Biology Online is a Biology blog and dictionary site that provides up to date articles on the latest developments in biological science. The Biology Online Dictionary is a completely free and open dictionary with over 60,000 biology terms. It uses the wiki concept, so that anyone can make a contribution.
Category: Molecular Biology

Colon cancer : Independent prognostic genes and mechanisms

Colon Cancer is the third most deadly cancer worldwide. There were more than 1.4 million cases each year and 694,000 deaths globally. The treatment of colon cancer includes chemotherapy, surgery and radiation therapy. However, advances in diagnosis and treatment leads to development and improvement in survival. Numerous data point out that genetic changes function as vital role in the development of colon and rectal cancer. In which regulatory molecules mRNA affects various molecular and cellular target including cancer cells. That is why, development in research used mRNA as based diagnostic biomarkers for colon cancer in human. Furthermore, certain kind of mRNA used to predict survival in colon cancer patients. As well as a better knowledge of molecular mechanisms and associated gene is important for early diagnosis and treatment.

 

ULBP2 a novel prognostic biomarker in Colon Cancer

ULBP2 is a potential biomarker in colon cancer survival. Previous study shows that matrix metalloproteinase-9 reveals as an important marker for postoperative prognosis in colorectal cancer patients. Also extracellular matrix plays a vital role in cancer progression in which it provides structural and biochemical support in cells.  Despite from all of these, digestion is also considered to have a major role related to cancer preventive activity. Additionally, an in vitro of peptides gastrointestinal digestion can inhibit colon cancer cells proliferation and inflammation. Moreover, recent study showed that up and down regulated mRNAs are largely amass in extracellular matrix and digestion. As a result, it would entails that abnormality of extracellular matrix and digestion takes part in colon cancer progression.

 

Furthermore, the Wnt signaling pathway gives clinical importance on various diseases including colon cancer. Since alteration of this pathway are mostly observed in colorectal cancer with microsatellite instability. So, inhibiting this pathway might be helpful strategy for targeting chemotherapy-resistance cells. Also drug metabolism determined resistance of colorectal cancer resorcinol-based heat shock protein 90 inhibitors. Therefore, Wnt signaling and drug metabolism are both important pathway enriched by up and down regulated mRNAs.

 

Prognostic biomarkers are very important and have the power to change the course of disease if only knew beyond prognostic factors. In this research ULBP2 gene that encodes cell surface glycoprotein located at chromosome 6 demonstrates prognostic biomarker for colon cancer. High level of ULBP2 is deemed independent indicator for overall survival and identified as the sole outstanding mRNA.

 

Source: Prepared by Joan Tura from BMC Biological Research

Volume 51:10 March 29, 2018

How cell fixes DNA damage

DNA repair strategies – overview

DNA is crucial to life. It carries the fundamental blueprint for the proper functioning of a cell. Thus, a damaged DNA could indicate trouble. A mere structural change could lead to the disruption of the genetic code crucial to the building of proteins. Without an apt and prompt DNA repair, mutation arises. Many of these mutations can lead to genomic instability, and ultimately to metabolic dysfunctions, aging, or diseases, such as cancer. DNA repair strategies are of two major classes: (1) the direct reversal of the chemical process that caused the damage and (2) the replacement of damaged nitrogenous bases.1

 

 

DNA repair by direct reversal

The integrity of DNA structure must be kept up at all times as much as possible. Otherwise, the cell would not be able to function as it normally would. Inopportunely, DNAs are prone to damage when exposed to certain mutagens, such as radiation and chemicals. Exposure to them could lead to the incorporation of an incorrect nucleotide during DNA replication.1 One way to correct this is through a direct reversal DNA repair mechanism. In this DNA repair strategy, a template is not required and the change is superseded as the original nucleotide is restored.

 

 

DNA repair by excision

Damaged DNA may also be repaired by excision. Unlike the first DNA repair mechanism that does not require a template (as described above) DNA repair by excision requires one. DNA is a double helical structure. Because of this, the undamaged DNA strand could be used as a basis when correcting the damaged strand. It is done so by excising and replacing the damaged DNA with new nucleotides. There are three forms of excision repair: (1) base-excision repair (where a single nucleotide change is recognized and subsequently excised by glycosylases), (2) nucleotide excision repair (where multiple base changes are recognized and then cleaved by endonucleases), and (3) mismatch repair (when mismatched bases are later recognized and eventually corrected by excising the error). All these excision repair mechanisms lead to the definitive restoration of the original sequence.1

DNA repair mechanisms

 

 

Recent study on DNA repair

A recent study by a research team from the University of Southern California reported a DNA repair mechanism in fruit fly cells and mouse cells. They likened the mechanism to an emergency responding team. Accordingly, the DNA repair mechanism of the cell includes a team of paramedics (i.e. myosins) that carry damaged DNA to an emergency room (i.e. nuclear pore) located at the periphery of the nucleus. They found that broken DNA strands prompt a series of threads, called nuclear actin filaments, to assemble and form a transient “road” that links to the edge of the nucleus. The myosin (i.e. a protein conveyed to be “walking” because of the presence of “two legs”) treads the road formed by the nuclear actin filaments while it carries the injured DNA strand towards the nuclear pore. The nuclear pore is viewed by the researchers as the emergency room for damaged DNAs since it is where the cell repairs them.2

An illustration depicting myosins that act as paramedics carrying damaged DNA along nuclear actin filaments, which serve as a transient road towards the nuclear pore. (Illustrator: Vix Maria ©Biology-Online.org)

 

 

The cell with its own scheme for DNA repair is indeed remarkable. DNA carries the code that specifies how proteins are made. Without the cell’s innate ability to correct DNA damage, its integrity would be impaired as well. Two major strategies arise: one that rolls the error back to the original and the other that replaces the damage anew based on a template. The recent findings on DNA repair mechanism on fruit flies and mouse cells revealed how remarkable the process already is and how it can pave the way for more highly anticipating research in humans.

— written by Maria Victoria Gonzaga

References:
1 Farrar , S. (2018). Mechanisms of DNA Repair. Retrieved from https://www.news-medical.net/life-sciences/Mechanisms-of-DNA-Repair.aspx
2 University of Southern California. (2018, June 20). The world’s tiniest first responders: ‘Walking molecules’ haul away damaged DNA to the cell’s emergency room. ScienceDaily. Retrieved from www.sciencedaily.com/releases/2018/06/180620170951.htm

CRISPR caused gene damage? Rise and pitfall of the gene-editor

CRISPR as a gene editing tool made a prodigious leap forward in science. In 2015, it was heralded as Science’s 2015 Breakthrough of the Year.1 It stymied other impressive contenders like Ebola vaccine. It supersedes other gene-editing predecessors, such as TALENs (transcription activator-like effector nucleases) and ZFNs (zinc finger nucleases). Unlike these two, CRISPR does not need a custom protein for every targeted DNA sequence. It does, however, require a guide RNA (gRNA). Even so, the process of designing a gRNA is easier and less time-consuming than creating a custom protein. For that, it is favoured over other gene-editing tools.

 

 

The rise of a revolutionary gene-editing tool — CRISPR

CRISPR-Cas9 – a customizable tool that cuts and inserts small pieces of DNA at specific areas along a DNA strand. (Credit: Ernesto del Aguila III, National Human Genome Research Institute, NIH)

 

The discovery of CRISPR was indeed phenomenal. Short for clustered regularly interspaced short palindromic repeats, CRISPR swiftly opened avenues for biological and medical innovations. Initially identified as a family of viral DNA snippets, it was discovered to inherently protect bacteria against re-invading bacteriophages akin to our immune system’s adaptive immunity. This natural gene-editing system in bacteria has two key players: gRNA and Cas9 (CRISPR-associated enzyme). The gRNA finds and binds to specific DNA target. The Cas9 goes where the gRNA is, and then cuts the DNA target, disabling the latter. Now, scientists exploit it as a way to splice specific DNA targets and then replace them with a DNA that would yield the desired outcome. For instance, CRISPR can be used to correct physiological anomalies caused by gene mutations or defective genes.


CRISPR-Cas9 system. (Credit: marius walter, Wikimedia Commons under CC BY-SA 4.0 Int’l license)

 

 

 

CRISPR – a versatile gene-editing tool

CRISPR has been shown to have the potential to slow down the progression of cancers. It can switch off a gene in immune cells. The altered immune cells can be designed to fight cancer. In 2016, US FDA approved the clinical trial study where CRISPR technology would be used to cure patients with cancers. 2 Not only in biology and medicine, the use of CRISPR has also extended to agriculture and animal husbandry. Through it, the genes of crops and livestock can be improved. They can be made more resistant to certain diseases.

 

 

 

CRISPR causing gene damage?

One of the issues raised against CRISPR is ethical concerns. Similar to what was ethically raised against other gene-editing technologies, the concern is chiefly about the notion of bias and “playing God”. What are the standards that will define and permit judgment over a gene to be construed as either “good” or “bad”? But taking aside this issue, there is another issue being hurled against CRISPR. Marked of recent as “breaking news”, a study published in Nature warned about the possible pathogenic consequences of CRISPR when the researchers identified on-target mutagenesis in the form of large deletions and complex genomic rearrangements at target sites in mitotically active cells of mice and humans.3 This is not the first time that a study questioned the safety of CRISPR technology. In 2017, researchers from Columbia University reported that it led to hundreds of unexpected mutations. Nevertheless, this claim was retracted when they failed to replicate their results.4

 

 

CRISPR as a gene-editing tool wields so much potential beyond one can imagine. It is easy to use, feasible, and far-reaching. One can expect that issues would come along the way, and thus slow down its fast-paced utilization in different fields. It is a no-nonsense stumbling block for we belong in a community that moves forward through social discourse fueled by scientific nosiness and reasoning. Probing the dangers of CRISPR should be as extensive as exploring its benefits. We must be not too quick to adulate without first bringing out in the open its risks — especially ones that are as crucial as mutations and gene damage.

 

 

— written by Maria Victoria Gonzaga

 

 

References:

1 Science News Staff. (2015). And Science’s 2015 Breakthrough of the Year is…

ScienceMag.org. Retrieved from http://www.sciencemag.org/news/2015/12/and-science-s-2015-breakthrough-year

2 Reardon, S. (2016). First CRISPR clinical trial gets green light from US panel. Retrieved from

https://www.nature.com/news/first-crispr-clinical-trial-gets-green-light-from-us-panel-1.20137

3 Kosicki, M., Tomberg, K. & Bradley, A. (2018 July 16). Repair of double-strand breaks induced by CRISPR–Cas9 leads to large deletions and complex rearrangements. Nature Biotechnology. https://doi.org/10.1038/nbt.4192

4 Dockrill, P. (2018 July 16). BREAKING: CRISPR Could Be Causing Extensive Mutations And Genetic Damage After All. ScienceAlert.com. Retrieved from https://www.sciencealert.com/crispr-editing-causes-frequent-extensive-mutations-genetic-damage-target-deletion-site

A Protein Being Born – a live cell imaging of RNA translation

You probably already heard the concepts of translation in the central dogma of molecular biology. The dogma is an elucidation as to how a protein is born based on what the DNA holds. Based on it, the scheme begins at the DNA molecule being transcribed into RNA in a process called transcription, which is then followed by the RNA making a protein in a process called translation.

 

 

 

Crick’s central dogma: from transcription to translation

Francis Crick, the molecular biologist who was recognized together with James Watson as the first to formally reveal the helical structure of the DNA molecule in 1953, was also noted for his use of the term “central dogma”. He described the unidirectional flow of genetic information, i.e. from the transcription process to the translation process, and that the scheme does not entail reversion. Meaning, the scheme does not flow back from protein to DNA.

“The Central Dogma. This states that once ‘information’ has passed into protein it cannot get out again. In more detail, the transfer of information from nucleic acid to nucleic acid, or from nucleic acid to protein may be possible, but the transfer from protein to protein, or from protein to nucleic acid is impossible. Information means here the precise determination of sequence, either of bases in the nucleic acid or of amino acid residues in the protein.”1

— Francis Crick, 1958

The dogma is now succinctly known as this: DNA makes RNA, which in turn makes protein.

 

 

 

Real-time imaging of translation in vivo

In vivo transcription was the first to be quantified in real time whereas translation took a while before scientists were able to observe the process within a living cell. 2 It took them about 60 years from the time Francis Crick first described it. Translation is a process occurring in the cytoplasm of a cell by which the genetic code carried by the mRNA is decoded to produce the specific sequence of amino acids in a polypeptide chain. It consists of basically four stages: bioactivation, initiation, elongation, and termination. These translation processes had been more difficult to observe in living systems. Due to the limitations of laboratory tools and techniques it had eluded scientists for quite some time. Then, a team of researchers from the Colorado State University came up with state-of-the-art microscopic techniques, which helped them view for the first time the RNA translation in vivo. Fondly referred to as “Fixie”, the custom-built microscope helped the research team to create a real-time imaging of RNA translation within a living cell in a nanoscale precision.2 The research team was able to capture it firstly by using a tagging process by protein engineering and then using the “Fixie” microscope, which has two highly sensitive cameras enabling the imaging of RNA and proteins as two identifiable colors during the translation process.


In this video, it shows how a protein is being born. The red dots are RNA while the blue or green dots are the proteins. The large green spherical structure in the background is the cell nucleus. It can be seen that the mature proteins gather at the nucleus post-translation.

 

 

 

Real-time imaging of the translation of proteins by the RNA molecules can be regarded as a breakthrough. It can be likened to a key that opens the door to various research fields to explore. Proteins are crucial to the biomechanics of living things. They are the definitive goal of translation. Thus, research findings as fundamental as this is going to be irrefutably monumental.

 

 

— written by Maria Victoria Gonzaga

 

 

 

References:
1 Crick, F.H.C. (1958). “On Protein Synthesis”. In F.K. Sanders. Symposia of the Society for Experimental Biology, Number XII: The Biological Replication of Macromolecules. Cambridge University Press. pp. 138–163.

2 Manning, A. (2016). No longer lost in translation: CSU biochemists watch gene expression in real time. Colorado State University. Retrieved from https://source.colostate.edu/no-longer-lost-in-translation-csu-biochemists-watch-gene-expression-in-real-time/

Not Junk: ‘Jumping Gene’ Is Critical For Early Embryo

Jumping genes, also known as transposons, are gaining momentum. They are considered either as slacking junks or maleficent parasites in our genome. As such, they are largely taken for granted. However, it seems the tables have turned. There seem to be certain jumping genes that without them we would not move past our embryonic state.  Researchers from the University of California – San Francisco presented proof that certain jumping genes do perform a crucial role during the development of an embryo.  Without them, the embryo would not progress as it should.1

 

 

 

Jumping genes — junk DNAs

Transposons are small segments of DNA  with a special capability. They create copies of the genetic material and then insert at random sites in the genome.2 For that, they are dubbed as “jumping genes” based on the “jumping” activities that they do. Some consider jumping genes as junk DNA because they tend to replicate needlessly multiple copies of DNAs that already exist. Some of these genetic copies could be noncoding (junk) DNAs. Our genome is comprised mostly of junk — about 98-99%! Only 1 or 2 % of it codes for the building blocks of proteins. Scientists presumed that these noncoding regions are unnecessary and therefore viewed as an evolutionary mess in our genome. Apparently, half of our genome is comprised of jumping genes, and the most common is the long interspersed nuclear element-1 (LINE1).1

 

 

Jumping genes — parasitic stowaways

While some people view jumping genes as slackers that add up to the pile of junk littering our genome, others see them as parasitic stowaways. Because they can “jump” at seemingly random sites in the genome, they could insert themselves where they might cause gene disruptions, deleterious mutations, and chromosomal rearrangements resulting in diseases, including cancer.3

 

 

LINE1 — a paradoxical jumping gene

LINE1 (a jumping gene) is crucial during embryonic development

 

Researchers from the University of California – San Francisco recently reported that LINE1 (a jumping gene) is crucial during embryonic development. LINE1 accounts for 20% or more of the human genome. It is a retrotransposon, meaning it is amplified by first transcribing a segment of DNA into RNA, and then reverse-transcribed into DNA. The extra DNA copy will then be inserted at a different site in the genome.2 This jumping gene apparently acts as a critical regulator during the early embryonic development. It appears indispensable for an embryo to develop past the two-cell stage.1 This finding seems paradoxical since LINE1 has been implicated in various diseases, particularly cancers.4 Nevertheless, the important role of LINE1 was revealed when it was eliminated from the fertilized eggs, and consequently, they all remained at the two-cell phase. Accordingly, the role of the jumping gene in embryonic development is associated with the LINE1 RNA forming a complex with Nucleolin and Kap1 (gene regulatory proteins). The complex is believed to regulate embryonic development by turning off the dominant genes orchestrating the embryo’s two-cell state as well as by turning on the genes that promote further cell divisions and development.1

 

 

 

Jumping genes are mostly underappreciated largely because they are believed to be contributors to a pile of genetic junk or as parasitic stowaways. Despite being regarded as such, recent findings poised them as crucial genes.   While most studies focus on the 1-2% of the genome performing a blatantly important role, i.e. to code for amino acids whereby a protein could be spectacularly built from, the recent study implicates that the jumping genes, too, deserve a spot in the research field.

 

 

 

— written by Maria Victoria Gonzaga

 

 

 

References:
1 University of California – San Francisco. (2018, June 21). Not junk: ‘Jumping gene’ is critical for early embryo: Gene that makes up a fifth of the human genome is not a parasite, but key to the first stages of embryonic development. ScienceDaily. Retrieved from www.sciencedaily.com/releases/2018/06/180621141038.htm
2 Transposon. (n.d.). Biology-Online Dictionary. Retrieved from https://biology-online.org/dictionary/Transposon
3 Chénais, B. (2013). Transposable elements and human cancer: A causal relationship? Biochimica et Biophysica Acta (BBA) – Reviews on Cancer, 1835 (1), 28-35. https://doi.org/10.1016/j.bbcan.2012.09.001
4 Burns, K. H. (2017). Transposable elements in cancer. Nature Reviews Cancer, 17, 415–424. https://www.nature.com/articles/nrc.2017.35

Immune characterization of Breast Cancer Metastases

Breast cancer is the occurrence of lumps or thickening of the surrounding tissues of the breast mostly in women. Yet it also occurs rarely in men. It leads to the changes in shape and appearance of the breast. As well as the changes of skin like peeling, scaling and crusting of the surrounding nipples. Nowadays, extensive support for breast cancer awareness has helped generate advances in treatment and diagnosis. In which survival rates increased while the death rates continuously declining. Due to some factors such as personalized approach for treatment, early detection and have better knowledge of the disease. In this particular research a tumor-infiltrating lymphocytes has been evaluated to convey prognostic information of the breast cancer metastases. Assess its levels, immune composition and ligand expression in metastatic lesions.

 

Tumor-infiltrating lymphocytes as an Immunogenicity of Breast cancer

Evidences suggest the potential of tumor-infiltrating lymphocytes as biomarker in breast cancer metastatic stage. Even at onset of disease it proves as prognostic biomarker in human epidermal growth factor receptor positive with breast cancer. 94 patients have been studied retrospectively with metastatic breast cancer. Younger women showed significant lowered tumor-infiltrating lymphocytes compared to older patients above 50 years of age. Generally tumor-infiltrating lymphocytes are low but have been recognized significantly at high level with patients having this disease. Moreover, previous reports indicate that at secondary or recurrence of disease a lower tumor-infiltrating lymphocytes level occurs.

 

Analysis of the characteristics of tumor immune infiltrate differs across metastatic sites. It also suggests that cutaneous tissues might harbor permissive immune microenvironment for tumor growth. In which immune heterogeneity across metastatic sites need to be explored because it is relevant in treatment and immunotherapy. Other factors that are significant to tumor-infiltrating lymphocytes composition are those patients treated with multiple lines of chemotherapy. Indeed, heavily pretreated patients might have an impaired antitumor cytotoxic activity of the immune system.

 

Therefore, tumor-infiltrating lymphocytes showed strong prognostic value in breast cancer patients. Further examinations of its relevance as biomarker reflect a general activation of the immune system. Thus, it indicates that tumor-infiltrating lymphocytes is a simple method that effectively appreciates the immune activation status of tissue negative tumor. Certainly, given the availability of standardized method of the assessment, this immune marker is technically simple and clinically reliable. Finally, tumor-infiltrating lymphocytes provide novel hypothesis-generating data with regards to immune composition and complex interplay with breast cancer metastatic setting.

 

Source: Prepared by Joan Tura from Springer BMC Breast Cancer Research

Volume 20:62, 22 June 2018

Prognostic biomarkers in Pancreatic Cancer

Pancreatic cancer started at the tissue of the pancreas – an organ in the abdomen that lies behind the lower stomach.  Pancreas releases hormones that helps in maintaining the sugar level in the blood and assist in digestion. Pancreatic cancer is hardly detected at early stage and it is recorded as third deadliest cancer in the United States. Some of its symptom includes weight loss, diabetes, jaundice, blood clots, depression and fatigue. However, it is usually characterized at late stage that has been already metastasized. Current therapy of this disease involves adjuvant chemotherapy, surgical resection and radiotherapy. Yet despite of the advancement of the clinical management and therapy the outcome remains unsatisfactory to the patients. So, this novel research of prognostic biomarker helps pancreatic cancer treatment to maximize survival and avoid toxicity.

 

miRNAs as Prognostic Biomarkers for Pancreatic Cancer

Due to poor prognosis of pancreatic cancer early detection methods have been developed. To have an effective treatment options as well as the importance of critical biomarkers. However, miRNAs shows significance for early detection and diagnosis. It divulges to have great potentials as prognostic biomarkers in pancreatic cancer. miRNAs are small non-coding RNA with 18-22 nucleotides in length that have been known to be associated with tumorigenesis. It is also linked to apoptosis, cell cycle control, proliferation, chemoresistance, metastasis and invasion. This miRNAs modulates key targets and pathways in signaling as well as its unusual expression are associated with chemoresistance.

 

In terms of chemotherapeutic treatment of pancreatic cancer miRNAs elevated expression inhibits the anti-tumor activity. miRNAs is related to gemcitabine resistance by inhibiting tumor suppressor gene phosphatase and tensin homologue thereby activating the PI3K/AKT pathway.  It is also showed that miRNAs expression correlates with prolong overall survival benefits from chemotherapeutic treatment. Additionally, down regulation of miRNAs is responsible for progression of various malignancies including pancreas, breast, prostate, lung and liver cancer. It contains anti-cancer role via modulating targets implicated in cell cycle, apoptosis and DNA repair.

 

Therefore, it is clear that pancreatic cancer utilizes various mechanisms to maintain a highly resistant phenotype. miRNAs epigenetic controls allow cells to quickly adapt to the genotoxic stress caused by chemotherapy. It is also quickly modulates the mRNA translation in pancreatic cancer cells in response to chemotherapeutic treatment. As a result, various kinds of miRNAs showed great potentials as prognostic biomarkers in pancreatic cancer. Optimistically, these biomarkers will form a solid foundation to have better clinical treatment strategies.To avoid toxicity and enhance the survival rate benefits.

 

 

Source: Prepared by Joan Tura from Springer BMC Biomarkers Research

Volume 6:18, 2018

 

 

 

 

Evolutionary History of Endemic Gastropod Assemblage in Lake Malawi

Evolutionary evidence showcases the importance of ancient species that evolved through million years ago and still existed at present time. Environmental changes, geographic movement and plate tectonic changes can affect the evolutionary process of a certain species morphologically for survival. The paper signifies the lineage of certain endemic gastropod species in Lake Malawi. The authors try to trace the evolutionary origin of this particular species predicting that this is an endemic species of the certain lake.

 

Evolutionary history of gastropod species in Lake Malawi

Environmental conditions are one of the contributory factors that affect the morphology of the gastropod Lanistes. Two species are said to be endemic of Malawi Lake these are the Lanistes ovum and Lanistes ellipticus.  Phylogenetic analysis shows that these two species did not cluster to any species found at the vicinity of Lake Malawi. The spatial vicinity of the nearby lakes was also examined for the presence of this gastropod, through morphological analysis. And it shows similarity but not genetically using mitochondrial COI gene as a biomarker.

 

Theoretically, a possible potential transition since at Lake Kazuni at around 50 km from Lake Malawi has Lanistes ovum complexes. Fossil record will always admit the origin of the certain species through time. The authors give importance on lineages as basis for taxonomic purposes and evolutionary processes. In which molecular time is relevant in shifting the morphogenetic properties of a certain species.

 

Indeed, Lake Malawi consists of endemic species to the entire Malawi rift rather than endemic to the lake proper.  It also signifies phylogenetic relationship within genus through parallel evolution.  And provides evidence that gastropod Lanistes species are not restricted in certain area but are present throughout Malawi rift.

 

Source: Prepared by Joan Tura from Proceedings Biology Science 

2009 Aug 7; 276(1668): 2837–2846

 

 

 

Molecular Basis of Temperature-Dependent Gender of Red-Eared Slider Turtle

Imagine a child inside a womb with a sex yet to be decided not by the pair of sex chromosomes but by the ambient temperature – well, that is how the sex of red-eared slider turtle (Trachemys scripta elegans) and other reptile species is determined. Whether the baby red-eared slider turtle develops into a male or female will depend on the ambient temperature of the nest. The eggs hatching from a cooler nest will be males whereas those in a warmer nest will be females. Nevertheless, scientists recently identified the molecular basis associated with the temperature-dependent sex determination in red-eared slider turtle.

 

 

 

Temperature-dependent sex determination in red-eared slider turtle

Red-eared slider turtle. (Photo by Greg Hume, WikiMedia Commons under CC BY-SA 3.0 license)

 

In humans, the sex of the offspring is determined by the pair of chromosomes inherited from the parents. At fertilization, the sex of the embryo is already determined. A female embryo would have two X chromosomes whereas a male embryo would have X and Y chromosomes. This mechanism of sex-determination is referred to as genotypic sex determination (GSD). This is also how the sex of many animals, including certain reptiles, is determined. Another mechanism is temperature-dependent sex-determination (TSD). It is when the temperature predicts the sex of the developing embryo. This is observed in many reptiles, such as crocodiles, alligators, and turtles. In red-eared slider turtle, for instance, their sex can be predicted depending on the incubation temperature. There is a critical period during which the embryonic development is thermosensitive. Red-eared slider turtle eggs hatching from cooler nests will all be males whereas those hatching from warmer nests will all be females.1

 

 

 

Molecular basis of sex-determination in red-eared slider turtle

Red-eared slider turtle laying an egg. (Photo by Nephets, WikiMedia Commons under CC BY-SA 3.0 license)

 

How the temperature causes the baby red-eared slider turtle to turn into male or female is a long-time enigma. The phenomenon of TSD was observed for more than 50 years ago and since then scientists have attempted to dig further into the molecular level of TSD. Are there genes involved in the process, and if there are, which genes? Researchers from Duke University and Zhejiang Wanli University in China published their study on red-eared slider turtle.2 Eggs incubated at 32 °C hatched as females while those incubated at a cooler temperature (26 °C) hatched as males. When they silenced the Kdm6b gene the eggs that supposedly would develop into males at a cooler temperature (26 °C) hatched as females. Knockdown of Kdm6b red-eared slider turtle babies developed ovaries rather than testes.

 

 

 

The molecular role of red-eared slider turtle Kdm6b gene

Kdm6b gene appears to be the key gene essential to turning on the switch of “maleness” in red-eared slider turtle. The activity of this gene is vital during the critical period of gonad development. It became more active at cooler incubation temperature and then “silent” at a warmer temperature. 1 The gene promotes directly the transcription of the male sex-determining gene, Dmrt1. It does so by coding for a protein that removes the trimethylation of the histone, H3K27, near the promoter region of Dmrt1. 2 The methyl tags of the histone repress DNA activity and therefore removing them would allow expression of the genes along the DNA molecule.

 

 

 

This study was unable to identify the temperature-sensing trigger since the Kdm6b and its protein were not inherently sensing temperature changes. 1 For now, the molecular basis of the temperature-dependent sex-determination in the red-eared slider turtle as described above has not reached completion. Nonetheless, what was currently discovered in the red-eared slider turtle may serve as a model to understand the underlying mechanism in other reptile species where the temperature is a major sex-determining factor.

 

 

 

— written by Maria Victoria Gonzaga

 

 

 

References:
1 Duke University. (2018). How turning down the heat makes a baby turtle male: Scientists start to crack 50-year puzzle of how temperature influences a hatchling’s sex. ScienceDaily. Retrieved from www.sciencedaily.com/releases/2018/05/180510203722.htm
2 Ge, C., Ye, J., Weber, C., Sun, W., Zhang, H., Zhou, Y., Cai, C., Qian, G., & Capel, B. (2018). The histone demethylase KDM6B regulates temperature-dependent sex determination in a turtle species. Science 360 (6389): 645.

Human leptospirosis cases in Palermo Italy: Rodents and Climate

Leptospirosis is a corkscrew shaped that is known as one of the most widespread bacterial zoonoses in the world. Symptoms range from mild flu to severe multi-organ failure and fatal pulmonary hemorrhagic syndrome. In which the key factors of these diseases are from stray animals, poor sanitation, rodents, heavy rainfall and flooding. Many regions have been increasingly exposed to leptospirosis infection due to climate change, global warming, poverty and high urban density. Rodents are the main animal reservoir in urban settings mainly involved in pathogenic transmission. Moreover, a high prevalence in rodent population occurs in major cities such as in Baltimore, Tokyo and Copenhagen. In Italy sporadic cases of leptospirosis have been often related to river flooding. This study focused on molecular survey of rodents in the city of Palermo, Italy.

 

Human leptospirosis cases

Two cases in 2009 of leptospirosis in Palermo during spring and fall seasons and there were 22 locations monitored. A rodent is the main reservoir for leptospirosis related to heavy rainfall and flooding in urban streets and riverbanks. During street floods individual were potentially in contact with water contaminated by infected rodent urine. So, the risk of infection is high but because of good hygienic conditions and economic wellness severe symptoms is rare.  It is also possible that periodic exposures to serovars leave the immune competent population more resistant to infection. Other cases also in Northern Italy an elderly woman has a fatal infection after river flooding occurs.

 

Based on molecular testing leptospirosis are positive in all species of wild rodents living in almost all areas in the city. Mice and rats are the natural source for this pathogenic infection. The main common problem in Palermo, Italy is the urban street floods from heavy rains and waste accumulation. In which the city is represented by almost ten thousand stray dogs feeding on garbage. Previously, a patient was in contact with contaminated water in street flood after violent cloudburst. Waste collection also is one of the problem in Palermo that eventually facilitates the increased of rodent population.

 

High prevalence of leptospirosis occurs in mild wet climate, flooding of urban streets and socio-economic problems. Other Italian cities has presence of simultaneous risk factors for leptospirosis, and thus, a major concern from this underestimated zoonosis should be considered by public health authorities and clinicians particularly for elderly and immune-compromised individuals. However, severe symptomatic cases are referred to hospitals and the true prevalence of infection is probably not evaluated.

 

Source: Prepared by Joan Tura from Journal of Infection and Public Health

Volume 11, Issue 2, March–April 2018, Pages 209-214