bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fine-tuning GPCR-mediated neuromodulation by biasing signaling through different G-protein subunits
Authors: Park Jong-Chan , Luebbers Alex , Dao Maria , Semeano Ana , Papakonstantinou Maria P. , Broselid Stefan , Yano Hideaki , Martemyanov Kirill A. , Garcia-Marcos Mikel 
Published: March 2023

ABSTRACTGPCRs mediate neuromodulation through activation of heterotrimeric G-proteins (Gαβγ). Classical models depict that G-protein activation leads to a one-to-one formation of Gα-GTP and Gβγ species. Each of these species propagates signaling by independently acting on effectors, but the mechanisms by which response fidelity is ensured by coordinating Gα and Gβγ responses remain unknown. Here, we reveal a paradigm of G-protein regulation whereby the neuronal protein GINIP biases inhibitory GPCR responses to favor Gβγ over Gα signaling. Tight binding of GINIP to Gαi-GTP precludes its association with effectors (adenylyl cyclase) and, simultaneously, with Regulator-of-G-protein-Signaling (RGS) proteins that accelerate deactivation. As a consequence, Gαi-GTP signaling is dampened whereas Gβγ signaling is enhanced. We show that this mechanism is essential to prevent imbalances of neurotransmission that underlie increased seizure susceptibilityin vivo. Our findings reveal an additional layer of regulation within a quintessential mechanism of signal transduction that sets the tone of neurotransmission.
Litter Matters: The Importance of Decomposition Products for Soil Bacterial Diversity and abundance of key groups of the N cycle in Tropical Areas
Authors: Diniz Priscila Pereira , Borges Beatriz Maria Ferrari , Oliveira Aline Pacobahyba de , Coelho Maurício Rizzato , Aragão Osnar Obede da Silva , Ribeiro Thiago Gonçalves , Rocha Fernando Igne , Alves Bruno José Rodrigues , Coelho Márcia Reed Rodrigues , Dias Eustáquio Souza , Cole James R. , Howe Adina Chuang , Tsai Siu Mui , Jesus Ederson da Conceição 
Published: March 2023

AbstractThis study investigated the contribution of soil organic layers to bacterial diversity evaluations. We used a forest in the eastern Amazon and an adjacent pasture as model systems. Distinct organic and organo-mineral layers were identified in the forest and pasture floors, including the litter, partially and wholly decomposed organic material, and the mineral and rhizospheric soils. DNA was extracted, and 16S rRNA gene sequencing and qPCR were performed to assess bacterial community structure and the abundance of critical groups of the N cycle. We observed a clear vertical gradient in bacterial community composition. Species followed a log-normal distribution, with the highest richness and diversity observed in transitional organic layers of both land uses. Generally, critical groups of the N cycle were more abundant in these transitional layers, especially in the pasture’s fragmented litter and in the forest’s partially decomposed organic material. Considering the organic layers increased diversity estimates significantly, with the highest alpha and gamma bacterial diversity observed on the pasture floor and the highest beta diversity on the forest floor. The results show that organic layers harbor significant bacterial diversity in natural and anthropized systems and suggest that they can be crucial for maintaining the N cycle in these ecosystems, highlighting the need to consider them when studying soil bacterial diversity.
A Comparison of Deep Learning Architectures for Inferring Parameters of Diversification Models from Extant Phylogenies
Authors: Lajaaiti Ismaël , Lambert Sophia , Voznica Jakub , Morlon Hélène , Hartig Florian 
Published: March 2023

AbstractTo infer the processes that gave rise to past speciation and extinction rates across taxa, space and time, we often formulate hypotheses in the form of stochastic diversification models and estimate their parameters from extant phylogenies using Maximum Likelihood or Bayesian inference. Unfortunately, however, likelihoods can easily become intractable, limiting our ability to consider more complicated diversification processes. Recently, it has been proposed that deep learning (DL) could be used in this case as a likelihood-free inference technique. Here, we explore this idea in more detail, with a particular focus on understanding the ideal network architecture and data representation for using DL in phylogenetic inference. We evaluate the performance of different neural network architectures (DNN, CNN, RNN, GNN) and phylogeny representations (summary statistics, Lineage Through Time or LTT, phylogeny encoding and phylogeny graph) for inferring rates of the Constant Rate Birth-Death (CRBD) and the Binary State Speciation and Extinction (BISSE) models. We find that deep learning methods can reach similar or even higher accuracy than Maximum Likelihood Estimation, provided that network architectures and phylogeny representations are appropriately tuned to the respective model. For example, for the CRBD model we find that CNNs and RNNs fed with LTTs outperform other combinations of network architecture and phylogeny representation, presumably because the LTT is a sufficient and therefore less redundant statistic for homogenous BD models. For the more complex BiSSE model, however, it was necessary to feed the network with both topology and tip states information to reach acceptable performance. Overall, our results suggest that deep learning provides a promising alternative for phylogenetic inference, but that data representation and architecture have strong effects on the inferential performance.
Hepatic stellate cells maintain liver homeostasis through paracrine neurotrophin-3 signaling
Authors: Trinh Vincent Quoc-Huy , Lee Ting-Fang , Lemoinne Sara , Ray Kevin C. , Ybanez Maria D. , Tsuchida Takuma , Carter James K. , Agudo Judith , Brown Brian D. , Akat Kemal M. , Friedman Scott L. , Lee Youngmin A. 
Published: March 2023

AbstractOrgan homeostasis is maintained by regulated proliferation of distinct cell populations. In mouse liver, cyclin D1-positive hepatocytes in the midlobular zone repopulate the parenchyma at a constant rate to preserve liver homeostasis. The mitogenic cues that underlie this process are unknown. Hepatic stellate cells, the liver’s pericytes, are in close proximity to hepatocytes and have been implicated in supporting hepatocyte proliferation, but their role in liver homeostasis is unknown. Here, we employ a T cell-mediated hepatic stellate cell ablation model to remove nearly all hepatic stellate cells in the murine liver, enabling the unbiased characterization of hepatic stellate cell functions. In the normal murine liver, complete loss of hepatic stellate cells persists for up to 6 weeks and reduces liver mass. Our results show that hepatic stellate cells induce cyclin D1 in midlobular hepatocytes by release of neurotrophin-3 to promote hepatocyte proliferation via tropomyosin receptor kinase B signaling. These findings establish that hepatic stellate cells form the niche for midlobular hepatocytes and reveal a novel hepatocyte growth factor signaling pathway.One-Sentence SummaryHepatic stellate cells provide mitogenic cues for midlobular hepatocyte proliferation and metabolic zonation by secreting neurotrophin-3.
Regulatory sites of CaM-sensitive adenylyl cyclase AC8 revealed by cryo-EM and structural proteomics
Authors: Khanppnavar Basavraj , Schuster Dina , Lavriha Pia , Uliana Federico , Özel Merve , Mehta Ved , Leitner Alexander , Picotti Paola , Korkhov Volodymyr M. 
Published: March 2023

AbstractMembrane adenylyl cyclase AC8 is regulated by G proteins and calmodulin (CaM), mediating the crosstalk between the cAMP pathway and Ca2+signalling. Despite the importance of AC8 in physiology, including cognitive functions and memory, the structural basis of its regulation by G proteins and CaM is not well defined. Here we report the 3.5 Å resolution cryo-EM structure of the bovine AC8 bound to Ca2+/CaM and the stimulatory Gαs protein. The structure reveals the architecture of the ordered AC8 domains bound to Gαs and a small molecule activator forskolin. The extracellular surface of AC8 features a negatively charged pocket, a potential site for unknown interactors. Despite the well resolved forskolin density, the captured state of AC8 does not favour tight nucleotide binding. The structural proteomics approaches, limited proteolysis and crosslinking mass spectrometry, allow us to identify the contact sites between AC8 and its regulators, CaM, Gαs, and Gβγ, as well as to infer the conformational changes induced by these interactions. Our results provide a framework for understanding the role of flexible regions in the mechanism of AC regulation.
An 11-point time course midgut transcriptome across 72 h after blood feeding provides detailed temporal resolution of transcript expression in the arbovirus vector,Aedes aegypti
Authors: Tsujimoto Hitoshi , Adelman Zach N. 
Published: March 2023

AbstractAs the major vector for dengue, Zika, yellow fever, and chikungunya viruses, the mosquitoAedes aegyptiis one of the most important insects in public health. These viruses are transmitted by bloodfeeding, which is also necessary for the reproduction of the mosquito. Thus, the midgut plays an essential role in mosquito physiology as the center for bloodmeal digestion and as an organ that serves as the first line of defense against viruses. Despite its importance, transcriptomic dynamics with fine temporal resolution across the entire digestion cycle have not yet been reported. To fill this gap, we conducted a transcriptomic analysis ofAe. aegyptifemale midgut across a 72-h bloodmeal digestion cycle for 11 time points with a particular focus on the first 24 h. PCA analysis confirmed that 72 h is indeed a complete digestion cycle. Cluster and GO enrichment analysis showed the orchestrated modulation of thousands of genes to accomplish the midgut’s role as the center for digestion as well as nutrient transport with a clear progression with sequential emphasis on transcription, translation, energy production, nutrient metabolism, transport, and finally autophagy by 24-36hr. We further determined that many serine proteases are robustly expressed as if to prepare for unexpected physiological challenges. This study provides a powerful resource for the analysis of genomic features that coordinate the rapid and complex transcriptional program induced by mosquito bloodfeeding.
A Non-parametric Approach to the Construction of Life Tables at the Local Level with Application to Andhra Pradesh, India
Authors: Chaurasia Aalok Ranjan 
Published: March 2023

AbstractIn this paper, a non-parametric approach has been proposed for the construction of life table at the local level. The approach is based on the non-parametric modelling of the transition in age-specific probabilities of death at higher levels of administration and the relationship between the geometric mean of the age-specific probabilities of death and the probability of death in the first five years of life. The application of the approach has been demonstrated by constructing life tables for the districts of Andhra Pradesh, India using the data from the 2011 population census and the sample registration system.
Tau protein aggregation associated with SARS-CoV-2 main protease
Authors: Eberle Raphael Josef , Coronado Mônika Aparecida , Gering Ian , Korostov Karolina , Stefanski Anja , Stühler Kai , Kraemer-Schulien Victoria , Blömeke Lara , Bannach Oliver , Willbold Dieter 
Published: March 2023

AbstractThe primary function of virus proteases is the proteolytic processing of the viral polyprotein. These enzymes can also cleave host cell proteins, which is important for viral pathogenicity, modulation of cellular processes, viral replication, the defeat of antiviral responses and modulation of the immune response. It is known that COVID-19 can influence multiple tissues or organs and that infection can damage the functionality of the brain in multiple ways. After COVID-19 infections, amyloid-β, neurogranin, tau and phosphorylated tau were detected extracellularly, implicating possible neurodegenerative processes.The present study describes the possible induction of protein aggregation by the SARS-CoV-2 3CL protease (3CLpro) possibly relevant in neuropathology, such as aggregation of tau, alpha-synuclein and TPD-43. Further investigations demonstrated that tau was proteolytically cleaved by the viral protease 3CL and, consequently, generated aggregates. However, more evidence is needed to confirm that COVID-19 is able to trigger neurodegenerative diseases.
Relict duck-billed dinosaurs survived into the last age of the dinosaurs in subantarctic Chile
Authors: Alarcón-Muñoz Jhonatan , Vargas Alexander O. , Püschel Hans , Soto-Acuña Sergio , Manríquez Leslie , Leppe Marcelo , Kaluza Jonatan , Milla Verónica , Simon-Gutstein Carolina , Palma-Liberona José , Stinnesbeck Wolfgang , Frey Eberhard , Pino Juan Pablo , Bajor Dániel , Núñez Elaine , Ortiz Héctor , Mansilla Héctor , Rubilar-Rogers David , Cruzado-Caballero Penélope 
Published: March 2023

AbstractIn the dusk of the dinosaur era, the advanced duck-billed dinosaurs (Family Hadrosauridae) are thought to have outcompeted other herbivores, making ecosystems less diverse and more vulnerable to the Cretaceous-Paleogene asteroid impact. They were also among the first terrestrial organisms to disperse from North America into South America. Here, we present the first new species of subantarctic duck-billed dinosaur, CPAP 3054, of early Maastrichtian age in Magallanes, Chile. Surprisingly, unlike duckbills further north in Patagonia, CPAP 3054 is not an advanced duckbill, but descends from North American forms that were transitional to Hadrosauridae, diverging shortly before the origin of this family. In North America, these forms were replaced by hadrosaurids in the late Campanian. The survival into the Maastrichtian of a pre-hadrosaurid lineage suggests the ancestors of CPAP 3054 arrived earlier in South America than the hadrosaurids, reaching further south before the Cretaceous-Paleogene mass extinction, where they avoided competition from hadrosaurids.Additional noteThis work contains a new biological name. New names in preprints are not considered available by the ICZN. To avoid ambiguity, the new biological name is not included in this preprint, and the holotype specimen number CPAP 3054 is used as a placeholder. Paratypes described in this preprint are also used in the diagnosis.
Post-COVID-19 syndrome and related dysautonomia reduce quality of life, and increase anxiety and depressive symptoms: evidence from Greece
Authors: Galanis Petros , Katsiroumpa Aglaia , Vraka Irene , Kosiara Katerina , Siskou Olga , Konstantakopoulou Olympia , Katsoulas Theodoros , Gallos Parisis , Kaitelidou Daphne 
Published: March 2023

AbstractBackgroundPost-COVID-19 syndrome affects a significant number of SARS-CoV-2 infected individuals even asymptomatic cases causing several neurological and neuropsychiatric symptoms and signs.Materials and MethodsAn online cross-sectional study with a convenience sample was conducted in Greece from November 2022 to January 2023. We measured demographic and clinical characteristics of patients, post-COVID-19 dysautonomia, quality of life with the EQ-5D-3L, and anxiety and depressive symptoms with the Patient Health Questionnaire-4.ResultsStudy population included 122 patients with post-COVID-19 syndrome. One out of four patients (27.8%) manifested post-COVID-19 dysautonomia, while mean duration of COVID-19 symptoms was 11.6 months. Anxiety and depressive symptoms were worse after the post-COVID-19 syndrome (p<0.001 in both cases). A statistically significant reduction in quality of life was observed among patients after the post-COVID-19 syndrome (p<0.001 for both EQ-5D-3L index value and EQ-5D-3L VAS). Post-COVID-19 dysautonomia increased depression symptoms after the post-COVID-19 syndrome (p=0.02). We found a negative relationship between duration of COVID-19 symptoms and quality of life (p<0.001). Moreover, our results showed that depressive symptoms were more often among females after the post-COVID-19 syndrome (p=0.01). Also, quality of life was lower among females than males (p=0.004 for EQ-5D-3L index value, and p=0.007 for EQ-5D-3L VAS).ConclusionsOur results suggest that post-COVID-19 syndrome causes a tremendous impact on patients’ quality of life and mental health. In addition, we found that the groups most psychologically affected were patients with post-COVID-19 dysautonomia, females, and patients with longer duration of symptoms. Policy makers should attach priority to vulnerable groups in future psychiatric planning. Policy measures should focus on mental health of post-COVID-19 patients who seem to be particularly vulnerable.
The impact of blinding on trial results: A systematic review and meta-analysis
Authors: Pitre Tyler , Kirsh Sarah , Jassal Tanvir , Anderson Mason , Padoan Adelia , Xiang Alexander , Mah Jasmine , Zeraatkar Dena 
Published: March 2023

AbstractBackgroundBlinding—the concealment of the arm to which participants have been randomized—is an important consideration for assessing risk of bias of randomized trials. A growing body of evidence has, however, yielded inconsistent results on whether trials without blinding produce biased findings.ObjectiveTo conduct a systematic review and meta-analysis of the evidence addressing whether trials with and without blinding produce different results.MethodsWe searched MEDLINE, EMBASE, Cochrane Reviews, JBI EBP, and Web of Science, from inception to May 2022, for studies comparing the results of trials with and without blinding. Pairs of reviewers, working independently and in duplicate, reviewed search results for eligible studies and extracted data.We pooled the results of studies comparing trials with and without blinding of patients, healthcare providers/investigators, and outcome assessors/adjudicators using frequentist random-effects meta-analyses. We coded study results such that a ratio of odds ratio (ROR) < 1 and difference in standardized mean difference (dSMD) < 0 indicate that trials without blinding overestimate treatment effects.ResultsWe identified 47 eligible studies. For dichotomous outcomes, we found low certainty evidence that trials without blinding of patients and healthcare providers, outcome assessors/adjudicators, and patients may slightly overestimate treatment effects. For continuous outcomes, we found low certainty evidence that trials without blinding of outcome assessors/adjudicators and patients may slightly overestimate treatment effects.ConclusionOur systematic review and meta-analysis suggests that blinding may influence trial results in select situations—albeit the findings are of low certainty and the magnitude of effect is modest. In the absence of high certainty evidence suggesting that trials with and without blinding produce similar results, investigators should be cautious about interpreting the results of trials without blinding.
Very early neurological deterioration after thrombolysis in patients with acute ischemic stroke
Authors: Shen Ying-Chi , Yeh Shin-Joe , Chen Chih-Hao , Tang Sung-Chun , Tsai Li-Kai , Jeng Jiann-Shing 
Published: March 2023

AbstractBackgroundEarly neurological deterioration within 24 h after thrombolysis in patients with acute ischemic stroke (AIS) is associated with poor outcomes. Evidence is lacking regarding neurological deterioration within 1 h after thrombolysis.MethodsPatients who received intravenous thrombolysis with tissue plasminogen activator (tPA) for AIS between January 2018 and December 2021 were consecutively enrolled. Very early neurological deterioration (VEND) was defined as a ≥ 4-point increase in the National Institutes of Health Stroke Scale (NIHSS) score within 1 h after starting thrombolysis compared with the pre-treatment score. A modified Rankin Scale score of 3–6 at 3 months was defined as a poor functional outcome.ResultsOf the 353 AIS patients (age 69.7 ± 13.3 years, 57% men) receiving thrombolysis with tPA, 29 (8.4%) had VEND. VEND was associated with symptomatic intracranial atherosclerotic disease (ICAD) (41% vs. 17%,P= 0.005) and was an independent predictor of poor functional outcomes at 3 months (adjusted odds ratio 3.04,P= 0.043). The VEND group had higher NIHSS scores at 1 h (19.2 ± 7.3 vs. 9.0 ± 7.1,P< 0.001) and 24 h (14.1 ± 9.8 vs. 7.3 ± 7.5,P= 0.001) after initiating tPA than the non-VEND group. In patients with an initial NIHSS score < 6, VEND was significantly associated with ICAD, receiving endovascular thrombectomy (EVT), and poor functional outcomes. In patients with VEND, EVT with successful recanalization led to lower NIHSS scores at 24 h than in those without successful recanalization (12 ± 9 vs. 26 ± 7,P= 0.047), and 24-h NIHSS scores predicted poor functional outcomes.ConclusionsIn patients receiving thrombolysis, VEND was independently associated with poor functional outcomes. Identifying VEND is crucial for underlying ICAD and salvageability by EVT. Successful recanalization by EVT effectively reduced 24-h stroke severity in patients with VEND.
Eelgrass (Zosteraspp.) associated phytomyxids are host-specific congeneric parasites and predominant eukaryotes in the eelgrass rhizosphere on a global scale
Authors: Kolátková Viktorie , Mooney Megan , Kelly Kate , Hineva Elitsa , Gawryluk Ryan M. R. , Elliott Joel 
Published: March 2023

SUMMARYTogether with increasing environmental and anthropogenic pressures, pathogenic diseases are one of important factors contributing to the ongoing decline of seagrass meadows worldwide; yet the diversity and ecology of the microorganisms acknowledged as seagrass parasites remain critically understudied. Here we investigate phytomyxid parasites (Rhizaria: Endomyxa: Phytomyxea) of three different eelgrass (Zosteraspp.) species found in the Northern hemisphere. We present molecular evidence thatPlasmodiophora bicaudata, a long-recognized parasite of dwarf eelgrass taxa, is closely related to the novel phytomyxid recently discovered in root hairs ofZostera marina, and together they form a distinct clade within the order Phagomyxida, proposed here asFeldmanniellagen. nov. A full life cycle is systematically described in a phagomyxid representative for the first time, proving its conformity with the generalized phytomyxid life history, despite previous uncertainties. The presence of primary infection stages in nearly all collected eelgrass specimens, and subsequent analysis of amplicon sequences from a globalZ. marinadataset, reveal phytomyxids to be ubiquitous and one of the predominant microeukaryotes associated with eelgrass roots on a global scale. Our discoveries challenge the current view of Phytomyxea as rare entities in seagrass meadows and suggest their generally low pathogenicity in natural ecosystems.Originality-Significance StatementThis study addresses a group of microbial parasites critically understudied in the marine environment. It presents complex evidence that Phytomyxea - obligate intracellular biotrophs previously considered to be rare entities in the oceans, are in fact ubiquitous endobionts of seagrasses of the genusZostera– foundation species and important primary producers in coastal areas worldwide. Our work represents a significant contribution to the fields of aquatic microbiology and seagrass ecology and is seminal to understanding the biology of Phytomyxea outside of terrestrial ecosystems.