bluuebunny/crossref_metadata_2025_split huggingface dataset:
N-cadherin-Presented Slit Repulsive-Cues Direct Collective Schwann cell Migration
Authors: Hoving Julian J.A , Harford-Wright Elizabeth , Wingfield-Digby Patrick , Cattin Anne-Laure , Campana Mariana , Morgan Toby , Quereda Victor , Torchiaro Erica , Lloyd Alison C. 
Published: February 2019

AbstractCollective cell migration is fundamental for the development of organisms and in the adult, for tissue regeneration and in pathological conditions such as cancer. Migration as a coherent group requires the maintenance of cell-cell interactions, while contact-inhibition-of-locomotion (CIL), a local repulsive force, propels the group forward. Here we show that the cell-cell interaction molecule, N-cadherin, regulates both adhesion and repulsion processes during Schwann cell collective migration, which is required for peripheral nerve regeneration. However, distinct from its role in cell-cell adhesion, the repulsion process is independent of N-cadherin trans-homodimerisation and the associated adherens junction complex. Rather, the extracellular domain of N-cadherin acts to traffic a repulsive Slit2/Slit3 signal to the cell-surface. Inhibiting Slit2/Slit3 signalling inhibits CIL and subsequently collective SC migration, resulting in adherent, non-migratory cell clusters. These findings provide insight into how opposing signals can mediate collective cell migration and how CIL pathways are promising targets for inhibiting pathological cell migration.
Isolation of cardiomyocytes undergoing mitosis with complete cytokinesis
Authors: Milliron Hsiao-yun Y. , Weiland Matthew J. , Kort Eric J. , Jovinge Stefan 
Published: February 2019

AbstractRationale-Adult human cardiomyocytes (CMs) do not complete cytokinesis despite passing through the S-phase of the cell cycle. As a result polyploidization and multinucleation occur. In order to get a deeper understanding of the mechanisms surrounding division of CMs there is a crucial need for a technique to isolate CMs that complete cell division/cytokinesis.Objective-Markers of cell cycle progression based on DNA content cannot distinguish between mitotic CMs that fail to complete cytokinesis from those cells that undergo true cell division. With the use of molecular beacons (MB) targeting specific mRNAs we aimed to identify truly proliferative CMs derived from hiPSCs.Methods and Results-Fluorescence activated cell-sorting combined with molecular beacons was performed to sort CM populations enriched for mitotic cells. Expressions of cell-cycle specific genes were confirmed by means of RT-qPCR, single-cell RNA sequencing (scRNA-seq). We further characterized the sorted groups by proliferation assays and time-lapse microscopy which confirmed the proliferative advantage of MB-positive cell populations relative to MB-negative and G2/M populations. Gene expression analysis revealed that the MB-positive CM subpopulation exhibited patterns consistent with the biological processes of nuclear division, chromosome segregation, and transition from M to G1 phase. The use of dual-MBs targeting CDC20 and SPG20 mRNAs (CDC20+SPG20+) enabled the enrichment of cytokinetic events. Interestingly, cells that did not complete cytokinesis and remained binucleated were found to be CDC20−SPG20+ while polyploid CMs that replicated DNA but failed to complete karyokinesis were found to be CDC20−SPG20−.Conclusions-This study demonstrates a novel alternative to existing DNA content-based approaches for sorting CMs with true mitotic potential that can be used to study in detail the unique dynamics of CM nuclei during mitosis. Together with high-throughput scRNA-seq, our technique for sorting live CMs undergoing cytokinesis would provide a basis for future studies to uncover mechanisms underlying the development and regeneration of heart tissue.
Unpacking conditional neutrality: genomic signatures of selection on conditionally beneficial and conditionally deleterious mutations
Authors: Mee Jonathan A. , Yeaman Samuel 
Published: February 2019

AbstractIt is common to look for signatures of local adaptation in genomes by identifying loci with extreme levels of allele frequency divergence among populations. This approach to finding genes associated with local adaptation often assumes antagonistic pleiotropy, wherein alternative alleles are strongly favoured in alternative environments. Conditional neutrality has been proposed as an alternative to antagonistic pleiotropy, but conditionally neutral polymorphisms are transient and it is unclear how much outlier signal would be maintained under different forms of conditional neutrality. Here, we use individual-based simulations and a simple analytical heuristic to show that a pattern that mimics local adaptation at the phenotypic level, where each genotype has the highest fitness in its home environment, can be produced by the accumulation of mutations that are neutral in their home environment and deleterious in non-local environments. Because conditionally deleterious mutations likely arise at a rate many times higher than conditionally beneficial mutations, they can have a significant cumulative effect on fitness even when individual effect sizes are small. We show that conditionally deleterious mutations driving non-local maladaptation may be undetectable by even the most powerful genome scans, as differences in allele frequency between populations are typically small. We also explore the evolutionary effects of conditionally-beneficial mutations and find that they can maintain significant signals of local adaptation, and they would be more readily detectable than conditionally deleterious mutations using conventional genome scan approaches. We discuss implications for interpreting outcomes of transplant experiments and genome scans that are used to study the genetic basis of local adaptation.
Linear Input as a Fundamental Motif of Brain Connectivity Organization
Authors: O’Rawe Jonathan F. , Leung Hoi-Chung 
Published: February 2019

AbstractDescribing the pattern of region-to-region functional connectivity is an important step towards understanding information transfer and transformation between brain regions. Although fMRI data are limited in spatial resolution, recent advances in technology afford more precise mapping. Here, we extended previous methods, connective field mapping, to 3 dimensions to provide a more concise estimate of the organization and potential information transformation from one region to another. We first replicated previous work with the 3 dimensional model by showing that the topology of functional connectivity between early visual regions maintained along their eccentricity axis or the anterior-posterior dimension. We then examined higher order visual regions (e,g, fusiform face area) and showed that their pattern of connectivity, the convergence and biased sampling, seem to contribute to some of their core receptive field properties. We further demonstrated that linearity of input is a fundamental aspect of functional connectivity of the whole brain, with higher linearity between regions within a network than across networks; that is, high connective linearity was evident between early visual areas, and between prefrontal areas, but less evident between them. By decomposing the whole brain linearity matrix with manifold learning techniques, we found that the principle mode of the linearity maps onto decompositions in both functional connectivity and genetic expression reported in previous studies. The current work provides evidence supporting that linearity of input is likely a fundamental motif of functional connectivity between regions for information processing across the brain, with high linearity preserving the integrity of information from one region to another within a network.
Urinary glucocorticoids in harbour seal (Phoca vitulina) pups during rehabilitation
Authors: Wilson Susan C. , Villanueva Stella , Jones Kayleigh A. , Hayes William , Dmitrieva Lilia , Smyth Wesley 
Published: February 2019

ABSTRACTThe glucocorticoid (GC) hormone cortisol is often measured in animals to indicate their welfare and stress levels. However, the levels of other naturally occurring GCs are usually overlooked. We aimed to investigate whether aspects of the care and conditions of harbour seal (Phoca vitulina) pups in rehabilitation centres are reflected in urinary concentrations of four endogenous GCs. Urine samples were collected non-invasively from pups taken in as “orphans” at five different rehabilitation centres: three on the Irish Sea and two in the southern North Sea. Concentrations of urinary cortisol, cortisone, prednisolone and prednisone were analysed by mass spectrometry. Urinary concentrations of endogenous prednisolone and prednisone occurred in similar magnitude to cortisol, for the first time in any mammal species. The levels of all GC concentrations decreased as pups gained mass, but the most significant effect was for prednisone. Pups with mass less than 11kg, i.e. healthy average birth mass, had significantly higher levels of prednisone (but not of the other GCs) than pups of 11kg or more. Cortisol, cortisone and prednisolone concentrations were slightly higher for pups without access to water than those with water; however, we found no significant effect of social group on GC levels. Based on these findings, we tentatively suggest that the GCs may be elevated in harbour seal pups during rehabilitation in response to some physiological factors deviating from the norm of free-living pups. Our findings highlight the importance of measuring other GCs, in addition to cortisol, for understanding stressors affecting the welfare of seal pup in rehabilitation.
Propagating patterns of activity across motor cortex facilitate movement initiation
Authors: Balasubramanian Karthikeyan , Papadourakis Vasileios , Liang Wei , Takahashi Kazutaka , Best Matt , Suminski Aaron J. , Hatsopoulos Nicholas G. 
Published: February 2019

AbstractVoluntary movement initiation involves the modulation of neurons in the primary motor cortex (M1) around movement onset. Yet, similar modulations of M1 activity occur during movement planning when no movement occurs. Here, we show that a sequential spatio-temporal pattern of excitability based on beta oscillation amplitude attenuation propagates across M1 prior to the initiation of reaching movements in one of two oppositely oriented directions along the rostro-caudal axis. Using spatiotemporal patterns of intracortical microstimulation, we find that reaction time increases significantly when stimulation is delivered against but not with the natural propagation orientation suggesting that movement initiation requires a precise recruitment pattern in M1. Functional connections among M1 units emerge at movement onset that are oriented along the same rostro-caudal axis but not during movement planning. Finally, we show that beta amplitude profiles can more accurately decode muscle activity when these patterns conform to the natural propagating patterns. These findings provide the first causal evidence that large-scale, spatially organized propagating patterns of cortical excitability and activity are behaviorally relevant and may be a necessary component of movement initiation.
Single cell profiling of the VMH reveals a sexually dimorphic regulatory node of energy expenditure
Authors: van Veen J. Edward , Kammel Laura G. , Bunda Patricia C. , Shum Michael , Reid Michelle S. , Park Jae W. , Zhang Zhi , Massa Megan G. , Arneson Douglas , Hrncir Haley , Liesa Marc , Arnold Arthur P. , Yang Xia , Correa Stephanie M. 
Published: February 2019

AbstractEstrogen signaling in the central nervous system promotes weight loss by increasing thermogenesis and physical activity in the ventromedial hypothalamus (VMH), but the precise neuronal populations regulating these aspects of energy expenditure remain unclear. Here we define the molecular and functional heterogeneity of the VMH using single cell RNA sequencing, in situ hybridization, chemogenetic activation, and targeted gene knockdown. We describe six molecularly distinct neuron clusters in the VMH. In females, estrogen receptor alpha (ERα) is restricted to neurons expressing tachykinin-1 (Tac1) or reprimo (Rprm). Further, Tac1 and Rprm expression is enriched in females, a sex difference that is established by permanent effects of gonadal hormones early in life. Finally, while Tac1 ablation selectively impairs movement, here we show that silencing Rprm selectively dysregulates temperature without affecting physical activity. Together this work provides a novel architectural framework whereby distinct and sexually differentiated neuron populations within the VMH mediate sex-specific aspects of metabolic homeostasis.
Unmatched level of molecular convergence among deeply divergent complex multicellular fungi
Authors: Merényi Zsolt , Prasanna Arun N. , Zheng Wang , Kovács Károly , Hegedüs Botond , Bálint Balázs , Papp Balázs , Townsend Jeffrey P. , Nagy László G. 
Published: February 2019

AbstractConvergent evolution is pervasive in nature, but it is poorly understood how various constraints and natural selection limit the diversity of evolvable phenotypes. Here, we report that, despite >650 million years of divergence, the same genes have repeatedly been co-opted for the development of complex multicellularity in the two largest clades of fungi—the Ascomycota and Basidiomycota. Co-opted genes have undergone duplications in both clades, resulting in >81% convergence across shared multicellularity-related families. This convergence is coupled with a rich repertoire of multicellularity-related genes in ancestors that predate complex multicellular fungi, suggesting that the coding capacity of early fungal genomes was well suited for the repeated evolution of complex multicellularity. Our work suggests that evolution may be predictable not only when organisms are closely related or are under similar selection pressures, but also if the genome biases the potential evolutionary trajectories organisms can take, even across large phylogenetic distances.
Visible light-triggered NO generation from Naphthalimide-based probe for photoreceptor-mediated plant root growth regulation
Authors: Biswas Suprakash , Upadhyay Neha , Kar Debojyoti , Datta Sourav , Koner Apurba Lal 
Published: February 2019

ABSTRACTAn efficient visible light-triggered nitric oxide (NO) releasing fluorescent molecule is designed and synthesized by coupling 2,6-dimethyl nitrobenzene moiety at the peri-position of 1, 8-naphthalimide through an alkene bond. The NO-releasing ability is investigated in details using various spectroscopic techniques, and the photoproduct was also characterized. Further, the photo-generated NO has been employed to examine the effect of photoreceptor-mediated NO uptake on plant root growth regulation.
Spatio-temporal dynamics of face perception
Authors: Muukkonen I. , Ölander K. , Numminen J. , Salmela V.R. 
Published: February 2019

AbstractThe temporal and spatial neural processing of faces have been studied rigorously, but few studies have unified these dimensions to reveal the spatio-temporal dynamics postulated by the models of face processing. We used support vector machine decoding and representational similarity analysis to combine information from different locations (fMRI), timepoints (EEG), and theoretical models. By correlating information matrices derived from pair-wise decodings of neural responses to different facial expressions (neutral, happy, fearful, angry), we found early EEG timepoints (110-150 ms) to match fMRI data from early visual cortex (EVC), and later timepoints (170 – 250 ms) to match data from occipital and fusiform face areas (OFA/FFA) and posterior superior temporal sulcus (pSTS). The earliest correlations were driven by information from happy faces, and the later by more accurate decoding of fearful and angry faces. Model comparisons revealed systematic changes along the processing hierarchy, from emotional distance and visual feature coding in EVC to coding of intensity of expressions in right pSTS. The results highlight the importance of multimodal approach for understanding functional roles of different brain regions.
An orthogonal c-Cbl recognition mode targets LynA for rapid degradation and builds specificity into the LynA checkpoint
Authors: Brian Ben F. , Nunez Myra G. , Schwertfeger Kathryn L. , Freedman Tanya S. 
Published: February 2019

AbstractThe activity of Src-family kinases (SFKs), which phosphorylate immunoreceptor tyrosine-based activation motifs (ITAMs), is critical factor regulating myeloid-cell activation. In a previous paper (Freedman et al., 2015) we showed in macrophages that the SFK LynA is uniquely susceptible to rapid ubiquitin-mediated degradation, functioning as a rheostat regulating ITAM signaling. We now report the mechanism by which LynA is preferentially targeted for degradation and how cell specificity is built into the LynA rheostat. Using genetic and biochemical analysis, we found that the E3 ubiquitin ligase c-Cbl preferentially targets LynA via tyrosine 32 in its unique insert region. This orthogonal mode of c-Cbl recognition depresses the steady-state level of macrophage LynA. Mast cells, however, express little c-Cbl and have correspondingly high steady-state levels of LynA. Upon activation, mast-cell LynA is not rapidly degraded, and SFK-mediated signaling is amplified relative to macrophages. Cell-specific c-Cbl expression therefore builds cell specificity into the LynA checkpoint.
Social Instability is an Effective Chronic Stress Paradigm for both Male and Female Mice
Authors: Yohn Christine N. , Ashamalla Sandra A. , Bokka Leshya , Gergues Mark M. , Garino Alexander , Samuels Benjamin A. 
Published: February 2019

ABSTRACTDespite stress-associated disorders having a higher incidence rate in females, preclinical research mainly focuses on males. Chronic stress paradigms, such as chronic social defeat and chronic corticosterone administration, were mainly designed and validated in males and subsequent attempts to use these paradigms in females has demonstrated sex differences in the behavioral and HPA axis response to stress. Here, we developed a social stress paradigm, social instability stress (SIS), which exposes adult mice to unstable social hierarchies for 7 weeks. SIS effectively induces negative valence behaviors and hypothalamus-pituitary-adrenal (HPA) axis activation in both males and females. Importantly, while there were effects of estrous cycle on behavior, this variability did not impact the overall effects of SIS on behavior, suggesting estrous does not need to be tracked while utilizing SIS. Furthermore, the effects of SIS on negative valence behaviors were also reversed following chronic antidepressant treatment with fluoxetine (FLX) in both males and females. SIS also reduced adult hippocampal neurogenesis in female mice, while chronic FLX treatment increased adult hippocampal neurogenesis in both males and females. Overall, these data demonstrate that the SIS paradigm is an ethologically valid approach that effectively induces chronic stress in both adult male and adult female mice.
Preparation and corrosion resistance of titanium-zirconium/nickel-coated carbon nanotubes chemical nano-composite conversion coatings
Authors: Wang Xiaobo , Li Zhipeng , Zhan Wen , Tu Jesong , Zuo Xiaohua , Deng Xiangyi , Gui Boyi 
Published: February 2019

Purpose
This study aims to expand the reliability and special functions of lightweight materials for high-end equipment and green manufacturing, so that it is the first such research to carry out nano-composite technology of nickel-coated carbon nanotubes (Ni-CNTs)-based titanium-zirconium chemical conversion on aluminum alloy substrate.

Design/methodology/approach
Corrosion behavior of various coatings was investigated using dropping corrosion test, linear polarization and electrochemical impedance spectroscopy. The results showed that the corrosion resistance of the nano-composite conversion coatings was significantly improved to compare with the conventional titanium-zirconium conversion coating. The morphology and microdomain characteristics of the nano-composite conversion coatings were characterized by SEM/eds/EPMA, which indicated that the CNT or Ni-CNTs addition promoting the integrity coverage of coatings in a short time.

Findings
Surface morphology of titanium-zirconium (Ti-Zr)/Ni-CNT specimens exhibited smooth, compact and little pores. The nano-composite conversion coatings are mainly composed of Al, O, C and Ti elements and contain a small amount of F and Zr elements, which illuminated that CNT or Ni-CNT addition could co-deposit with aluminum and titanium metal oxides.

Originality/value
The study of corrosion resistance of nano-composite conversion coatings and the micro-zone film-formation characteristics would be provided theoretical support for the development of basic research on surface treatment of aluminum alloys.
The tinnitus patient information pack: usefulness in intrusive tinnitus
Authors: Hassaan Amro , Trinidade Aaron 
Published: February 2019

Purpose
The purpose of this paper is to determine a tinnitus patient information pack’s (TPIP) usefulness in patients suffering with tinnitus with respect to their need for further tinnitus retraining therapy (TRT) and in reducing TRT cancellations and non-attenders.

Design/methodology/approach
The paper consists of prospective case series in a district general hospital ENT out-patient department.

Findings
Patients with tinnitus-related symptoms constitute around 2 per cent of the ENT OPD workload at the West Middlesex Hospital, Chelsea & Westminster NHS Trust, London, i.e., 365 patients with intrusive tinnitus were referred by the ENT surgeon for TRT; 56/365 patients (15.3 per cent) failed to attend and 60 (16.4 per cent) cancelled their appointments. The following year, a TPIP was administered to all tinnitus sufferers, despite the affliction’s intrusiveness, and told to contact the audiology department if they felt that TRT was required, which resulted in 43/233 patients (18.5 per cent) over a one-year period self-referring for TRT; 2/233 (0.9 per cent) did not attend, and 1/233 (0.4 per cent) were cancelled appointments.

Practical implications
The patient-focussed TPIP acts as an initial therapy for the tinnitus sufferer by providing reassurance and self-therapy. This results in patients who are less likely to seek TRT, leading to more efficient clinical resource usage (p<0.01).

Originality/value
The data suggest that all tinnitus sufferers presenting to ENT clinics could be handed a TPIP and empowered with the decision whether they require further intervention.
Adherence to surgical antimicrobial prophylaxis: “checking-the-box” is not enough
Authors: Karamchandani Kunal , Barden Kyle , Prozesky Jansie 
Published: February 2019

Purpose
The purpose of this paper is to review surgical antimicrobial prophylaxis administration practices in a small cohort and assess compliance with national guidelines.

Design/methodology/approach
Patients that developed surgical site infections (SSI) in a tertiary care academic medical center over a two-year period were identified. Their electronic medical records were reviewed for compliance with national guidelines with respect to surgical antibiotic prophylaxis.

Findings
Over a two-year period, 283 SSI patients were identified. An appropriate antibiotic was chosen in 80 percent, an appropriate dose was administered in 45 percent and timing complied in 89 percent. The antibiotics were appropriately re-dosed in only 9.2 percent in whom the requirement was met. The prescribing guidelines were adhered to in entirety in only 54 patients (23.8 percent).

Practical implications
Timely and appropriate antibiotic administration prior to surgery is essential to prevent SSI. Proper diligence is required to accomplish this task effectively.

Originality/value
Based on the findings, it appears that merely, “checking a box” for antibiotic administration during surgery is not enough, and a multidisciplinary approach should be followed to ensure “appropriate” antibiotic administration.