Pharmacogenomics: The Right Drug to the Right Person

Pharmacogenomics is the branch of pharmacology which deals with the influence of genetic variation on drug response in patients by correlating gene expression or single-nucleotide polymorphisms with a drug's efficacy or toxicity. It aims to develop rational means to optimize drug therapy, with respect to the patients genotype, to ensure maximum efficacy with minimal adverse effects. Such approaches promise the advent of personalized medicine, in which drugs and drug combinations are optimized for each individual's unique genetic makeup. Pharmacogenomics is the whole genome application of pharmacogenetics, which examines the single gene interactions with drugs

What Do Americans Think About Federal Tax Options to Support Transportation? Results from Year Thirteen of a National Survey

69A3551747127This report summarizes the results from the thirteenth year of a national public opinion survey asking U.S. adults questions related to their views on federal transportation taxes. A nationally-representative sample of 2,620 respondents completed the online survey from January 31 to March 10, 2022

What Do Americans Think About Federal Tax Options to Support Transportation? Results from Year Thirteen of a National Survey [Brief]

69A3551747127This research brief summarizes results from the thirteenth year of an annual survey series exploring national support for raising additional federal transportation revenues through higher gas taxes or new mileage fees

RNA Polymerase II CTD phosphatase Rtr1 fine-tunes transcription termination

RNA Polymerase II (RNAPII) transcription termination is regulated by the phosphorylation status of the C-terminal domain (CTD). The phosphatase Rtr1 has been shown to regulate serine 5 phosphorylation on the CTD; however, its role in the regulation of RNAPII termination has not been explored. As a consequence of RTR1 deletion, interactions within the termination machinery and between the termination machinery and RNAPII were altered as quantified by Disruption-Compensation (DisCo) network analysis. Of note, interactions between RNAPII and the cleavage factor IA (CF1A) subunit Pcf11 were reduced in rtr1Δ, whereas interactions with the CTD and RNA-binding termination factor Nrd1 were increased. Globally, rtr1Δ leads to decreases in numerous noncoding RNAs that are linked to the Nrd1, Nab3 and Sen1 (NNS) -dependent RNAPII termination pathway. Genome-wide analysis of RNAPII and Nrd1 occupancy suggests that loss of RTR1 leads to increased termination at noncoding genes. Additionally, premature RNAPII termination increases globally at protein-coding genes with a decrease in RNAPII occupancy occurring just after the peak of Nrd1 recruitment during early elongation. The effects of rtr1Δ on RNA expression levels were lost following deletion of the exosome subunit Rrp6, which works with the NNS complex to rapidly degrade a number of noncoding RNAs following termination. Overall, these data suggest that Rtr1 restricts the NNS-dependent termination pathway in WT cells to prevent premature termination of mRNAs and ncRNAs. Rtr1 facilitates low-level elongation of noncoding transcripts that impact RNAPII interference thereby shaping the transcriptome

Status of billfish fishery along the Indian coast

The landings of billfishes along the Indian coast showing an increasing trend since the 1990s and the estimated landings during 2019 was reported to be 14759 tonnes. In India, five species Istiophorus platypterus, Kajikia audax, Istiompax indica, Makaira nigricans and Xiphias gladius are reported regularly while rare landings of Tetrapturus angustirostris are also recorded. The average annual billfish landings during 2012-2019 in different maritime states indicates that Kerala (4942.9 t) leads followed by Tamil Nadu 3386.8 t, Andhra Pradesh 2215.3 t, Gujarat 944.5 t, Maharashtra 277.8 t and so on. Mechanised gillnetter forms the chief craft and gear operated for billfish resources. I.platypterus dominated among the billfish species landed during all the years followed by I.indica, X.gladius, M.nigricans and K.audax. The fishes commanded rate of `100 per kg for I. platypterus, 120-140 for X. gladius and 160-200 for Marlins

Fishery, systematics and stock dynamics of billfishes landed along the Indian coast

Sailfishes, marlins, spearfishes and swordfishes commonly referred to as billfishes are highly migratory species, with a worldwide distribution in tropical and subtropical oceans. The landings of billfishes along the Indian coast registered an increasing trend with an estimated landing of 14,759 t in 2019. Kerala (41%) contributed the maximum followed by Tamil Nadu (28%), Andhra Pradesh (18%), Gujarat (8%) and Maharashtra (2%) to the total billfish landings during the last decade. Mechanised gillnetter cum hook and line was the major gear landing billfishes. The major species landed during 2012-2019 were Istiophorus platypterus (52.2%), Istiompax indica (21.1%), Makaira nigricans (7.3%), Xiphias gladius (17.2%) and Kajikia audax (2.3%). Four of these species could be easily distinguished by COI barcodes but, the striped marlin, K. audax showed high sequence similarity with K. albida and cannot be distinguished by barcodes alone. Control region (889 bp) provided a better phylogenetic signal, consistent with that of the whole mitochondrial genome topology. The stock status plots of billfishes depicted that, all the species were in the developing and exploited phase. Growth, mortality and exploitation rates estimated for four billfishes indicated that the present fishing rates and biomass levels are at safe levels and there is considerable scope for enhancing their fishery

Infiltration of Proinflammatory M1 Macrophages into the Outer Retina Precedes Damage in a Mouse Model of Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a major cause of blindness in the developed world. Oxidative stress and inflammation are implicated in AMD, but precise mechanisms remain poorly defined. Carboxyethylpyrrole (CEP) is an AMD-associated lipid peroxidation product. We previously demonstrated that mice immunized with CEP-modified albumin developed AMD-like degenerative changes in the outer retina. Here, we examined the kinetics of lesion development in immunized mice and the presence of macrophages within the interphotoreceptor matrix (IPM), between the retinal pigment epithelium and photoreceptor outer segments. We observed a significant and time-dependent increase in the number of macrophages in immunized mice relative to young age-matched controls prior to overt pathology. These changes were more pronounced in BALB/c mice than in C57BL/6 mice. Importantly, IPM-infiltrating macrophages were polarized toward the M1 phenotype but only in immunized mice. Moreover, when Ccr2-deficient mice were immunized, macrophages were not present in the IPM and no retinal lesions were observed, suggesting a deleterious role for these cells in our model. This work provides mechanistic evidence linking immune responses against oxidative damage with the presence of proinflammatory macrophages at sites of future AMD and experimentally demonstrates that manipulating immunity may be a target for modulating the development of AMD

A communal catalogue reveals Earth's multiscale microbial diversity

Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.Peer reviewe

A communal catalogue reveals Earth’s multiscale microbial diversity

Our growing awareness of the microbial world’s importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth’s microbial diversity

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

Funder: laura and john arnold foundationBACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care