Notes

Your 1-min sit-to-stand test--A simple practical ability check throughout cystic fibrosis?
g., ASTRAL, ASTRID, and IQ-TREE) under a wide range of model conditions, and establish that high accuracy can be obtained even when ASTRAL-Pro is not able to correctly roots and tags the gene family trees. We also compare results using MI, an alternative decomposition strategy from Yang and Smith (2014), and find that DISCO provides better accuracy, most likely as a result of covering more of the gene family tree leafset in the output decomposition.The global RNA-binding protein ProQ has emerged as a central player in post-transcriptional regulatory networks in bacteria. While the N-terminal domain (NTD) of ProQ harbors the major RNA-binding activity, the role of the ProQ C-terminal domain (CTD) has remained unclear. Here, we have applied saturation mutagenesis coupled to phenotypic sorting and long-read sequencing to chart the regulatory capacity of Salmonella ProQ. Parallel monitoring of thousands of ProQ mutants allowed mapping of critical residues in both the NTD and the CTD, while the linker separating these domains was tolerant to mutations. Single amino acid substitutions in the NTD associated with abolished regulatory capacity strongly align with RNA-binding deficiency. An observed cellular instability of ProQ associated with mutations in the NTD suggests that interaction with RNA protects ProQ from degradation. Mutation of conserved CTD residues led to overstabilization of RNA targets and rendered ProQ inert in regulation, without affecting protein stability in vivo. Furthermore, ProQ lacking the CTD, although binding competent, failed to protect an mRNA target from degradation. Together, our data provide a comprehensive overview of residues important for ProQ-dependent regulation and reveal an essential role for the enigmatic ProQ CTD in gene regulation.A growing body of evidence has underscored the role of horizontal gene transfer (HGT) in animal evolution. Previously, we discovered the horizontal transfer of the gene encoding the eukaryotic genotoxin cytolethal distending toxin B (cdtB) from the pea aphid Acyrthosiphon pisum secondary endosymbiont (APSE) phages to drosophilid and aphid nuclear genomes. Here, we report cdtB in the nuclear genome of the gall-forming "swede midge" Contarinia nasturtii (Diptera Cecidomyiidae) via HGT. We searched all available gall midge genome sequences for evidence of APSE-to-insect HGT events and found five toxin genes (aip56, cdtB, lysozyme, rhs, and sltxB) transferred horizontally to cecidomyiid nuclear genomes. Surprisingly, phylogenetic analyses of HGT candidates indicated APSE phages were often not the ancestral donor lineage of the toxin gene to cecidomyiids. We used a phylogenetic signal statistic to test a transfer-by-proximity hypothesis for animal HGT, which suggested that microbe-to-insect HGT was more likely between taxa that share environments than those from different environments. Many of the toxins we found in midge genomes target eukaryotic cells, and catalytic residues important for toxin function are conserved in insect copies. This class of horizontally transferred, eukaryotic cell-targeting genes is potentially important in insect adaptation.Multi-cancer early detection (MCED) tests may soon be available to screen for many cancers using a single blood test, yet little is known about these tests beyond their diagnostic performance. Taking lessons from the history of cancer early detection, we highlight three factors that influence how performance of early detection tests translates into benefit and benefit-harm tradeoffs the ability to readily confirm a cancer signal, the population testing strategy, and the natural histories of the targeted cancers. We explain why critical gaps in our current knowledge about each factor prevent reliably projecting the expected clinical impact of MCED testing at this point in time. CQ31 Our goal is to communicate how much uncertainty there is about the possible effects of MCED tests on population health so that patients, providers, regulatory agencies, and the public are well informed about what is reasonable to expect from this potentially important technological advance. We also urge the community to invest in a coordinated effort to collect data on MCED test dissemination and outcomes so that these can be tracked and studied while the tests are rigorously evaluated for benefit, harm, and cost.Interconversions between nucleic acid structures play an important role in transcriptional and translational regulation and also in repair and recombination. These interconversions are frequently promoted by nucleic acid chaperone proteins. To monitor their kinetics, Förster resonance energy transfer (FRET) is widely exploited using ensemble fluorescence intensity measurements in pre-steady-state stopped-flow experiments. Such experiments only provide a weighted average of the emission of all species in solution and consume large quantities of materials. Herein, we lift these limitations by combining time-resolved fluorescence (TRF) with droplet microfluidics (DmF). We validate the innovative TRF-DmF approach by investigating the well characterized annealing of the HIV-1 (+)/(-) Primer Binding Sequences (PBS) promoted by a HIV-1 nucleocapsid peptide. Upon rapid mixing of the FRET-labelled (-)PBS with its complementary (+)PBS sequence inside microdroplets, the TRF-DmF set-up enables resolving the time evolution of sub-populations of reacting species and reveals an early intermediate with a ∼50 ps donor fluorescence lifetime never identified so far. TRF-DmF also favorably compares with single molecule experiments, as it offers an accurate control of concentrations with no upper limit, no need to graft one partner on a surface and no photobleaching issues.
The solvent accessible surface is an essential structural property measure related to the protein structure and protein function. Relative solvent accessible area (RSA) is a standard measure to describe the degree of residue exposure in the protein surface or inside of protein. However, this computation will fail when the residues information is missing.

In this paper, we proposed a novel method for estimation RSA using the Cα atom distance matrix with the deep learning method (EAGERER). The new method, EAGERER, achieves Pearson correlation coefficients of 0.921-0.928 on two independent test datasets. We empirically demonstrate that EAGERER can yield better Pearson correlation coefficients than existing RSA estimators, such as coordination number, half sphere exposure, and SphereCon. To the best of our knowledge, EAGERER represents the first method to estimate the solvent accessible area using limited information with a deep learning model. It could be useful to the protein structure and protein function prediction.

The method is free available at https//github.com/cliffgao/EAGERER.

Supplementary data are available at Bioinformatics online.
Supplementary data are available at Bioinformatics online.
Feeding practices highly influence the nutritional status of children between 6 and 23 months of age in developing countries, including Ethiopia. Therefore, this study was conducted to investigate the association of feeding practices and sociodemographic factors on underweight and wasting of children aged 6-23 months in Ethiopia.

Data on 8003 children 6-23 months of age from four Ethiopia demographic and health surveys (EDHS) from 2000 to 2016 were analyzed using complex sample crosstabs for multivariate analysis. The association of feeding practices and sociodemographic factors on underweight and wasting was assessed via multiple logistic regression analyses adjusting the covariates. The outcomes were reported based on the adjusted odds ratios (ORs) with 95% confidence interval (CI).

Male children, very small at birth size children, diarrhea and fever, and short stature mother were risk factors for underweight and wasting (p < 0.05-0.001). Also, minimum dietary diversity, rich and middle-income famia also observed improvement from 18.9% in 2000 to 16.7% in 2005, then further reduced to 15.4% and 13.9% in 2011 and 2016 EDHS, respectively.• Male children, very small at birth size children, diarrhea and fever (for the last 2 weeks), and short stature mother were risk factors for underweight and wasting.• Minimum dietary diversity, rich and middle-income families, vitamin A in the previous 6 months and antenatal care visits during pregnancy were protective factors for both underweight and wasting.• Minimum meal frequency was significantly related to lower odds of wasting.• Higher age of the children was significantly associated with underweight; however, less likely wasted.Motivation is a hallmark of healthy aging, but the motivation to engage in effortful behavior diminishes with increasing age. Most neurobiological accounts of altered motivation in older adults assume that these deficits are caused by a gradual decline in brain tissue, while some psychological theories posit a switch from gain orientation to loss avoidance in motivational goals. Here, we contribute to reconcile the psychological and neural perspectives by providing evidence that frontopolar cortex (FPC), a brain region involved in cost-benefit weighting, increasingly underpins effort avoidance rather than engagement with age. Using anodal transcranial direct current stimulation together with effort-reward trade-offs, we find that the FPC's function in effort-based decisions remains focused on cost-benefit calculations but appears to switch from reward seeking to cost avoidance with increasing age. This is further evidenced by exploratory, independent analysis of structural brain changes, showing that the relationship between the density of frontopolar neural tissue and willingness to exert effort differs in young versus older adults. Our results inform aging-related models of decision making by providing preliminary evidence that, in addition to cortical thinning, changes in goal orientation need to be considered in order to understand alterations in decision making over the lifespan.The uncontrolled spread of the COVID-19 pandemic has led to the emergence of different SARS-CoV-2 variants across the globe. The ongoing global vaccination strategy to curtail the COVID-19 juggernaut, is threatened by the rapidly spreading Variants of Concern (VOC) and other regional mutants, which are less responsive to neutralization by infection or vaccine derived antibodies. We have previously developed the hiVNT system which detects SARS-CoV-2 neutralizing antibodies in sera in less than three hours. In this study, we modify the hiVNT for rapid qualitative screening of neutralizing antibodies (nAb) to multiple VOC of SARS-CoV-2, and assess the neutralizing efficacy of the BNT162b2 mRNA vaccine on seven epidemiologically relevant SARS-CoV-2 variants. Here we show that the BNT162b2 mRNA vaccine can activate humoral immunity against the major SARS-CoV-2 mutants that are currently in circulation. Albeit a small sample size, we observed that one dose of vaccine was sufficient to elicit a protective humoral response in previously infected people. Using a panel of seven SARS-CoV-2 variants and a single prototype virus, our modified hiVNT would be useful for large-scale community wide testing to detect protective immunity that may confer vaccine/immune passport in the ongoing COVID-19 pandemic.
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