bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extended intergenic DNA contributes to neuron-specific expression of neighboring genes in the mammalian nervous system
Authors: Jaura Ravneet , Yeh Ssu-Yu , Montanera Kaitlin N. , Ialongo Alyssa , Anwar Zobia , Lu Yiming , Puwakdandawa Kavindu , Rhee Ho Sung 
Published: May 2022

AbstractMammalian genomes comprise largely intergenic noncoding DNA with numerous cis-regulatory elements. Whether and how the size of intergenic DNA affects gene expression in a tissue-specific manner remain unknown. Here we show that genes with extended intergenic regions are preferentially expressed in neural tissues but repressed in other tissues in mice and humans. Extended intergenic regions contain twice as many active enhancers in neural tissues compared to other tissues. Neural genes with extended intergenic regions are globally co-expressed with neighboring neural genes controlled by distinct enhancers in the shared intergenic regions. Moreover, generic neural genes expressed in multiple tissues have significantly longer intergenic regions than neural genes expressed in fewer tissues. The intergenic regions of the generic neural genes have many tissue-specific active enhancers containing distinct transcription factor binding sites specific to each neural tissue. We also show that genes with extended intergenic regions are enriched for neural genes only in vertebrates. The expansion of intergenic regions may reflect the regulatory complexity of tissue-type-specific gene expression in the nervous system.
Feasibility of whole genome and transcriptome profiling in pediatric and young adult cancers
Authors: Shukla N. , Levine M. F. , Gundem G. , Domenico D. , Spitzer B. , Bouvier N. , Arango-Ossa J. E. , Glodzik D. , Medina-Martínez J. S. , Bhanot U. , Gutiérrez-Abril J. , Zhou Y. , Fiala E. , Stockfisch E. , Li S. , Rodriguez-Sanchez M. I. , O’Donohue T. , Cobbs C. , Roehrl M. H. A. , Benhamida J. , Iglesias Cardenas F. , Ortiz M. , Kinnaman M. , Roberts S. , Ladanyi M. , Modak S. , Farouk-Sait S. , Slotkin E. , Karajannis M. A. , Dela Cruz F. , Glade Bender J. , Zehir A. , Viale A. , Walsh M. F. , Kung A. L. , Papaemmanuil E. 
Published: May 2022

AbstractThe utility of cancer whole genome and transcriptome sequencing (cWGTS) in oncology is increasingly recognized. However, implementation of cWGTS is challenged by the need to deliver results within clinically relevant timeframes, concerns about assay sensitivity, reporting and prioritization of findings. In a prospective research study we develop a workflow that reports comprehensive cWGTS results in 9 days. Comparison of cWGTS to diagnostic panel assays demonstrates the potential of cWGTS to capture all clinically reported mutations with comparable sensitivity in a single workflow. Benchmarking identifies a minimum of 80× as optimal depth for clinical WGS sequencing. Integration of germline, somatic DNA and RNA-seq data enable data-driven variant prioritization and reporting, with oncogenic findings reported in 54% more patients than standard of care. These results establish key technical considerations for the implementation of cWGTS as an integrated test in clinical oncology.
HDLBP binds ER-targeted mRNAs by multivalent interactions to promote protein synthesis of transmembrane and secreted proteins
Authors: Zinnall Ulrike , Milek Miha , Minia Igor , Vieira-Vieira Carlos H. , Müller Simon , Mastrobuoni Guido , Hazapis Orsalia-Georgia , Del Giudice Simone , Schwefel David , Bley Nadine , Voigt Franka , Chao Jeffrey A. , Kempa Stefan , Hüttelmaier Stefan , Selbach Matthias , Landthaler Markus 
Published: May 2022

AbstractThe biological role of RNA-binding proteins in the secretory pathway is not well established. Here, we describe that human HDLBP/Vigilin directly interacts with more than 80% of ER-localized mRNAs. PAR-CLIP analysis reveals that these transcripts represent high affinity HDLBP substrates and are specifically bound in their coding sequences (CDS), in contrast to CDS/3’UTR-bound cytosolic mRNAs. HDLBP crosslinks strongly to long CU-rich motifs, which frequently reside in CDS of ER-localized mRNAs and result in high affinity multivalent interactions. In addition to HDLBP-ncRNA interactome, quantification of HDLBP-proximal proteome confirms association with components of the translational apparatus and the signal recognition particle. Absence of HDLBP results in decreased translation efficiency of HDLBP target mRNAs, impaired protein synthesis and secretion in model cell lines, as well as decreased tumor growth in a lung cancer mouse model. These results highlight a general function for HDLBP in the translation of ER-localized mRNAs and its relevance for tumor progression.
Steering the reaction pathway of syngas-to-light olefins with coordination unsaturated sites of ZnGaOx spinel
Authors: Li Na , Zhu Yifeng , Jiao Feng , Pan Xiulian , Jiang Qike , Cai Jun , Li Yifan , Tong Wei , Xu Changqi , Qu Shengcheng , Bai Bing , Miao Dengyun , Liu Zhi , Bao Xinhe 
Published: May 2022

AbstractSignificant progress has been demonstrated in the development of bifunctional oxide-zeolite catalyst concept to tackle the selectivity challenge in syngas chemistry. Despite general recognition on the importance of defect sites of metal oxides for CO/H2 activation, the actual structure and catalytic roles are far from being well understood. We demonstrate here that syngas conversion can be steered along a highly active and selective pathway towards light olefins via ketene-acetate (acetyl) intermediates by the surface with coordination unsaturated metal species, oxygen vacancies and zinc vacancies over ZnGaOx spinel−SAPO-34 composites. It gives 75.6% light-olefins selectivity and 49.5% CO conversion. By contrast, spinel−SAPO-34 containing only a small amount of oxygen vacancies and zinc vacancies gives only 14.9% light olefins selectivity at 6.6% CO conversion under the same condition. These findings reveal the importance to tailor the structure of metal oxides with coordination unsaturated metal sites/oxygen vacancies in selectivity control within the oxide-zeolite framework for syngas conversion and being anticipated also for CO2 hydrogenation.
Structural basis for inhibition of the Cation-chloride cotransporter NKCC1 by the diuretic drug bumetanide
Authors: Zhao Yongxiang , Roy Kasturi , Vidossich Pietro , Cancedda Laura , De Vivo Marco , Forbush Biff , Cao Erhu 
Published: May 2022

AbstractCation-chloride cotransporters (CCCs) NKCC1 and NKCC2 catalyze electroneutral symport of 1 Na+, 1 K+, and 2 Cl−across cell membranes. NKCC1 mediates trans-epithelial Cl−secretion and regulates excitability of some neurons and NKCC2 is critical to renal salt reabsorption. Both transporters are inhibited by the so-called loop diuretics including bumetanide, and these drugs are a mainstay for treating edema and hypertension. Here, our single-particle electron cryo-microscopy structures supported by functional studies reveal an outward-facing conformation of NKCC1, showing bumetanide wedged into a pocket in the extracellular ion translocation pathway. Based on these and the previously published inward-facing structures, we define the translocation pathway and the conformational changes necessary for ion translocation. We also identify an NKCC1 dimer with separated transmembrane domains and extensive transmembrane and C-terminal domain interactions. We further define an N-terminal phosphoregulatory domain that interacts with the C-terminal domain, suggesting a mechanism whereby (de)phosphorylation regulates NKCC1 by tuning the strength of this domain association.
Autophagy regulation by RNA alternative splicing and implications in human diseases
Authors: González-Rodríguez Patricia , Klionsky Daniel J. , Joseph Bertrand 
Published: May 2022

AbstractAutophagy and RNA alternative splicing are two evolutionarily conserved processes involved in overlapping physiological and pathological processes. However, the extent of functional connection is not well defined. Here, we consider the role for alternative splicing and generation of autophagy-related gene isoforms in the regulation of autophagy in recent work. The impact of changes to the RNA alternative splicing machinery and production of alternative spliced isoforms on autophagy are reviewed with particular focus on disease relevance. The use of drugs targeting both alternative splicing and autophagy as well as the selective regulation of single autophagy-related protein isoforms, are considered as therapeutic strategies.
Ultra-compact snapshot spectral light-field imaging
Authors: Hua Xia , Wang Yujie , Wang Shuming , Zou Xiujuan , Zhou You , Li Lin , Yan Feng , Cao Xun , Xiao Shumin , Tsai Din Ping , Han Jiecai , Wang Zhenlin , Zhu Shining 
Published: May 2022

AbstractIdeal imaging, which is constantly pursued, requires the collection of all kinds of optical information of the objects in view, such as three-dimensional spatial information (3D) including the planar distribution and depth, and the colors, i.e., spectral information (1D). Although three-dimensional spatial imaging and spectral imaging have individually evolved rapidly, their straightforward combination is a cumbersome system, severely hindering the practical applications of four-dimensional (4D) imaging. Here, we demonstrate the ultra-compact spectral light-field imaging (SLIM) by using a transversely dispersive metalens array and a monochrome imaging sensor. With only one snapshot, the SLIM presents advanced imaging with a 4 nm spectral resolution and near-diffraction-limit spatial resolution. Consequently, visually indistinguishable objects and materials can be discriminated through SLIM, which promotes significant progress towards ideal plenoptic imaging.
Towards a microwave single-photon counter for searching axions
Authors: Pankratov A. L. , Revin L. S. , Gordeeva A. V. , Yablokov A. A. , Kuzmin L. S. , Il’ichev E. 
Published: May 2022

AbstractThe major task of detecting axions or axion-like particles has two challenges. On the one hand, the ultimate sensitivity is required, down to the energy of a single microwave photon of the yoctojoule range. On the other hand, since the detected events are supposed to be rare, the dark count rate of the detector must be extremely low. We show that this trade-off can be approached due to the peculiar switching dynamics of an underdamped Josephson junction in the phase diffusion regime. The detection of a few photons’ energy at 10 GHz with dark count time above 10 s and the efficiency close to unity was demonstrated. Further enhancements require a detailed investigation of the junction switching dynamics.
Safety and immunogenicity of four-segmented Rift Valley fever virus in the common marmoset
Authors: Wichgers Schreur Paul J. , Mooij Petra , Koopman Gerrit , Verstrepen Babs E. , Fagrouch Zahra , Mortier Daniella , van Driel Nikki , Kant Jet , van de Water Sandra , Bogers Willy M. , Punt Carine , van Keulen Lucien , Verschoor Ernst J. , Kortekaas Jeroen 
Published: May 2022

AbstractRift Valley fever virus (RVFV) is an emerging mosquito-borne bunyavirus that is highly pathogenic to wild and domesticated ruminants, camelids, and humans. While animals are exclusively infected via mosquito bites, humans can also be infected via contact with contaminated tissues or blood. No human vaccine is available and commercialized veterinary vaccines do not optimally combine efficacy with safety. We previously reported the development of two novel live-attenuated RVF vaccines, created by splitting the M genome segment and deleting the major virulence determinant NSs. The vaccine candidates, referred to as the veterinary vaccine vRVFV-4s and the human vaccine hRVFV-4s, were shown to induce protective immunity in multiple species after a single vaccination. Anticipating accidental exposure of humans to the veterinary vaccine and the application of hRVFV-4s to humans, the safety of each vaccine was evaluated in the most susceptible nonhuman primate model, the common marmoset (Callithrix jacchus). Marmosets were inoculated with high doses of each vaccine and were monitored for clinical signs as well as for vaccine virus dissemination, shedding, and spreading to the environment. To accurately assess the attenuation of both vaccine viruses, separate groups of marmosets were inoculated with the parent wild-type RVFV strains. Both wild-type strains induced high viremia and disseminated to primary target organs, associated with mild-to-severe morbidity. In contrast, both vaccines were well tolerated with no evidence of dissemination and shedding while inducing potent neutralizing antibody responses. The results of the studies support the unprecedented safety profile of both vaccines for animals and humans.
Therapeutic efficacy of an Ad26/MVA vaccine with SIV gp140 protein and vesatolimod in ART-suppressed rhesus macaques
Authors: Ventura John D. , Nkolola Joseph P. , Chandrashekar Abishek , Borducchi Erica N. , Liu Jinyan , Mercado Noe B. , Hope David L. , Giffin Victoria M. , McMahan Katherine , Geleziunas Romas , Murry Jeffrey P. , Yang Yunling , Lewis Mark G. , Pau Maria G. , Wegmann Frank , Schuitemaker Hanneke , Fray Emily J. , Kumar Mithra R. , Siliciano Janet D. , Siliciano Robert F. , Robb Merlin L. , Michael Nelson L. , Barouch Dan H. 
Published: May 2022

AbstractDeveloping an intervention that results in virologic control following discontinuation of antiretroviral therapy (ART) is a major objective of HIV-1 cure research. In this study, we investigated the therapeutic efficacy of a vaccine consisting of adenovirus serotype 26 (Ad26) and modified vaccinia Ankara (MVA) with or without an SIV Envelope (Env) gp140 protein with alum adjuvant in combination with the TLR7 agonist vesatolimod (GS-9620) in 36 ART-suppressed, SIVmac251-infected rhesus macaques. Ad26/MVA therapeutic vaccination led to robust humoral and cellular immune responses, and the Env protein boost increased antibody responses. Following discontinuation of ART, virologic control was observed in 5/12 animals in each vaccine group, compared with 0/12 animals in the sham control group. These data demonstrate therapeutic efficacy of Ad26/MVA vaccination with vesatolimod but no clear additional benefit of adding an Env protein boost. SIV-specific cellular immune responses correlated with virologic control. Our findings show partial efficacy of therapeutic vaccination following ART discontinuation in SIV-infected rhesus macaques.
MCM complexes are barriers that restrict cohesin-mediated loop extrusion
Authors: Dequeker Bart J. H. , Scherr Matthias J. , Brandão Hugo B. , Gassler Johanna , Powell Sean , Gaspar Imre , Flyamer Ilya M. , Lalic Aleksandar , Tang Wen , Stocsits Roman , Davidson Iain F. , Peters Jan-Michael , Duderstadt Karl E. , Mirny Leonid A. , Tachibana Kikuë 
Published: May 2022

AbstractEukaryotic genomes are compacted into loops and topologically associating domains (TADs)1–3, which contribute to transcription, recombination and genomic stability4,5. Cohesin extrudes DNA into loops that are thought to lengthen until CTCF boundaries are encountered6–12. Little is known about whether loop extrusion is impeded by DNA-bound machines. Here we show that the minichromosome maintenance (MCM) complex is a barrier that restricts loop extrusion in G1 phase. Single-nucleus Hi-C (high-resolution chromosome conformation capture) of mouse zygotes reveals that MCM loading reduces CTCF-anchored loops and decreases TAD boundary insulation, which suggests that loop extrusion is impeded before reaching CTCF. This effect extends to HCT116 cells, in which MCMs affect the number of CTCF-anchored loops and gene expression. Simulations suggest that MCMs are abundant, randomly positioned and partially permeable barriers. Single-molecule imaging shows that MCMs are physical barriers that frequently constrain cohesin translocation in vitro. Notably, chimeric yeast MCMs that contain a cohesin-interaction motif from human MCM3 induce cohesin pausing, indicating that MCMs are ‘active’ barriers with binding sites. These findings raise the possibility that cohesin can arrive by loop extrusion at MCMs, which determine the genomic sites at which sister chromatid cohesion is established. On the basis of in vivo, in silico and in vitro data, we conclude that distinct loop extrusion barriers shape the three-dimensional genome.
Limited cross-variant immunity from SARS-CoV-2 Omicron without vaccination
Authors: Suryawanshi Rahul K. , Chen Irene P. , Ma Tongcui , Syed Abdullah M. , Brazer Noah , Saldhi Prachi , Simoneau Camille R. , Ciling Alison , Khalid Mir M. , Sreekumar Bharath , Chen Pei-Yi , Kumar G. Renuka , Montano Mauricio , Gascon Ronne , Tsou Chia-Lin , Garcia-Knight Miguel A. , Sotomayor-Gonzalez Alicia , Servellita Venice , Gliwa Amelia , Nguyen Jenny , Silva Ines , Milbes Bilal , Kojima Noah , Hess Victoria , Shacreaw Maria , Lopez Lauren , Brobeck Matthew , Turner Fred , Soveg Frank W. , George Ashley F. , Fang Xiaohui , Maishan Mazharul , Matthay Michael , Morris Mary Kate , Wadford Debra , Hanson Carl , Greene Warner C. , Andino Raul , Spraggon Lee , Roan Nadia R. , Chiu Charles Y. , Doudna Jennifer A. , Ott Melanie 
Published: May 2022

AbstractSARS-CoV-2 Delta and Omicron are globally relevant variants of concern. Although individuals infected with Delta are at risk of developing severe lung disease, infection with Omicron often causes milder symptoms, especially in vaccinated individuals1,2. The question arises of whether widespread Omicron infections could lead to future cross-variant protection, accelerating the end of the pandemic. Here we show that without vaccination, infection with Omicron induces a limited humoral immune response in mice and humans. Sera from mice overexpressing the human ACE2 receptor and infected with Omicron neutralize only Omicron, but not other variants of concern, whereas broader cross-variant neutralization was observed after WA1 and Delta infections. Unlike WA1 and Delta, Omicron replicates to low levels in the lungs and brains of infected animals, leading to mild disease with reduced expression of pro-inflammatory cytokines and diminished activation of lung-resident T cells. Sera from individuals who were unvaccinated and infected with Omicron show the same limited neutralization of only Omicron itself. By contrast, Omicron breakthrough infections induce overall higher neutralization titres against all variants of concern. Our results demonstrate that Omicron infection enhances pre-existing immunity elicited by vaccines but, on its own, may not confer broad protection against non-Omicron variants in unvaccinated individuals.
A compilation of fecal microbiome shotgun metagenomics from hematopoietic cell transplantation patients
Authors: Yan Jinyuan , Liao Chen , Taylor Bradford P. , Fontana Emily , Amoretti Luigi A. , Wright Roberta J. , Littmann Eric R. , Dai Anqi , Waters Nicholas , Peled Jonathan U. , Taur Ying , Perales Miguel-Angel , Siranosian Benjamin A. , Bhatt Ami S. , van den Brink Marcel R. M. , Pamer Eric G. , Schluter Jonas , Xavier Joao B. 
Published: May 2022

AbstractHospitalized patients receiving hematopoietic cell transplants provide a unique opportunity to study the human gut microbiome. We previously compiled a large-scale longitudinal dataset of fecal microbiota and associated metadata, but we had limited that analysis to taxonomic composition of bacteria from 16S rRNA gene sequencing. Here we augment those data with shotgun metagenomics. The compilation amounts to a nested subset of 395 samples compiled from different studies at Memorial Sloan Kettering. Shotgun metagenomics describes the microbiome at the functional level, particularly in antimicrobial resistances and virulence factors. We provide accession numbers that link each sample to the paired-end sequencing files deposited in a public repository, which can be directly accessed by the online services of PATRIC to be analyzed without the users having to download or transfer the files. Then, we show how shotgun sequencing enables the assembly of genomes from metagenomic data. The new data, combined with the metadata published previously, enables new functional studies of the microbiomes of patients with cancer receiving bone marrow transplantation.
Work schedule and seasonal influences on sleep and fatigue in helicopter and fixed-wing aircraft operations in extreme environments
Authors: Fletcher Adam , Stewart Simon , Heathcote Karen , Page Peter , Dorrian Jillian 
Published: May 2022

AbstractSleep and fatigue were investigated in aviation search and rescue, firefighting, emergency medical services and offshore transfer operations in 210 participants, for 21 days each, across 17 datasets in seven countries. Sleep data were collected using wrist-worn actigraphs and sleep diaries. Sustained attention was assessed using a 5-min Psychomotor Vigilance Task (PVT). Duty information was provided from corporate IT systems. Despite the number of 24 h operations, most work occurred during daytime hours, and most sleep occurred at night. There were seasonal changes in work and sleep patterns, with naps used to augment total sleep time. The proportion of sleep occurring during duty varied from zero to 30%. Differences in PVT response times were trivial to small. Legislation that defines flight, duty time and minimum rest limits assume that sleep is not obtained during duty periods, apart from some napping under Fatigue Risk Management Systems (FRMS). However, especially in cases where the aviation service requires waiting for tasks (e.g. search and rescue, emergency medical response), this assumption may not always hold. FRMS should accommodate different modes of working that safely facilitate sleep during duty time where appropriate.
Impact of Bayesian penalized likelihood reconstruction on quantitative and qualitative aspects for pulmonary nodule detection in digital 2-[18F]FDG-PET/CT
Authors: Lohaus Niklas , Enderlin Florian , Skawran Stephan , Maurer Alexander , Abukwaik Ahmad M. A. , Franzen Daniel , Huellner Martin W. , Messerli Michael 
Published: May 2022

AbstractTo evaluate the impact of block sequential regularized expectation maximization (BSREM) reconstruction on quantitative and qualitative aspects of 2-[18F]FDG-avid pulmonary nodules compared to conventional ordered subset expectation maximization (OSEM) reconstruction method. Ninety-one patients with 144 2-[18F]FDG-avid pulmonary nodules (all ≤ 20 mm) undergoing PET/CT for oncological (re-)staging were retrospectively included. Quantitative parameters in BSREM and OSEM (including point spread function modelling) were measured, including maximum standardized uptake value (SUVmax). Nodule conspicuity in BSREM and OSEM images was evaluated by two readers. Wilcoxon matched pairs signed-rank test was used to compare quantitative and qualitative parameters in BSREM and OSEM. Pulmonary nodule SUVmax was significantly higher in BSREM images compared to OSEM images [BSREM 5.4 (1.2–20.7), OSEM 3.6 (0.7–17.4); p = 0.0001]. In a size-based analysis, the relative increase in SUVmax was more pronounced in smaller nodules (≤ 7 mm) as compared to larger nodules (8–10 mm, or > 10 mm). Lesion conspicuity was higher in BSREM than in OSEM (p < 0.0001). BSREM reconstruction results in a significant increase in SUVmax and a significantly improved conspicuity of small 2-[18F]FDG-avid pulmonary nodules compared to OSEM reconstruction. Digital 2-[18F]FDG-PET/CT reading may be enhanced with BSREM as small lesion conspicuity is improved.