Category Archives: Molecular Genetics

Photo: Michael Behe discusses Biological Truth & Myth: Insights from the Foundation of Life" (screenshot).

Last year I wrote an article here at Evolution News titled Harvard Molecular Geneticist Vindicates Michael Behes Main Argument in Darwin Devolves. I discussed a 2020 paper by Andrew Murray in the journal Current Biology. That paper stated:

In laboratory-based experimental evolution of novel phenotypes and the human domestication of crops, the majority of the mutations that lead to adaptation are loss-of-function mutations that impair or eliminate the function of genes rather than gain-of-function mutations that increase or qualitatively alter the function of proteins.

Murrays paper vindicated Behes thesis which also argued that random mutation and natural selection are in fact fiercely devolutionary. That is since mutation easily breaks or degrades genes, which, counterintuitively, can sometimes help an organism to survive, so the damaged genes are hastily spread by natural selection. (Darwin Devolves, p. 10) He continues:

Darwinian evolution proceeds mainly by damaging or breaking genes, which, counterintuitively, sometimes helps survival. In other words, the mechanism is powerfully devolutionary. It promotes the rapid loss of genetic information. [p. 37, emphasis in original.]

Now Behe has been vindicated again by a 2021 paper in Nature Heredity, which agrees that loss-of-function mutations are prevalent in the evolutionary process:

Views on loss-of-function mutations those abolishing a genes biomolecular activity have changed considerably over the last half century. Early theories of molecular evolution that emerged during the 1960s and 1970s saw little potential for loss-of-function mutations to contribute to adaptation (Maynard Smith1970). Except in the case of inactivated gene duplicates, nonfunctional alleles were often assumed to be lethal, with adaptation being generally regarded as a process explained only by the fixation of single, mutationally rare alleles that improved or altered a genes function (Orr2005). Only relatively recently, through discoveries enabled by the availability of molecular sequence data, were alternative views of adaptive loss-of-function alleles formalized, most notably with the less is more ideas proposed by Olson (1999). Classical paradigms of molecular evolution had by that time been challenged, for example, by evidence that natural loss-of-function variants of CCR5 lead to reduced HIV susceptibility in humans (Libert et al.1998). Discoveries during the subsequent two decades have continued to support the idea that loss of function contributes to adaptation (Murray2020), with cases of adaptive or beneficial loss of function being discovered across diverse organisms, genes, traits, and environments.

You might notice that the final citation in the quote above is to Murray (2020) thats the same Andrew Murray mentioned above, the Harvard geneticist I wrote about last year who similarly proposed that evolutionary adaptations frequently proceed by breaking functionality at the molecular level. Professor Murrays paper was appropriately cited, but unfortunately this 2021 paper conspicuously avoids citing Behes 2010 paper in the respected Quarterly Review of Biology, Experimental evolution, loss-of-function mutations, and the first rule of adaptive evolution. There, Behe makes similar arguments. Nor does it cite Behes 2019 book Darwin Devolves. But its enough to accept the vindication even if we dont get the citation.

Citing away to the relevant literature (excluding Behe), this 2021 paper continues:

Today, reductive genome evolution is viewed as a powerful force of adaptation (Wolf and Koonin 2013) and gene loss is considered an important source of adaptive genetic variation (Albalat and Caestro 2016; Murray 2020). While the existence of adaptive loss of function is no longer seriously disputed, the assumed maladaptive nature of loss of function from early theories can persist in the language of population genetics such as in the continued use of deleterious as a synonym for loss-of-function (Moyers et al. 2018). he existence of a category of alleles distinguished by a derived loss of biochemical function has been described by various names: amorphic (Muller 1932), loss-of-function (Jones 1972), nonfunctional (Nei and Roychoudhury 1973), knockout (Kulkarni et al. 1999),null (Engel et al. 1973), pseudogene (Jacq et al. 1977), or simply gene loss (Zimmer et al. 1980). Total gene loss is the most obvious case of loss of function. Comparisons of gene content between distantly related species have revealed considerable evidence for adaptation via complete deletion of genes or even entire sets of functionally related genes (Wang et al. 2006; Blomme et al. 2006; Will et al. 2010; McLean et al. 2011; Griesmann et al. 2018; van Velzen et al. 2018; Sharma et al. 2018; Huelsmann et al. 2019; McGowen et al. 2020; Baggs et al. 2020).

The article goes on to explore various mutational mechanisms which lead to loss of function in genes, and complete gene loss, providing a theoretical basis for Behes thesis:

First principles and empirical evidence indicate that many types of mutations can have effects that are equivalent to total gene loss, and for the purposes of this review, we employ this definition of complete gene losses being functionally equivalent to other loss-of-function mutations such as premature stop codons. However, there is the practical difficulty that these different types of mutations vary in how easily they can be detected and correctly annotated as loss-of-function alleles (Fig. 3). Insertions and deletions that interrupt the reading frame of a protein coding region (frameshift mutations), for example, might be readily classified as loss-of-function alleles because the downstream amino acid sequence will be severely disrupted. Yet a frameshift mutation at the extreme 3 end of a coding region affecting only a few amino acids might be functionally distinct from a frameshift mutation at the extreme 5 end disrupting the entire coding sequence. One simple heuristic to address this ambiguity is a threshold, measured by the portion of the gene affected by functionally disruptive mutations, at which an allele is classified as loss-of-function. This approach can be used to classify premature stop codons, frameshift, splice site disruptions, start loss, and inframe insertions and deletions. In humans (MacArthur et al. 2012; Karczewski et al. 2020) and Arabidopsis thaliana (Monroe et al. 2018; Baggs et al. 2020), loss-of-function mutations affecting only a small fraction (e.g., <10%) of total coding sequence in a gene were ignored when classifying loss-of-function variants.

The paper then explores methods for detecting when loss-of-function has been selected by natural selection:

Loss-of-function alleles were once often held up as a paragon of deleterious genetic variation. Today a more nuanced appreciation for their potential role in adaptation has emerged. This new paradigm inspires investigations into deeper questions about the causes and consequences of adaptation by genetic loss of function. For example: Do species or populations differ in their capacity to adapt via loss of function, and if so, why? Does the high effective mutation rate of loss-of-function alleles lead to bias in the probabilities of different evolutionary outcomes? What is the contribution of adaptive loss of function to the phenomena of antagonistic pleiotropy and reproductive isolation? How does adaptation by loss of function affect long term evolutionary trajectories of populations and future evolvability?

Focus on the last question: What does the prevalence of function-damaging mutations imply for the evolutionary process? This question is an important one, and its one to which Michael Behe, through the lens of intelligent design, has proposed an answer. The answer is essentially that a mechanism that proceeds primarily by breaking molecular features cannot easily account for the origin of new functional biological features at the molecular level. Heres what Behe writes in Darwin Devolves:

From the dawn of life to the present, beneficial degradation has been a constant background theres no way to avoid it. From the beginning the Darwinian mechanism has been self-limiting, capable to an extent of eliminating or modifying preexisting molecular systems and in the process giving rise to new varieties of creatures below the biological classification level of family (described in Chapter 6), but incapable of building functionally complex molecular structures. To explain them, we must look elsewhere. (p. 251)

The literature is looking at the same data that intelligent design proponents are looking at, making similar observations, and asking similar questions. While ID proponents dont always get recognized in the literature for their contributions, a careful analysis nonetheless shows that ID thinking is highly relevant to answering questions that everyone is asking.

Original post:
Vindicated But Not Cited: Paper in Nature Heredity Supports Michael Behe's Devolution Hypothesis - Discovery Institute

AURORA, Colo. (KDVR) The novel coronavirus can rapidly mutate inside of compromised patients and give way to new and more dangerous variants, according to new research from a University of Colorado School of Medicine scientist.

David Pollock, a professor of biochemistry and molecular genetics, co-authored the research in the journal Nature.

He studied a patient in his 70s who had COVID-19 and cancer. In just weeks, the virus mutated multiple times and variants that survived were the strongest and most dangerous.

Its allowing for a much more rapid accumulation of mutationsthan if they go on to infect other people, Pollock said.

In the case of the patient Pollock studied, who ultimately died, the variants were not allowed to escape and infect others. But in other cases the variants do. This has most likely led to the more infectious and possibly more harmful variants in the United Kingdom, South Africa and Brazil.

This is like a pandemic in a pandemic, Pollock said. These are spreading amongst the people who are infected.

These variants are also affecting the COVID-19 vaccine. This is most notable with the Johnson & Johnson vaccine, which went through clinical trials later than the vaccines currently approved.

The vaccine was 72% effective in the United States, but just 58% effective in South Africa, where a variant was running rampant.

The worry and the concern is that the vaccines will be less effective, Pollock said. Its much better to take the vaccine. Youre much (more) likely to be better off if youre protected against the old virus.

Pollock said one way to get ahead of the variants is to do more genome sequencing. Hes now pushing the state to do that.

See original here:
More needs to be done to find and fight COVID-19 variants, says Colorado researcher - FOX 31 Denver

Introduction

Tuberculosis (TB) continues to be one of the most important public health problems, causing high morbidity and mortality, primarily in low- and middle-income countries.1 Globally the total TB incidence has declined by an average of 1.6% per year since 2000.1 However, the reduction in the number of extrapulmonary TB (EPTB) cases has been slower, resulting in a proportionate increase in EPTB compared to pulmonary TB (PTB).2 EPTB represented 30% of all case of TB notified in Ethiopia, which is greater than the global average of 16%.1 TB lymphadenitis (TBLN) accounted for 80% of all EPTB cases reported in Ethiopia.3

Multidrug resistant (MDR)-TB, which is defined as being resistant at list for rifampicin (RIF) and isoniazid (INH), remains a public health problem in many parts of the world.1 Globally, half a million people developed MDR/RIF resistant (RIFR)-TB in 2019.1 Ethiopia is one of 14 countries included in all three World Health Organization (WHO) high burden country lists for TB, TB/HIV, and MDR-TB.1 Together with an increasing number of drug resistant TBs around the world, the number of cases of primary MDR-TB with EPTB presentation is also going to rise.4 However, drug resistant EPTB is largely neglected and it does not receive specific attention in international control strategies.5 As a result, drug resistant isolates from EPTB are not well investigated, particularly in low-income countries.

The causative agents of TB are species of the Mycobacterium tuberculosis complex (MTBC) comprising of seven human adopted lineages (Lineage 17) which show biogeographic specificities in that the individual lineages are associated with particular geographic locations.6 Also, the MTBC includes species that are more commonly found in animals, but with zoonotic ability.7 Lineages 2, 3 and 4 are referred to as modern lineages, whereas Lineages 1, 5 and 6 are called ancient. Lineage 7 is phylogenetically localized between ancient and modern lineages and considered as a premodern lineage.6,8,9 Although both modern and ancient lineages exist in Ethiopia, the modern lineages, particularly 4 and 3, are the most prevalent types.10,11

Mycobacterium tuberculosis (M. tuberculosis) is described as a clonal bacterium, with no known plasmid and does not engage in horizontal gene transfer. Consequently, drug resistance in M. tuberculosis is usually mediated by chromosomal mutations and rearrangements.12,13 Molecular studies identied katG and rpoB as major targets conferring resistance of M. tuberculosis to INH and RIF respectively. Also, mutations in the regulatory region of the inhA operon, encoding a putative enzyme involved in mycolic acid biosynthesis, causes overexpression of the InhA protein, leading to INH resistance through a titration mechanism.14,15

Despite low genetic diversity in M. tuberculosis compared to other bacteria, the strain genetic background has been reported to plays a role in the global emergence of drug resistant TB. For instance, Beijing strains that belong to Lineage 2 have been frequently associated with drug resistance.16,17 Therefore, describing drug resistance conferring mutations in M. tuberculosis and their strain diversity circulating in a specific geographical area is important for both biological and epidemiological reasons. Although several studies conducted in Ethiopia assessed drug resistance patterns and genetic diversity of M. tuberculosis isolates from PTB patients, only limited data is available in the same regard from TBLN patients. With this background, this study aims to evaluate gene mutations conferring drug resistance and to further investigate variations among M. tuberculosis strains of TBLN patients.

This study was conducted using M. tuberculosis isolates retrieved from Armauer Hansen Research Institute (AHRI) laboratory biorepository that have been collected between 2016 and 2017 from Bishoftu, Gondar, Mekele and Hawassa in Ethiopia, as part of the Ethiopia Control of Bovine Tuberculosis (ETHICOBOT) study. Isolates were retrieved from culture positive Fine Need Aspirate (FNA) specimens collected from TBLN patients using a convenient sampling method. Clinical and demographic information for each isolate was retrieved from the ETHICOBOT study database using structured data extraction sheets.

RIF and INH resistance conferring mutation was detected using GenoType MTBDRplus VER 2.0. (Hain Life Science GmbH, Nehren, Germany) according to the manufacturers instruction. The test is based on DNA strip technology and has three steps: DNA extraction, amplification, and reverse hybridization. GenoType MTBDRplus VER 2.0 detects the absence and/or presence of wild type (WT) and/or mutant (MUT) DNA sequences within specific regions of three genes: the rpoB gene-gene (coding for the -subunit of the RNA polymerase), for the identification of RIFR; the katG gene (coding for the catalase peroxidase), for high level INH resistance (INHR); and the promoter region of the inhA gene (coding for the NADH enoyl ACP reductase), for low level INHR. GenoType MTBDRplus included eight rpoB WT probes, four rpoB MUT probes in positions of rpoB MUT1 (D516V), rpoB MUT2A (H526Y), rpoB MUT2B (H526D) and rpoB MUT3 (S531L), one katG WT probe, two katG MUT probes with katG MUT1 (S315T1) and katG MUT2 (S315T2), two inhA WT probes and four inhA MUT probes with inhA MUT1 (C15T), inhA MUT2 (A16G), inhA MUT3A (T8C) and inhA MUT3B (T8A). According to the manufacturers recommendations, the missing of a WT probe or presence of a MUT probe were considered as resistant.

Spoligotyping was carried out as described by Kamerbeek et al.18 Spoligotype patterns of each strain were prepared in binary and octal format and entered into spoligotyping database SITVIT2 (http://www.pasteur-guadeloupe.fr:8081/SITVIT2/), which is an updated version of SITVITWEB.19 Strains matching a preexisting pattern in the database were identified with Spoligo International Type (SIT) number, otherwise considered as orphans or new. Run TB-Lineage online tools (http://tbinsight.cs.rpi.edu/run_tb_lineage.html) was used to predict major M. tuberculosis lineages.20 Nomenclature for lineage names and numbers were assigned as proposed previously. For instance, Lineage 1 (Indo Oceanic; IO), Lineage 3 (East African-Indian; EAI), Lineage 4 (Euro-American; EA) and Lineage 7 (Ethiopian).21,22

Standard operational procedures for all laboratory tests were employed uniformly throughout the study. PCR was carried out in three separate rooms for DNA extraction, PCR mix preparation and amplification using dedicated pipettes and sterile tips. Furthermore, DNA from M. bovis Bacille Calmette-Guerin and M. tuberculosis H37Rv were used as positive controls while DNA free water from Qiagen was used as a negative control in each batch of the test.

Data were double entered to an Excel file format and statistical analysis was performed using SPSS version 20 (IBM Corp, Armonk, NY, USA). Descriptive statistics were used to depict the demographic variables. The Fisher exact was calculated to test the association between drug resistant conferring mutation and specific lineages of M. tuberculosis isolates. P-value 0.05 was considered statistically significant.

Ethical approval was obtained from the AHRI/ALERT Ethics Review Committee. Since the entire repository data were anonymized, no personal identifiers were collected during data retrieval.

A total of 91 M. tuberculosis isolates obtained from TBLN patients were included in this study, of which 54 (59.3%) were from females and 37 (40.7%) from males. The patients mean age was 32 years with a range of 976 years (Table 1). Of the 91 isolates included in this study, 35 (38.5%), 27 (29.7%), 21 (23.1%) and 8 (8.8%) were collected from Bishoftu, Gondar, Mekele and Hawassa, respectively.

Table 1 Demographic Characteristics of Study Participants from Different Places in Ethiopia, 20162017

Of 91 isolates tested for GenoType MTBDRplus VER 2.0, mutations conferring resistance to RIF and INH were observed in two (2.2%) and six (6.6%) isolates, respectively. Two (2.2%) of them were MDR isolates. Of isolates with resistant mutations, two (2.2%) were in the rpoB gene, four (4.4%) were in the katG gene and two (2.3%) were in the inhA promoter region. In two RIFR isolates, mutation was observed at codon S531L indicated by missing of rpoB WT8 probe with gain in rpoB MUT3 probes. Four of the six INHR isolates had a katG mutation. In three of these isolates, the mutation was observed at codon S315T1 indicated by absence of KatG WT with gain in katG MUT1 whereas one isolate had a mutation at S315T2 indicated by the absence of KatG WT with gain of KatG MUT2. Mutations in the inhA promoter gene occurred in two INHR isolates. One of these isolates had a mutation at codon C15T which was indicated by the omission of inhA WT1 and with the presence of the inhA MUT1 band. In one isolate inhA MUT1 band developed without missing the WT probe (Table 2). All drug resistant isolates were from treatment naive TBLN patients.

Table 2 Mutations Identified in Isoniazid and Rifampicin Resistant M. tuberculosis Strains

Among the 91 spoliogotyped isolates, 82 (90.1%) were classified into 28 different spoligotyping patterns according to the SITVIT2 database. The remaining 9 (9.9%) isolates were not registered in the database and thereby seen as new or orphans strains. The dominating identified SITs were SIT25, SIT149 and SIT53, each consisting of 19 (20.9%), 11 (12.1%) and 9 (9.9%) isolates, respectively (Figure 1).

Figure 1 Spoligotypes and major lineage classifications of clinical M. tuberculosis strains isolated from TBLN patients in different places in Ethiopia, 20162017.

Lineage 3 (EAI) was the most prevalent lineage in Gondar (18/27, 66.7%) and Mekele (11/21, 52.3%), whereas Lineage 4 (EA) was the most prevalent lineage in Bishoftu (27/35, 77.1%) and Hawassa (7/8, 87.5%). Two strains belonging to Lineage 1 (IO) were isolated in this study, both of them were from Mekele (SIT726). Furthermore, two Lineage 7 (Ethiopian) isolates were identified, one from Mekele (SIT910) and one from Gondar (SIT1729). Overall, Lineage 3 and Lineage 4 were the most prevalent lineages identified in this study, each accounted for 41.7% (38/91) and 53.8% (49/91), respectively. Whereas Lineage 1 and Lineage 7 were the least prevalent lineages, each accounted for 2.2% of the total isolates (Table 3).

Table 3 M. tuberculosis Lineage Distribution in Different Sample Collection Places in Ethiopia, 20162017

Cluster analysis based on spoligotyping patterns showed that 63 isolates were grouped into 9 clusters; as one cluster consisted of 219 isolates. The clustering rate was 69.2%. Statistically significant different rate of clustering observed between major MTBC lineages (Fishers Exact test = 8.413; P = 0.017) (Table 4).

Table 4 Cluster Distribution Among Different Mycobacterium tuberculosis Lineages

Isolates with drug resistance conferring mutations for any of the anti-TB drugs (RIF or INH), tested for by GenoType MTBDRplus, belonged to Lineage 3 (50%; 3/6) and Lineage 4 (50%; 3/6). However, an association between having anti-TB drug conferring mutation and major M. tuberculosis lineages were not statistically significant (Fisher exact test: 1.355; p > 0.05). Four out of six (66.7%) of the drug resistant isolates in this study belonged to a clustered strain (strains with shared SIT). Out of the three resistant strains of Lineage 3, one MDR-TB isolate with rpoB and KatG mutations was of SIT25, and two INHR isolates with inhA mutation had SIT26 and Orphan spoligotypes, whereas, among the resistant strains of Lineage 4, one MDR-TB isolate with rpoB and KatG mutations was of SIT149, two INHR isolates with a katG mutation were of SIT 50 and SIT 149 (Table 2).

This study presented the magnitude of drug resistance conferring mutation and genetic diversity of M. tuberculosis strains that cause TBLN in Ethiopia. Among the 91 isolates included in this study, mutations conferring resistance to RIF, INH, and to both of these drugs (MDR-TB), were observed in 2 (2.2%), 6 (6.6%), and 2 (2.2%) isolates, respectively. 2.2% MDR prevalence in this study was comparable with previous studies reported from Ethiopia among TBLN (14%)2325 and PTB patients (13%).2527. The problem of MDR in TBLN patients should not be ignored and early diagnosis of drug resistance is crucial to avoid the devastating effect of MDR TB.

The two RIFR isolates identified in this study contained the S531L mutation in the rpoB gene, which is the most frequently reported rpoB mutation in the Ethiopian strains,23,2830 indicating the possible transmission of strains with similar types of mutations in the community. However, mutations at other codons including H526D and D516V had also been reported among RIFR isolates.2831 Both RIFR strains in this study were INHR. Mono resistance to RIF is quite rare and almost all RIFR strains were also resistant to other drugs, especially to INH, which is why RIFR is considered as a surrogate marker for MDR-TB.15

Resistance to INH is frequently associated with a mutation at two genes; katG and inhA. In this study, 67% (4/6) of INHR isolates had a katG gene mutation at codon S315T. In contrast to this, 100% frequency of KatG mutation at codon S315T among INHR isolates had been reported from Ethiopia.23,28,30,32 Moreover, in the current study, gene mutations attributed to low level INHR mainly caused by the mutations in the promoter region of inhA gene were also observed. Such mutations were more frequent in our study (43%, 3/7) than the 1012% reported by other studies conducted in Ethiopia,29,33 in Pakistan (17%),34 and in Switzerland (23%).35 Mutations in inhA gene not only causes resistance to INH but also to the structurally related drug ethionamide, which shares the same target.14 Of the two isolates with inhA mutation, one of them had a mutation at C15T, whereas the other one had inhAMUT1 without mutation on the corresponding WT probe indicating heteroresistant isolates, ie concomitant infection with drug-resistant and drug-susceptible strains. TB infection with a heteroresistant M. tuberculosis population can be caused by infection with two different strains or the splitting of a single strain into susceptible and resistant organisms through microevolution.36,37 The relevance of heteroresistant TB should not be underestimated especially in highly endemic areas like Ethiopia, where there is a chance of co-infection with different M. tuberculosis strains with different resistant conferring mutations.

The M. tuberculosis population structure in this study was highly diverse and comprised of 28 different SITs and nine orphans or new strains. It is not unexpected, considering the samples are collected from different regions of the country. Lineage 3 and Lineage 4 were the most prevalent lineages identified in this study, each accounted for 41.7% and 53.8%, respectively. Similar patterns of lineage distribution were reported from different regions of Ethiopia among EPTB3841 and PTB patients.26,30 Likewise, a study that analyzed the distribution of genotypes among PTB and TBLN patients in Ethiopia, reported a similar distribution of genotypes between the two manifestations of the disease.8 This may indicate the absence of pathogen-specific genetic factors associated with the high rate of TBLN in Ethiopia and also suggested a similar route of PTB and TBLN transmission in the community. Lineage 4 has a broad distribution in Europe and America, Africa and the Middle-East whereas Lineage 3 has a relatively narrow distribution occurring in East Africa and Central and South Asia.9

Lineage 1 and Lineage 7 were the least prevalent lineages in this study, each accounted for 2.2% of the 91 TBLN isolates, which is in line with the overall relatively low prevalence of these lineages in Ethiopia.10,11 Lineage 1 is found in areas around the Indian Ocean and the Philippines.9 The Lineage 1 isolates (two isolates) in this study were isolated from Mekele TBLN patients. Previously, Lineage 1 was also reported from Southern,8,42 Central39 and North Ethiopia.32,43 The two Lineage 7 isolates identified in this study were isolated from Mekele and Gondar TBLN patients. This is the newly identified lineage initially reported in higher frequency from Woldia in Northern Ethiopia.8 Since then, it has been reported from different regions of the country.38,40,44,45 Lineage 7 has also been reported among Ethiopian immigrants in Djibouti and the Netherlands.46,47 The reason why Lineage 7 is restricted to native Ethiopians and Ethiopian immigrants is not yet well understood but it has been indicated that Lineage 7 has a lower rate of progression towards disease relative to other lineages, with subsequent out competition by other M. tuberculosis lineages.44 That may explain the geographical restriction of Lineage 7 to Ethiopia. Lineage 7 has contributed to the rejection of the virgin soil hypothesis of human TB in sub-Saharan Africa. According to virgin soil hypothesis, TB in the African region was due to European contact during the colonial period as it was originally free of TB.48

In our study, the overall clustering rate (strains with shared SIT) was 65.6% which is in line with other studies conducted in Ethiopia.8,26,41,49 A high rate of clustering maybe indicates active transmission of the disease and an ineffective TB control programme in the country. However, the low discrimination power of spoligotyping should be considered.50

The majority (4/6, 66.7%) of isolates with drug resistant conferring mutations in this study belonged to clustered strains, suggesting the possibility of transmission of drug resistant isolates between patients in the country. Moreover, all drug resistant isolates identified in the current study were from treatment of nave TBLN patients. That supports exposure of the patients to drug resistant M. tuberculosis strains in the community, rather than susceptible strains becoming resistant during the TB treatments. This needs to be carefully considered to prevent the spread of drug resistant clones in the country. Of the six isolates with drug resistant conferring mutations, two (33%) of them were SIT 149 whereas the rest were SIT 25, SIT 26, SIT 50 and one orphan strain. The high frequency of SIT149 among drug resistant M. tuberculosis isolates has been previously reported in Ethiopia.51,52 However, Bereket et al indicated that the observed association between SIT149 and the development of drug resistance may not necessarily indicate that the stains are prone to be drug resistant but could rather be association consequences of their high prevalence in the population.25

No significant associations were found between a particular lineage and any drug resistant conferring mutation. However, this might have been due to the low sample size. Apart from results shown for Lineage 2,16,17 the association between different M. tuberculosis lineages and TB drug resistance is rather inconsistent. For instance, Biadglegne et al40 and Tadesse et al38 showed a significant association between drug resistance and Lineage 3, whereas Amir et al found an association between Lineage 4 and drug resistance conferring mutations.32 In contrast, other studies did not find associations between the genotype of M. tuberculosis isolates and their drug resistance pattern.53,54 This shows that there is uncertainty on the strain-specific propensity for the acquisition of drug resistance conferring mutation among M. tuberculosis isolates. More work needs to be done to define whether some M. tuberculosis genotypes are more prone than others to develop drug resistance.

Overall, although the sensitivity of the GenoType MTBDRplus assay to detect strains with a novel mutation or gene mutation outside the resistance determining region is limited, the present study demonstrated the feasibility of estimating the magnitude of gene mutations conferring drug resistance and genetic diversity of drug resistant M. tuberculosis isolates in TBLN patients. Lineage 3 and Lineage 4 were the most prevalent lineage types identified in this study with high clustering rates of SIT 25, SIT149 and SIT 53. A drug resistant conferring mutation was detected among clustered strains, which could suggest clonal resistant strains transmission in the community. However, the tool we used to characterize the different M. tuberculosis strains, spoligotyping, is prone to convergent evolution and has low resolution power for cluster analysis. This warrants the need for future studies with a better tool of discrimination power like whole-genome sequencing (WGS) to understand the transmission dynamics of drug resistant TB and strengthen the control programs of TBLN in Ethiopia.

We would like to thank study participants for taking part in the study and all members of the ETHICOBOTS project who had a great contribution to the success of this study. The members of the ETHICOBOTS consortium are: Abraham Aseffa, Adane Mihret, Bamlak Tessema, Bizuneh Belachew, Eshcolewyene Fekadu, Fantanesh Melese, Gizachew Gemechu, Hawult Taye, Rea Tschopp, Shewit Haile, Sosina Ayalew, Tsegaye Hailu, all from the Armauer Hansen Research Institute, Ethiopia; Rea Tschopp from the Swiss Tropical and Public Health Institute, Switzerland; Adam Bekele, Chilot Yirga, Mulualem Ambaw, Tadele Mamo, Tesfaye Solomon, all from the Ethiopian Institute of Agricultural Research, Ethiopia; Tilaye Teklewold from the Amhara Regional Agricultural Research Institute, Ethiopia; Solomon Gebre, Getachew Gari, Mesfin Sahle, Abde Aliy, Abebe Olani, Asegedech Sirak, Gizat Almaw, Getnet Mekonnen, Mekdes Tamiru, Sintayehu Guta, all from the National Animal Health Diagnostic and Investigation Centre, Ethiopia; James Wood, Andrew Conlan, Alan Clarke, all from Cambridge University, United Kingdom; Henrietta L. Moore and Catherine Hodge, both from University College London, United Kingdom; Constance Smith at University of Manchester, United Kingdom; R. Glyn Hewinson, Stefan Berg, Martin Vordermeier, Javier Nunez-Garcia, all from the Animal and Plant Health Agency, United Kingdom; Gobena Ameni, Berecha Bayissa, Aboma Zewude, Adane Worku, Lemma Terfassa, Mahlet Chanyalew, Temesgen Mohammed, Yemisrach Zeleke, all from Addis Ababa University, Ethiopia.

This work was supported by Armauer Hansen Research Institute (AHRI) and the Biotechnology and Biologic Sciences Research Council, the Department for International Development, the Economic & Social Research Council, the Medical Research Council, the Natural Environment Research Council and the Defence Science & Technology Laboratory, under the Zoonoses and Emerging Livestock Systems (ZELS) program, ref: BB/L018977/1.

The authors report no conflicts of interest for this work.

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[Full text] Drug Resistance Conferring Mutation and Genetic Diversity of Mycobacte | IDR - Dove Medical Press

More than than 30% of Americans are at risk of kidney disease, and nearly 20% of all Medicare spending is for kidney disease in patients 65 and older. Yet there is still much not known about the development of kidney disease.

Dr. Indra Chandrasekarand her team of researchers recently published an article in the biomedical research journal JCI Insight, highlighting the impact of key cellular processes on kidney health and function. The discovery allows researchers to better understand how kidney disease forms.

The kidney carries out many functions that are necessary to maintain overall health. As a result, any disruption to those functions can cause kidney disease. To find where kidney disease starts, the Chandrasekar Lab chose to study functions at the cellular level.

When researchers turned off the genes for certain proteins in mice at 4 weeks of age, the mice began to exhibit worsening dilation of the kidney tubules accompanied by eventual kidney degeneration and cyst formation by 12 weeks of age. Along with these structural changes came functional changes within the kidneys, including more acidic urine, excretion of protein and salts, and inflammation as the disease progressed.

This work highlights a new and major role for the proteins, called nonmuscle myosin II (NM2A and NM2B), in maintaining the health and function of the kidneys. This finding provides key knowledge to the kidney disease field as the pursuit of a cure continues to drive the valuable work being performed at Sanford Research.

Dr. Indra Chandrasekar sat down to talk with Sanford Health News about her history with Sanford Research and her recent work.

The myosin motor family, and NM2 proteins in particular, has been studied for over five decades. NM2s role in cell migration, adhesion and cell division has been carefully examined in vitro as well as with organismal and developmental context. Work in the Chandrasekar Lab is focused on understanding the physiological and cell-type specific role for NM2 mediated cellular transport mechanisms using mouse kidney as a model. Turning off the NM2 genes in adult mouse kidney tubular epithelial cells demonstrates that NM2 function is critical for the transport of two important proteins within kidney. These two proteins are called uromodulin (UMOD) and sodium, potassium, chloride cotransporter (NKCC2), that are essential for maintaining electrolyte balance and blood pressure in our body.

Mutations in UMOD and NKCC2 genes in humans lead to kidney disease. Membrane-associated NKCC2 has been the target of several blood-pressure regulating medicines currently on the market. Therefore, it is critical to further explore and understand how NM2 proteins regulate UMOD and NKCC2 transport and function in within the kidney cells.

Personally, this published work has been our teams mission for the past several years. As the Nobel-prize winning neurobiologist Rita Levi-Montalcini once said, I dont believe there would be any science at all without intuition. The findings described in this manuscript began as an intuition that stemmed from my postdoctoral work. I am very happy with how it turned out and extremely grateful for our teams hard work.

As a cell biologist, I am fascinated by the molecular and cellular complexity of the kidney. Considering that mutations in MYH9 (NM2A protein) in humans are linked to kidney disease, and that the epithelial cells of the kidney are great models to study cellular transport pathways, it was an easy organ of choice. Moreover, the availability of excellent mouse genetic tools to perform cell-type specific, inducible and conditional gene inactivation in the kidney is also a positive.

The impact of our published work is twofold:

I worked at a local clinical laboratory in town during the first year of my undergraduate biochemistry program. My job was to prepare, stain and perform microscopic analysis of peripheral blood smears from patient blood. I was fascinated by the cellular morphology, staining characteristics and intracellular organelles present in the varying types of blood cells. I wanted to understand how different cell types in our body function and what happens when they do not perform their assigned jobs. This interest led me to Dr. Brigitte M. Jockushs laboratory in Germany for my Graduate work. Professor Jockusch is a well-respected expert in the field of cytoskeletal research and cell biology. Being in her lab was a great privilege. I continued my training with prominent cell biologists such as Dr. John A. Cooper and Dr. Paul C. Bridgman at the Washington University in St. Louis.

During my training as a post-doctoral scientist at Washington University in St. Louis, I had determined a new, critical role for nonmuscle myosin 2 (NM2) motors in processes by which proteins are transported into and within cells. At Sanford Research, I got the opportunity to follow on my previous findings and to start an independent research program to understand the molecular mechanisms underlying kidney tubular transport defects to human kidney diseases. The excellent, state-of-the-art facilities to conduct basic and clinical research at Sanford Research has led us to publish a manuscript of high impact that reports that the loss of NM2 proteins in adult kidney epithelium results in progressive chronic kidney disease.

I enjoy thinking about new ideas and concepts and testing those using experiments in the lab to gain insights into cellular mechanisms. I love performing advanced microscopy experiments. However, the most enjoyment comes from passing along the valuable techniques and scientific concepts to future scientists who are trainees and let them excel in whatever they desire in their life.

Posted In Genetics, Health Care Heroes, Research

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A clue to the causes of kidney disease: It's in your cells - Sanford Health News

It was supposed to be a temporary gig.

Avantika Patel was 25, newly married and still learning how to speak English after arriving in Southern California from a small town in India. Her husband was working as an engineer, she had a degree in microbiology and a plan to attend graduate school.

'They had those classified ads back then and my husband pointed one out,' she said. 'He said: 'Do you know this place in Thousand Oaks - Applied Molecular Genetics?''

She didn't.

Applied Molecular Genetics had just started the prior year with George Rathmann as the chief executive officer and had just three staff members. When she went for the interview at the small, modest building in the Spring of 1982, there were barely two dozen. She said it went well, but then she didn't hear from the company for months.

Patel didn't think much more about the job.

But Applied Molecular Genetics had been thinking about her and contacted Patel in November. They asked if she'd like to work as a research associate. She was already working at Jafra Cosmetics and the new job meant a pay cut of a few thousand dollars. But it looked interesting and exciting and it seemed to mesh with her graduate school goal.

Patel decided to give it a chance. A year turned into five. She had her first child. Five turned into 10 and she soon had a second child. The company was also growing. Fifty staff. Then 150. Then about a thousand. A first major drug to reach market that treated kidney disease exploded the company onto the map. Then came a cancer-related drug in 1992. Staff grew to 2,500. Money wasn't an issue anymore with early stock shares and several splits since.

By now the company was known as Amgen. Patel was making a name for herself with a straightforward, no-nonsense approach to the job and becoming an invaluable asset in learning how to guide drugs through the rigorous U.S. Food and Drug Administration approval process. The temporary job she'd applied to a decade prior was becoming a permanent part of her life.

Avantika Patel, second from the right, pictured in front of the building she began working in 39 years ago. She retired this year as Amgen's longest-tenured employee. Amgen file photo.

For the next three decades, she would help steer three major drugs to market, become a go-to person to salvage drug studies that were off-track and become a mentor and friend to what she called 'my Amgen family.'

But that ended Jan. 29, when Patel retired as the longest-serving staff member at Amgen.

'It was the hardest decision I've ever made,' she said.

A Passage from India

Patel was the daughter of a coal mine owner and a housewife, who married at 18. Neither had finished college. The town she grew up in was small and had limited options for a girl who had a keen love of science - specifically microbiology.

She left home at 16 to study, ultimately obtaining a degree in microbiology and with thoughts that she would put her education to work in India. But she was also part of traditional Indian culture and had an arranged marriage that set her up with a man who was already in the United States studying engineering at Fairleigh Dickinson University in New Jersey.

As he moved to Southern California for a job, she left India to be with him. A new husband. A new country. A new life.

'It was difficult,' she said. 'I was a girl who came from a small town in India where women were not highly educated. I thought I would never know my potential without furthering my education. But being at Amgen, I learned how to overcome my fears and be self-taught.'

Her husband, Chandrakant Patel, said she was driven to learn and work. 'I didn't know much about genetics, but it was all she talked about - genetics, genetics, genetics. I knew she was going to get into it somehow and be successful.'

Avantika Patel works in the lab in her first year at Amgen. Amgen file photo.

Working in clinical trials and cutting-edge studies, the plan of getting a doctorate couldn't compete with what she was learning at Amgen - while helping her balance raising a family. Amgen was with her along the way - as her son was one of the first to stay at Amgen's new childcare center in 1993 - known as Camp Amgen. She celebrated birthdays, anniversaries and the birth of her second son in that first decade.

Besides, the work at Amgen had become personal in another way.

She was beginning her own battle with kidney disease.

Scientist and Patient

Patel said her mother had kidney disease and it wasn't shocking to her that she developed it as well. In 2003, her doctor put her on a drug she had worked on at Amgen before it went to market in 1989.

The study was personal to her - both from her own health and from what had happened with her mother. She said the importance of scientific advancements are driven by empathy and a desire to ease suffering of others.

She was put on an organ transplant list. But being O positive meant the wait could be long due to its commonality.

Deb Lium, who began working with Patel in 2000, said she knew about a year before Patel started dialysis that things were rough for her.

'I remember she would leave during the day sometimes because she was in pain,' Lium said. 'But she is so strong and the work is so important to her, she couldn't stop. It's just who she is.'

The dialysis treatments began in 2009 and the routine was brutal.

Three days a week, Patel would get up early to be at work by 7 a.m. She would leave work around 4 p.m. to make a half-hour drive to Simi Valley for dialysis. She remembered the big needle to take blood out. There were excruciating cramps in her body. She said sometimes she would scream and cry from the pain.

'She was tired and exhausted, but she was tough,' Chandrakant said. 'She wouldn't complain, either.'

But then she'd be at work the next morning. Sometimes, when she'd travel for work, she would find a dialysis center in the city she was at just so it wouldn't interrupt her work.

'She always kept the pain to herself,' Lium said. 'But I could tell sometimes it was hard for her.'

Then Patel got the call in 2014. There was a kidney available. Dialysis would mercifully be over.

Her husband said he remembered the call. He was driving home from work and she had arrived home before him. The phone rang and she answered and got the news and immediately called him while he was in the car.

'I remember she said it was a perfect match,' Chandrakant Patel said. 'I drove home as fast as I could. We were so excited.'

Patel got the transplant a few hours later.

She struggled with sepsis for the first year, but as the kidney settled into its new home, it adapted and she continued to work.

'After the surgery, you realize how fragile life is,' Patel said. 'Mentally, I'm a strong person so the physical discomfort didn't bother me as much. I could distract myself from it by diving into the work. But I also noticed I didn't have as much energy as I used to and so I started to think about leaving.'

Long Legacy

When Patel told Maryam Huber she was contemplating retirement, Huber wasn't surprised. She had known the physical toll of the kidney disease and the dialysis and surgery for the transplant had taken a cumulative toll on her.

Huber, who has known her for more than 15 years, said Amgen is losing a library of institutional knowledge and one of the most empathetic workers she has ever known - even though she could be abrupt and blunt with her pragmatism at the same time. She has helped see several major Amgen drugs come to market.

'It was all in service to get help to patients,' Huber said. 'She knew getting the job done meant helping people. She didn't want to waste time.'

From a 2005 Amgen file photo featuring the longest-tenured staff in front of Building 1, displaying the original Amgen logo. Avantika Patel is second from the right.

Patel said she knows she will have a lot more time on her hands once she leaves Amgen.

Susan Cupples, who is close to Patel and was at her son's baby shower 20 years ago, laughed when she thought about Patel spending time on a beach relaxing or sitting around doing nothing. 'She needs a purpose and I think she will find it.'

Patel said Amgen was 'my second family.' It was only the second employer she ever worked for and she said she gave it all she had. She said Amgen had returned the favor many times over and she can't imagine a better 39 years.

But she said she will probably do volunteer work involving clinical research. She will have more time to dote on her grandchildren and be with her family. She said she will miss Amgen terribly.

'I stayed because this is what I was meant to do and I loved what I did here,' Patel said. 'I worked as long as I could, but it finally was time to leave.'

And so, she will. After a long, temporary 39 years.

Avantika Patel retired from Amgen after working with the company for 39 years and was its longest-tenured employee, coming on board just one year after it was founded in 1980. Photo: Stacey Gleason.

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Amgen : After 39 Years With Amgen, She Calls It a Career - Marketscreener.com

We can slow it down by canceling all these events, which we completely should do. But its still going to spread to most places.

Maciej Boni, a biologist at Penn State University, speaking to The Scientistabout how the high number of undetected cases makes it difficult to track viral spread based on confirmed infections (March 12)

Abdul Mannan Baig, a researcher at Aga Khan University in Pakistan, speaking to The Scientistabout indications that SARS-CoV-2 can target the nervous system (March 24)

Kishana Taylor, a postdoc in microbiology and molecular genetics at the University of California, Davis, speaking to The Scientistabout pandemic-related hiring freezes in academia (March 26)

Kathleen Millen, a neuroscientist at Seattle Childrens Hospital Research Institute, in an email to The Scientistabout how pandemic-related lab shutdowns affected the scientific community (March 27)

A cryogenic electron microscope-based visualization of SARS-CoV-2 spike protein is helping researchers understand precise molecular interactions with antibodies.

VISUALIZATION BY RUBEN DIAZ, BASED ON WORK BY DAVID VEESLER, UNIVERSITY OF WASHINGTON

Anthony Fauci, director of the US National Institute of Allergy and Infectious Disease, speaking with CNNs Sanjay Guptaabout the effects of the COVID-19 pandemic on the psyches of his daughters and other Americans (April 1)

Peter Daszak, president of the nonprofit EcoHealth Alliance, talking to 60 Minutes about the ongoing politicization of science with regard to the COVID-19 pandemic (May 10)

Erica Ollmann Saphire, an immunologist at the La Jolla Institute for Immunology, speaking to The Scientistabout the promise of antibody candidates that could prevent SARS-CoV-2 from entering cells (June 2)

Jillian Carmichael, a postdoc in virologist Benhur Lees lab at Mount Sinais Icahn School of Medicine, speaking with The Scientistabout missing out on research during the pandemic due to the closure of daycares and schools (June 25)

Nelly Yatich, epidemiologist in Nairobi, Kenya, discussing with The Scientist the challenges of determining the basic reproductive number, R0, which describes the initial spread of an infection in a completely susceptible population (July 13)

Hannah Davis, an artist living in Brooklyn, speaking to The Scientist about memory loss, sporadic bursts of blurred vision, a racing heart, difficulties breathing, insomnia, and various aches and pains that she experienced for months after testing positive for COVID-19 (July 17)

Ravinder Sehgal holds one of the birds he studied at a site in southwest Cameroon.

COURTESY OF RAVINDER SEHGAL

A. David Paltiel of Yale School of Public Health speaking to UPIabout his paper that indicated that masks, social distancing, and testing college students every two days could limit the spread of SARS-CoV-2 on campuses this fall (July 31)

Ravinder Sehgal, a biologist at San Francisco State University, speaking to The Scientistabout how a pandemic-related university travel ban limited his field research in infectious diseases (August 20)

Miriam Merad, who directs the Precision Medicine Institute at Mount Sinai, speaking to The Scientist about the rapid pace of COVID-19-related research this year (September 16)

Rick Bright (center) with National Institute of Allergy and Infectious Diseases Director Anthony Fauci (left) and Marilyn Serafini, former president and co-CEO of the Alliance for Health Reform

Patricia Garca, a Solidarity Trial investigator and the former health minister of Peru, speaking with The Scientistin the wake of the Surgisphere scandal (October 1)

An amended whistleblower complaint filed by attorneys representing Rick Bright, an immunologist who resigned from his post at the National Institutes of Health on October 6

Albert Bourla, chairman and chief executive of Pfizer, speaking to CNBC after the firm announced preliminary results from a Phase 3 trial of its COVID-19 vaccine, developed in collaboration with BioNTech, that suggest it is 90 percent effective in preventing the disease (November 9)

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2020 in Scientists Own Words - The Scientist

DUBLIN--(BUSINESS WIRE)--The "Global Adaptive Optics Market Analysis and Forecast, 2020 - 2026" report has been added to ResearchAndMarkets.com's offering.

The Global Adaptive Optics Market size is expected to reach $433.2 Million by 2026, rising at a market growth of 13.5% CAGR during the forecast period.

Adaptive Optics (AO) is quickly picking up demand as a possibility for enhancing the performance of optical systems. Optical instruments experience errors while measuring and imaging because of distortions found in light waves. Adaptive optics assists with nullifying these mistakes, in this way, improving the performance of the optical instruments. The increasing prevalence of retinal degeneration diseases is anticipated to impel the development of the market. Age-related Macular Degeneration (AMD) and Retinitis Pigmentosa (RP) are the most well-known retinal degenerative diseases across the world.

High-resolution phenotyping with adaptive optics imaging alongside molecular genetics analyses is anticipated to improve the clinical imaging of AMD and RP in the beginning phases. The increasing use of Adaptive optics for clinical application and research is anticipated to fuel the overall market development. Adaptive optics alongside Optical Coherence Tomography (OCT) is slowly penetrating the market because of its viability in giving enhanced and high-speed imaging. Advanced deformable mirrors are being created to exactly control the incident wavefront by reshaping a reflecting membrane with the assistance of precise magnetic actuators.

The improvement of these deformable mirrors is anticipated to decrease the size, cost, and complexity of AO-OCT gadgets, accordingly, making adaptive optics broadly adopted for different clinical applications. In this manner, the development of cutting edge Adaptive optics devices alongside increasing endeavors of vision researchers, ophthalmologists, and entrepreneurs in its development and research, is anticipated to drive the market.

The increasing prevalence of various retinal infections, for example, retinal degenerations, inherited color vision deficiencies, albinism, glaucoma, and numerous other eye diseases is anticipated to drive the market. Furthermore, the increasing awareness of Adaptive Optics (AO) and its efficient utilization in research for retinal imaging is also anticipated to contribute towards market development.

The market research report covers the analysis of key stake holders of the market. Key companies profiled in the report include Teledyne Technologies, Inc., Northrop Grumman Corporation, Adaptica S.r.l (He Vision Group), Thorlabs, Inc., Iris AO, Inc., Active Optical Systems Ltd., Flexible Optical B.V., Imagine Optic SA, Boston Micromachines Corporation and Phasics Corporation.

Key Topics Covered:

Chapter 1. Market Scope & Methodology

1.1 Market Definition

1.2 Objectives

1.3 Market Scope

1.4 Segmentation

1.5 Methodology for the research

Chapter 2. Market Overview

2.1 Introduction

2.1.1 Overview

2.1.2 Market Composition

2.2 Key Factors Impacting the Market

2.2.1 Market Drivers

2.2.2 Market Restraints

Chapter 3. Recent Developments in Global Adaptive Optics Market

Chapter 4. Global Adaptive Optics Market by Component

4.1 Global Wavefront Sensors Market by Region

4.2 Global Deformable Mirrors (Wavefront Correctors) Market by Region

4.3 Global Control System Market by Region

Chapter 5. Global Adaptive Optics Market by Application

5.1 Global Microscopy Market by Region

5.2 Global Ophthalmology Market by Region

5.3 Global Laser Application Market by Region

5.4 Global Other Applications Market by Region

Chapter 6. Global Adaptive Optics Market by Region

Chapter 7. Company Profiles

For more information about this report visit https://www.researchandmarkets.com/r/tbrs9o

The rest is here:
Global Adaptive Optics (Wavefront Sensors, Deformable Mirrors and Control System) Markets Report 2020-2026 - ResearchAndMarkets.com - Business Wire

BOSTON, Dec. 22, 2020 /PRNewswire/ --Valo Health, LLC (Valo), has announced an exclusive drug discovery and development partnership with Global Genomics Group, (G3), giving Valo access to the largest and most-detailed cardio-metabolic dataset in the world. Since the inception of the partnership, Valo has identified subpopulations across the cardiometabolic spectrum that have not been resolved before now, and are leading to the discovery of underlying genetics, biomarkers, and new disease-modifying targets. Using its Opal Computational Platform, Valo has been able to identify six validated targets and approximately 20 early potential targets and disease subpopulations.

"This partnership fits perfectly into Valo's strategy to utilize deep clinical human disease data with the powerful platform we have built to redefine diseases and identify sub diseases and patient populations," said Brett Blackman, Valo's Chief Innovation Officer."At the heart of Valo is our strong belief that human-centric data, coupled with leading-edge computation, will transform and accelerate how drugs are discovered and developed."

Valo is using their machine learning algorithms and G3's high dimensional best-in-class patient data to resolve never before patient-disease subpopulations that guide their discovery of novel targets. This provides confidence in identifying the right patient population to develop a disease-modifying medicine at the start of a discovery program. Valo's Opal Computational Platform takes the novel target and rapidly creates clinical candidates to test in those populations, dramatically cutting time and cost while increasing the probability of a drug's success.

"Working with Valo we are poised to transform and de-risk drug development, based on genetic validation of drug targets and on the use of biomarkers to conduct precision clinical trials in the right patient populations," said Szilard Voros, CEO, and co-founder of Global Genomics Group (G3). "For years, everyone has been talking about genetics -and biomarker-driven clinical trials - with Valo, we are actually now doing it."

G3's proprietary data comes from the Genetic Loci and the Burden of Atherosclerotic Lesions (GLOBAL) clinical study (NCT01738828) and represents one of the largest such disease-centric data sets in the world, designed and executed by G3. The GLOBAL study generated extremely large and complex data sets including whole genome sequencing and phenotypic associations to identify and link biological target (genotype) - phenotype - biomarker(s) as well as 3 billion data points from each of the nearly 8,000 patients with cardiovascular disease and from control subjects. G3 has over 320K blood samples and 8,000 advanced CT imaging datasets for evaluation, all standardized, normalized, and curated.

About ValoValo Health, LLC (Valo)is a technology company that is using human-centric data and machine learning-anchored computation to transform and accelerate the drug discovery and development process. By integrating data across the drug development lifecycle, the discovery and development of life-changing treatments can be accelerated, with the potential to reduce cost, time, and failure rate. The company's Opal Computational Platform, a fully-integrated, componentized, end-to-end drug development platform, offers a unique approach to therapeutic development, that enables Valo to advance a robust pipeline of candidates across cardiovascular disease, oncology, and neurodegeneration. Headquartered in Boston, MA, Valo has offices in San Francisco, CA, Princeton, NJ, and Branford, CT. To learn more, visit http://www.valohealth.com

About G3 TherapeuticsG3 Therapeutics is a global leader in the application of unbiased biological big data in transforming the drug discovery and drug development process. G3 Therapeutics has assembled a revelatory platform that utilizes deep phenotyping, deep molecular profiling and deep learning for the discovery, genetic validation and development of novel drug targets. G3 Therapeutics' foundational biological big data platform has been built on the GLOBAL Clinical Study (NCT01738828), enrolling over 7,500 individuals from around the world. G3 Therapeutics' deep molecular profiling approach includes whole genome sequencing, as well as the measurement of all other relevant "omics" measurements including DNA methylation, RNA sequencing, proteomics, metabolomics, and lipidomics. G3 Therapeutics has already discovered and patented relevant biomarkers and is starting the development of several novel drugs based on its proprietary platform and discoveries.

View original content to download multimedia:http://www.prnewswire.com/news-releases/valo-announces-exclusive-partnership-with-g3-the-worlds-largest-and-detailed-cardio-metabolic-datasets-301197305.html

SOURCE Valo Health, LLC

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Valo Announces Exclusive Partnership with G3 the World's Largest and Detailed Cardio-Metabolic Datasets - BioSpace

Researchers at the Institute of Molecular Biology and Genetics of National Academy of Sciences of Ukraine have developed a combined PCR test capable of simultaneous detection of SARS-CoV-2 and influenza A and B viruses.

"New PCR tests were checked on patients samples provided by the Center for Public Health. We hope that the Ministry of Health will be interested in the combined PCR test," said Director of IMBG, Academician Mykhailo Tukalo, the Institute of Molecular Biology and Genetics posted on Facebook.

The Institute notes that the test run time is about 6 hours.

Given the similarity of flu and coronavirus symptoms, such a PCR test is especially relevant now when Ukraine is expecting a seasonal flu epidemic.

Also, according to the Institute, scientists complete the development of a test that will detect simultaneously five viruses in a human body, in particular, rhinovirus and measles.

As reported, in January 2020, the Institute of Molecular Biology and Genetics developed and certified coronavirus test systems commissioned by the National Security and Defense Council.

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Ukraine develops test for simultaneous detection of COVID-19, two flu types - Ukrinform. Ukraine and world news

Below, one of our 10 newsmakers: Ryan Pourjam

With just 265 words, 13-year-old Ryan Pourjam laid bare the human tragedy of the downing of Ukraine International Airlines flight PS752.

In a grey sweater and blue jeans, Ryan stood before a gathering of more than 200 mourners at Carleton University in the memory of his dad, Mansour Pourjam, one of 176 people who died in the crash, just the week before.

It happened at a time when the world was on edge. Iran was on high alert after having launched a missile attack on American bases in Iraq in retaliation for a U.S. drone strike on Jan. 3 that had killed prominent Iranian general Qasem Soleimani. In the tense hours that followed, Irans Revolutionary Guard mistook the Boeing 737, which had taken off from Tehran airport just minutes before, for an incoming American cruise missile. It launched two surface-to air-missiles at the defenceless airliner.

The innocents aboard Flight PS752 were collateral damage in the realpolitik of Mideast conflict.

Mansour was one of 57 Canadians, eight of them from Ottawa, who lost their lives in the Jan. 8 crash.

Also killed were Alireza Pey, CEO and founder of Kanata-based MessageHopper; Roja Azadian, who was travelling alone after her husband learned at Tehran airport that his ticket had been cancelled; architect Fereshteh Maleki Dizaje, whowas returning from celebrating her daughters wedding in Tehran; and Fareed Arasteh, a Carleton University PhD student in molecular genetics who had been married in Tehran only days before. A trio of uOttawa students were also aboard the doomed flight:Alma Oladi, a PhD student in mathematics with a specialty in genomics statistics; Saeed Kashani, a PhD student in chemistry; and Mehraban Badiei, a first-year student in health sciences.

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Newsmakers 2020: Ryan Pourjam and the tragedy that devastated Ottawa's Iranian community - Ottawa Citizen