMW-HA by removing the gooey substance from naked mole rat cells. As predicted, those rats became susceptible to tumors, thereby suggesting its role in conferring resistance against cancer. The research, published in the journal Nature showed that mole rat hyaluronan activates a powerful anti-cancer gene called p16 which prevents cells proliferation when too many of them crowd together. The important gene HAS2 was responsible for producing high levels of HMW-HA in mole rats owing to production-boosting mutations to the enzyme that synthesizes HA and low activity of the enzyme that degrades the molecule.

Researchers then tried to prompt tumor growth by exposing the mole rats to proteins that cause cancer in mice. Nothing happened until the production of hyaluronan was altered. The biologists speculate that naked mole rats have evolved a higher concentration of HA in the skin to provide skin elasticity needed for life in underground tunnels. This trait may have then been co-opted to provide cancer resistance and longevity to this species.

The finding establishes hyaluronan as a key player in cancer that could lead to exciting new opportunities in cancer treatments for human patients.

Source: Xiao Tian, Jorge Azpurua, Christopher Hine, Amita Vaidya, Max Myakishev-Rempel, Julia Ablaeva, Zhiyong Mao, Eviatar Nevo, Vera Gorbunova, Andrei Seluanov. High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat. Nature, 2013; DOI: 10.1038/nature12234

 

How to Trigger the Fruit Growth Hormone

Research shows ethylene is responsible for regulating the action of other hormones in the plant developmental pathways.

If someone told you to put your rock hard green McIntosh apple with a banana as that would make it ripe, you sure would scoff a little. But, believe your ears and do that yourself. It’s an easy way to get that red juicy goodness without spending a single penny! It sounds like magic –  but it’s pure science. A very recent study by scientists from the Salk institute for Biological Studies have published their finding in the online international journal eLIFE – stating that the plant hormone ethylene alone activates thousand of other genes in a plant.

Ethylene is a gaseous plant hormone that acts at trace levels to stimulate or regulate a variety of processes, including the regulation of plant growth, the ripening of fruit and the shedding of leaves. It is also produced in response to wounding or pathogen attack, exposure to environmental signals such as extreme temperature or drought conditions. All these effects are produced by altering the expression of different genes. Although the effects of ethylene on plants are well documented, much less is known about how its many functions are controlled and coordinated at the molecular level. So how does it work?

It was validated in the model plant Arabidopsis thaliana, by performing molecular level studies to see what happens when it is exposed to ethylene gas? What genes are turned on and what they actually do? It was evidenced that ethylene directly activates a protein, known as EIN3 which is a master regulator in ethylene signaling pathway. Scientists used a technique called ChIP-Seq to identify those regions of DNA where EIN3 binds to. And the number was surprising: over a thousand!

Two interesting things were discovered. First, when EIN3 is activated by ethylene, it activates all those genes that activate its own production. Second, it targets all other hormone signaling pathway in plant because half of the genomic targets of the EIN3 protein were found to be in other hormone signaling pathways.

This clearly shows how ethylene genetically controls the intricate signaling and developmental pathways in the plant. The piece of knowledge generated from this study would help in mapping interconnections between the hormone pathways that have implications on agriculture.

 

Reference: Katherine Noelani Chang, Shan Zhong, Matthew T Weirauch, Gary Hon, Mattia Pelizzola, Hai Li, Shao-shan Carol Huang, Robert J Schmitz, Mark A Urich, Dwight Kuo, Joseph R Nery, Hong Qiao, Ally Yang, Abdullah Jamali, Huaming Chen, Trey Ideker, Bing Ren, Ziv (2013). Temporal transcriptional response to ethylene gas drives growth hormone cross-regulation in Arabidopsis eLife

Probiotics in Food Affect Brain Functions

The general reputation of bacteria is that it causes disease, so the idea of tossing down a few billion a day for your health might seem — literally and figuratively — hard to swallow. Probiotics (from pro and biota, meaning “for life”), are basically live microorganisms that confer a health benefit on the host. It’s not surprising why then, therefore, Europeans consume a lot of these beneficial micro-organisms because of their tradition of eating foods fermented with bacteria, such as yogurt. The study reported in Gastroenterology by UCLA scientist’s shows that changing the bacterial environment or microbiota in the gut can have significant implications on your brain functions.

A research was conducted on 36 healthy women in the age group of 18 to 55 having no past gastrointestinal or psychiatric symptoms. These women were divided into the group of three: one group consumed a specific yogurt containing a mix of several probiotics which were bacteria thought to have a positive effect on the intestines, twice a day for four weeks; another group consumed a dairy product that looked and tasted like the yogurt but contained no probiotics; and a third group ate no product at all. The women were given an emotion recognition task where they had to view the pictures of people with angry or frightened faces and match them to other faces showing the same emotions. This was basically done to measure the involvement of brain regions to visual stimuli. The participants then underwent a technique called as Nuclear Magnetic Resonance imaging which scanned the brain of these women before and after this four-week study period. The results were interesting.

The researchers found that, women who ate the probiotic yogurt showed a decrease in activity of two important areas of brain whereas women who ate no probiotics showed stable or increased activity. It was only suspected until proved that there is a two way gut-brain connection. Certainly, some chemicals produced by gut bacteria triggers such signals to the brain. This is an interesting finding which opens up a scope in future that leads to expansion of research aimed at finding new strategies to prevent or treat digestive, mental and neurological disorders by modulating dietary changes in human.

Reference:Tillisch, K., Labus, J., Kilpatrick, L., Jiang, Z., Stains, J., Ebrat, B., Guyonnet, D., Legrain-Raspaud, S., Trotin, B., Naliboff, B., & Mayer, E. (2013). Consumption of Fermented Milk Product with Probiotic Modulates Brain ActivityGastroenterology DOI: 10.1053/j.gastro.2013.02.043

Carnivorous Plant Ejects Junk DNA

Research shows Utricularia gibba maintains a small genome size by resisting gene duplications.

Nature is beautiful and so are its mechanisms. The carnivorous humped bladderwort (U. gibba) is unique in showing a wonderful evolutionary trait which would put all of us in awe; wondering if we could, would we ever remove a part of us which we thought is never going to be of any use. The finding published online inNature overturns the notion that repetitive, non-coding DNA or “Junk DNA” is necessary for life.

While duplication of genes and mobile elements such as transposons are the basis of increasing complexity of plant genome, U. gibba; a relative of the tomato, has experienced a net gain of just 1.5% in its size, since their split 87,000 years ago. It has retained only a single copy of its genes. This means it has ejected everything it doesn’t need and therefore now has a genome only 10th the  size of a tomato’s genome.

It is well known that transposons play a primary role in increasing genome size. The bladderwort is unique in having almost no retrotransposons whatsoever. Apparently, this intelligent carnivore has retained all the miRNA silencing genes. miRNA’s do not encode their own proteins, but they do bind messenger RNA, preventing their encoded proteins from being constructed and this is how they are exceptional in suppressing these retrotransposons in the bladderwort. This indicates that, despite its small genome, the general repertoire of miRNA mediated gene regulation in plants is conserved in U. gibba.

This first-of-its-kind study has again fueled the debate deciding whether junk DNA is either Trash or Treasure. The question still remains as to why the genomes have accumulated so much non-coding DNA when this carnivore could do well with bare essentials.

 

Source: Ibarra-Laclette, E., Lyons, E., Hernández-Guzmán, G., Pérez-Torres, C., Carretero-Paulet, L., Chang, T., Lan, T., Welch, A., Juárez, M., Simpson, J., Fernández-Cortés, A., Arteaga-Vázquez, M., Góngora-Castillo, E., Acevedo-Hernández, G., Schuster, S., Himmelbauer, H., Minoche, A., Xu, S., Lynch, M., Oropeza-Aburto, A., Cervantes-Pérez, S., de Jesús Ortega-Estrada, M., Cervantes-Luevano, J., Michael, T., Mockler, T., Bryant, D., Herrera-Estrella, A., Albert, V., & Herrera-Estrella, L. (2013). Architecture and evolution of a minute plant genome Nature DOI: 10.1038/nature12132