bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure of the endocytic adaptor complex reveals the basis for efficient membrane anchoring during clathrin-mediated endocytosis
Authors: Lizarrondo Javier , Klebl David P. , Niebling Stephan , Abella Marc , Schroer Martin A. , Mertens Haydyn D. T. , Veith Katharina , Thuenauer Roland , Svergun Dmitri I. , Skruzny Michal , Sobott Frank , Muench Stephen P. , Garcia-Alai Maria M. 
Published: May 2021

AbstractDuring clathrin-mediated endocytosis, a complex and dynamic network of protein-membrane interactions cooperate to achieve membrane invagination. Throughout this process in yeast, endocytic coat adaptors, Sla2 and Ent1, must remain attached to the plasma membrane to transmit force from the actin cytoskeleton required for successful membrane invagination. Here, we present a cryo-EM structure of a 16-mer complex of the ANTH and ENTH membrane-binding domains from Sla2 and Ent1 bound to PIP2that constitutes the anchor to the plasma membrane. Detailed in vitro and in vivo mutagenesis of the complex interfaces delineate the key interactions for complex formation and deficient cell growth phenotypes demonstrate its biological relevance. A hetero-tetrameric unit binds PIP2molecules at the ANTH-ENTH interfaces and can form larger assemblies to contribute to membrane remodeling. Finally, a time-resolved small-angle X-ray scattering study of the interaction of these adaptor domains in vitro suggests that ANTH and ENTH domains have evolved to achieve a fast subsecond timescale assembly in the presence of PIP2and do not require further proteins to form a stable complex. Together, these findings provide a molecular understanding of an essential piece in the molecular puzzle of clathrin-coated endocytic sites.
Coevolutionary transitions from antagonism to mutualism explained by the Co-Opted Antagonist Hypothesis
Authors: Johnson Christopher A. , Smith Gordon P. , Yule Kelsey , Davidowitz Goggy , Bronstein Judith L. , Ferrière Régis 
Published: May 2021

AbstractThere is now good evidence that many mutualisms evolved from antagonism; why or how, however, remains unclear. We advance the Co-Opted Antagonist (COA) Hypothesis as a general mechanism explaining evolutionary transitions from antagonism to mutualism. COA involves an eco-coevolutionary process whereby natural selection favors co-option of an antagonist to perform a beneficial function and the interacting species coevolve a suite of phenotypic traits that drive the interaction from antagonism to mutualism. To evaluate the COA hypothesis, we present a generalized eco-coevolutionary framework of evolutionary transitions from antagonism to mutualism and develop a data-based, fully ecologically-parameterized model of a small community in which a lepidopteran insect pollinates some of its larval host plant species. More generally, our theory helps to reconcile several major challenges concerning the mechanisms of mutualism evolution, such as how mutualisms evolve without extremely tight host fidelity (vertical transmission) and how ecological context influences evolutionary outcomes, and vice-versa.
Organophotocatalytic selective deuterodehalogenation of aryl or alkyl chlorides
Authors: Li Yanjun , Ye Ziqi , Lin Yu-Mei , Liu Yan , Zhang Yumeng , Gong Lei 
Published: May 2021

AbstractDevelopment of practical deuteration reactions is highly valuable for organic synthesis, analytic chemistry and pharmaceutic chemistry. Deuterodehalogenation of organic chlorides tends to be an attractive strategy but remains a challenging task. We here develop a photocatalytic system consisting of an aryl-amine photocatalyst and a disulfide co-catalyst in the presence of sodium formate as an electron and hydrogen donor. Accordingly, many aryl chlorides, alkyl chlorides, and other halides are converted to deuterated products at room temperature in air (>90 examples, up to 99% D-incorporation). The mechanistic studies reveal that the aryl amine serves as reducing photoredox catalyst to initiate cleavage of the C-Cl bond, at the same time as energy transfer catalyst to induce homolysis of the disulfide for consequent deuterium transfer process. This economic and environmentally-friendly method can be used for site-selective D-labeling of a number of bioactive molecules and direct H/D exchange of some drug molecules.
Running the full human developmental clock in interspecies chimeras using alternative human stem cells with expanded embryonic potential
Authors: Thomas Justin , Zimmerlin Ludovic , Huo Jeffrey S. , Considine Michael , Cope Leslie , Zambidis Elias T. 
Published: May 2021

AbstractHuman pluripotent stem cells (hPSCs) can generate specialized cell lineages that have great potential for regenerative therapies and disease modeling. However, the developmental stage of the lineages generated from conventional hPSC cultures in vitro are embryonic in phenotype, and may not possess the cellular maturity necessary for corrective regenerative function in vivo in adult recipients. Here, we present the scientific evidence for how adult human tissues could generate human–animal interspecific chimeras to solve this problem. First, we review the phenotypes of the embryonic lineages differentiated from conventional hPSC in vitro and through organoid technologies and compare their functional relevance to the tissues generated during normal human in utero fetal and adult development. We hypothesize that thedevelopmental incongruenceof embryo-stage hPSC-differentiated cells transplanted into a recipient adult host niche is an important mechanism ultimately limiting their utility in cell therapies and adult disease modeling. We propose that this developmental obstacle can be overcome with optimized interspecies chimeras that permit the generation of adult-staged, patient-specific whole organs within animal hosts with human-compatible gestational time-frames. We suggest that achieving this goal may ultimately have to await the derivation of alternative, primitive totipotent-like stem cells with improved embryonic chimera capacities. We review the scientific challenges of deriving alternative human stem cell states with expanded embryonic potential, outline a path forward for conducting this emerging research with appropriate ethical and regulatory oversight, and defend the case of why current federal funding restrictions on this important category of biomedical research should be liberalized.
Increased face detection responses on the mooney faces test in people at clinical high risk for psychosis
Authors: Silverstein Steven M. , Thompson Judy L. , Gold James M. , Schiffman Jason , Waltz James A. , Williams Trevor F. , Zinbarg Richard E. , Mittal Vijay A. , Ellman Lauren M. , Strauss Gregory P. , Walker Elaine F. , Woods Scott W. , Levin Jason A. , Kafadar Eren , Kenney Joshua , Smith Dillon , Powers Albert R. , Corlett Philip R. 
Published: May 2021

AbstractIdentifying state-sensitive measures of perceptual and cognitive processes implicated in psychosis may allow for objective, earlier, and better monitoring of changes in mental status that are predictive of an impending psychotic episode, relative to traditional self-report-based clinical measures. To determine whether a measure of visual perception that has demonstrated sensitivity to the clinical state of schizophrenia in multiple prior studies is sensitive to features of the at-risk mental state, we examined differences between young people identified as being at clinical high risk for psychosis (CHR;n = 37) and non-psychiatric matched controls (n = 29) on the Mooney Faces Test (MFT). On each trial of the MFT, participants report whether they perceive a face in a degraded face image. The CHR group reported perceiving a greater number of faces in both upright and inverted MFT stimuli. Consistent with prior work, males reported more faces on the MFT than females in both conditions. However, the finding of greater reported face perception among CHR subjects was robustly observed in the female CHR group relative to the female control group. Among male CHR participants, greater reported face perception was related to increased perceptual abnormalities. These preliminary results are consistent with a small but growing literature suggesting that heightened perceptual sensitivity may characterize individuals at increased clinical risk for psychosis. Further studies are needed to determine the contributions of specific perceptual, cognitive, and motivational mechanisms to the findings.
Both high fat and high carbohydrate diets impair vagus nerve signaling of satiety
Authors: Loper Hailley , Leinen Monique , Bassoff Logan , Sample Jack , Romero-Ortega Mario , Gustafson Kenneth J. , Taylor Dawn M. , Schiefer Matthew A. 
Published: May 2021

AbstractObesity remains prevalent in the US. One potential treatment is vagus nerve stimulation (VNS), which activates the sensory afferents innervating the stomach that convey stomach volume and establish satiety. However, current VNS approaches and stimulus optimization could benefit from additional understanding of the underlying neural response to stomach distension. In this study, obesity-prone Sprague Dawley rats consumed a standard, high-carbohydrate, or high-fat diet for several months, leading to diet-induced obesity in the latter two groups. Under anesthesia, the neural activity in the vagus nerve was recorded with a penetrating microelectrode array while the stomach was distended with an implanted balloon. Vagal tone during distension was compared to baseline tone prior to distension. Responses were strongly correlated with stomach distension, but the sensitivity to distension was significantly lower in animals that had been fed the nonstandard diets. The results indicate that both high fat and high carbohydrate diets impair vagus activity.
Heme cytotoxicity is the consequence of endoplasmic reticulum stress in atherosclerotic plaque progression
Authors: Pethő Dávid , Hendrik Zoltán , Nagy Annamária , Beke Lívia , Patsalos Andreas , Nagy László , Póliska Szilárd , Méhes Gábor , Tóth Csaba , Potor László , Eaton John W. , Jacob Harry S. , Balla György , Balla József , Gáll Tamás 
Published: May 2021

AbstractHemorrhage and hemolysis with subsequent heme release are implicated in many pathologies. Endothelial cells (ECs) encounter large amount of free heme after hemolysis and are at risk of damage from exogenous heme. Here we show that hemorrhage aggravates endoplasmic reticulum (ER) stress in human carotid artery plaques compared to healthy controls or atheromas without hemorrhage as demonstrated by RNA sequencing and immunohistochemistry. In EC cultures, heme also induces ER stress. In contrast, if cultured ECs are pulsed with heme arginate, cells become resistant to heme-induced ER (HIER) stress that is associated with heme oxygenase-1 (HO-1) and ferritin induction. Knocking down HO-1, HO-2, biliverdin reductase, and ferritin show that HO-1 is the ultimate cytoprotectant in acute HIER stress. Carbon monoxide-releasing molecules (CORMs) but not bilirubin protects cultured ECs from HIER stress via HO-1 induction, at least in part. Knocking down HO-1 aggravates heme-induced cell death that cannot be counterbalanced with any known cell death inhibitors. We conclude that endothelium and perhaps other cell types can be protected from HIER stress by induction of HO-1, and heme-induced cell death occurs via HIER stress that is potentially involved in the pathogenesis of diverse pathologies with hemolysis and hemorrhage including atherosclerosis.
Asymmetric shape of distal phalanx of human finger improves precision grasping
Authors: Kumagai Ayane , Obata Yoshinobu , Yabuki Yoshiko , Jiang Yinlai , Yokoi Hiroshi , Togo Shunta 
Published: May 2021

AbstractIn morphology field, the functions of an asymmetric-shaped distal phalanx in human finger have only been inferred. In this study, we used an engineering approach to empirically examine the effects of the shape of distal phalanx on the ability of precision grasping. Hence, we developed artificial fingertips consisting of four parts, namely bones, nails, skin, and subcutaneous tissue, that substitute the actual human fingertips. Furthermore, we proposed a method to evaluate the grasping ability of artificial fingers. When a cylindrical object was grasped by an artificial fingertip, a pull-out experiment was conducted. Thus, the asymmetric type was found to be superior in terms of drawing force, holding time, and work of friction than the symmetric type. Our results clearly demonstrate that the asymmetric shape, particularly the mirror-reversed shape of the distal phalanx, improves the ability of precision grasping and suggests that the human distal phalanx is shaped favorably for object grasping.
Adipocyte calcium sensing receptor is not involved in visceral adipose tissue inflammation or atherosclerosis development in hyperlipidemic Apoe−/− mice
Authors: Sundararaman Sai Sahana , Peters Linsey J. F. , Jansen Yvonne , Gencer Selin , Yan Yi , Nazir Sumra , Bonnin Marquez Andrea , Kahles Florian , Lehrke Michael , Biessen Erik A. L. , Jankowski Joachim , Weber Christian , Döring Yvonne , van der Vorst Emiel P. C. 
Published: May 2021

AbstractThe calcium sensing receptor (CaSR) is a G-protein coupled receptor that especially plays an important role in the sensing of extracellular calcium to maintain its homeostasis. Several in-vitro studies demonstrated that CaSR plays a role in adipose tissue metabolism and inflammation, resulting in systemic inflammation and contributing to atherosclerosis development. The aim of this study was to investigate whether adipocyte CaSR plays a role in adipose tissue inflammation in-vivo and atherosclerosis development. By using a newly established conditional mature adipocyte specific CaSR deficient mouse on a hyperlipidemic and atherosclerosis prone Apoe−/− background it could be shown that CaSR deficiency in adipocytes does neither contribute to initiation nor to progression of atherosclerotic plaques as judged by the unchanged lesion size or composition. Additionally, CaSR deficiency did not influence gonadal visceral adipose tissue (vAT) inflammation in-vivo, although a small decrease in gonadal visceral adipose cholesterol content could be observed. In conclusion, adipocyte CaSR seems not to be involved in vAT inflammation in-vivo and does not influence atherosclerosis development in hyperlipidemic Apoe−/− mice.
TERTp mutations and p53 expression in head and neck cutaneous basal cell carcinomas with different aggressive features
Authors: Castanheira António , Vieira Maria João , Pinto Mafalda , Dias Carolina , Prada Luísa , Macedo Sofia , Fernandes Margarida Sá , Vieira Fortunato , Soares Paula , Mota Alberto , Lopes José Manuel , Boaventura Paula 
Published: May 2021

AbstractCutaneous basal cell carcinoma (cBCC) is an economic burden to health services, due to its great morbidity and increasing incidence in old people. Infiltrative cBCCs and cBCCs with micronodular pattern are considered as more aggressive. The role of p53 expression and TERTp mutation on cBCC behavior remains to be clarified. We aimed to assess TERTp mutations and p53 expression in relation to the cBCC histological subtype in a cohort of patients referred to an ENT Department of a tertiary Hospital of Northern Portugal. We performed a retrospective clinicopathological and histological review of the head and neck cBCCs followed-up at the otorhinolaryngology department of Trás-os-Montes e Alto Douro hospital (January 2007–June 2018). We assessed TERTp mutations in 142 cBCCs and p53 protein expression, through immunohistochemistry, in 157 cBCCs. We detected TERTp mutations in 43.7% of cBCCs and p53 overexpression in 60.5% of cBCCs. We spotted association of p53 overexpression and TERTp mutation with necrosis. In the infitrative-growth pattern cBCCs, there was no significant association with the clinical and histological features evaluated, except for necrosis. In the indolent-growth cBCCs, we identified a significant association of TERTp mutation status with female sex, necrosis, multiple cBCCs, and p53 positive expression. Our results suggest that TERTp mutation may be useful to identify more aggressive features in the indolent-growth pattern cBCCs (nodular and superficial subtypes). Further studies with larger cohorts are warranted to clarify the relevance of TERTp mutation in cBCCs.
Cisplatin and phenanthriplatin modulate long-noncoding RNA expression in A549 and IMR90 cells revealing regulation of microRNAs, Wnt/β-catenin and TGF-β signaling
Authors: Monroe Jerry D. , Moolani Satya A. , Irihamye Elvin N. , Lett Katheryn E. , Hebert Michael D. , Gibert Yann , Smith Michael E. 
Published: May 2021

AbstractThe monofunctional platinum(II) complex, phenanthriplatin, acts by blocking transcription, but its regulatory effects on long-noncoding RNAs (lncRNAs) have not been elucidated relative to traditional platinum-based chemotherapeutics, e.g., cisplatin. Here, we treated A549 non-small cell lung cancer and IMR90 lung fibroblast cells for 24 h with either cisplatin, phenanthriplatin or a solvent control, and then performed microarray analysis to identify regulated lncRNAs. RNA22 v2 microRNA software was subsequently used to identify microRNAs (miRNAs) that might be suppressed by the most regulated lncRNAs. We found that miR-25-5p, -30a-3p, -138-5p, -149-3p, -185-5p, -378j, -608, -650, -708-5p, -1253, -1254, -4458, and -4516, were predicted to target the cisplatin upregulated lncRNAs, IMMP2L-1, CBR3-1 and ATAD2B-5, and the phenanthriplatin downregulated lncRNAs, AGO2-1, COX7A1-2 and SLC26A3-1. Then, we used qRT-PCR to measure the expression of miR-25-5p, -378j, -4516 (A549) and miR-149-3p, -608, and -4458 (IMR90) to identify distinct signaling effects associated with cisplatin and phenanthriplatin. The signaling pathways associated with these miRNAs suggests that phenanthriplatin may modulate Wnt/β-catenin and TGF-β signaling through the MAPK/ERK and PTEN/AKT pathways differently than cisplatin. Further, as some of these miRNAs may be subject to dissimilar lncRNA targeting in A549 and IMR90 cells, the monofunctional complex may not cause toxicity in normal lung compared to cancer cells by acting through distinct lncRNA and miRNA networks.
Therapeutically actionable signaling node to rescue AURKA driven loss of primary cilia in VHL-deficient cells
Authors: Chowdhury Pratim , Perera Dimuthu , Powell Reid T. , Talley Tia , Tripathi Durga Nand , Park Yong Sung , Mancini Michael A. , Davies Peter , Stephan Clifford , Coarfa Cristian , Dere Ruhee 
Published: May 2021

AbstractLoss of primary cilia in cells deficient for the tumor suppressor von Hippel Lindau (VHL) arise from elevated Aurora Kinase A (AURKA) levels. VHL in its role as an E3 ubiquitin ligase targets AURKA for degradation and in the absence of VHL, high levels of AURKA result in destabilization of the primary cilium. We identified NVP-BEZ235, a dual PI3K/AKT and mTOR inhibitor, in an image-based high throughput screen, as a small molecule that restored primary cilia in VHL-deficient cells. We identified the ability of AKT to modulate AURKA expression at the transcript and protein level. Independent modulation of AKT and mTOR signaling decreased AURKA expression in cells confirming AURKA as a new signaling node downstream of the PI3K cascade. Corroborating these data, a genetic knockdown of AKT in cells deficient for VHL rescued the ability of these cells to ciliate. Finally, inhibition of AKT/mTOR using NVP-BEZ235 was efficacious in reducing tumor burden in a 786-0 xenograft model of renal cell carcinoma. These data highlight a previously unappreciated signaling node downstream of the AKT/mTOR pathway via AURKA that can be targeted in VHL-null cells to restore ciliogenesis.
Dynamic mode decomposition of inertial particle caustics in Taylor–Green flow
Authors: Samant Omstavan , Alageshan Jaya Kumar , Sharma Sarveshwar , Kuley Animesh 
Published: May 2021

AbstractInertial particles advected by a background flow can show complex structures. We consider inertial particles in a 2D Taylor–Green (TG) flow and characterize particle dynamics as a function of the particle’s Stokes number using dynamic mode decomposition (DMD) method from particle image velocimetry (PIV) like-data. We observe the formation of caustic structures and analyze them using DMD to (a) determine the Stokes number of the particles, and (b) estimate the particle Stokes number composition. Our analysis in this idealized flow will provide useful insight to analyze inertial particles in more complex or turbulent flows. We propose that the DMD technique can be used to perform similar analysis on an experimental system.
Serum iron and risk of nonalcoholic fatty liver disease and advanced hepatic fibrosis in US adults
Authors: Yang Huan-Huan , Chen Guo-Chong , Li De-Ming , Lan Lei , Chen Li-Hua , Xu Jia-Ying , Qin Li-Qiang 
Published: May 2021

AbstractEpidemiological evidence on the relationship between serum iron and liver diseases is limited. This study aims to investigate whether serum iron is associated with nonalcoholic fatty liver disease (NAFLD) and advanced hepatic fibrosis (AHF). Cross-sectional data for adults aged ≥ 18 years who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 were analyzed. Odds ratio (ORs) and 95% confidence intervals (CIs) of NAFLD and AHF associated with serum iron were estimated using multivariable logistic regression models. A total of 18,031 males and 18,989 females were included in the analysis. After multivariable adjustment for potential confounders, serum iron was significantly and inversely associated with NAFLD in both genders (P-trend < 0.001) and AHF in females (P-trend = 0.018). Compared to the bottom quartile, those in higher quartiles of serum iron had no significant ORs for AHF in males, but the trend across the quartiles was significant (P-trend = 0.046). In conclusion, higher serum iron level was associated with lower risk of NAFLD in males and females, and with lower risk of AHF in females but not in males. No significant racial/ethnical differences in these associations were observed.
iTRAQ-mediated analysis of the relationship between proteomic changes and yak longissimus lumborum tenderness over the course of postmortem storage
Authors: Yang Yayuan , Yang Jieyuan , Ma Jibing , Yu Qunli , Han Ling 
Published: May 2021

AbstractTo identify differentially expressed proteins associated with energy metabolism and tenderness during the postmortem aging of yak longissimus lumborum muscle samples, we collected tissue samples from yaks raised at different altitudes. At 12 h post-slaughter, we identified 290 differentially expressed proteins (DEPs) in these samples, whereas 436 such DEPs were detected after 72 h. Identified DEPs were clustered into four main functional categories: cell structural proteins, glycogen metabolic proteins, energy reserve metabolic proteins, and cellular polysaccharide metabolic proteins. Further bioinformatics analysis revealed that these proteins were associated with carbon metabolism, glycolysis, and the biosynthesis of amino acids. Our functional insights regarding these identified proteins contribute to a more detailed molecular understanding of the processes of energy metabolism in yak muscle tissue, and represent a valuable resource for future investigations.