Mutations

As of today (November 30, 2021), the Delta variant remains the world's most prevalent mutation of the original SARS-CoV-2 virus first identified in January 2020 that is responsible for the global COViD-19 pandemic.

The previously named B.1.1.529 variant now known as the Omicron variant was first reported by South African scientists on 9 November 2021 and then quickly visualized (see image below) by researchers at the Bambino Gesu hospital in Rome. This does not mean that the variant necessarily first arose in South Africa. Variants can also arise independently and spontaneously in multiple locations.

On November 26, the WHO designated the Omicron variant a variant of concern (VOC) subject to special reporting and investigation. The Omicron variant is the most mutated form of SARS-CoV-2 yet sequenced.  <download to read more>

Introduction: The emergence of HIV-1 recombinant forms and drug combined antiretroviral therapy (cART) resistance are frequent in the therapeutic course of HIV-infected children in Low and Middle-Income Countries (LMIC) precisely in Central African Republic (CAR) as evidenced by studies carried out in the Bangui capital. Vertical tran-smission rate including breastfeeding is 12.4. The aim is to analyze retrospectively the molecular characterization of sequencing results and mutation detected in HIV infected children under cART since infancy.
Methods: The 2019 retrospective review of the clinical, therapeutical, and immunological-molecular records of six children who were performed the genome sequencing, followed in Bouar, at the St Michel IST/HIV Center, in the north-west of the CAR. These perinatal HIV-infected children were not tested early and started late cART regimens, used for vertical transmission prevention and treatment initiation of HIV infection in CAR.
Results: We analyzed results from viral RNA extracted amplification and sequencing of 6 children plasma samples collected under first line ART. Sequencing of viral genomes revealed high level resistance mutations to NRTIs (ABC/FTC/3TC) and to NNRTIs (EFV/NVP used locally and DOR/ETR/ RPV unused) with ambiguous positions in amino-acids comparison and deletion. Three CRF02_AG strains formed a cluster by strongly detaching from other CAR and worldwide strains with robust boostrap at 91.
Conclusions: The genomes sequencing showed that resistance mutations made the treatment inefficient confirming the clinical, immunological, and virol-ogical failure and an emerging CRF02_AG genotype variant, probably of foreign origin. This discovery clearly highlights the importance of ART genetic resistance testing and personalized medicine.

Over the last twenty years, a keen imaginative realism has
characterized the representation of several projects worldwide.
It is an ongoing process that is shaping not only the image but
the very idea of the Architecture project. This risky phenomenon
gives way to the ‘standardization’ (Micheli, Lo Ricco, 2003) of the
contemporary world by promoting an immediate ‘visibility’ of the
project. Countering the spread of this phenomenon – which sees the
realistic fixation of render as the most obvious limit – an ‘assemblage
design’ is proposed: is a project approach – named out of the actornetwork theory (Latour, 2015) – able to comprehendere (from Latin
‘keep together) and ‘translate’ through collages the heterogeneity and
fluidity of the reality we live.
From these premises the contribution aims to investigate the
potential of the collage as a project tool that ‘keeps together’ various
techniques. The collage expression process, born in Art with [...]

Adnan Oktar (Harun Yahya)

When you hold this book in your hand, you are actually holding molecules. As you sip a cup of coffee, you are actually drinking molecules, and that coffee aroma that reaches your nose actually consists of scent molecules that you are breathing in. Your tongue that tastes the coffee and your eyes that read these lines are also nothing more than assortments of organic molecules.

When you breathe, you are actually inhaling molecules from the outside atmosphere. It is by means of these very molecules that you can see, smell and taste. And just like everything around you, your body itself is also made up of molecules.

But exactly what are these molecules that comprise you, your skin, the chair you sit in, a cat's fur—and indeed, the entire universe? In fact, those molecules are nothing more than the mutual electron bonds shared among atoms far too small to be seen with the naked eye.

By sharing electrons with each other, atoms link up in long-lasting partnerships, forming molecules. The results, invisible to the naked eye, are an astonishing and infinite variety of objects animate and inanimate, from planets to human beings, from rivers to green forests, from antelopes to railways, and from daisies to apples.

In words accessible to everyone, this book examines how Allah (God) has created molecules and their extraordinary features by the seemingly simple means of bonds between atoms. Learning how invisible molecules make up all the matter the universe, using your reason and conscience, you can begin to see our Lord's infinite power, intellect and incomparable creations, will understand just how helpless we are before Him, and bow to Allah's great might.

Objective To describe the clinical and genetic findings in a cohort of individuals with bathing epilepsy, a rare form of reflex epilepsy. Methods We investigated by Sanger and targeted resequencing the SYN1 gene in 12 individuals from 10 different families presenting with seizures triggered primarily by bathing or showering. An additional 12 individuals with hot-water epilepsy were also screened. Results In all families with bathing epilepsy, we identified 8 distinct pathogenic or likely pathogenic variants and 2 variants of unknown significance in SYN1, 9 of which are novel. Conversely, none of the individuals with hot-water epilepsy displayed SYN1 variants. In mutated individuals, seizures were typically triggered by showering or bathing regardless of the water temperature. Additional triggers included fingernail clipping, haircutting, or watching someone take a shower. Unprovoked seizures and a variable degree of developmental delay were also common. Conclusion Bathing epilepsy is genetically distinct reflex epilepsy caused mainly by SYN1 mutations.

Based on the currently available genome sequence data, we provided direct genetic evidence that the SARS-COV-2 genome has a much lower mutation rate and genetic diversity than SARS during the 2002-2003 outbreak.  The spike (S) protein encoding gene of SARS-COV-2 is found relatively more conserved than other protein-encoding genes, which is a good indication for the ongoing antiviral drug and vaccine development.  Minimum Evolution phylogeny analysis revealed the putative original status of SARS-CoV-2 and the early-stage spread history.  We confirmed a previously reported rearrangement in the S protein arrangement of SARS-COV-2, and propose that this rearrangement should have occurred between human SARS-CoV and a bat SARS-CoV, at a time point much earlier before SARS-COV-2 transmission to human.  We provided first evidence that a mutated SARS-COV-2 with reduced human ACE2 receptor binding affinity have emerged in India based on a sample collected on 27th January 2020.

jeunes gays en danger ». Le titre de ce dossier publié par le mensuel gay et lesbien Têtu en mars 2005 est illustratif du regard des acteurs de la lutte contre le sida sur les jeunes homosexuels 1. Cette représentation suggère l'existence d'une population socialement homogène : se dessine alors le portrait de jeunes gays, victimes autant que responsables d'une dégradation plus générale des comportements de prévention dans la population homosexuelle. Le dossier comprend notamment l'interview d'un psychologue, Roger Francart, dont les propos condensent les idées les plus courantes sur la relation entre jeunes et prévention : « Les jeunes savent pertinemment qu'il y a une forte potentialité de contamination, mais la notion de risque encouru est excitante. (…) *Ils+ jouent à une sorte de roulette russe perpétuelle, qui se transforme un jour en cauchemar. C'est un plaisir suicidaire. (…) Ils n'ont pas vécu les années sombres du sida et le décès de proches. De plus ils semblent détachés de la réalité quotidienne que représentent les traitements liés au sida 2. » La grille de lecture mobilisée traduit bien la préoccupation pour une jeunesse homosexuelle perçue comme vulnérable vis-à-vis du VIH. Dans le contexte des controverses médiatiques sur le bareback 3 , les jeunes incarnent ici une catégorie emblématique d'une exigence de responsabilité préventive, qui implique la transmission de savoirs et l'exemplarité de la communauté homosexuelle. Ainsi, à

"Patient's with different kinds of cancer(s) have been cured by the use of drugs!"

As We Know It, in 1930, "Cancer of the Lung was a Rare Disease...in the 70's a Drastic Change Occurred - Lung Cancer Had Become The Leading Cause Of Death From Cancer Among Males In The United States of America!"

"Scientists Are Hopeful That Many Cancers Will Be Cured By 'Chemo' In The Future!"

Does this all sound too "Science Fiction?" Does a few movie titles come to mind? How about "The Thing From Another World," starring James Arness grab you? You'd probably remember the version of the "Thing" starring 'Kurt Russell. How about "Alien" starring Sigourney Weaver? There are many other moving pictures plays depicting alien assimilations on the big screen as well the "Boob-Tube!" Remember "The Invaders" with Roy Thinnes? I often wondered were many of the 'Sci-Fi' authors got their material. But this Man-killer of which we speak, is life action continuing and constant danger(s).

Background. Activation of oncogenes downstream the EGFR gene contributes to colorectal tumorigenesis and determines the sensitivity to anti-EGFR treatments. The aim of this study was to evaluate the prognostic value of KRAS, BRAF, NRAS and PIK3CA mutations in a large collection of CRC patients from genetically-homogeneous Sardinian population. Methods. A total of 1284 Sardinian patients with histologically-proven diagnosis of colorectal carcinoma (CRC) and presenting with metastatic disease were included into the study. Genomic DNA was isolated from formalin-fixed, paraffin-embedded primary tumour tissue samples of CRC patients and screened for mutations in RAS and BRAF genes, using pyrosequencing assays, and in PIK3CA gene, using automated DNA sequencing assays. Results. Overall, mutation rates were 35.6% for KRAS, 4.1% for NRAS, and 2.1% for BRAF. Among available DNA samples, 114/796 (14.3%) primary CRCs were found to carry a mutation in the PIK3CA gene. In this subset of patients analysed in all four genes, a pathogenetic mutation of at least one gene was discovered in about half (378/796; 47.5%) of CRC cases. A mutated BRAF gene was found to steadily act as a negative prognostic factor for either time to progression as metastatic disease (from detection of primary CRC to diagnosis of first distant metastasis; p=0.009) or partial survival (from diagnosis of advanced disease to the time of death or last control; p=0.006) or overall survival (p<0.001). No significant impact on prognosis was observed for mutated KRAS, NRAS, and PIK3CA genes or combined RAS mutations (all RAS). Conclusions. Our study defines both prevalence and prognostic role of main activated oncogenes in a population-based large collection of CRC patients.

The economic, political, social, cultural, technological, etc. changes the XXI-st century is facing trigger modifications at the level of the economy, society, organization and of the management of this one. Such transformations result in the appearance of new trends at the international level, and an example would be the fact that the economy, society, organization and management that are based

Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in ten canonical pathways: cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGFβ signaling, p53 and β-catenin/Wnt. We charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity. Eighty-nine percent of tumors had at least one driver alteration in these pathways, and 57% percent of tumors had at least one alteration potentially targetable by currently available drugs. Thirty percent of tumors had...

Single nucleotide polymorphisms in the IL17A gene are associated with many types of cancer. Therefore, the identification of functional and structural polymorphisms in IL17A is important to study and determine therapeutic targets and their potential impact. In this study, several computational methods have been used to identify non-synonymous SNPs that are deleterious in the IL17A gene, including SIFT, PolyPhen2, PROVEAN, SNAP. PhD-SNP, SNP&GO and Pmut were used to predict disease-associated nsSNPs. I-mutant and Mupro were used to predict protein stability. ConSurf was used to predict conserved residues and functional regions of the protein. Finally, SOPMA followed by Project Hope software was used to predict the effect of these mutations on protein structure and function. Our study concludes that ten nsSNPs (R69Q, A92S, C94S, R95C, C99F, D107G, V121I, V142M, T145I and P149L) were shown to be potentially deleterious in IL17A. The present study represents a comprehensive in silico analysis of the IL17A gene and will be a useful tool for future studies.

Background: Somatic mutations of the PIK3CA gene have been described in non-small cell lung cancer (NSCLC), but limited data is available on their biological relevance. This study was performed to characterize PIK3CA-mutated NSCLC clinically and genetically. Patients and methods: Tumor tissue collected consecutively from 1144 NSCLC patients within a molecular screening network between March 2010 and March 2012 was analyzed for PIK3CA mutations using dideoxy-sequencing and next-generation sequencing (NGS). Clinical, pathological, and genetic characteristics of PIK3CA-mutated patients are described and compared with a control group of PIK3CA-wildtype patients. Results: Among the total cohort of 1144 patients we identified 42 (3.7%) patients with PIK3CA mutations in exon 9 and exon 20. These mutations were found with a higher frequency in sqamous cell carcinoma (8.9%) compared to adenocarcinoma (2.9%, p<0.001). The most common PIK3CA mutation was exon 9 E545K. The majority of patients (57.1%) had additional oncogenic driver aberrations. With the exception of EGFR-mutated patients, non of the genetically defined subgroups in this cohort had a significantly better median overall survival. Further, PIK3CA-mutated patients had a significantly higher incidence of malignancy prior to lung cancer (p<0.001). Conclusion: PIK3CA-mutated NSCLC represents a clinically and genetically heterogeneous subgroup in adenocarcinomas as well as in squamous cell carcinomas with a higher prevalence of these mutations in sqamous cell carcinoma. PIK3CA mutations have no negative impact on survival after surgery or systemic therapy. However, PIK3CA mutated lung cancer frequently develops in patients with prior malignancies.

ObjectiveTo describe the clinical and genetic findings in a cohort of individuals with bathing epilepsy, a rare form of reflex epilepsy.MethodsWe investigated by Sanger and targeted resequencing the SYN1 gene in 12 individuals from 10 different families presenting with seizures triggered primarily by bathing or showering. An additional 12 individuals with hot-water epilepsy were also screened.ResultsIn all families with bathing epilepsy, we identified 8 distinct pathogenic or likely pathogenic variants and 2 variants of unknown significance in SYN1, 9 of which are novel. Conversely, none of the individuals with hot-water epilepsy displayed SYN1 variants. In mutated individuals, seizures were typically triggered by showering or bathing regardless of the water temperature. Additional triggers included fingernail clipping, haircutting, or watching someone take a shower. Unprovoked seizures and a variable degree of developmental delay were also common.ConclusionBathing epilepsy is genet...

In a recent paper (1) it was argued that in order to mutate to more enhanced organisms an organism must have some mechanisms, just as the sender or mutative influences to be able to receive, implement and make mutative impacts active. The conclusion was that this was not observed and thus that evolution must be part of pseudo scientifically assumptions. One can believe it as many people also actively do. But then evolution must be considered as a religion and not part of correct science. On top of that, it also should be treated in society as such and not be taught as correct science to gullible people such as children. In order to prove this statement an research was conducted parallel to that paper. Which is partially presented here. If mutations enhance organisms that this must be visible in mutations with humans. On his case study of syndromes the syndromes have been evaluated whether or not a syndrome was genetically originated or not. There are about 1400+ syndromes known (2) and how ever this is a preliminairy result, since only half of the data has been it can already be estimated that the majority of syndromes is of genetic origin. About maximum 74% is genetically originated.

Frequently, treatment of patients with non-small cell lung cancer with tyrosine kinase inhibitors is stopped because of new or progressive bone metastases. Osteoblas- tic response is considered a healing reaction during effec- tive systemic therapy, defined by osteoblastic demarcation of preexisting or “new” bone lesions, whereas disease response can be identified in other tumor locations.1 In this study, we describe three patients with non-small cell lung cancer harboring sensitizing epidermal growth factor re- ceptor (EGFR) mutations with osteoblastic responses dur- ing disease control by tyrosine kinase inhibitor treatment.

Due to the non-availability of sources of resistance in Sri Lanka to Phytophthora blight in sesame (Sesamum indicum) caused by Phytophthora nicotianae var. parasitica, a mutation breeding programme was initiated. Seeds of three genotypes were subjected to six doses of gamma rays from 100 Gy to 750 Gy from a Co-60 source. Seeds of M2 bulks, sampled by variety and treatment from the first five capsules formed on M1 plants, were grown in a field with a history of repeated incidence of the disease. The best 21 lines, having the highest survival and seed production, identified in the screening of M3 and M4 progeny rows of selected M2 single plants were then tested in a replicated field trial with the recommended cultivar 'MI 3' as a control. The plant survival in selected lines averaged 43.3 percent as against 7.2 percent in the recommended variety. Eight selections recorded significantly higher seed yield than 'MI 3' at P < 0.01 and another three at P < 0.05. Gamma ray treatments of 450 Gy and 600 Gy produced more lines tolerant to the disease than the other doses used.

La mediation patrimoniale beneficie de nouveaux outils et approches en lien avec les mutations actuelles de la culture patrimoniale. S&#39;inspirant des regional studies, on montre que le processus de patrimonialisation du pont tournant peut conduire a l&#39;ancrage local d&#39;une economie collaborative en lien avec la densite du patrimoine industriel urbain des XIXe et XXeme siecle en Europe et dans le monde et les groupes sociaux mobilises. L&#39;existence du pont Colbert en fonctionnement participe de la vitalite des identites territoriales appuyees sur une culture materielle rare : il agit sur les usagers locaux, sensibles a l&#39;esthetique de la construction metallique, et diffuse l&#39;image d&#39;une modernite pionniere notamment grâce aux outils numeriques. La question de la sauvegarde du pont Colbert, si elle est controversee, presente des enjeux de developpement territorial mobilisant des reseaux locaux et mondiaux dans une logique d&#39;economie de la culture, des conna...

Drug resistance is a major challenge for the treatment of many diseases and a significant concern throughout the drug development process. The ability to understand and predict the effects of mutations on protein-ligand affinities and their roles in the emergence of resistance would significantly aid treatment and drug design strategies. In order to study and understand the impacts of missense mutations on the interaction of ligands with the proteome, we have developed Platinum (http://structure.bioc.cam.ac.uk/platinum). This manually curated, literature-derived database, comprising over 1000 mutations, associates for the first time experimental information on changes in affinity with three-dimensional structures of protein-ligand complexes. To minimize differences arising from experimental techniques and to directly compare binding affinities, Platinum considers only changes measured by the same group and with the same amino-acid sequence used for structure determination, providing...

Potential multitargeted prophylactic nano-vaccine (Sevid  “Copr”) against COVID-19 composed of engineered-exosomes dispaying SARS-CoV-2 antigenic viral-derived miRNAs interacting with mutant immunoresistant genes encoding structural and nonstructural viral proteins. 

Prof Dr John N. Giannios, Leader of the Postgraduate Programme in GENOMIC MEDICINE AND HEALTHCARE IN UNIVERSITY OF SOUTH WALES, UNITED KINGDOM.
In the process of engineering exosomes displaying SARS-CoV-2 antigens in the form of viral-encoded miRNAs interacting with emerging mutations or variants in genes encoding structural viral proteins (SPs) including S,M,N,E  that may lead to immune-escape and severe infection, and nonstructural viral proteins (NSPs) consisting of ORF-1a, ORF-1b, ORF-3a, ORF-6, ORF-7a, ORF-7b, ORF-8 and ORF-10 which may influence viral-replication and methylation inducing host-responses to viral-infections, such as COVID-19.  The aim is to synthesize a prophylactic nano-vaccine against COVID-19 for the activation of immunological-memory consisting of sensitized T lymphocytes and activated B lymphocytes allowing the human organisms  to react promptly in a efficient way to potential SARS-CoV-2 exposures. This potential nano-vaccine aims to target various immunoresistant viral-mutations  so individuals infected by SARS-CoV-2 are  exposed to the same antigenic v-miRNAs leading to the activation of adaptive-immunity which aims to circumvent the clinical phenotype of COVID-19. After intramuscular-injection, this potential nano-vaccine aims to activate antigen-specific B and T lymphocytes expanding their numbers so they can become memory-lymphocytes attacking the specific viral-antigenic miRNAs. This immunological-memory which is mediated by a secondary-response aims to attack the mutated SARS-CoV-2 viruses, and destroy them before the appearance of clinical related symptoms. This antigen specific memory targeting various emerging novel deleterious variants against these mutant positive strand RNA-viruses which become more immunoresistant when they are copied in their host-organisms is aiming not only to prevent COVID-19 disease but also to reduce significantly disease severity by escalating a very strong, and rapid immune-response to antigenic viral-miRNAs in which the hosts have been previously exposed. Furthermore, the specific miRNAs can act as synergistic post-transcriptional regulators of precise immune-responses influencing  protein-coding gene-expression by hybridization of multiple-mRNAs while interacting with epigenomic alterations and epitranscriptomic factors. Finally, adjuvants will be added in this potential multitargeted nano-vaccine termed as SEVID “Copr”, which is in the process of patenting, for improving the intensity and duration of its primary-response that aims to result in antigen-specific memory for the immunological eradication of various mutant forms of SARS-CoV-2.

Isoniazid (INH) is still one of the two most effective antitubercular drugs and is included in all recommended multitherapeutic regimens. Because of the increasing resistance of Mycobacterium tuberculosis to INH, mainly associated with mutations in the katG gene, new INH-based compounds have been proposed to circumvent this problem. In this work, we present a detailed comparative study of the molecular determinants of the interactions between wt KatG or its S315T mutant form and either INH or INH-C 10 , a new acylated INH derivative. MD simulations were used to explore the conformational space of both proteins, and results indicate that the S315T mutation did not have a significant impact on the average size of the access tunnel in the vicinity of these residues. Our simulations also indicate that the steric hindrance role assigned to Asp137 is transient and that electrostatic changes can be important in understanding the enzyme activity data of mutations in KatG. Additionally, molecular docking studies were used to determine the preferred modes of binding of the two substrates. Upon mutation, the apparently less favored docking solution for reaction became the most abundant, suggesting that S315T mutation favors less optimal binding modes. Moreover, the aliphatic tail in INH-C 10 seems to bring the hydrazine group closer to the heme, thus favoring the apparent most reactive binding mode, regardless of the enzyme form. The ITC data is in agreement with our interpretation of the C 10 alkyl chain role and helped to rationalize the significantly lower experimental MIC value observed for INH-C 10. This compound seems to be able to counterbalance most of the conformational restrictions introduced by the mutation, which are thought to be responsible for the decrease in INH activity in the mutated strain. Therefore, INH-C 10 appears to be a very promising lead compound for drug development.

One of the most intriguing features of biological systems is their ability to regulate the steady-state fluxes of the underlying biochemical reactions; however, the regulatory mechanisms and their physicochemical properties are not fully understood. Fundamentally , flux regulation can be explained with a chemical kinetic formalism describing the transitions between discrete states, with the reaction rates defined by an underlying free energy landscape. Which features of the energy landscape affect the flux distribution? Here we prove that the ratios of the steady-state fluxes of quasi-first-order biochemical processes are invariant to energy perturbations of the discrete states and are only affected by the energy barriers. In other words, the nonequilibrium flux distribution is under kinetic and not thermodynamic control. We illustrate the generality of this result for three biological processes. For the network describing protein folding along competing pathways, the probabilities of proceeding via these pathways are shown to be invariant to the stability of the intermediates or to the presence of additional misfolded states. For the network describing protein synthesis, the error rate and the energy expenditure per peptide bond is proven to be independent of the stability of the intermediate states. For molecular motors such as myosin-V, the ratio of forward to backward steps and the number of adenosine 5'-triphosphate (ATP) molecules hydrolyzed per step is demonstrated to be invariant to energy perturbations of the intermediate states. These findings place important constraints on the ability of mutations and drug perturbations to affect the steady-state flux distribution for a wide class of biological processes.

Background: Cushing’s syndrome or hypercortisolism is a common endocrinopathy in dogs. In approximately 15% of
cases, the disorder is caused by adrenocorticotropin (ACTH)-independent hypersecretion of cortisol by an adrenocortical
tumor (AT). Without other explanation, the cortisol hypersecretion has been referred to as autonomous.
Objectives: To investigate whether ACTH-independent hypersecretion of cortisol may be associated with aberrant activation
of the melanocortin 2 receptor (MC2R)-cyclic AMP (cAMP)-protein kinase A (PKA) pathway.
Animals: All analyses were performed on 44 cortisol-secreting ATs (14 adenomas and 30 carcinomas) derived from
dogs diagnosed with ACTH-independent hypercortisolism.
Methods: Mutation analysis was performed of genes encoding the stimulatory G protein alpha subunit (GNAS),
MC2R, and PKA regulatory subunit 1A (PRKAR1A) in all ATs.
Results: Approximately one-third of all ATs harbored an activating mutation of GNAS. Missense mutations, known to
result in constitutive activation, were present in codon 201 in 11 ATs, in codon 203 (1 AT), and in codon 227 (3 ATs). No
functional mutations were found in MC2R and PRKAR1A.
Conclusions and Clinical Importance: Activation of cAMP signaling is a frequent event in canine cortisol-secreting ATs
and may play a crucial role in both ACTH-independent cortisol production and tumor formation. To the best of our
knowledge, this is the first report of potentially causative mutations in canine cortisol-secreting ATs.
Key words: Adrenal; Cushing’s syndrome; Dog; Gs alpha.

Motivation: Driver (epi)genomic alterations underlie the positive selection of cancer subpopulations, which promotes drug resistance and relapse. Even though substantial heterogeneity is witnessed in most cancer types, mutation accumulation patterns can be regularly found and can be exploited to reconstruct predictive models of cancer evolution. Yet, available methods cannot infer logical formulas connecting events to represent alternative evolutionary routes or convergent evolution.
Results: We introduce PMCE, an expressive framework that leverages mutational profiles from cross-sectional sequencing data to infer probabilistic graphical models of cancer evolution including arbitrary logical formulas, and which outperforms the state-of-the-art in terms of accuracy and robustness to noise, on simulations.
The application of PMCE to 7866 samples from the TCGA database allows us to identify a highly significant correlation between the predicted evolutionary paths and the overall survival in 7 tumor types, proving that our approach can effectively stratify cancer patients in reliable risk groups.
Availability: PMCE is freely available at https://github.com/BIMIB-DISCo/PMCE, in addition to the code to replicate all the analyses presented in the manuscript.
Contacts: [email protected], [email protected].

Background: The presence of different missense mutations in sheep breeds have shown that the bone morphogenetic protein receptor 1B (BMPR1B), bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) genes play a vital role in ovulation rate and prolificacy in ewes. Therefore, the present study aims to investigate BM-PR1B, BMP15 and GDF9 gene mutations in prolific ewes of Iranian fat-tailed Lori-Bakhtiari sheep.

Constantine Adraktas
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Incorporation of molecular data into the Revised International Prognostic Scoring System in treated patients with myelodysplastic syndromes + another 3

The widespread utility of hypervariable loci in genetic studies derives from the high mutation rate, and thus the high polymorphism, of these loci. Recent evidence suggests that mutation rates can be extremely high and may be male biased (occurring in the male germ-line). These two factors combined may result in erroneous overestimates of extrapair paternity, since legitimate offspring with novel alleles will have more mismatches with respect to the biological father than the biological mother. As mutations are male driven, increasing the number of hypervariable loci screened may simply increase the number of mismatches between fathers and their legitimate offspring. Here we describe a simple statistic, the probability of resemblance (P R ), to distinguish between mismatches due to parental misassignment versus mutation in either sex or null alleles. We apply this method to parentage data on thick-billed murres (Uria lomvia), and demonstrate that, without considering either mutations or male-biased mutation rates, cases of extrapair paternity (7% in this study) would be grossly overestimated (14.5%-22%). The probability of resemblance can be utilized in parentage studies of any sexually reproducing species when allele or haplotype frequency data are available for putative parents and offspring. We suggest calculating this probability to correctly categorize legitimate offspring when mutations and null alleles may cause mismatches.

Febrile seizures (FS) are the most common seizure syndrome and are potentially a prelude to more severe epilepsy. Although zinc (Zn(2+)) metabolism has previously been implicated in FS, whether or not variation in proteins essential for Zn(2+) homeostasis contributes to susceptibility is unknown. Synaptic Zn(2+) is co-released with glutamate and modulates neuronal excitability. SLC30A3 encodes the zinc transporter 3 (ZNT3), which is primarily responsible for moving Zn(2+) into synaptic vesicles. Here we sequenced SLC30A3 and discovered a rare variant (c.892C &gt; T; p.R298C) enriched in FS populations but absent in population-matched controls. Functional analysis revealed a significant loss-of-function of the mutated protein resulting from a trafficking deficit. Furthermore, mice null for ZnT3 were more sensitive than wild-type to hyperthermia-induced seizures that model FS. Together our data suggest that reduced synaptic Zn(2+) increases the risk of FS and more broadly support the ...

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy.

Une des cles de l&#39;afrocentrisme souvent sous-jacent dans le rap tient au repli des valeurs politiques et nationales sur une pratique familiale. Cette reduction du politique au familial est la consequence d&#39;une improbable citoyennete pour les representants de la communaute noire aux Etats-Unis

Cosa vuol dire variante del virus e veramente dobbiamo spaventarci di quanto sta accadendo? Conversazione di Formiche.net con Giuseppe Novelli, genetista e professore Una nuova variante del Covid-19 è stata scoperta e annunciata negli ultimi giorni da Londra. Sabato la Gran Bretagna ha quindi deciso di adottare un lockdown totale già da ieri. Questa mutazione si trasmetterebbe in maniera più veloce, tanto da indurre molti Paesi europei, tra cui l'Italia, a sospendere i collegamenti con il Regno Unito. La notizia arriva in un momento in cui si cominciava a intravedere una luce in fondo al tunnel della pandemia, grazie alla campagna vaccinale iniziata proprio in Inghilterra e che sembrerebbe presto iniziare anche nel nostro Paese. Ma cosa vuol dire variante del virus e veramente dobbiamo spaventarci di quanto sta accadendo? Formiche.net ha chiesto a Giuseppe Novelli, genetista e professore di genetica medica presso l'Università Tor Vergata di Roma e l'Università del Nevada degli Stati Uniti, di fare chiarezza sugli eventi delle ultime ore, con un approfondimento sul virus e i vaccini. Professore, parliamo subito di questa variante del virus isolata in Uk che sta allarmando il mondo intero. Ci può spiegare esattamente di cosa si tratta? I virus mutano, devono farlo. Solo i ceppi che sviluppano mutazioni migliori dell'originale sopravviveranno, gli altri eliminati. Questa non è l'unica variante del virus, ne conosciamo migliaia. Questa è inusuale perché altamente mutata, cioè modificata in più punti del genoma del virus.

The genetic association between cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations and male infertility due to congenital bilateral absence of vas deferens (CBAVD) is well established. Mutant CFTR, however may also be involved in the etiology of male infertility in non-CBAVD cases. The present study was conducted to estimate the frequency of ∆I507 and ∆F508 CFTR gene mutations in Iranian infertile males. We undertook the first study of association between these CFTR mutations and non-obstructive azoospermia in Iran. In this case-control study, 100 fertile healthy fathers and 100 non-obstructive azoosperm-ia's men were recruited from Isfahan Infertility Center (IIC) and Sari Saint Mary's Infertility Center, between 2008 and 2009. Screening of F508del and I507del mutations was carried out by the multiplex-ARMS-PCR. Significance of differences in mutation frequencies between the patient and control groups was assessed by Fisher's exact test. The ΔF508 was detected in three patients. However there are no significant association was found between the presence of this mutated allele and infertility [OR=9.2 (allele-based) and 7.2 (individual-based), P=0.179]. None of the samples carried the ΔI507 mutation. Altogether, we show that neither ΔI507 nor ΔF508 is involved in this population of Ira-nian infertile males with non-obstructive azoospermia. Citation: Heidari S, Hojati Z, Motovali-Bashi M. Screening of two neighboring CFTR mutations in Iranian infertile men with non-obstructive azoospermia. Int J Fertil Steril. 2017; 10(4): 390-394.

This ain’t new to talk about, that technology and evolution has gone beyond our imagination uptil now. Everyone has hooked badly to the technology and materialistic world. And ofcourse it has cut short times in many of the processes that often used to go longer when it comes to get done with the process. t is amazing how things are going faster and faster. We are living so fast, ain’t we?
Things have become easy and fast in every part of the world, yeah!, Healthcare industries have boomed with portentous equipment & machines with the help of people who work in collaboration with information technology and this way, it has become easy to come up with solutions, be it into healthcare, mechanical world or any other industrial domain.

Trend now!! Well healthcare is going to face a big challenge in tackling with issues coming up in terms of healthcare problems, deformities, diseases that have been detected for the first time and have no solution right now. It will need another span of time to study the particular disease and issues and to come up with solution.

One disease comes and research starts on that, by the time solution comes, it would start coming with cases in some part of the world with sever deformities and sometimes that is through the same virus but different strain of the virus. Mind, strains designed manually during research and developed due to mutations are horrible in terms of result in human and in animals.

Background: Oat, Avena sativa is the sixth most important cereal in the world. Presently oat is mostly used as feed for animals. However, oat also has special properties that make it beneficial for human consumption and has seen a growing importance as a food crop in recent decades. Increased demand for novel oat products has also put pressure on oat breeders to produce new oat varieties with specific properties such as increased or improved β-glucan-, antioxidant-and omega-3 fatty acid levels, as well as modified starch and protein content. To facilitate this development we have produced a TILLING (Targeting Induced Local Lesions IN Genomes) population of the spring oat cultivar SW Belinda.

Breast cancer is the most prevalent disease and second leading cause of death among women in many countries. Mutations and consequent DNA damage in several genes such as oncogenes and tumour suppressor genes have been implicated with abnormal behavior of somatic cells, resulting into malignant growth termed cancer. DNA damage/changes in chromosomal DNA and failure of DNA repair mechanism are important factors for cancer causation. Aberrant behavior of cells leading to uncontrolled proliferation causing cancer is attributable to amplicon formation, large deletions in some genes, mutations, and recombination breakpoints etc. which cause aberrant gene expression. Several patented genes found to be associated with breast cancer, have been discussed, such as BRCA1, BRCA2, DAP kinase, MYH, BCSGs, BCW 2 and Id-2 etc. Several of the genes/markers associated with breast cancer can be considered as appropriate candidates for developing early detection systems/protocols for breast cancer.