BioXplorer

Azoospermia caused by the same molecular mechanisms as Cystic Fibrosis

primoto — Wed, 11 May 2011 19:31:19 +0000

A recent research article reveals that the molecular causes for Azoospermia and Cystic Fibrosis could be common!

But first, some background information…

Azoospermia in brief

Azoospermia is a male medical condition of having low or not having any measurable level of sperm in semen. This results in very low levels of fertility or even sterility. Some forms of azoospermia are susceptible to medical treatment. Azoospermia affects about 1% of the male population and is the reason for up to 20% of male infertility cases.
From medical point of view there are three types of azoospermia – pretesticular, testicular and posttesticular azoospermia. Based on these types and the genetic causes of the disease vary:

Pretesticular azoospermia is associated with gonadotropin deficiency (induced by diseases like congential hypopituitarism, Kallmann syndrome, Prader-Willi syndrome).
Testicular azoospermia is seen in Klinefelter syndrome(XXY) and the XX male syndrome and defects of the Y chromosome (a section of the long arm of the Y chromosome has been termed Azoospermia Factor)
Recent studies (and the one I am referring now) demonstrates that posttesticular azoospermia can caused malfunctioning (e.g. point mutations) of the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

Cystic Fibrosis main facts

Cystic fibrosis (also known as CF or mucoviscidosis) is a common inherited chronic lung disease that causes thick, sticky mucus to build up in the lungs and digestive tract.

Cystic fibrosis is caused by a mutation in a gene which encodes a regulatory protein of a transmembrane conductance – cystic fibrosis transmembrane conductance regulator (CFTR). This gene is involved in the regulation the components of sweat, digestive juices, and mucus. In the human genome there are to copies of this gene – so that if the person have a mutation just in one of the CFTR loci, the cystic fibrosis will not be developped. Therefore, CF is considered an autosomal recessive disease.

A recent research paper published in PloS ONE, reveals clear relation between the mechanisms which cause Cystic Fibrosis and Azoospermia.

As a model study organisms were used CFTR knockout mice. They showed decreased expression levels in testis for cystic fibrosis transmembrane conductance regulator (CFTR) and cAMP-responsive element binding protein (CREB). The CFTR is involved in HCO₃⁻ transport and the expression of the HCO₃⁻ sensor – a soluble adenylyl cyclase (sAC). Inhibition of CFTR or depletion of HCO₃⁻ could reduce FSH-stimulated, sAC-dependent cAMP production and phosphorylation of CREB, the key transcription factor in spermatogenesis. The present study reveals a previously undefined role of CFTR and sAC in regulating the cAMP-CREB signaling pathway in Sertoli cells, defect of which may result in impaired spermatogenesis and azoospermia. Altered CFTR-sAC-cAMP-CREB functional loop may also underline the pathogenesis of various Cystic Fibrosis and related diseases.

With the developments in genetic testing, laboratories now offer a wide range of DNA test services covering areas such as the genetic health tests and paternity testing.

The full study revealing the linkage between azoospermia and cystic fibrosis is available for free at PloS ONE.

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Human Microbiome – Discover a New Universe Hidden in Your Body!

primoto — Mon, 18 Apr 2011 17:32:50 +0000

Human Microbiome Project will map the genetic sequences of bacterial world hidden in our bodies!

If you recall the biology course in the college, the average human being is a collection of about 10 trillion eukaryotic cells – each with a nucleus storing 23 chromosome pairs of nucleic DNA, and a collection of membrane-bound organelles including mitochondria with genetic material of their own. What is less obviously that each of us is also carrying around 100 trillion prokaryotic cells, from thousands of different bacteria species.

Following up on the Human Genome Project – which aimed to decode the three billion nucleotides in the human genome – the Human Microbiome Project seeks to identify and annotate the genetic sequences of those bacteria.

Many of those bacteria play critical roles in biological processes that sustain human life – digestion is just one of them. Others may be the benign residents of niches where more harmful microorganisms might otherwise live. Already, it has been theorized that these bacteria has an impact on diseases including diabetes, autism, cancer, and cardiovascular diseases.

The initial estimates are that collectively these bacterial species are thought to have 100 times more genetic material than the colony of human cells. Well, this is expected to be so, since the variety of distinct organism is expected to be huge…

Some initial DNA sequencing projects sequencing DNA from the human gut – have found that there are thousands of species, and that the bacterial micro-environments are dramatically different in different areas of our bodies – the mouth has its own microbial environment (microbiome), for example, which is very different from the skin. On the other hand there are big similarities between people – if you look at the bacteria living in the gut of two different people, they have a lot in common. It might turn out that many of these bacteria are “inherited” or transferred as “Lamarck’s dogma” have been postulated long time ago – that they are passed on from parents at some point during childhood, or maybe even acquired from others in our community.

The Human Microbiome Project is one of the several metagenomics efforts following the most popular to the public one – Craig Venter’s Global Ocean Sampling Expedition. The project outcomes might serve both the practical function of helping to better understand and treat human disease and the more esoteric one of refining our understanding of what it means to be a human being, biochemically at least.

Currently, researchers can grow only some of the bacteria, fungi and viruses in a laboratory setting. However, new genomic techniques can identify minute amounts of microbial DNA in an individual and determine its identity by comparing the genetic signature to known sequences in the project’s data base.

The Human Microbiome Project reference collection consists of 178 microbial genomes of total approximately 900 microbial genomes of bacteria, viruses and fungi. These data will then be used by the researchers to characterize the microbial communities found in samples taken from healthy human volunteers and, later, those with specific illnesses. Samples are currently being collected for Human Microbiome Project from five areas of the body:

the digestive tract
the mouth
the skin
the nose
the vagina

Although that the Human Microbiome Project have been initiated in 2008, it still did not provide any valuable insights (or at least to my knowledge!). There were some published comparative analysis (they have identified 29,693 previously undiscovered, proteins in the reference collection and compared their results to the available sequenced microbial genomes and found 14,064 novel proteins). Probably the reason is that just the sequencing of the Human Microbiome is just the first step, the more important part is to identify the structural and fucntional elements within the sequences and to annotate them.

Let’s give to the Human Microbiome project the time needed!

Resources:

Project home

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Life on the edge: amazing creatures thriving in extreme environments

primoto — Mon, 04 Apr 2011 11:19:53 +0000

The second issue of Emerging Cancer Therapeutics focuses on multiple myelomas also known as plasma cell myeloma, Kahler’s Disease and myelomatosis. It is estimated that over 20,000 new cases are diagnosed each year with over 10,000 people dying from these malignancies. Multiple myelomas are highly treatable but rarely curable. Thus it is crucial for the practitioner to be up-to-date on the latest insights regarding their management.

Management options and outcomes for individuals with multiple myelomas improved dramatically with the introduction of chemotherapy. Even further improvements in prognosis have occurred because of the introduction of newer therapies such as pulse corticosteroids, thalidomide, bortezomib, and autologous and allogeneic stem cell transplantation. With the increased number of therapeutic options to choose from, the clinician is better placed to offer effective therapy nut at the same time is challenged to keep abreast of the rapidly changing treatment landscape and the newly emerging data that is shaping the treatment options today and in the future. Multiple Myeloma provides a comprehensive and in-depth review of this group of malignancies. This volume reviews the current literature, provides critical evaluations of the data and offers evidence-based recommendations. Written by leaders in their fields, chapters update the epidemiology of multiple myeloma, genetic abnormalities in myeloma, MGUS, Initial therapy, the role of stem transplantation, risk factors and management.

Publisher: Basic Books; 1 edition (January 2001)
Language: English
ISBN-10: 0738204455
ISBN-13: 978-0738204451

Disclaimer: The site does not host any copyrighted by a third party materials. The books content preview is provided by Google Books API.

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(The most) Extremophile Bacteria

primoto — Mon, 04 Apr 2011 11:02:54 +0000

Extremophile bacteria suggests new possible life systems?!

Life (as we know it!) is mostly composed of 6 elements – carbon, hydrogen, nitrogen, oxygen, sulfur, and phosphorus. These six elements make up all the viable organic compounds in the organisms – nucleic acids, proteins, and lipids – the bulk of living matter.

In theory it is possible that some other elements in the periodic table could serve the same functions as the “core” 6 elements.

There is a category of organisms (almost all of them are bacteria) called Extremophiles, which could not only survive, but “feel just perfect” in conditions far from those considered as “normal” for the rest of the living beings. All of the known extremophile bacteria could live in highly severe conditions – very low or very high temperatures, highly acidic (low pH values) and similar, but there was none that could replace one of the core elements with alternative and to use it for building it’s structural and functional units. You can read more about extremophiles in Life on the Edge!

Recently, a new Halomonadaceae extremophile bacteria, strain GFAJ-1 was isolated from Mono Lake in California, US. The bacterium is capable to substitutes phosphorus with arsenic to sustain its growth. The researchers prove that this organism synthesize arsenate containing macromolecules that normally contained phosphate – mostly proteins and nucleic acids.

What I come up with, based on these findings is that these “abnormal” substitutions could be triggered just because of the extreme conditions, in which these organisms live. As we know that the conditions on distant planets differ to much from the “normal” conditions on Earth, I can imagine that similar to this extremophile bacteria organisms could be considered as quite normal on other planets and vice versa!

Do you think than on the distant planet HD 189733 b, arsenate utilizing living forms will be classified as “extremophile bacteria“, or they will be considered as normal?

With the developments in genetic testing, laboratories now offer a wide range of DNA test services covering areas such as the genetic health tests and paternity test.

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Multiple Myeloma – Emerging Cancer Therapeutics

primoto — Mon, 28 Mar 2011 10:53:21 +0000

Hardcover: 176 pages
Publisher: Demos Medical Publishing; 1 edition (July 30, 2010)
Language: English
ISBN-10: 1933864915
ISBN-13: 978-1933864914

Disclaimer: The site does not host any copyrighted by a third party materials. The books content preview is provided by Google Books API.

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Multiple Myeloma Genome Sequenced

primoto — Mon, 28 Mar 2011 08:42:58 +0000

Mapping the Multiple Myeloma Genome Will Provide New Clues to It’s C

auses

This week, a set of multiple myeloma genomes sequencing project have been successfully completed! The initial analysis of the sequencing data revealed the assortment of mutated genes involved in the multiple myeloma (that have never been suspected before). This makes possible the identification of the molecular mechanisms and could suggest chemical pathways to target in future therapies (some of which are already in development). For the first time, scientists have accessed the molecular causes of multiple myeloma – an aggressive, incurable blood cancer with a 5-year survival rate of 40%.

Multiple Myeloma Molecular Mechanisms

Multiple Myeloma is a cancer of blood plasma cells, which are responsible for the production of antibodies. The abnormal are attacking solid bone (causing bone lesions) and in the bone marrow where they interfere with the production of normal blood cells (malignant white blood cells). In most multiple myeloma cases is observed elevated production of paraprotein (frequently called M protein), an abnormal antibody that interferes with the production of normal antibodies leading to immunodeficiency, kidney problems or hypercalcemia. When myeloma cells collect in several of your bones, the disease is called Multiple Myeloma.

More about the molecular mechanism of multiple myeloma and the emerging trends in the disease therapeutics could be found in the book Multiple Myeloma – Emerging Cancer Therapeutics.

The disease develops in 1–4 per 100,000 people per year (about 20,000 new cases in the US a year.). It is more common in men, and is twice as common in blacks as it is in whites. With conventional treatment, the prognosis is 3–4 years, which may be extended to 5–7 years or longer with advanced treatments.

Sequencing and Analysis of the Multiple Myeloma genome

To map out its genetic code, researchers sequenced 38 tumor genomes from multiple myeloma patients, and then compared them with the patients’ normal DNA sequences. Further they have compared the sequences to the normal genome that provides clues about what makes a normal cell into a cancer cell. The aim was to discover mutations that are recurring at low frequency, so that it will make possible to extract significant patterns from the data.

The study identified a set fo genes which were never thought before to have an implication in multiple myeloma. For example the study identified that 4% of the multiple myeloma patients have mutations in the BRAF gene – a gene related to skin myeloma, but never found to be causing multiple myeloma.

That means an immediate trial could be done in a subset of multiple myeloma patients using a drug already in late-stage development.

The new hope – Next-generation sequencing, will allow scientists to comprehensively analyze the cancer genome at high resolutions and to provide valuable insights of molecular mechanism multiple myeloma.

With the developments in genetic testing, laboratories now offer a wide range of DNA test services covering areas such as the genetic health tests and paternity test.

Tissue Engineering: From Lab to Clinic

primoto — Fri, 25 Mar 2011 08:37:38 +0000

Tissue engineering is a multidisciplinary field incorporating the principles of biology, chemistry, engineering, and medicine to create biological substitutes of native tissues for scientific research or clinical use. Applications of this technology include studies of tissue development and function, investigations of drug response, and tissue repair and replacement. Tissue engineering is rapidly becoming one of the most promising treatment options for patients suffering from tissue failure. This abundantly illustrated and clearly structured guide, written by leading experts, is intended to serve as a reference for all clinicians and researchers who deal with tissue engineering issues in their daily practice and for students studying tissue engineering at both the undergraduate and the graduate level. It will also be invaluable for professionals in related research areas, particularly those where cell and tissue culture is a new or emerging tool. The book is divided into three sections that present the latest findings in tissue engineering and their application in clinical practice. The first section discusses the basics and principles of tissue engineering, including scaffolds, cells, and technologies. The second and third sections then address in detail the tissue engineering of specific organs and tissue types. A visual approach is emphasized throughout, with numerous self-explanatory graphics, diagrams, and photos.

Hardcover: 643 pages
Publisher: Springer; 1st Edition. edition (March 10, 2011)
Language: English
ISBN-10: 3642028236
ISBN-13: 978-3642028236
ASIN: 3642028233

Disclaimer: The site does not host any copyrighted by a third party materials. The books content preview is provided by Google Books API.

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Exploring The Universe

primoto — Mon, 21 Mar 2011 12:25:04 +0000

I was quite lucky today!

My day started with interactive exploring the Universe with the interactive media “Scale of the Universe” developed by Cary Huang at htwins.

You can start Exploring the Universe from the “quantum foam” – the first physical sense. Continue through neutrinos, quarks and moving to the chemical world of atoms and molecules. Then zoom out to the Biology World of DNA,proteins, viruses, bacteria, small organisms, human and population level. You can end up in the deep space, passing through the Solar system, The Milky way and, at the end “THE UNIVERSE”.

While you are exploring the universe, you will notice that we are not in the center of the it

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Largest genome on Earth

primoto — Fri, 18 Mar 2011 18:10:23 +0000

Which species has the largest genome?

Humans? No…

Ahhh, I remember the polyploidy was a process observed in higher plants. Then, well it could be a plant?

OK, here is the answer – the largest genome belongs to Paris japonica, a rare Japanese flower.

The flower has the unbelievable 149 billion base pairs, which is about 50 times the size of a human genome and makes it the owner of the largest genome ever found (till now!). The former champion was marbled lungfish – 130 billion base pairs weighed in at an impressive 132.83 picograms.The plant is an octoploid and a “suspected” allopolyploid, containing genetic material from 4 species. At the end the plant has 40 chromosomes (close to the haplotype of humans). The genome of the new record-holder would be taller than Big Ben if stretched out end to end.

Just for comparison, the smallest known genome of an eukaryote is that of a mammalian parasite known as Encephalitozoon intestinalis – 2.25 million base pairs.

Besides the huge amount of information coded, to have the largest genome tend to be a liability – plants with lots of DNA have more trouble tolerating pollution and extreme climatic extinctions—and they grow more slowly than plants with less DNA, because it takes so long to replicate their genome.

With the developments in genetic testing, laboratories now offer a wide range of DNA test services covering areas such as the genetic health tests and paternity test.

The largest genome study is revealed in a paper in the Botanical Journal of the Linnean Society.

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Spliceosome

primoto — Thu, 17 Mar 2011 18:47:21 +0000

It was very hard to select my first “Bio Celebrity”. At the end my choice is – The Spliceosome!

The spliceosome is the component that makes possible the “maturation” of the mRNAs (removing the introns from the transcribed pre-mRNAs) and which was more important for my choice, the spliceosome determines the genetic diversity in eukaryotes in the context of the alternative splicing.

Each spliceosome is composed of five small nuclear RNA proteins, called snRNPs and a range of non-snRNP associated protein factors. The snRNPs that make up the nuclear spliceosome are named U1, U2, U4, U5 and U6. All of the are highly interconnected (via RNA-RNA interactions ) and also interact with proteins, forming a huge complex. The RNA component of the snRNP is rich in uridine.

The mRNA splicing is a quite complicated process and determines the assembled of the spliceosome. The splicing is quite well described in the post’s video.

BioXplorer

Azoospermia caused by the same molecular mechanisms as Cystic Fibrosis

Azoospermia in brief

Cystic Fibrosis main facts

The full study revealing the linkage between azoospermia and cystic fibrosis is available for free at PloS ONE.

Incoming search terms:

Human Microbiome – Discover a New Universe Hidden in Your Body!

Human Microbiome Project will map the genetic sequences of bacterial world hidden in our bodies!

Let’s give to the Human Microbiome project the time needed!

Incoming search terms:

Life on the edge: amazing creatures thriving in extreme environments

Incoming search terms:

(The most) Extremophile Bacteria

Extremophile bacteria suggests new possible life systems?!

Do you think than on the distant planet HD 189733 b, arsenate utilizing living forms will be classified as “extremophile bacteria“, or they will be considered as normal?

Incoming search terms:

Multiple Myeloma – Emerging Cancer Therapeutics

Incoming search terms:

Multiple Myeloma Genome Sequenced

Mapping the Multiple Myeloma Genome Will Provide New Clues to It’s C

auses

Multiple Myeloma Molecular Mechanisms

Sequencing and Analysis of the Multiple Myeloma genome

Read more about Sequencing the Multiple Myeloma Genome in Nature magazine, the article has full free access!

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Tissue Engineering: From Lab to Clinic

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Exploring The Universe

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Largest genome on Earth

OK, here is the answer – the largest genome belongs to Paris japonica, a rare Japanese flower.

The largest genome study is revealed in a paper in the Botanical Journal of the Linnean Society.

Incoming search terms:

Spliceosome

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