https://www.novareader.co Default RSS Feed en-us Newgen KnowledgeWorks https://www.novareader.co/book/isbn/10.1073/pnas.2024850118 We use three indexes to identify how age-specific mortality rates in the United States compare to those in a composite of five large European countries since 2000. First, we examine the ratio of age-specific death rates in the United States to those in Europe. These show a sharp deterioration in the US position since 2000. Applying European age-specific death rates in 2017 to the US population, we then show that adverse mortality conditions in the United States resulted in 400,700 excess deaths that year. Finally, we show that these excess deaths entailed a loss of 13.0 My of life. In 2017, excess deaths and years of life lost in the United States represent a larger annual loss of life than that associated with the COVID-19 epidemic in 2020.

]]> https://www.novareader.co/book/isbn/10.1073/pnas.2101562118 The autophagy protein ATG2, proposed to transfer bulk lipid from the endoplasmic reticulum (ER) during autophagosome biogenesis, interacts with ER residents TMEM41B and VMP1 and with ATG9, in Golgi-derived vesicles that initiate autophagosome formation. In vitro assays reveal TMEM41B, VMP1, and ATG9 as scramblases. We propose a model wherein membrane expansion results from the partnership of a lipid transfer protein, moving lipids between the cytosolic leaflets of apposed organelles, and scramblases that reequilibrate the leaflets of donor and acceptor organelle membranes as lipids are depleted or augmented. TMEM41B and VMP1 are implicated broadly in lipid homeostasis and membrane dynamics processes in which their scrambling activities likely are key.

]]> https://www.novareader.co/book/isbn/10.1073/pnas.2021852118 Although individual subjects can be identified with high accuracy using correlation matrices computed from resting-state functional MRI (rsfMRI) data, the performance significantly degrades as the scan duration is decreased. Recurrent neural networks can achieve high accuracy with short-duration (72 s) data segments but are designed to use temporal features not present in the correlation matrices. Here we show that shallow feedforward neural networks that rely solely on the information in rsfMRI correlation matrices can achieve state-of-the-art identification accuracies (≥99.5%

) with data segments as short as 20 s and across a range of input data size combinations when the total number of data points (number of regions ×

number of time points) is on the order of 10,000

.

]]> https://www.novareader.co/book/isbn/10.1073/pnas.2103090118 The ventromedial hypothalamus (VMH) is a critical neural node that senses blood glucose and promotes glucose utilization or mobilization during hypoglycemia. The VMH neurons that control these distinct physiologic processes are largely unknown. Here, we show that melanocortin 3 receptor (Mc3R)-expressing VMH neurons (VMH^MC3R) sense glucose changes both directly and indirectly via altered excitatory input. We identify presynaptic nodes that potentially regulate VMH^MC3R neuronal activity, including inputs from proopiomelanocortin (POMC)-producing neurons in the arcuate nucleus. We find that VMH^MC3R neuron activation blunts, and their silencing enhances glucose excursion following a glucose load. Overall, these findings demonstrate that VMH^MC3R neurons are a glucose-responsive hypothalamic subpopulation that promotes glucose disposal upon activation; this highlights a potential site for targeting dysregulated glycemia.

]]> https://www.novareader.co/book/isbn/10.1073/pnas.2020258118 Increasingly, human behavior can be monitored through the collection of data from digital devices revealing information on behaviors and locations. In the context of higher education, a growing number of schools and universities collect data on their students with the purpose of assessing or predicting behaviors and academic performance, and the COVID-19–induced move to online education dramatically increases what can be accumulated in this way, raising concerns about students’ privacy. We focus on academic performance and ask whether predictive performance for a given dataset can be achieved with less privacy-invasive, but more task-specific, data. We draw on a unique dataset on a large student population containing both highly detailed measures of behavior and personality and high-quality third-party reported individual-level administrative data. We find that models estimated using the big behavioral data are indeed able to accurately predict academic performance out of sample. However, models using only low-dimensional and arguably less privacy-invasive administrative data perform considerably better and, importantly, do not improve when we add the high-resolution, privacy-invasive behavioral data. We argue that combining big behavioral data with “ground truth” administrative registry data can ideally allow the identification of privacy-preserving task-specific features that can be employed instead of current indiscriminate troves of behavioral data, with better privacy and better prediction resulting.

]]> https://www.novareader.co/book/isbn/10.1073/pnas.2025739118 Different models have been proposed to elucidate the origins of the founding populations of America, along with the number of migratory waves and routes used by these first explorers. Settlements, both along the Pacific coast and on land, have been evidenced in genetic and archeological studies. However, the number of migratory waves and the origin of immigrants are still controversial topics. Here, we show the Australasian genetic signal is present in the Pacific coast region, indicating a more widespread signal distribution within South America and implicating an ancient contact between Pacific and Amazonian dwellers. We demonstrate that the Australasian population contribution was introduced in South America through the Pacific coastal route before the formation of the Amazonian branch, likely in the ancient coastal Pacific/Amazonian population. In addition, we detected a significant amount of interpopulation and intrapopulation variation in this genetic signal in South America. This study elucidates the genetic relationships of different ancestral components in the initial settlement of South America and proposes that the migratory route used by migrants who carried the Australasian ancestry led to the absence of this signal in the populations of Central and North America.

]]> https://www.novareader.co/book/isbn/10.1073/pnas.2023476118 With more time being spent on caregiving responsibilities during the COVID-19 pandemic, female scientists’ productivity dropped. When female scientists conduct research, identity factors are better incorporated in research content. In order to mitigate damage to the research enterprise, funding agencies can play a role by putting in place gender equity policies that support all applicants and ensure research quality. A national health research funder implemented gender policy changes that included extending deadlines and factoring sex and gender into COVID-19 grant requirements. Following these changes, the funder received more applications from female scientists, awarded a greater proportion of grants to female compared to male scientists, and received and funded more grant applications that considered sex and gender in the content of COVID-19 research. Further work is urgently required to address inequities associated with identity characteristics beyond gender.

]]> https://www.novareader.co/book/isbn/10.1073/pnas.2020434118 Grapheme-color synesthetes experience color when seeing achromatic symbols. We examined whether similar neural mechanisms underlie color perception and synesthetic colors using magnetoencephalography. Classification models trained on neural activity from viewing colored stimuli could distinguish synesthetic color evoked by achromatic symbols after a delay of ∼100 ms. Our results provide an objective neural signature for synesthetic experience and temporal evidence consistent with higher-level processing in synesthesia.

]]> https://www.novareader.co/book/isbn/10.1073/pnas.2019215118 The pathogenic consequences of 369 unique human HsMLH1 missense variants has been hampered by the lack of a detailed function in mismatch repair (MMR). Here single-molecule images show that HsMSH2-HsMSH6 provides a platform for HsMLH1-HsPMS2 to form a stable sliding clamp on mismatched DNA. The mechanics of sliding clamp progression solves a significant operational puzzle in MMR and provides explicit predictions for the distribution of clinically relevant HsMLH1 missense mutations.

]]> https://www.novareader.co/book/isbn/10.1073/pnas.2021581118 Acid-sensing ion channels (ASICs) are expressed in the nervous system, activated by acidosis, and implicated in pain pathways. Mambalgins are peptide inhibitors of ASIC1 and analgesic in rodents via inhibition of centrally expressed ASIC1a and peripheral ASIC1b. This activity has generated interest in mambalgins as potential therapeutics. However, most mechanism and structure–activity relationship work on mambalgins has focused on ASIC1a, and neglected the peripheral analgesic target ASIC1b. Here, we compare mambalgin potency and mechanism of action at heterologously expressed rat and human ASIC1 variants. Unlike the nanomolar inhibition at ASIC1a and rodent ASIC1b, we find mambalgin-3 only weakly inhibits human ASIC1b and ASIC1b/3 under severe acidosis, but potentiates currents under mild/moderate acidosis. Our data highlight the importance of understanding the activity of potential ASIC-targeting pharmaceuticals at human channels.

]]> https://www.novareader.co/book/isbn/10.1073/pnas.2022761118 Americans are much more likely to be socially connected to copartisans, both in daily life and on social media. However, this observation does not necessarily mean that shared partisanship per se drives social tie formation, because partisanship is confounded with many other factors. Here, we test the causal effect of shared partisanship on the formation of social ties in a field experiment on Twitter. We created bot accounts that self-identified as people who favored the Democratic or Republican party and that varied in the strength of that identification. We then randomly assigned 842 Twitter users to be followed by one of our accounts. Users were roughly three times more likely to reciprocally follow-back bots whose partisanship matched their own, and this was true regardless of the bot’s strength of identification. Interestingly, there was no partisan asymmetry in this preferential follow-back behavior: Democrats and Republicans alike were much more likely to reciprocate follows from copartisans. These results demonstrate a strong causal effect of shared partisanship on the formation of social ties in an ecologically valid field setting and have important implications for political psychology, social media, and the politically polarized state of the American public.

]]> https://www.novareader.co/book/isbn/10.1073/pnas.2023513118 Reconstructions of movement in extinct animals are critical to our understanding of major transformations in vertebrate locomotor evolution. Estimates of joint range of motion (ROM) have long been used to exclude anatomically impossible joint poses from hypothesized gait cycles. Here we demonstrate how comparative ROM data can be harnessed in a different way to better constrain locomotor reconstructions. As a case study, we measured nearly 600,000 poses from the hindlimb joints of the Helmeted Guineafowl and American alligator, which represent an extant phylogenetic bracket for the archosaurian ancestor and its pseudosuchian (crocodilian line) and ornithodiran (bird line) descendants. We then used joint mobility mapping to search for a consistent relationship between full potential joint mobility and the subset of joint poses used during locomotion. We found that walking and running poses are predictably located within full mobility, revealing additional constraints for reconstructions of extinct archosaurs. The inferential framework that we develop here can be expanded to identify ROM-based constraints for other animals and, in turn, will help to unravel the history of vertebrate locomotor evolution.

]]> https://www.novareader.co/book/isbn/10.1073/pnas.2022303118 An analytical derivation of the vibrational density of states (DOS) of liquids, and, in particular, of its characteristic linear in frequency low-energy regime, has always been elusive because of the presence of an infinite set of purely imaginary modes—the instantaneous normal modes (INMs). By combining an analytic continuation of the Plemelj identity to the complex plane with the overdamped dynamics of the INMs, we derive a closed-form analytic expression for the low-frequency DOS of liquids. The obtained result explains, from first principles, the widely observed linear in frequency term of the DOS in liquids, whose slope appears to increase with the average lifetime of the INMs. The analytic results are robustly confirmed by fitting simulations data for Lennard-Jones liquids, and they also recover the Arrhenius law for the average relaxation time of the INMs, as expected.

]]> https://www.novareader.co/book/isbn/10.1073/pnas.2020043118 Countering misinformation can reduce belief in the moment, but corrective messages quickly fade from memory. We tested whether the longer-term impact of fact-checks depends on when people receive them. In two experiments (total N = 2,683), participants read true and false headlines taken from social media. In the treatment conditions, “true” and “false” tags appeared before, during, or after participants read each headline. Participants in a control condition received no information about veracity. One week later, participants in all conditions rated the same headlines’ accuracy. Providing fact-checks after headlines (debunking) improved subsequent truth discernment more than providing the same information during (labeling) or before (prebunking) exposure. This finding informs the cognitive science of belief revision and has practical implications for social media platform designers.

]]> https://www.novareader.co/book/isbn/10.1073/pnas.2021022118 The ability to cast a mail ballot can safeguard the franchise. However, because there are often additional procedural protections to ensure that a ballot cast in person counts, voting by mail can also jeopardize people’s ability to cast a recorded vote. An experiment carried out during the COVID-19 pandemic illustrates both forces. Philadelphia officials randomly sent 46,960 Philadelphia registrants postcards encouraging them to apply to vote by mail in the lead-up to the June 2020 primary election. While the intervention increased the likelihood a registrant cast a mail ballot by 0.4 percentage points (P = 0.017)—or 3%—many of these additional mail ballots counted only because a last-minute policy intervention allowed most mail ballots postmarked by Election Day to count.

]]> https://www.novareader.co/book/isbn/10.1073/pnas.2018936118 Research reveals that a “finite pool of worry” constrains concern about and action on climate change. Nevertheless, a longitudinal panel survey of 1,858 UK residents, surveyed in April 2019 and June 2020, reveals little evidence for diminishing climate change concern during the COVID-19 pandemic. Further, the sample identifies climate change as a bigger threat than COVID-19. The findings suggest climate change has become an intransigent concern within UK public consciousness.

]]> https://www.novareader.co/book/isbn/10.1073/pnas.2013194117 In vivo clonal expansion of HIV-infected T cells is an important mechanism of viral persistence. In some cases, clonal expansion is driven by HIV proviral DNA integrated into one of a handful of genes. To investigate this phenomenon in vitro, we infected primary CD4+ T cells with an HIV construct expressing GFP and, after nearly 2 mo of culture and multiple rounds of activation, analyzed the resulting integration site distribution. In each of three replicates from each of two donors, we detected large clusters of integration sites with multiple breakpoints, implying clonal selection. These clusters all mapped to a narrow region within the STAT3 gene. The presence of hybrid transcripts splicing HIV to STAT3 sequences supports a model of LTR-driven STAT3 overexpression as a driver of preferential growth. Thus, HIV integration patterns linked to selective T cell outgrowth can be reproduced in cell culture. The single report of an HIV provirus in a case of AIDS-associated B-cell lymphoma with an HIV provirus in the same part of STAT3 also has implications for HIV-induced malignancy.

]]> https://www.novareader.co/book/isbn/10.1073/pnas.2015400117 The plant growth hormone auxin controls cell identity, cell division, and expansion. In the primary root of Arabidopsis there is a robust auxin gradient with a peak concentration at the tip of the meristem and a significant decrease throughout the elongation zone. The molecular mechanisms of how such a steep auxin gradient is established and maintained, and how this auxin gradient within the root dynamically adjusts in response to environmental stimuli are still largely unknown. Here, using a large-scale Arabidopsis mutant screening, we described the identification of PIN2 (PIN-FORMED 2), an auxin efflux facilitator, as a key downstream regulator in glucose-TOR (target of rapamycin) energy signaling. We demonstrate that glucose-activated TOR phosphorylates and stabilizes PIN2 and therefore influences the gradient distribution of PIN2 in the Arabidopsis primary root. Interestingly, dysregulation of TOR or PIN2 disrupts the glucose-promoted low auxin region located in the elongation zone that is essential for cell elongation. Taken together, our results shed light on how carbon and metabolic status can be tightly integrated with the hormone-driven processes to orchestrate complex plant growth programs.

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