bluuebunny/crossref_metadata_2025 huggingface dataset:
Sarcopenic obesity is associated with telomere shortening: findings from the NHANES 1999–2002
Authors: Goddard Thomas , Tsintzas Kostas , Stephan Blossom C. M. , Prado Carla M. , Mazidi Mohsen , Siervo Mario
Published: November 2021

Sarcopenic obesity (SO) is characterised by the concurrent presence of sarcopenia and excess adiposity. Telomere shortening has been associated with sarcopenia and obesity alone but the association between SO and telomere length (TL) has not been investigated. This study aimed to investigate SO and TL in an adult population. Data were from 5397 individuals (mean age = 44.7 years, 51.3% male) enrolled in the National Health and Nutrition Examination Survey. Body composition (BC) was assessed by Dual Energy X-Ray Absorptiometry. Two models were used to assess SO: a BC model including four phenotypes derived from the combination of high or low adiposity and muscle mass; and, a truncal fat mass to appendicular skeletal mass ratio (TrFM/ASM). TL was assessed using quantitative polymerase chain reaction and expressed as base pairs. The mean TL, relative to the reference DNA, was calculated and expressed as the mean T/S ratio. A General Linear Model was applied to determine associations between TL for SO. In adjusted analysis, only individuals with SO, defined as the presence of high adiposity-low muscle mass (four-phenotype model), had significantly shorter telomeres (p = 0.05) than the reference group (i.e. low adiposity-high muscle mass), with a mean T/S ratio of 1.02 (95%CI: 0.98–1.05) compared to 1.05 (95%CI: 1.01–1.09), respectively. TrFM/ASM was not associated with TL. Preliminary findings suggest that sarcopenia and obesity may act synergistically to shorten telomeres.
Chromatin-accessibility estimation from single-cell ATAC-seq data with scOpen
Authors: Li Zhijian , Kuppe Christoph , Ziegler Susanne , Cheng Mingbo , Kabgani Nazanin , Menzel Sylvia , Zenke Martin , Kramann Rafael , Costa Ivan G.
Published: November 2021

A major drawback of single-cell ATAC-seq (scATAC-seq) is its sparsity, i.e., open chromatin regions with no reads due to loss of DNA material during the scATAC-seq protocol. Here, we propose scOpen, a computational method based on regularized non-negative matrix factorization for imputing and quantifying the open chromatin status of regulatory regions from sparse scATAC-seq experiments. We show that scOpen improves crucial downstream analysis steps of scATAC-seq data as clustering, visualization, cis-regulatory DNA interactions, and delineation of regulatory features. We demonstrate the power of scOpen to dissect regulatory changes in the development of fibrosis in the kidney. This identifies a role of Runx1 and target genes by promoting fibroblast to myofibroblast differentiation driving kidney fibrosis.
Independent somatic evolution underlies clustered neuroendocrine tumors in the human small intestine
Authors: Elias Erik , Ardalan Arman , Lindberg Markus , Reinsbach Susanne E. , Muth Andreas , Nilsson Ola , Arvidsson Yvonne , Larsson Erik
Published: November 2021

Small intestine neuroendocrine tumor (SI-NET), the most common cancer of the small bowel, often displays a curious multifocal phenotype with several tumors clustered together in a limited intestinal segment. SI-NET also shows an unusual absence of driver mutations explaining tumor initiation and metastatic spread. The evolutionary trajectories that underlie multifocal SI-NET lesions could provide insight into the underlying tumor biology, but this question remains unresolved. Here, we determine the complete genome sequences of 61 tumors and metastases from 11 patients with multifocal SI-NET, allowing for elucidation of phylogenetic relationships between tumors within single patients. Intra-individual comparisons revealed a lack of shared somatic single-nucleotide variants among the sampled intestinal lesions, supporting an independent clonal origin. Furthermore, in three of the patients, two independent tumors had metastasized. We conclude that primary multifocal SI-NETs generally arise from clonally independent cells, suggesting a contribution from a cancer-priming local factor.
CLAVATA3 mediated simultaneous control of transcriptional and post-translational processes provides robustness to the WUSCHEL gradient
Authors: Plong Alexander , Rodriguez Kevin , Alber Mark , Chen Weitao , Reddy G. Venugopala
Published: November 2021

Regulation of the homeodomain transcription factor WUSCHEL concentration is critical for stem cell homeostasis in Arabidopsis shoot apical meristems. WUSCHEL regulates the transcription of CLAVATA3 through a concentration-dependent activation-repression switch. CLAVATA3, a secreted peptide, activates receptor kinase signaling to repress WUSCHEL transcription. Considering the revised regulation, CLAVATA3 mediated repression of WUSCHEL transcription alone will lead to an unstable system. Here we show that CLAVATA3 signaling regulates nuclear-cytoplasmic partitioning of WUSCHEL to control nuclear levels and its diffusion into adjacent cells. Our work also reveals that WUSCHEL directly interacts with EXPORTINS via EAR-like domain which is also required for destabilizing WUSCHEL in the cytoplasm. We develop a combined experimental and computational modeling approach that integrates CLAVATA3-mediated transcriptional repression of WUSCHEL and post-translational control of nuclear levels with the WUSCHEL concentration-dependent regulation of CLAVATA3. We show that the dual control by the same signal forms a seamless connection between de novo WUSCHEL synthesis and sub-cellular partitioning in providing robustness to the WUSCHEL gradient.
Within-host evolution of SARS-CoV-2 in an immunosuppressed COVID-19 patient as a source of immune escape variants
Authors: Weigang Sebastian , Fuchs Jonas , Zimmer Gert , Schnepf Daniel , Kern Lisa , Beer Julius , Luxenburger Hendrik , Ankerhold Jakob , Falcone Valeria , Kemming Janine , Hofmann Maike , Thimme Robert , Neumann-Haefelin Christoph , Ulferts Svenja , Grosse Robert , Hornuss Daniel , Tanriver Yakup , Rieg Siegbert , Wagner Dirk , Huzly Daniela , Schwemmle Martin , Panning Marcus , Kochs Georg
Published: November 2021

The origin of SARS-CoV-2 variants of concern remains unclear. Here, we test whether intra-host virus evolution during persistent infections could be a contributing factor by characterizing the long-term SARS-CoV-2 infection dynamics in an immunosuppressed kidney transplant recipient. Applying RT-qPCR and next-generation sequencing (NGS) of sequential respiratory specimens, we identify several mutations in the viral genome late in infection. We demonstrate that a late viral isolate exhibiting genome mutations similar to those found in variants of concern first identified in UK, South Africa, and Brazil, can escape neutralization by COVID-19 antisera. Moreover, infection of susceptible mice with this patient’s escape variant elicits protective immunity against re-infection with either the parental virus and the escape variant, as well as high neutralization titers against the alpha and beta SARS-CoV-2 variants, B.1.1.7 and B.1.351, demonstrating a considerable immune control against such variants of concern. Upon lowering immunosuppressive treatment, the patient generated spike-specific neutralizing antibodies and resolved the infection. Our results suggest that immunocompromised patients could be a source for the emergence of potentially harmful SARS-CoV-2 variants.
Real-time observation of Cooper pair splitting showing strong non-local correlations
Authors: Ranni Antti , Brange Fredrik , Mannila Elsa T. , Flindt Christian , Maisi Ville F.
Published: November 2021

Controlled generation and detection of quantum entanglement between spatially separated particles constitute an essential prerequisite both for testing the foundations of quantum mechanics and for realizing future quantum technologies. Splitting of Cooper pairs from a superconductor provides entangled electrons at separate locations. However, experimentally accessing the individual split Cooper pairs constitutes a major unresolved issue as they mix together with electrons from competing processes. Here, we overcome this challenge with the first real-time observation of the splitting of individual Cooper pairs, enabling direct access to the time-resolved statistics of Cooper pair splitting. We determine the correlation statistics arising from two-electron processes and find a pronounced peak that is two orders of magnitude larger than the background. Our experiment thereby allows to unambiguously pinpoint and select split Cooper pairs with 99% fidelity. These results open up an avenue for performing experiments that tap into the spin-entanglement of split Cooper pairs.
Evolving contact mechanics and microstructure formation dynamics of the lithium metal-Li7La3Zr2O12 interface
Authors: Chang Wesley , May Richard , Wang Michael , Thorsteinsson Gunnar , Sakamoto Jeff , Marbella Lauren , Steingart Daniel
Published: November 2021

The dynamic behavior of the interface between the lithium metal electrode and a solid-state electrolyte plays a critical role in all-solid-state battery performance. The evolution of this interface throughout cycling involves multiscale mechanical and chemical heterogeneity at the micro- and nano-scale. These features are dependent on operating conditions such as current density and stack pressure. Here we report the coupling of operando acoustic transmission measurements with nuclear magnetic resonance spectroscopy and magnetic resonance imaging to correlate changes in interfacial mechanics (such as contact loss and crack formation) with the growth of lithium microstructures during cell cycling. Together, the techniques reveal the chemo-mechanical behavior that governs lithium metal and Li7La3Zr2O12 interfacial dynamics at various stack pressure regimes and with voltage polarization.
An innate contribution of human nicotinic receptor polymorphisms to COPD-like lesions
Authors: Routhier Julie , Pons Stéphanie , Freidja Mohamed Lamine , Dalstein Véronique , Cutrona Jérôme , Jonquet Antoine , Lalun Nathalie , Mérol Jean-Claude , Lathrop Mark , Stitzel Jerry A. , Kervoaze Gwenola , Pichavant Muriel , Gosset Philippe , Tournier Jean-Marie , Birembaut Philippe , Dormoy Valérian , Maskos Uwe
Published: November 2021

Chronic Obstructive Pulmonary Disease is a generally smoking-linked major cause of morbidity and mortality. Genome-wide Association Studies identified a locus including a non-synonymous single nucleotide polymorphism in CHRNA5, rs16969968, encoding the nicotinic acetylcholine receptor α5 subunit, predisposing to both smoking and Chronic Obstructive Pulmonary Disease. Here we report that nasal polyps from rs16969968 non-smoking carriers exhibit airway epithelium remodeling and inflammation. These hallmarks of Chronic Obstructive Pulmonary Disease occur spontaneously in mice expressing human rs16969968. They are significantly amplified after exposure to porcine pancreatic elastase, an emphysema model, and to oxidative stress with a polymorphism-dependent alteration of lung function. Targeted rs16969968 expression in epithelial cells leads to airway remodeling in vivo, increased proliferation and production of pro-inflammatory cytokines through decreased calcium entry and increased adenylyl-cyclase activity. We show that rs16969968 directly contributes to Chronic Obstructive Pulmonary Disease-like lesions, sensitizing the lung to the action of oxidative stress and injury, and represents a therapeutic target.
Single-cell normalization and association testing unifying CRISPR screen and gene co-expression analyses with Normalisr
Authors: Wang Lingfei
Published: November 2021

Single-cell RNA sequencing (scRNA-seq) provides unprecedented technical and statistical potential to study gene regulation but is subject to technical variations and sparsity. Furthermore, statistical association testing remains difficult for scRNA-seq. Here we present Normalisr, a normalization and statistical association testing framework that unifies single-cell differential expression, co-expression, and CRISPR screen analyses with linear models. By systematically detecting and removing nonlinear confounders arising from library size at mean and variance levels, Normalisr achieves high sensitivity, specificity, speed, and generalizability across multiple scRNA-seq protocols and experimental conditions with unbiased p-value estimation. The superior scalability allows us to reconstruct robust gene regulatory networks from trans-effects of guide RNAs in large-scale single cell CRISPRi screens. On conventional scRNA-seq, Normalisr recovers gene-level co-expression networks that recapitulated known gene functions.
Metamachines of pluripotent colloids
Authors: Aubret Antoine , Martinet Quentin , Palacci Jeremie
Published: November 2021

Machines enabled the Industrial Revolution and are central to modern technological progress: A machine’s parts transmit forces, motion, and energy to one another in a predetermined manner. Today’s engineering frontier, building artificial micromachines that emulate the biological machinery of living organisms, requires faithful assembly and energy consumption at the microscale. Here, we demonstrate the programmable assembly of active particles into autonomous metamachines using optical templates. Metamachines, or machines made of machines, are stable, mobile and autonomous architectures, whose dynamics stems from the geometry. We use the interplay between anisotropic force generation of the active colloids with the control of their orientation by local geometry. This allows autonomous reprogramming of active particles of the metamachines to achieve multiple functions. It permits the modular assembly of metamachines by fusion, reconfiguration of metamachines and, we anticipate, a shift in focus of self-assembly towards active matter and reprogrammable materials.
Sensory-motor cortices shape functional connectivity dynamics in the human brain
Authors: Kong Xiaolu , Kong Ru , Orban Csaba , Wang Peng , Zhang Shaoshi , Anderson Kevin , Holmes Avram , Murray John D. , Deco Gustavo , van den Heuvel Martijn , Yeo B. T. Thomas
Published: November 2021

Large-scale biophysical circuit models provide mechanistic insights into the micro-scale and macro-scale properties of brain organization that shape complex patterns of spontaneous brain activity. We developed a spatially heterogeneous large-scale dynamical circuit model that allowed for variation in local synaptic properties across the human cortex. Here we show that parameterizing local circuit properties with both anatomical and functional gradients generates more realistic static and dynamic resting-state functional connectivity (FC). Furthermore, empirical and simulated FC dynamics demonstrates remarkably similar sharp transitions in FC patterns, suggesting the existence of multiple attractors. Time-varying regional fMRI amplitude may track multi-stability in FC dynamics. Causal manipulation of the large-scale circuit model suggests that sensory-motor regions are a driver of FC dynamics. Finally, the spatial distribution of sensory-motor drivers matches the principal gradient of gene expression that encompasses certain interneuron classes, suggesting that heterogeneity in excitation-inhibition balance might shape multi-stability in FC dynamics.
Coordination environment dependent selectivity of single-site-Cu enriched crystalline porous catalysts in CO2 reduction to CH4
Authors: Zhang Yu , Dong Long-Zhang , Li Shan , Huang Xin , Chang Jia-Nan , Wang Jian-Hui , Zhou Jie , Li Shun-Li , Lan Ya-Qian
Published: November 2021

The electrochemical CO2reduction to high-value-added chemicals is one of the most promising and challenging research in the energy conversion field. An efficient ECR catalyst based on a Cu-based conductive metal-organic framework (Cu-DBC) is dedicated to producing CH4with superior activity and selectivity, showing a Faradaic efficiency of CH4as high as ~80% and a large current density of −203 mA cm−2at −0.9 V vs. RHE. The further investigation based on theoretical calculations and experimental results indicates the Cu-DBC with oxygen-coordinated Cu sites exhibits higher selectivity and activity over the other two crystalline ECR catalysts with nitrogen-coordinated Cu sites due to the lower energy barriers of Cu-O4sites during ECR process. This work unravels the strong dependence of ECR selectivity on the Cu site coordination environment in crystalline porous catalysts, and provides a platform for constructing highly selective ECR catalysts.
Structural basis of human ghrelin receptor signaling by ghrelin and the synthetic agonist ibutamoren
Authors: Liu Heng , Sun Dapeng , Myasnikov Alexander , Damian Marjorie , Baneres Jean-Louis , Sun Ji , Zhang Cheng
Published: November 2021

The hunger hormone ghrelin activates the ghrelin receptor GHSR to stimulate food intake and growth hormone secretion and regulate reward signaling. Acylation of ghrelin at Ser3 is required for its agonistic action on GHSR. Synthetic agonists of GHSR are under clinical evaluation for disorders related to appetite and growth hormone dysregulation. Here, we report high-resolution cryo-EM structures of the GHSR-Gi signaling complex with ghrelin and the non-peptide agonist ibutamoren as an investigational new drug. Our structures together with mutagenesis data reveal the molecular basis for the binding of ghrelin and ibutamoren. Structural comparison suggests a salt bridge and an aromatic cluster near the agonist-binding pocket as important structural motifs in receptor activation. Notable structural variations of the Gi and GHSR coupling are observed in our cryo-EM analysis. Our results provide a framework for understanding GHSR signaling and developing new GHSR agonist drugs.
Molecular mechanisms of the CdnG-Cap5 antiphage defense system employing 3′,2′-cGAMP as the second messenger
Authors: Fatma Shirin , Chakravarti Arpita , Zeng Xuankun , Huang Raven H.
Published: November 2021

Cyclic-oligonucleotide-based antiphage signaling systems (CBASS) are diverse and abundant in bacteria. Here, we present the biochemical and structural characterization of two CBASS systems, composed of CdnG and Cap5, from Asticcacaulis sp. and Lactococcus lactis. We show that CdnG from Asticcacaulis sp. synthesizes 3′,2′-cGAMP in vitro, and 3′,2′-cGAMP is the biological signaling molecule that activates Cap5 for DNA degradation. Crystal structures of Cap5, together with the SAVED domain in complex with 3′,2′-cGAMP, provide insight into the architecture of Cap5 as well as molecular recognition of 3′,2′-cGAMP by the SAVED domain of Cap5. Amino acid conservation of the SAVED domain of Cap5, together with mutational studies, led us to propose a mechanism of Back-to-Front stacking of two SAVED domains, mediated by 3′,2′-cGAMP, to activate HNH nuclease domain for DNA degradation. This study of the most abundant CBASS system provides insights into the mechanisms employed by bacteria in their conflicts against phage.
Hepatic expression of GAA results in enhanced enzyme bioavailability in mice and non-human primates
Authors: Costa-Verdera Helena , Collaud Fanny , Riling Christopher R. , Sellier Pauline , Nordin Jayme M. L. , Preston G. Michael , Cagin Umut , Fabregue Julien , Barral Simon , Moya-Nilges Maryse , Krijnse-Locker Jacomina , van Wittenberghe Laetitia , Daniele Natalie , Gjata Bernard , Cosette Jeremie , Abad Catalina , Simon-Sola Marcelo , Charles Severine , Li Mathew , Crosariol Marco , Antrilli Tom , Quinn William J. , Gross David A. , Boyer Olivier , Anguela Xavier M. , Armour Sean M. , Colella Pasqualina , Ronzitti Giuseppe , Mingozzi Federico
Published: November 2021

Pompe disease (PD) is a severe neuromuscular disorder caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). PD is currently treated with enzyme replacement therapy (ERT) with intravenous infusions of recombinant human GAA (rhGAA). Although the introduction of ERT represents a breakthrough in the management of PD, the approach suffers from several shortcomings. Here, we developed a mouse model of PD to compare the efficacy of hepatic gene transfer with adeno-associated virus (AAV) vectors expressing secretable GAA with long-term ERT. Liver expression of GAA results in enhanced pharmacokinetics and uptake of the enzyme in peripheral tissues compared to ERT. Combination of gene transfer with pharmacological chaperones boosts GAA bioavailability, resulting in improved rescue of the PD phenotype. Scale-up of hepatic gene transfer to non-human primates also successfully results in enzyme secretion in blood and uptake in key target tissues, supporting the ongoing clinical translation of the approach.
Multidrug-resistant Neisseria gonorrhoeae infection in heterosexual men with reduced susceptibility to ceftriaxone, first report in Thailand
Authors: Kueakulpattana Naris , Wannigama Dhammika Leshan , Luk-in Sirirat , Hongsing Parichart , Hurst Cameron , Badavath Vishnu Nayak , Jenjaroenpun Piroon , Wongsurawat Thidathip , Teeratakulpisan Nipat , Kerr Stephen J. , Abe Shuichi , Phattharapornjaroen Phatthranit , Shein Aye Mya Sithu , Saethang Thammakorn , Chantaravisoot Naphat , Amarasiri Mohan , Higgins Paul G. , Chatsuwan Tanittha
Published: November 2021

The global rapid emergence of azithromycin/ceftriaxone resistant Neisseria gonorrhoeae threatens current recommend azithromycin/ceftriaxone dual therapy for gonorrhea to ensure effective treatment. Here, we identified the first two N. gonorrhoeae isolates with decreased ceftriaxone susceptibility in Thailand. Among 134 N. gonorrhoeae isolates collected from Thai Red Cross Anonymous Clinic, Bangkok, two isolates (NG-083 and NG-091) from urethral swab in male heterosexual patients had reduced susceptibility to ceftriaxone (MICs of 0.125 mg/L). Both were multidrug resistant and strong biofilm producers with ceftriaxone tolerance (MBEC > 128 mg/L). NG-083 and NG-091 remained susceptible to azithromycin (MIC of 1 mg/L and 0.5 mg/L, respectively). Reduced susceptibility to ceftriaxone was associated with alterations in PBP2, PBP1, PorB, MtrR, and mtrR promoter region. NG-083 belonged to sequence type (ST) 7235 and NG-091 has new allele number of tbpB with new ST. Molecular docking revealed ceftriaxone weakly occupied the active site of mosaic XXXIV penicillin-binding protein 2 variant in both isolates. Molecular epidemiology results revealed that both isolates display similarities with isolates from UK, USA, and The Netherlands. These first two genetically related gonococcal isolates with decreased ceftriaxone susceptibility heralds the threat of treatment failure in Thailand, and importance of careful surveillance.
Link between serum lipid signature and prognostic factors in COVID-19 patients
Authors: Dei Cas Michele , Ottolenghi Sara , Morano Camillo , Rinaldo Rocco , Roda Gabriella , Chiumello Davide , Centanni Stefano , Samaja Michele , Paroni Rita
Published: November 2021

Although the serum lipidome is markedly affected by COVID-19, two unresolved issues remain: how the severity of the disease affects the level and the composition of serum lipids and whether serum lipidome analysis may identify specific lipids impairment linked to the patients' outcome. Sera from 49 COVID-19 patients were analyzed by untargeted lipidomics. Patients were clustered according to: inflammation (C-reactive protein), hypoxia (Horowitz Index), coagulation state (D-dimer), kidney function (creatinine) and age. COVID-19 patients exhibited remarkable and distinctive dyslipidemia for each prognostic factor associated with reduced defense against oxidative stress. When patients were clustered by outcome (7 days), a peculiar lipidome signature was detected with an overall increase of 29 lipid species, including—among others—four ceramide and three sulfatide species, univocally related to this analysis. Considering the lipids that were affected by all the prognostic factors, we found one sphingomyelin related to inflammation and viral infection of the respiratory tract and two sphingomyelins, that are independently related to patients' age, and they appear as candidate biomarkers to monitor disease progression and severity. Although preliminary and needing validation, this report pioneers the translation of lipidome signatures to link the effects of five critical clinical prognostic factors with the patients' outcomes.
Targeting eIF4F translation complex sensitizes B-ALL cells to tyrosine kinase inhibition
Authors: Vo Thanh-Trang , Herzog Lee-or , Buono Roberta , Lee Jong-Hoon Scott , Mallya Sharmila , Duong Madeleine R. , Thao Joshua , Gotesman Moran , Fruman David A.
Published: November 2021

The mechanistic target of rapamycin (mTOR) is a kinase whose activation is associated with poor prognosis in pre-B cell acute lymphoblastic leukemia (B-ALL). These and other findings have prompted diverse strategies for targeting mTOR signaling in B-ALL and other B-cell malignancies. In cellular models of Philadelphia Chromosome-positive (Ph+) B-ALL, mTOR kinase inhibitors (TOR-KIs) that inhibit both mTOR-complex-1 (mTORC1) and mTOR-complex-2 (mTORC2) enhance the cytotoxicity of tyrosine kinase inhibitors (TKIs) such as dasatinib. However, TOR-KIs have not shown substantial efficacy at tolerated doses in blood cancer clinical trials. Selective inhibition of mTORC1 or downstream effectors provides alternative strategies that may improve selectivity towards leukemia cells. Of particular interest is the eukaryotic initiation factor 4F (eIF4F) complex that mediates cap-dependent translation. Here we use novel chemical and genetic approaches to show that selective targeting of either mTORC1 kinase activity or components of the eIF4F complex sensitizes murine BCR-ABL-dependent pre-B leukemia cells to dasatinib. SBI-756, a small molecule inhibitor of eIF4F assembly, sensitizes human Ph+ and Ph-like B-ALL cells to dasatinib cytotoxicity without affecting survival of T lymphocytes or natural killer cells. These findings support the further evaluation of eIF4F-targeted molecules in combination therapies with TKIs in B-ALL and other blood cancers.
Claudin-9 constitutes tight junctions of folliculo-stellate cells in the anterior pituitary gland
Authors: Higashi Atsuko Y. , Higashi Tomohito , Furuse Kyoko , Ozeki Kana , Furuse Mikio , Chiba Hideki
Published: November 2021

The anterior pituitary gland regulates growth, metabolism, and reproduction by secreting hormones. Folliculo-stellate (FS) cells are non-endocrine cells located among hormone-producing cells in the anterior pituitary glands. They form follicular lumens, which are sealed by tight junctions (TJs). Although FS cells are hypothesized to contribute to fine-tuning of endocrine cells, little is known about the exact roles of FS cells. Here, we investigated the molecular composition of TJs in FS cells. We demonstrated that occludin is a good marker for TJs in the pituitary gland and examined the structure of the lumens surrounded by FS cells. We also found that claudin-9 is a major component of TJs in the FS cells. In immunoelectron microscopy, claudin-9 was specifically localized at TJs of the FS cells. The expression of claudin-9 was gradually increased in the pituitary gland after birth, suggesting that claudin-9 is developmentally regulated and performs some specific functions on the paracellular barrier of follicles in the pituitary gland. Furthermore, we found that angulin-1, angulin-2, and tricellulin are localized at the tricellular contacts of the FS cells. Our findings provide a first comprehensive molecular profile of TJs in the FS cells, and may lead us towards unveiling the FS cell functions.
Responses of turkey vultures to unmanned aircraft systems vary by platform
Authors: Pfeiffer Morgan B. , Blackwell Bradley F. , Seamans Thomas W. , Buckingham Bruce N. , Hoblet Joshua L. , Baumhardt Patrice E. , DeVault Travis L. , Fernández-Juricic Esteban
Published: November 2021

A challenge that conservation practitioners face is manipulating behavior of nuisance species. The turkey vulture (Cathartes aura) can cause substantial damage to aircraft if struck. The goal of this study was to assess vulture responses to unmanned aircraft systems (UAS) for use as a possible dispersal tool. Our treatments included three platforms (fixed-wing, multirotor, and a predator-like ornithopter [powered by flapping flight]) and two approach types (30 m overhead or targeted towards a vulture) in an operational context. We evaluated perceived risk as probability of reaction, reaction time, flight-initiation distance (FID), vulture remaining index, and latency to return. Vultures escaped sooner in response to the fixed-wing; however, fewer remained after multirotor treatments. Targeted approaches were perceived as riskier than overhead. Vulture perceived risk was enhanced by flying the multirotor in a targeted approach. We found no effect of our treatments on FID or latency to return. Latency was negatively correlated with UAS speed, perhaps because slower UAS spent more time over the area. Greatest visual saliency followed as: ornithopter, fixed-wing, and multirotor. Despite its appearance, the ornithopter was not effective at dispersing vultures. Because effectiveness varied, multirotor/fixed-wing UAS use should be informed by management goals (immediate dispersal versus latency).
Highly sensitive low field Lorentz-force MEMS magnetometer
Authors: Mbarek Sofiane Ben , Alcheikh Nouha , Ouakad Hassen M. , Younis Mohammad I.
Published: November 2021

We present a highly sensitive Lorentz-force magnetic micro-sensor capable of measuring low field values. The magnetometer consists of a silicon micro-beam sandwiched between two electrodes to electrostatically induce in-plane vibration and to detect the output current. The method is based on measuring the resonance frequency of the micro-beam around the buckling zone to sense out-of-plane magnetic fields. When biased with a current of 0.91 mA (around buckling), the device has a measured sensitivity of 11.6 T−1, which is five orders of magnitude larger than the state-of-the-art. The measured minimum detectable magnetic field and the estimated resolution of the proposed magnetic sensor are 100 µT and 13.6 µT.Hz−1/2, respectively. An analytical model is developed based on the Euler–Bernoulli beam theory and the Galerkin discretization to understand and verify the micro-sensor performance. Good agreement is shown between analytical results and experimental data. Furthermore, the presented magnetometer is promising for measuring very weak biomagnetic fields.
Functional roles of the membrane-associated AAV protein MAAP
Authors: Galibert Lionel , Hyvönen Amira , Eriksson Reetta A. E. , Mattola Salla , Aho Vesa , Salminen Sami , Albers Justin D. , Peltola Sanna K. , Weman Saija , Nieminen Tiina , Ylä-Herttuala Seppo , Lesch Hanna P. , Vihinen-Ranta Maija , Airenne Kari J.
Published: November 2021

With a limited coding capacity of 4.7 kb, adeno-associated virus (AAV) genome has evolved over-lapping genes to maximise the usage of its genome. An example is the recently found ORF in the cap gene, encoding membrane-associated accessory protein (MAAP), located in the same genomic region as the VP1/2 unique domain, but in a different reading frame. This 13 KDa protein, unique to the dependovirus genus, is not homologous to any known protein. Our studies confirm that MAAP translation initiates from the first CTG codon found in the VP1 ORF2. We have further observed MAAP localised in the plasma membrane, in the membranous structures in close proximity to the nucleus and to the nuclear envelope by co-transfecting with plasmids encoding the wild-type AAV (wt-AAV) genome and adenovirus (Ad) helper genes. While keeping VP1/2 protein sequence identical, both inactivation and truncation of MAAP translation affected the emergence and intracellular distribution of the AAV capsid proteins. We have demonstrated that MAAP facilitates AAV replication and has a role in controlling Ad infection. Additionally, we were able to improve virus production and capsid integrity through a C-terminal truncation of MAAP while other modifications led to increased packaging of contaminating, non-viral DNA. Our results show that MAAP plays a significant role in AAV infection, with profound implications for the production of therapeutic AAV vectors.
Plasmon-induced transparency sensor for detection of minuscule refractive index changes in ultra-low index materials
Authors: Farhadi Shahriar , Miri Mehdi , Farmani Ali
Published: November 2021

Detection of low-index materials such as aerogels and also detection of refractive index variations in these materials is still a challenging task. Here, a high figure of merit (FOM) sensor based on plasmon-induced transparency (PIT) is proposed for the detection of aerogel refractive index changes. In the proposed PIT sensor, the transparency window in an opaque region arises from the coupling between surface plasmon polariton (SPP) mode and planar waveguide mode. By comprising sub-wavelength grating (SWG) in the planar waveguide region, the maximum of the electric field of waveguide occurs in a low index media. This facilitates detection of the aerogels when they are used as the low index material (sensing material). Application of the subwavelength grating waveguide also improves the sensitivity of the sensor by a factor of six compared to a conventional structure with a homogenous waveguide. The proposed structure has a quality factor of Q ≥ 1800, and a reflection of 86%, and can detect the refractive index changes as low as Δn = 0.002 (around n = 1.0). The lineshape, Q-factor, and resonant wavelength of the transparency spectrum can be controlled by tailoring the structural parameters. Our work also has potential application in switching, filtering, and spectral shaping.
Serum HE4 and CA125 combined to predict and monitor recurrence of type II endometrial carcinoma
Authors: Quan Quan , Liao Qianqian , Yin Wanchun , Zhou Shuwei , Gong Sainan , Mu Xiaoling
Published: November 2021

There is no recognized serum biomarker to predict the recurrence of endometrial carcinoma (EC). We aimed to explore serum human epididymis protein 4 (HE4) and cancer antigen 125 (CA125) as the biomarkers to predict and monitor recurrence of type II EC. 191 patients diagnosed with type II EC were involved for this retrospective study. Comparing recurrent with non-recurrent patients, HE4 levels resulted a statistically significant difference at primary diagnosis and recurrence, respectively (P = 0.002 and P = < 0.001), while CA125 levels resulted statistically significant (P = < 0.001) at recurrence. According to receiver operating characteristic curve analysis, the areas under the curve were significant for HE4 levels at primary diagnosis and recurrence predicting recurrence. Furthermore, CA125 levels at recurrence were significant. And the combination of both markers showed the higher sensitivity and specificity than single one. Patients with higher HE4 levels were associated with worse disease-free survival and overall survival, the opposite was true for patients with lower HE4 levels. The preoperative HE4 levels could be used to evaluate the risk factors of type II EC. Which suggested that HE4 levels might associated with the prognosis of type II EC. And combination of HE4 and CA125 could be applied to monitor recurrence during follow-up.
Design considerations for workflow management systems use in production genomics research and the clinic
Authors: Ahmed Azza E. , Allen Joshua M. , Bhat Tajesvi , Burra Prakruthi , Fliege Christina E. , Hart Steven N. , Heldenbrand Jacob R. , Hudson Matthew E. , Istanto Dave Deandre , Kalmbach Michael T. , Kapraun Gregory D. , Kendig Katherine I. , Kendzior Matthew Charles , Klee Eric W. , Mattson Nate , Ross Christian A. , Sharif Sami M. , Venkatakrishnan Ramshankar , Fadlelmola Faisal M. , Mainzer Liudmila S.
Published: November 2021

The changing landscape of genomics research and clinical practice has created a need for computational pipelines capable of efficiently orchestrating complex analysis stages while handling large volumes of data across heterogeneous computational environments. Workflow Management Systems (WfMSs) are the software components employed to fill this gap. This work provides an approach and systematic evaluation of key features of popular bioinformatics WfMSs in use today: Nextflow, CWL, and WDL and some of their executors, along with Swift/T, a workflow manager commonly used in high-scale physics applications. We employed two use cases: a variant-calling genomic pipeline and a scalability-testing framework, where both were run locally, on an HPC cluster, and in the cloud. This allowed for evaluation of those four WfMSs in terms of language expressiveness, modularity, scalability, robustness, reproducibility, interoperability, ease of development, along with adoption and usage in research labs and healthcare settings. This article is trying to answer,which WfMS should be chosen for a given bioinformatics application regardless of analysis type?. The choice of a given WfMS is a function of both its intrinsic language and engine features. Within bioinformatics, where analysts are a mix of dry and wet lab scientists, the choice is also governed by collaborations and adoption within large consortia and technical support provided by the WfMS team/community. As the community and its needs continue to evolve along with computational infrastructure, WfMSs will also evolve, especially those with permissive licenses that allow commercial use. In much the same way as the dataflow paradigm and containerization are now well understood to be very useful in bioinformatics applications, we will continue to see innovations of tools and utilities for other purposes, like big data technologies, interoperability, and provenance.
Features and applications of haplotypes in crop breeding
Authors: Bhat Javaid Akhter , Yu Deyue , Bohra Abhishek , Ganie Showkat Ahmad , Varshney Rajeev K.
Published: November 2021

Climate change with altered pest-disease dynamics and rising abiotic stresses threatens resource-constrained agricultural production systems worldwide. Genomics-assisted breeding (GAB) approaches have greatly contributed to enhancing crop breeding efficiency and delivering better varieties. Fast-growing capacity and affordability of DNA sequencing has motivated large-scale germplasm sequencing projects, thus opening exciting avenues for mining haplotypes for breeding applications. This review article highlights ways to mine haplotypes and apply them for complex trait dissection and in GAB approaches including haplotype-GWAS, haplotype-based breeding, haplotype-assisted genomic selection. Improvement strategies that efficiently deploy superior haplotypes to hasten breeding progress will be key to safeguarding global food security.
Truncating tau reveals different pathophysiological actions of oligomers in single neurons
Authors: Hill Emily , Karikari Thomas K. , Lantero-Rodriguez Juan , Zetterberg Henrik , Blennow Kaj , Richardson Magnus J. , Wall Mark J.
Published: November 2021

Tau protein is involved in maintaining neuronal structure. In Alzheimer’s disease, small numbers of tau molecules can aggregate to form oligomers. However, how these oligomers produce changes in neuronal function remains unclear. Previously, oligomers made from full-length human tau were found to have multiple effects on neuronal properties. Here we have cut the tau molecule into two parts: the first 123 amino acids and the remaining 124-441 amino acids. These truncated tau molecules had specific effects on neuronal properties, allowing us to assign the actions of full-length tau to different regions of the molecule. We identified one key target for the effects of tau, the voltage gated sodium channel, which could account for the effects of tau on the action potential. By truncating the tau molecule, we have probed the mechanisms that underlie tau dysfunction, and this increased understanding of tau’s pathological actions will build towards developing future tau-targeting therapies.
Mitochondrial-nuclear cross-talk in the human brain is modulated by cell type and perturbed in neurodegenerative disease
Authors: Fairbrother-Browne Aine , Ali Aminah T. , Reynolds Regina H. , Garcia-Ruiz Sonia , Zhang David , Chen Zhongbo , Ryten Mina , Hodgkinson Alan
Published: November 2021

Mitochondrial dysfunction contributes to the pathogenesis of many neurodegenerative diseases. The mitochondrial genome encodes core respiratory chain proteins, but the vast majority of mitochondrial proteins are nuclear-encoded, making interactions between the two genomes vital for cell function. Here, we examine these relationships by comparing mitochondrial and nuclear gene expression across different regions of the human brain in healthy and disease cohorts. We find strong regional patterns that are modulated by cell-type and reflect functional specialisation. Nuclear genes causally implicated in sporadic Parkinson’s and Alzheimer’s disease (AD) show much stronger relationships with the mitochondrial genome than expected by chance, and mitochondrial-nuclear relationships are highly perturbed in AD cases, particularly through synaptic and lysosomal pathways, potentially implicating the regulation of energy balance and removal of dysfunction mitochondria in the etiology or progression of the disease. Finally, we presentMitoNuclearCOEXPlorer, a tool to interrogate key mitochondria-nuclear relationships in multi-dimensional brain data.
Quantifying cell-generated forces: Poisson’s ratio matters
Authors: Javanmardi Yousef , Colin-York Huw , Szita Nicolas , Fritzsche Marco , Moeendarbary Emad
Published: November 2021

Quantifying mechanical forces generated by cellular systems has led to key insights into a broad range of biological phenomena from cell adhesion to immune cell activation. Traction force microscopy (TFM), the most widely employed force measurement methodology, fundamentally relies on knowledge of the force-displacement relationship and mechanical properties of the substrate. Together with the elastic modulus, the Poisson’s ratio is a basic material property that to date has largely been overlooked in TFM. Here, we evaluate the sensitivity of TFM to Poisson’s ratio by employing a series of computer simulations and experimental data analysis. We demonstrate how applying the correct Poisson’s ratio is important for accurate force reconstruction and develop a framework for the determination of error levels resulting from the misestimation of the Poisson’s ratio. In addition, we provide experimental estimation of the Poisson’s ratios of elastic substrates commonly applied in TFM. Our work thus highlights the role of Poisson’s ratio underpinning cellular force quantification studied across many biological systems.
The separation characteristics and performance evaluation of the silica-based poly(pentabromostyrene) stationary phase in capillary electrochromatography
Authors: Zhong Zhihua , Chu Zhanying , Dong Ziyi , Zhang Weibing , Zhang Lingyi
Published: November 2021

A novel mixed-mode capillary column with a poly(pentabromostyrene)–silica composite (SiO2@pPBS) as the stationary phase was prepared for packed capillary electrochromatography (p-CEC).
Ginsenoside as a new stabilizer enhances the transfection efficiency and biocompatibility of cationic liposome
Authors: Wang Mao-Ze , Xu Yang , Xie Jia-Feng , Jiang Zhi-Hong , Peng Li-Hua
Published: November 2021

Ginsenoside-based compounds were utilized as membrane stabilizers to prepare CLs (GCLs). GCLs are demonstrated as promising non-viral vectors with excellent transfection efficiency and biocompatibility, possessing great potential for gene delivery.
Reversible 1D chain-reaction gives rise to an atomic-scale Newton's cradle
Authors: Leung Lydie , Timm Matthew J. , Polanyi John C.
Published: November 2021

A continuous cycle of F-atom is initiated by two electron-pulses, one pulse at the left and one pulse at the right. The F-atoms are knocked-on twice in moving from left to right, and twice more in moving back from right to left.
Brønsted acid-catalyzed solvent-controlled regioselective hydrothiolation and diastereoselective cascade cyclization of dienes
Authors: Ji Kai , Lu Ka , Huang Jie , Li Zi-Hao , Ding Tong-Mei , Chen Zhi-Min
Published: November 2021

A highly regio- and diastereo-selective Brønsted acid-catalyzed tandem hydrothiolation/Friedel-Crafts reaction of linear 1,3-dienes has been first developed. Meanwhile, by simply changing the solvent, 4,3-addition hydrothiolation of 1,3-dienes was also discovered.
Amino acid hydrogen oxalate quasiracemates – hydrocarbon side chains
Authors: Wells Russell G. , Sahlstrom Katriel D. , Ekelem Franklin I. , Wheeler Kraig A.
Published: November 2021

Amino acid hydrogen oxalate quasiracemates form robust crystal structure motifs that are assessed for conformational similarity and degree of inversion symmetry.
Features of the conformation of galunisertib molecules in the crystal structures of its solvates
Authors: Serezhkin Viktor N. , Savchenkov Anton V.
Published: November 2021

A comparison of galunisertib in crystal structures of pure polymorphs and solvates enables studying the effects of solvate molecules on galunisertib conformations and highlights the features of realized noncovalent interactions.
Light fueled mixing in open surface droplet microfluidics for rapid probe preparation
Authors: Li Dongliang , Chen Rong , Zhu Xun , Ye Dingding , Yang Yang , Li Wei , Li Haonan , Yang Yijing , Liao Qiang
Published: November 2021

A contactless, flexible, and interference-free light fueled mixing method is developed to enhance the mixing and binding between the ssDNA and dynabeads in a droplet for rapid probe preparation.
Photocatalytic reaction mechanisms at the gas–solid interface for environmental and energy applications
Authors: Xiao Lei , Chen Peng , Yang Weiping , Zhao Xiaoli , Dong Fan
Published: November 2021

Five gas–solid photocatalytic reactions including the oxidation of NOx, VOCs and NH3, and reduction of CO2 and N2 are summarized. Besides, basic properties of gas molecules, their adsorption and activation, and various reaction pathways are analyzed.
Umbelliferyloxymethyl phosphonate compounds-weakly binding zinc ionophores with neuroprotective properties
Authors: Guesne Sebastien , Connole Laura , Kim Stephanie , Motevalli Majid , Robson Lesley , Michael-Titus Adina T. , Sullivan Alice
Published: November 2021

Umbelliferyloxymethyl phosphonates:non-chelating ionophores that A protect rat hippocampal cells from toxic Aβ42 B partition Zn from water to octanol C inhibit Zn promoted aggregation of Aβ42, D delay Zn signaling by FluoZin-3 in neuronal cells.
An innovative approach towards the simultaneous enhancement of the oxygen reduction and evolution reactions using a redox mediator in polymer based Li–O2 batteries
Authors: Sultana Fozia , Althubeiti Khaled , Abualnaja Khamael M. , Wang Jiahui , Zaman Abid , Ali Asad , Arbab Safeer Ahmad , Uddin Sarir , Yang Qing
Published: November 2021

For safety concerns, polymer-based Li–O2 batteries have received more attention than traditional non-aqueous Li–O2 batteries.
Elucidation of the electron transfer environment in the MMOR FAD-binding domain from Methylosinus sporium 5
Authors: Lee Chaemin , Ha Sung Chul , Rao Zhili , Hwang Yunha , Kim Da Som , Kim So Young , Yoo Heeseon , Yoon Chungwoon , Na Jeong-Geol , Park Jung Hee , Lee Seung Jae
Published: November 2021

Biophysical studies of MMOR–FAD demonstrate that Tyr160 is a key regulator for electron transfer.
Large-scale aqueous synthesis of Cu(In,Ga)Se2 nanoparticles for photocatalytic degradation of ciprofloxacin
Authors: Gonçalves Bruna F. , Martins Pedro M. , LaGrow Alec P. , Botelho Gabriela , Salonen Laura M. , Lanceros-Méndez Senentxu , Kolen'ko Yury V.
Published: November 2021

Novel large-scale aqueous synthesis of CIGS phase-pure nanoparticles with tetragonal chalcopyrite structure, uniform chemical composition, and excellent optical properties. Nanoparticles for innovative photocatalytic degradation of CIP contaminant.
Mapping the protonation states of the histidine brace in an AA10 lytic polysaccharide monooxygenase using CW-EPR spectroscopy and DFT calculations
Authors: Lindley Peter J. , Parkin Alison , Davies Gideon J. , Walton Paul H.
Published: November 2021

Using a combination of CW-EPR X-band spectroscopy and DFT calculations, we show that the active site of a chitin-active AA10 lytic polysaccharide monooxygenase can exist in three different protonation states, representing the ionisation of the coordinating groups.