bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the flux of high-energy cosmogenic neutrinos and the influence of the extragalactic magnetic field
Authors: Wittkowski David , Kampert Karl-Heinz 
Published: June 2019

ABSTRACT
Cosmogenic neutrinos originate from interactions of cosmic rays propagating through the universe with cosmic background photons. Since both high-energy cosmic rays and cosmic background photons exist, the existence of high-energy cosmogenic neutrinos is certain. However, their flux has not been measured so far. Therefore, we calculated the flux of high-energy cosmogenic neutrinos arriving at the Earth on the basis of elaborate 4D simulations that take into account three spatial degrees of freedom and the cosmological time-evolution of the universe. Our predictions for this neutrino flux are consistent with the recent upper limits obtained from large-scale cosmic-ray experiments. We also show that the extragalactic magnetic field has a strong influence on the neutrino flux. The results of this work are important for the design of future neutrino observatories, since they allow to assess the detector volume and observation time that are necessary to detect high-energy cosmogenic neutrinos in the near future. An observation of such neutrinos would push multimessenger astronomy to hitherto unachieved energy scales.
Molossops temminckii (Chiroptera: Molossidae)
Authors: Gamboa Alurralde Santiago , Díaz M Mónica 
Published: June 2019

AbstractThe dwarf dog-faced bat, Molossops temminckii (Burmeister, 1854), is a small molossid bat that occurs from Colombia, Venezuela, and Guyana, southwestward through Ecuador, Peru, Bolivia, Paraguay, Brazil, Uruguay, and Argentina. It is one of two species in the genus Molossops and usually roosts in man-made structures, rock crevices, and hollow trees. The species is insectivorous, inhabits a variety of habitats, and is typically found in low altitude zones. Diagnostic characters include triangular ears separated by a wide space, one lower incisor in each ramus, and a last upper molar with three clearly marked commissures. Molossops temminckii is listed as “Least Concern” by the International Union for Conservation of Nature and Natural Resources.
Extreme divergence between one-to-one orthologs: the structure of N15 Cro bound to operator DNA and its relationship to the λ Cro complex
Authors: Hall Branwen M , Roberts Sue A , Cordes Matthew H J 
Published: June 2019

Abstract
The gene cro promotes lytic growth of phages through binding of Cro protein dimers to regulatory DNA sites. Most Cro proteins are one-to-one orthologs, yet their sequence, structure and binding site sequences are quite divergent across lambdoid phages. We report the cocrystal structure of bacteriophage N15 Cro with a symmetric consensus site. We contrast this complex with an orthologous structure from phage λ, which has a dissimilar binding site sequence and a Cro protein that is highly divergent in sequence, dimerization interface and protein fold. The N15 Cro complex has less DNA bending and smaller DNA-induced changes in protein structure. N15 Cro makes fewer direct contacts and hydrogen bonds to bases, relying mostly on water-mediated and Van der Waals contacts to recognize the sequence. The recognition helices of N15 Cro and λ Cro make mostly nonhomologous and nonanalogous contacts. Interface alignment scores show that half-site binding geometries of N15 Cro and λ Cro are less similar to each other than to distantly related CI repressors. Despite this divergence, the Cro family shows several code-like protein–DNA sequence covariations. In some cases, orthologous genes can achieve a similar biological function using very different specific molecular interactions.
Retrosigmoid Transtentorial Resection of a Petroclival Meningioma: 2-Dimensional Operative Video
Authors: Eser Ocak Pinar , Yilmazlar Selcuk 
Published: June 2019

Abstract
In this video, we aimed to demonstrate retrosigmoid-transtentorial resection of a 4.5 × 4 × 4.5 cm3 left-sided petroclival meningioma compressing the brainstem in a 62-yr-old male who presented with decreased hearing on the left and imbalance.
The patient was placed in park-bench position and a left-sided suboccipital craniotomy was performed. The mass was severely compressing the brainstem as well as the cranial nerves V, VI, VII, and VIII while IV was encased by the tumor. The circumferential dissection of the tumor was facilitated while the surgical corridor and exposure were enlarged by incising the tentorium. Uneventfully, the meningioma was resected in piecemeal fashion as it was not coming out easily with the ultrasonic aspirator. All relevant cranial nerves and adjacent vascular structures were protected. Early postoperative CT scan demonstrated changes due to the surgery and resolution of the compression on the brainstem. The patient made excellent recovery and he was discharged home on postoperative day 4 safely.
Petroclival meningiomas are one of the most challenging tumors for neurosurgeons due to their close proximity to the vascular structures, cranial nerves as well as the brainstem. The retrosigmoid approach provides a direct route during microsurgical resection of these tumors. By incising the tentorium, the corridor can be widened while addressing the supratentorial portion of the tumor with relative ease.
A possible solution to the Hubble constant discrepancy: Cosmology where the local volume expansion is driven by the domain average density
Authors: Kasai Masumi , Futamase Toshifumi 
Published: June 2019

Abstract
The Hubble constant problem is the discrepancy between different measurements of the Hubble constant on different scales. We show that this problem can be resolved within the general relativistic framework of the perturbation theory in the inhomogeneous universe, with the help of a spatial averaging procedure over a finite local domain in the $t={\rm{const.}}$ hypersurface. The idea presented in this paper is unique in the sense that it has all of the following properties. a) It is based on the general relativistic perturbation theory, with ordinary dust matter only. No strange matter nor energy components are required. b) The employment of the spatially invariant averaging procedure on the finite domain is essential. c) The key is the first-order effect of the inhomogeneities in the linear perturbation theory. No nonlinear effects are required.
Recognizing and Effectively Managing Hypermobility-Related Conditions
Authors: Russek Leslie N , Stott Patricia , Simmonds Jane 
Published: June 2019

Abstract
Hypermobility spectrum disorder (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS) can cause widespread or chronic pain, fatigue, and proprioceptive and coordination deficits resulting in functional restrictions. These conditions are common and often unrecognized, and patients are likely to present in physical therapy for musculoskeletal injuries, pain, or coordination deficits. Although physical therapy is considered central to managing these conditions, many patients report pain and iatrogenic injuries due to inappropriate interventions. The diagnostic classification for these conditions was revised in 2017 to supersede previous diagnostic categories of Joint Hypermobility Syndrome and Ehlers-Danlos Syndrome—hypermobility type/type III. It is now known that these conditions affect multiple body systems and not just joints and that patients require a holistic approach. This Perspective article will describe the 2017 diagnostic classification system, clinical presentation, examination, evaluation, and management of patients with HSD/hEDS. Both adult and pediatric cases are presented to illustrate the patient management concepts discussed. This knowledge can lead to more effective management of this patient population.
The Central Role of Protein Kinase C Epsilon in Cyanide Cardiotoxicity and Its Treatment
Authors: Cheung Joseph Y , Merali Salim , Wang JuFang , Zhang Xue-Qian , Song Jianliang , Merali Carmen , Tomar Dhanendra , You Hanning , Judenherc-Haouzi Annick , Haouzi Philippe 
Published: June 2019

Abstract
In adult mouse myocytes, brief exposure to sodium cyanide (CN) in the presence of glucose does not decrease ATP levels, yet produces profound reduction in contractility, intracellular Ca2+ concentration ([Ca2+]i) transient and L-type Ca2+ current (ICa) amplitudes. We analyzed proteomes from myocytes exposed to CN, focusing on ionic currents associated with excitation-contraction coupling. CN induced phosphorylation of α1c subunit of L-type Ca2+ channel and α2 subunit of Na+-K+-ATPase. Methylene blue (MB), a CN antidote that we previously reported to ameliorate CN-induced reduction in contraction, [Ca2+]i transient and ICa amplitudes, was able to reverse this phosphorylation. CN decreased Na+-K+-ATPase current contributed by α2 but not α1 subunit, an effect that was also counteracted by MB. Peptide consensus sequences suggested CN-induced phosphorylation was mediated by protein kinase C epsilon (PKCε). Indeed, CN stimulated PKC kinase activity and induced PKCε membrane translocation, effects that were prevented by MB. Pretreatment with myristoylated PKCε translocation activator or inhibitor peptides mimicked and inhibited the effects of CN on ICa and myocyte contraction, respectively. We conclude that CN activates PKCε, which phosphorylates L-type Ca2+ channel and Na+-K+-ATPase, resulting in depressed cardiac contractility. We hypothesize that this inhibition of ion fluxes represents a novel mechanism by which the cardiomyocyte reduces its ATP demand (decreased ion fluxes and contractility), diminishes ATP turnover and preserves cell viability. However, this cellular protective effect translates into life-threatening cardiogenic shock in vivo, thereby creating a profound disconnect between survival mechanisms at the cardiomyocyte level from those at the level of the whole organism.
Aggressive interactions affect foraging and use of space in a drift foraging salmonid, Salvelinus malma (Salmoniformes: Salmonidae)
Authors: Cullen Jeffrey L , Grossman Gary D 
Published: June 2019

Abstract
Although intraspecific interactions likely affect habitat choice and foraging behaviour in animals, our knowledge regarding how these factors interact is frequently limited to either lab or field studies, but not both. We observed pairs of dominant and subordinate drift-foraging Dolly Varden char (Salvelinus malma) in an Alaskan stream, and quantified intraspecific interactions and foraging behaviour. Dominant individuals had higher foraging rates, occupied slower holding velocities and were displaced shorter distances during bouts compared to subordinate individuals. Individuals initiated bouts more frequently from the downstream position, than from lateral or upstream positions. Dominant individuals were more likely to occupy the upstream position after a bout than subordinates, which ensures that dominants have the first opportunity to capture drifting prey.
Taxonomic and phylogenetic review of Necrosuchus ionensis (Alligatoroidea: Caimaninae) and the early evolution and radiation of caimanines
Authors: Cidade Giovanne M , Fortier Daniel , Hsiou Annie S 
Published: June 2019

Abstract
Alligatoroidea is the most species-rich crocodylomorph clade of the Cenozoic of South America, with nearly all species belonging to the Caimaninae clade. However, the earliest records of Caimaninae in South America, which are from the Palaeocene, are based mostly on incomplete specimens, which increases the importance of detailed taxonomic and phylogenetic studies on these taxa. This paper offers a taxonomic and phylogenetic review of Necrosuchus ionensis, a caimanine species from the Salamanca Formation of the Palaeocene of Argentina. Necrosuchus ionensis is considered a valid species, albeit with a different diagnosis from that proposed by previous authors. The phylogenetic analysis shows, for the first time, that N. ionensis belongs to the derived Caimaninae clade Jacarea. However, a better understanding of the Jacarea clade is needed, and alternative placements for N. ionensis might be considered. Nevertheless, the placement of N. ionensis as a derived caimanine raises interesting perspectives on the early evolution and radiation of caimanines, which are thoroughly discussed in this paper together with other results obtained in this study, such as the recovery of the North American caimanines Bottosaurus and Tsoabichi as a clade.
Polycomb contraction differentially regulates terminal human hematopoietic differentiation programs
Authors: Lorzadeh A. , Hammond C. , Wang F. , Knapp D.J.H.F. , Wong J.CH. , Zhu J.Y.A , Cao Q. , Heravi-Moussavi A. , Carles A. , Wong M. , Sharafian Z. , Moksa M. , Bilenky M. , Lavoie P.M. , Eaves C.J. , Hirst M. 
Published: June 2019

AbstractLifelong production of the many types of mature blood cells from less differentiated progenitors is a hierarchically ordered process that spans multiple cell divisions. The nature and timing of the molecular events required to integrate the environmental signals, transcription factor activity, epigenetic modifications, and changes in gene expression involved are thus complex and still poorly understood. We now show that the more primitive types of human cells in this system display a unique repressive H3K27me3 signature that is retained by mature lymphoid cells but is lost in terminally differentiated monocytes and erythroblasts. Additional intervention data implicate that control of this chromatin state change is a requisite part of the process, whereby normal human hematopoietic progenitor cells make lymphoid and myeloid fate decisions.
Not just BLAST nt: WGS database joins the party
Authors: Martí Jose Manuel , Garay Carlos P. 
Published: June 2019

AbstractSince its introduction in 1990 and with over 50k citations, the NCBI BLAST family has been an essential tool of in silico molecular biology. The BLAST nt database, based on the traditional divisions of GenBank, has been the default and most comprehensive database for nucleotide BLAST searches and for taxonomic classification software in metagenomics. Here we argue that this is no longer the case. Currently, the NCBI WGS database contains one billion reads (almost five times more than GenBank), and with 4.4 trillion nucleotides, WGS has about 14 times more nucleotides than GenBank. This ratio is growing with time. We advocate a change in the database paradigm in taxonomic classification by systematically combining the nt and WGS databases in order to boost taxonomic classifiers sensitivity. We present here a case in which, by adding WGS data, we obtained over five times more classified reads and with a higher confidence score. To facilitate the adoption of this approach, we provide the draftGenomes script.Author summaryCulture-independent methods are revolutionizing biology. The NIH/NCBI Basic Local Alignment Search Tool (BLAST) is one of the most widely used methods in computational biology. The BLAST nt database has become a de facto standard for taxonomic classifiers in metagenomics. We believe that it is time for a change in the database paradigm for such a classification. We advocate the systematic combination of the BLAST nt database with genomes of the massive NCBI Whole-Genome Shotgun (WGS) database. We make draftGenomes available, a script that eases the adoption of this approach. Current developments and technologies make it feasible now. Our recent results in several metagenomic projects indicate that this strategy boosts the sensitivity in taxonomic classifications.
HER2 Cancer Protrusion Growth Signaling Regulated by Unhindered, Localized Filopodial Dynamics
Authors: Lam Wai Yan , Wang Yi , Mostofian Barmak , Jorgens Danielle , Kwon Sunjong , Chin Koei , Carpenter M. Alexandra , Jacob Thomas , Heiser Katie , Agrawal Anurag , Wang Jing , Nan Xiaolin , Chang Young Hwan , Zuckerman Daniel M. , Gray Joe , Bruchez Marcel , Lidke Keith A. , Vu Tania Q. 
Published: June 2019

AbstractProtrusions are plasma membrane extensions that are found in almost every cell in the human body. Cancer cell filopodial and lamellipodial protrusions play key roles in the integral processes of cell motility and signaling underlying tumor invasion and metastasis. HER2 (ErbB-2) is overexpressed in diverse types of tumors and regulates PI3K-pathway-mediated protrusion growth. It is known that HER2 resides at breast cancer cell protrusions, but how protrusion-based HER2 spatiotemporal dynamics shape cancer signaling is unclear. Here, we study how HER2 location and motion regulate protrusion signaling and growth using quantitative spatio-temporal molecular imaging approaches. Our data highlight morphologically-segregated features of filopodial and lamellipodial protrusions, in in vitro 2D breast cancer cells and in vivo intact breast tumor. Functional-segregation parallels morphological-segregation, as HER2 and its activated downstream pAKT-PI3K signaling remain spatially-localized at protrusions, provoking new protrusion growth proximal to sites of HER2 activation. HER2 in SKBR3 breast cancer cell filopodia exhibits fast, linearly-directed motion that is distinct from lamellipodia and non-protrusion subcellular regions (∼3-4 times greater diffusion constant, rapid speeds of 2-3 um2/s). Surprisingly, filopodial HER2 motion is passive, requiring no active energy sources. Moreover, while HER2 motion in lamellipodia and non-protrusion regions show hindered diffusion typical of membrane proteins, HER2 diffuses freely within filopodia. We conclude that HER2 activation, propagation, and functional protrusion growth is a local process in which filopodia have evolved to exploit Brownian thermal fluctuations within a barrier-free nanostructure to transduce rapid signaling. These results support the importance of developing filopodia and other protrusion-targeted strategies for cancer.
Pharmacological enrichment of polygenic risk for precision medicine in complex disorders
Authors: Reay William R. , Atkins Joshua R. , Carr Vaughan J. , Green Melissa J. , Cairns Murray J. 
Published: June 2019

ABSTRACTIndividuals with complex disorders typically have a heritable burden of common variation that can be expressed as a polygenic risk score (PRS). While PRS has some predictive utility, it lacks the molecular specificity to be directly informative for clinical interventions. We therefore sought to develop a framework to quantify an individual’s common variant enrichment in clinically actionable systems responsive to existing drugs. This was achieved with a metric designated the pharmagenic enrichment score (PES), which we demonstrate for individual SNP profiles in a cohort of cases with schizophrenia. A large proportion of these had elevated PES in one or more of eight clinically actionable gene-sets enriched with schizophrenia associated common variation. Notable candidates targeting these pathways included vitamins, insulin modulating agents, and protein kinase inhibitors with putative neuroprotective properties. Interestingly, elevated PES was also observed in individuals with otherwise low common variant burden. The biological saliency of PES profiles were observed directly through their impact on gene expression in a subset of the cohort with matched transcriptomic data, supporting our assertion that this framework can integrate an individual’s common variant risk to inform personalised interventions, including drug repositioning, for complex disorders such as schizophrenia.
Mesenchymal-Epithelial Transition Regulates Initiation of Pluripotency Exit before Gastrulation
Authors: Hamidi Sofiane , Nakaya Yukiko , Nagai Hiroki , Alev Cantas , Kasukawa Takeya , Chhabra Sapna , Lee Ruda , Niwa Hitoshi , Warmflash Aryeh , Shibata Tatsuo , Sheng Guojun 
Published: June 2019

ABSTRACTThe pluripotent epiblast gives rise to all tissues and organs in an adult body. Its differentiation starts at gastrulation when the epiblast generates mesoderm and endoderm germ layers through a process called epithelial-mesenchymal transition (EMT). Although gastrulation EMT coincides with loss of epiblast pluripotency, pluripotent cells in development and in vitro can adopt either mesenchymal or epithelial morphology. The relationship between epiblast’s cellular morphology and its pluripotency is not well understood. In this work, using chicken epiblast and mammalian pluripotency stem cell (PSC) models, we show that PSCs undergo a mesenchymal-epithelial transition (MET) prior to EMT-associated pluripotency loss. Epiblast MET and its subsequent EMT are two distinct processes. The former, a partial MET, is associated with reversible initiation of pluripotency exit; whereas the latter, a full EMT, is associated with complete and irreversible pluripotency loss. We provide evidence that integrin-mediated cell-matrix interaction is a key player in pluripotency exit regulation. We propose that epiblast partial MET is an evolutionarily conserved process among all amniotic vertebrates and its developmental function is to mediate planar symmetry-breaking within an epithelialized epiblast, taking place after epiblast MET but before gastrulation EMT.
Patch-DCA: Improved Protein Interface Prediction by utilizing Structural Information and Clustering DCA scores
Authors: Vajdi Amir , Zarringhalam Kourosh , Haspel Nurit 
Published: June 2019

AbstractOver the past decade there have been impressive advances in determining the 3D structures of protein complexes. However, there are still many complexes with unknown structures, even when the structures of the individual proteins are known. The advent of protein sequence information provides an opportunity to leverage evolutionary information to enhance the accuracy of protein-protein interface prediction. To this end, several statistical and machine learning methods have been proposed. In particular, direct coupling analysis has recently emerged as a promising approach for identification of protein contact maps from sequential information. However, the ability of these methods to detect protein-protein inter-residue contacts remains relatively limited.In this work, we propose a method to integrate sequential and co-evolution information with structural and functional information to increase the performance of protein-protein interface prediction. Further, we present a post-processing clustering method that improves the average relative F1 score by 70 % and 24 % and the precision by 80 % and 36 % in comparison with two state-of-the-art methods PSICOV and GREMLIN.