bluuebunny/crossref_metadata_2025_split huggingface dataset:
International Survey of Clinical Monitoring Practices in Pancreas and Islet Transplantation
Authors: Ward Casey , Odorico Jon S. , Rickels Michael R. , Berney Thierry , Burke George W. , Kay Thomas W.H. , Thaunat Olivier , Uva Pablo D. , de Koning Eelco J.P. , Arbogast Helmut , Scholz Hanne , Cattral Mark S. , Stratta Robert J. , Stock Peter G. ,   for the International Pancreas and Islet Transplant Association Beta-Cell Replacement Therapy Monitoring Task Force
Published: January 2022

Background.
The long-term outcomes of both pancreas and islet allotransplantation have been compromised by difficulties in the detection of early graft dysfunction at a time when a clinical intervention can prevent further deterioration and preserve allograft function. The lack of standardized strategies for monitoring pancreas and islet allograft function prompted an international survey established by an International Pancreas and Islet Transplant Association/European Pancreas and Islet Transplant Association working group.

Methods.
A global survey was administered to 24 pancreas and 18 islet programs using Redcap. The survey addressed protocolized and for-cause immunologic and metabolic monitoring strategies following pancreas and islet allotransplantation. All invited programs completed the survey.

Results.
The survey identified that in both pancreas and islet allograft programs, protocolized clinical monitoring practices included assessing body weight, fasting glucose/C-peptide, hemoglobin A1c, and donor-specific antibody. Protocolized monitoring in islet transplant programs relied on the addition of mixed meal tolerance test, continuous glucose monitoring, and autoantibody titers. In the setting of either suspicion for rejection or serially increasing hemoglobin A1c/fasting glucose levels postpancreas transplant, Doppler ultrasound, computed tomography, autoantibody titers, and pancreas graft biopsy were identified as adjunctive strategies to protocolized monitoring studies. No additional assays were identified in the setting of serially increasing hemoglobin A1c levels postislet transplantation.

Conclusions.
This international survey identifies common immunologic and metabolic monitoring strategies utilized for protocol and for cause following pancreas and islet transplantation. In the absence of any formal studies to assess the efficacy of immunologic and metabolic testing to detect early allograft dysfunction, it can serve as a guidance document for developing monitoring algorithms following beta-cell replacement.
Accurate sex classification from neural responses to sexual stimuli
Authors: Putkinen Vesa , Nazari-Farsani Sanaz , Karjalainen Tomi , Santavirta Severi , Hudson Matthew , Seppälä Kerttu , Sun Lihua , Karlsson Henry K. , Hirvonen Jussi , Nummenmaa Lauri 
Published: January 2022

AbstractSex differences in brain activity evoked by sexual stimuli remain elusive despite robust evidence for stronger enjoyment of and interest towards sexual stimuli in men than in women. To test whether visual sexual stimuli evoke different brain activity patterns in men and women, we measured haemodynamic brain activity induced by visual sexual stimuli in two experiments in 91 subjects (46 males). In one experiment, the subjects viewed sexual and non-sexual film clips and dynamic annotations for nudity in the clips was used to predict their hemodynamic activity. In the second experiment, the subjects viewed sexual and non-sexual pictures in an event-related design. Males showed stronger activation than females in the visual and prefrontal cortices and dorsal attention network in both experiments. Furthermore, using multivariate pattern classification we could accurately predict the sex of the subject on the basis of the brain activity elicited by the sexual stimuli. The classification generalized across the experiments indicating that the sex differences were consistent. Eye tracking data obtained from an independent sample of subjects (N = 110) showed that men looked longer than women at the chest area of the nude female actors in the film clips. These results indicate that visual sexual stimuli evoke discernible brain activity patterns in men and women which may reflect stronger attentional engagement with sexual stimuli in men than women.
Insights into the structure and function of the human organic anion transporter 1 in lipid bilayer membranes
Authors: Janaszkiewicz Angelika , Tóth Ágota , Faucher Quentin , Martin Marving , Chantemargue Benjamin , Guellec Chantal Barin-Le , Marquet Pierre , Di Meo Florent 
Published: January 2022

AbstractThe human SLC22A6/OAT1 plays an important role in the elimination of a broad range of endogenous substances and xenobiotics thus attracting attention from the pharmacological community. Furthermore, OAT1 is also involved in key physiological events such as the remote inter-organ communication. Despite its significance, the knowledge about hOAT1 structure and the transport mechanism at the atomic level remains fragmented owing to the lack of resolved structures. By means of protein-threading modeling refined by μs-scaled Molecular Dynamics simulations, the present study provides the first robust model of hOAT1 in outward-facing conformation. Taking advantage of the AlphaFold 2 predicted structure of hOAT1 in inward-facing conformation, we here provide the essential structural and functional features comparing both states. The intracellular motifs conserved among Major Facilitator Superfamily members create a so-called “charge-relay system” that works as molecular switches modulating the conformation. The principal element of the event points at interactions of charged residues that appear crucial for the transporter dynamics and function. Moreover, hOAT1 model was embedded in different lipid bilayer membranes highlighting the crucial structural dependence on lipid-protein interactions. MD simulations supported the pivotal role of phosphatidylethanolamine components to the protein conformation stability. The present model is made available to decipher the impact of any observed polymorphism and mutation on drug transport as well as to understand substrate binding modes.
Cell surface receptor kinase FERONIA linked to nutrient sensor TORC signaling controls root hair growth at low temperature linked to low nitrate inArabidopsis thaliana
Authors: Martínez Pacheco Javier , Song Limei , Kuběnová Lenka , Ovečka Miroslav , Gabarain Victoria Berdion , Peralta Juan Manuel , Lehuedé Tomás Urzúa , Ibeas Miguel Angel , Ricardi Martiniano M. , Zhu Sirui , Shen Yanan , Schepetilnikov Mikhail , Ryabova Lyubov A , Alvarez José M. , Gutierrez Rodrigo A. , Grossman Guido , Šamaj Jozef , Yu Feng , Estevez José M. 
Published: January 2022

AbstractRoot hairs (RH) are excellent model systems for studying cell size and polarity since they elongate several hundred-fold their original size. Their tip growth is determined both by intrinsic and environmental signals. Although nutrient availability and temperature are key factors for a sustained plant growth, the molecular mechanisms underlying their sensing and downstream signaling pathways remain unclear. Here, we identified that low temperature (10°C) triggers a strong RH elongation response involving the cell surface receptor kinase FERONIA (FER) and the nutrient sensing TOR Complex 1 (TORC). In this study, we found that FER is required to perceive limited nutrient availability caused by low temperature. FER interacts with and activates TORC downstream components to trigger RH growth. In addition, the small GTPase Rho-related protein from plants 2 (ROP2) is also involved in this RH growth response linking FER and TOR. We also found that limited nitrogen nutrient availability can mimic the RH growth response at 10°C in a NRT1.1-dependent manner. These results uncover a molecular mechanism by which a central hub composed by FER-ROP2-TORC is involved in the control of RH elongation under low temperature and nitrogen deficiency.
Pervasive conditional selection of driver mutations and modular epistasis networks in cancer
Authors: Iranzo Jaime , Gruenhagen George , Calle-Espinosa Jorge , Koonin Eugene V. 
Published: January 2022

SummaryCancer driver mutations often display mutual exclusion or co-occurrence, underscoring the key role of epistasis in carcinogenesis. However, estimating the magnitude of epistasis and quantifying its effect on tumor evolution remains a challenge. We developed a method to quantify COnditional SELection on the Excess of Nonsynonymous Substitutions (Coselens) in cancer genes. Coselens infers the number of drivers per gene in different partitions of a cancer genomics dataset using covariance-based mutation models and determines whether coding mutations in a gene affect selection for drivers in any other gene. Using Coselens, we identified 296 conditionally selected gene pairs across 16 cancer types in the TCGA dataset. Conditional selection affects 25-50% of driver substitutions in tumors with >2 drivers. Conditionally co-selected genes form modular networks, whose structures challenge the traditional interpretation of within-pathway mutual exclusivity and across-pathway synergy, suggesting a more complex scenario, where gene-specific across-pathway epistasis shapes differentiated cancer subtypes.
Head Removal Enhances Planarian Electrotaxis
Authors: Sabry Ziad , Wang Rui , Jahromi Aryo , Rabeler Christina , Kristan William B. , Collins Eva-Maria S. 
Published: January 2022

AbstractSensing electric fields is an ability that certain animal species utilize for communication, hunting, and spatial orientation. Freshwater planarians move toward the cathode in a static electric field (cathodic electrotaxis). First described by Raymond Pearl more than a century ago, planarian electrotaxis has received little attention and the underlying mechanisms and evolutionary significance remain unknown. We developed an apparatus and scoring metrics for automated quantitative and mechanistic studies of planarian behavior upon exposure to a static electric field. Using this automated setup, we characterized electrotaxis in the planarian Dugesia japonica and found that this species responds to voltage instead of to current, in contrast to results from previous studies using other species. Because longer planarians exhibited more robust electrotaxis than shorter planarians, we hypothesized that signals from the head impede cathodic electrotaxis. To test this hypothesis, we took advantage of the regenerative abilities of planarians and compared electrotaxis in head and tail fragments of various lengths. We found that tail and trunk fragments electrotaxed while head fragments did not, regardless of size. However, we could restore cathodic electrotaxis in head fragments via decapitation, demonstrating that the presence of the head impaired cathodic electrotaxis. This result is in stark contrast to other stimulated behaviors such as phototaxis, thermotaxis or chemotaxis, which are weaker or absent in headless fragments. Thus, electrotaxis may be an important ability of headless planarian fragments to support survival prior to head regeneration.Summary statementWe present a new method for quantitative studies of planarian electrotaxis and show that Dugesia japonica move toward the cathode. This behavior is enhanced by removal of the head.
The Interaction Between The Noradrenergic Neurons In The Locus Coeruleus And Beta-1 Adrenergic Receptor (β1-AR) In The Cardiomyocytes Was Implicated In Modulating SUDEP
Authors: Lian XiTing , Yu Qian , Ma HaiXiang , Gu LeYuan , Xu Qing , Wang YuLing , Shen Yue , Zhang HongHai 
Published: January 2022

AbstractSudden unexpected death of epilepsy (SUDEP) is the leading cause of of death in patients with epilepsy. Due to the complicated pathogenesis of SUDEP, however, the exact mechanism of SUDEP remains elusive. Currently, although it is recognized that the seizure-induced respiratory arrest (S-IRA) may be a main cause for SUDEP, other factors resulting in SUDEP can not be excluded e.g arrhythmias. Our previous findings indicated that the incidence of S-IRA and SUDEP evoked by acoustic stimulation or pentetrazol (PTZ) injection was significantly reduced by atomoxetine, a norepinephrine reuptake inhibitor (NRI), suggesting that noradrenergic neurotransmission modulates S-IRA and SUDEP. Given that norepinephrine acts on the target to modulate respiratory and circulation function by targeting adrenergic receptor α and beta (a-AR and β-AR) and the arrhythmias can be contributed to SUDEP. Meanwhile, to further test whether cardiac factors are implicated in S-IRA and SUDEP, we choose esmolol hydrochloride, a selective antagonist of β1-AR to test it in our models. Our findings demonstrated that the lower incidence of S-IRA and SUDEP evoked by acoustic stimulation or PTZ injection in DBA/1 mice by administration with atomoxetine was significantly reversed by intraperitoneal (IP) of esmolol hydrochloride. Importantly, the data of electrocardiogram (ECG) showed that the cardiac arrhythmia including the ventricular tachycardia, ventricular premature beat and atrioventricular block can be evoked by acoustic stimulation or PTZ injection in our model. Administration of atomoxetine significantly reduced these arrhythmias and the incidence of S-IRA and SUDEP in our models. However, administration of esmolol hydrochloride with the dose without affecting ECG and mortality changing of DBA/1 significantly blocking the protective effects of atomoxetine on S-IRA and SUDEP in our models. Thus, the dysfunction of respiratory and circulation may be implicated in the pathogenesis of S-IRA and SUDEP. Enhancing the central norepinephrinergic neurotransmission in the brain contributes to inhibition of seizure-induced respiratory arrest by targeting β1-AR locating in the cardiomyocytes. Furthermore, the suppression effects of S-IRA by atomoxetine was significantly reversed by the norepinephrine neuronal degradation in the LC in our models. Furthermore, PTZ-induced Tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of norepinephrine, activity but not TH content from the serum of left ventricle and the whole heart tissue was reduced following the S-IRA. Our findings will show a new light on decoding the pathogenesis of SUDEP concerning the pathway between the LC and heart.
A theory of cortical map formation in the visual brain
Authors: Najafian Sohrab , Koch Erin , Teh Kai Lun , Jin Jianzhong , Rahimi-Nasrabadi Hamed , Zaidi Qasim , Kremkow Jens , Alonso Jose-Manuel 
Published: January 2022

AbstractThe cerebral cortex receives multiple afferents from the thalamus that segregate by stimulus modality forming cortical maps for each sense. In vision, the primary visual cortex maps the multiple dimensions of the visual stimulus in patterns that vary across species for reasons unknown. Here we introduce a general theory of cortical map formation, which proposes that map diversity emerges from species variations in the thalamic afferent density sampling sensory space. In the theory, increasing afferent sampling density enlarges the cortical domains representing the same visual point, allowing the segregation of afferents and cortical targets by multiple stimulus dimensions. We illustrate the theory with an afferent-density model that accurately replicates the maps of different species through afferent segregation followed by thalamocortical convergence pruned by visual experience. Because thalamocortical pathways use similar mechanisms for axon segregation and pruning, the theory may extend to other sensory areas of the mammalian brain.
Control of Leaf Width by the APC/CTAD1-WL1-NAL1 Pathway in Rice
Authors: You Jing , Xiao Wenwen , Zhou Yue , Ye Li , Yu Peng , Yu Guoling , Zhang Xinfang , He Zhifeng , Xiang Yan , Sang Xianchun , Li Yunfeng , Zhao Fangming , Ling Yinghua , He Guanghua , Zhang Ting 
Published: January 2022

AbstractLeaf morphology is one of the most important features of the ideal plant architecture. However, the genetic and molecular mechanisms controlling leaf morphology in crops remain largely unknown, despite their central importance. Here we demonstrate that the APC/CTAD1-WL1-NAL1 pathway regulates leaf width in rice, and mutation of WL1 leads to width leaf variation. WL1 interacts with TAD1 and is degraded by APC/CTAD1, with the loss of TAD1 function resulting in narrow leaves. The WL1 protein directly binds to the regulatory region of NAL1 and recruits the corepressor TOPLESS-RELATED PROTEIN to inhibit NAL1 expression by down-regulating the level of histone acetylation of chromatin. Furthermore, biochemical and genetic analyses revealed that TAD1, WL1, and NAL1 function in a common pathway to control leaf width. Our study establishes an important framework for the APC/CTAD1-WL1-NAL1 pathway-mediated control of leaf width in rice and introduces novel perspectives for using this regulatory pathway for improving crop plant architecture.
Innovative multidimensional models in a high-throughput-format for different cell types of endocrine origin
Authors: Bornstein Stefan , Shapiro Igor , Malyukov Maria , Züllig Richard , Luca Edlira , Gelfgat Evgeny , Beuschlein Felix , Nölting Svenja , Berruti Alfredo , Sigala Sandra , Peitzsch Mirko , Steenblock Charlotte , Ludwig Barbara , Kugelmeier Patrick , Hantel Constanze 
Published: January 2022

AbstractThe adrenal gland provides an important function by integrating neuronal, immune, vascular, metabolic and endocrine signals under a common organ capsule. It is the central organ of the stress response system and has been implicated in numerous stress-related disorders. While for other diseases, regeneration of healthy organ tissue has been aimed at such approaches are lacking for endocrine diseases - with the exception of type-I-diabetes. Moreover, tumor formation is very common, however, appropriate high-throughput applications reflecting the high heterogeneity and furthermore relevant 3D-structures in vitro are still widely lacking. Recently, we have initiated the development of standardized multidimensional models of a variety of endocrine cell/tissue sources in a new multiwell-format. Firstly, we confirmed common applicability for pancreatic pseudo-islets. Next, we translated applicability for spheroid establishment to adrenocortical cell lines as well as patient material to establish spheroids from malignant, but also benign adrenal tumors. We aimed furthermore at the development of bovine derived adrenal organoids and were able to establish steroidogenic active organoids containing both, cells of cortical and medullary origin. Overall, we hope to open new avenues for basic research, endocrine cancer and adrenal tissue-replacement-therapies as we demonstrate potential for innovative mechanistic insights and personalized medicine in endocrine (tumor)-biology.
Atlasing white matter and grey matter joint contributions to resting-state networks in the human brain
Authors: Nozais Victor , Forkel Stephanie J , Petit Laurent , Talozzi Lia , Corbetta Maurizio , Thiebaut de Schotten Michel , Joliot Marc 
Published: January 2022

AbstractOver the past two decades, the study of resting-state functional magnetic resonance imaging has revealed that functional connectivity within and between networks are linked to cognitive states and pathologies. However, the white matter connections supporting connectivity remain only partially described. We developed a method to jointly map the white and grey matter contributing to each resting-state network. Using the Human Connectome Project, we generated an atlas of 30 resting-state networks. The method also allows highlighting the overlap between networks, which revealed that most of the brain’s white matter (89%) is shared between multiple networks, with 16% shared by at least 7 resting-state networks. These overlaps, especially the existence of regions shared by numerous networks, suggest that white matter lesions in these areas might strongly impact the correlations and the communication within resting-state networks. We provide an open-source software to explore the joint contribution of white and grey matter to RSNs and facilitate the study of the impact of white matter damage on RSNs. In a first clinical application of the software, we were able to link stroke patients and impacted resting-state networks, showing that their symptoms aligned well with the estimated functions of the networks.
A single-cell atlas reveals shared and distinct immune responses and metabolism during SARS-CoV-2 and HIV-1 infections
Authors: Pan Tony , Cao Guoshuai , Tang Erting , Zhao Yu , Penaloza-MacMaster Pablo , Fang Yun , Huang Jun 
Published: January 2022

SummarySARS-CoV-2 and HIV-1 are RNA viruses that have killed millions of people worldwide. Understanding the similarities and differences between these two infections is critical for understanding disease progression and for developing effective vaccines and therapies, particularly for 38 million HIV-1+individuals who are vulnerable to SARS-CoV-2 co-infection. Here, we utilized single-cell transcriptomics to perform a systematic comparison of 94,442 PBMCs from 7 COVID-19 and 9 HIV-1+patients in an integrated immune atlas, in which 27 different cell types were identified using an accurate consensus single-cell annotation method. While immune cells in both cohorts show shared inflammation and disrupted mitochondrial function, COVID-19 patients exhibit stronger humoral immunity, broader IFN-I signaling, elevated Rho GTPase and mTOR pathway activities, and downregulated mitophagy. Our results elucidate transcriptional signatures associated with COVID-19 and HIV-1 that may reveal insights into fundamental disease biology and potential therapeutic targets to treat these viral infections.HighlightsCOVID-19 and HIV-1+patients show disease-specific inflammatory immune signaturesCOVID-19 patients show more productive humoral responses than HIV-1+patientsSARS-CoV-2 elicits more enriched IFN-I signaling relative to HIV-IDivergent, impaired metabolic programs distinguish SARS-CoV-2 and HIV-1 infections