bluuebunny/crossref_metadata_2025_split huggingface dataset:
The neuronal ceroid lipofuscinosis‐related protein CLN8 regulates endo‐lysosomal dynamics and dendritic morphology
Authors: Pesaola Favio , Quassollo Gonzalo , Venier Ana Clara , De Paul Ana Lucía , Noher Ines , Bisbal Mariano 
Published: May 2021

Background InformationThe endo‐lysosomal system (ELS) comprises a set of membranous organelles responsible for transporting intracellular and extracellular components within cells. Defects in lysosomal proteins usually affect a large variety of processes and underlie many diseases, most of them with a strong neuronal impact. Mutations in the endoplasmic reticulum‐resident CLN8 protein cause CLN8 disease. This condition is one of the 14 known neuronal ceroid lipofuscinoses (NCLs), a group of inherited diseases characterised by accumulation of lipofuscin‐like pigments within lysosomes. Besides mediating the transport of soluble lysosomal proteins, recent research suggested a role for CLN8 in the transport of vesicles and lipids, and autophagy. However, the consequences of CLN8 deficiency on ELS structure and activity, as well as the potential impact on neuronal development, remain poorly characterised. Therefore, we performed CLN8 knockdown in neuronal and non‐neuronal cell models to analyse structural, dynamic and functional changes in the ELS and to assess the impact of CLN8 deficiency on axodendritic development.ResultsCLN8 knockdown increased the size of the Golgi apparatus, the number of mobile vesicles and the speed of endo‐lysosomes. Using the fluorescent fusion protein mApple‐LAMP1‐pHluorin, we detected significant lysosomal alkalisation in CLN8‐deficient cells. In turn, experiments in primary rat hippocampal neurons showed that CLN8 deficiency decreased the complexity and size of the somatodendritic compartment.ConclusionsOur results suggest the participation of CLN8 in vesicular distribution, lysosomal pH and normal development of the dendritic tree. We speculate that the defects triggered by CLN8 deficiency on ELS structure and dynamics underlie morphological alterations in neurons, which ultimately lead to the characteristic neurodegeneration observed in this NCL.SignificanceThis is, to our knowledge, the first characterisation of the effects of CLN8 dysfunction on the structure and dynamics of the ELS. Moreover, our findings suggest a novel role for CLN8 in somatodendritic development, which may account at least in part for the neuropathological manifestations associated with CLN8 disease.
Specifying current physical therapy practice for paediatric trials: A survey of UK physical therapists
Authors: Duff Catherine J. , Kolehmainen Niina , McAnuff Jennifer 
Published: May 2021

AbstractBackgroundAdvancing physical therapy interventions for children and young people is a high research priority. This includes research to describe and specify the control condition, typically ‘current care’, for effectiveness trials.This paper aims to identify physical therapy outcomes commonly targeted, and intervention techniques and approaches commonly used, by physiotherapists working with children (aged 2–19 years) with mobility limitations in the United Kingdom.MethodsA cross‐sectional survey. Participants were recruited through the interactive Chartered Society of Physiotherapy members‐only online discussion forum, the Association of Paediatric Chartered Physiotherapists, direct emails and snowball sampling within the authors' professional networks and Twitter. Data were collected using a structured online questionnaire and analysed using descriptive statistics.ResultsWe received 146 responses, 95/146 (65.1%) of which were fully complete. Therapists reported targeting 367 unique outcome constructs, of which 193 (52.6%) mapped onto activities and participation (e.g. moving around using equipment, maintaining body position and walking), 158 (43.1%) on body functions (e.g. muscle strength, joint mobility and gait functions), 11 (3.0%) on body structure (e.g. muscle length) and 3 (0.8%) on environmental factors (e.g. access home environment, access school environment and family confidence). The most commonly used interventions related to postural management (115/133 of respondents, 86.4%) and exercise therapy (116/137, 84.67%) and included techniques such as ‘use equipment’ (118/137, 86.1%), ‘instruct how to do something’ (117/137, 85.4%), ‘practice’ (105/137, 76.6%) and ‘stretch’ (99/137, 72.3%).ConclusionsIn designing trials, current care can be described as a combination of biomechanical and physiological techniques and approaches targeted at body functions and through that to activity and participation. Although some environmental behaviour change techniques and strategies were reported, the explicit use of these in current care appears limited.
Anti-JMH alloantibody in inherited JMH-negative patients leads to immunogenic destruction of JMH-positive RBCs
Authors: Yuan Zhaohu , Wei Yaming , Chen Xiaojie , He Shufei , Cai Kui , Zhong Minglu , Huang Huiying , Tong Xinxin , Liu Zhen , Yang Xuexin 
Published: May 2021

SummaryThe clinical significance of the specific anti-John Milton Hagen (JMH) alloantibody in inherited JMH-negative patients remains unclear. During clinical blood transfusion, it is often classified as an anti-JMH autoantibody in acquired JMH-negative patients, which might further lead to the occurrence of haemolysis events. In this study, we found that the proportion of inherited JMH-negative people in the Guangzhou population was 0.41%, based on the study of 243 blood samples by flow cytometry. Gene sequencing analysis revealed two novel variants located in exon 11 (c.1348G&gt;A, p.Ala449Thr) and exon 14 (c.1989G&gt;T, p.Leu663Phe). Specific antigen presentation showed that JMH-positive RBCs (red blood cells) could be internalized by SEMA7A−/− dendritic cells (DCs) and that SEMA7A−/− DCs activated by the semaphorin 7a (Sema7a) protein or JMH-positive erythrocytes further induced activation of CD4+ T cells to secrete interferon (IFN)-γ. Transfusion of JMH-positive RBCs could lead to the production of the specific anti-JMH alloantibody in Sema7a knock-out (KO) C57 mice. After erythrocyte sensitization, complement C3 was specifically fixed, causing the destruction of JMH-positive erythrocytes. The anti-JMH alloantibody caused immunological destruction of JMH-positive erythrocytes and promoted the clearance of JMH-positive RBCs. We should be cautious when making conclusions about the clinical significance of the anti-JMH alloantibody.
Prognostic factors associated with unhealed perineal wounds post‐proctectomy for perianal Crohn's disease: a two‐centre study
Authors: Grant Rebecca K. , Elosua‐González Alfonso , Bouri Sonia , Sahnan Kapil , Brindle William M. , Dilke Stella M. , Vincent Matthew L. M. , Adegbola Samuel O. A. , Warusavitarne Janindra H. , Tozer Philip J. , Arnott Ian D. R. , Hart Ailsa L. 
Published: May 2021

AbstractAimThe aim of this work was to determine the factors associated with poor wound healing in patients with perianal Crohn's disease (pCD) who had undergone proctectomy in the era of biologic therapies.MethodCase record review was performed on 103 patients with pCD who underwent proctectomy at St Mark's Hospital, Harrow and the Western General Hospital, Edinburgh between 2005 and 2017. Healing rates at 6 and 12 months post‐proctectomy were considered; univariate analysis was performed.ResultsSixty out of 103 patients (58.3%) had failure of wound healing at 6 months and 41/103 (39.8%) at 12 months. In total, 63.1% (65/103) patients received biologic therapies prior to proctectomy; however, exposure to biologics was not a significant factor in predicting failure of wound healing at 12 months (infliximab p = 0.255; adalimumab p = 0.889; vedolizumab p = 0.153). Male gender was the only variable associated with poor wound healing at 12 months on univariate analysis (p = 0.017). A lower pre‐operative C‐reactive protein was associated with early wound healing at 6 months compared with at 12 months (p = 0.041) on univariate analysis. Other parameters not associated with rates of wound healing included smoking status, corticosteroid exposure, thiopurine exposure, number of previous biologics, perianal sepsis on MRI within the last 12 months, duration of CD prior to proctectomy and pre‐operative albumin.ConclusionMore than a third of patients had unhealed wounds 12 months after proctectomy. We report that unhealed wounds are more common in male patients. Importantly, our results also suggest that exposure to biologics does not affect rates of wound healing.
FAIMCS: A fast and accurate influence maximization algorithm in social networks based on community structures
Authors: Bagheri Esmaeil , Dastghaibyfard Gholamhossein , Hamzeh Ali 
Published: May 2021

AbstractFinding a number of nodes that are able to maximize the spread of influence through the social network and are called influence maximization has numerous applications in marketing. One such application is to find influential members for promoting a product across a large network. Even though numerous algorithms have been proposed, challenges such as scalability, time constraints, and low accuracy have motivated the researchers for better solutions. Some of the newly proposed algorithms are scalable, but fail to provide adequate accuracy. On the other hand, some greedy algorithms provide a good level of accuracy but are very time consuming for large networks. In this paper, an algorithm is proposed called FAIMCS that can quickly find influential nodes across large networks with high accuracy. FAIMCS, reduces computational overhead considerably by eliminating major portions of the social network graph which have little influence. FAIMCS uses community detection algorithm to determine each community's quota of influential nodes based on the structure of that community. Finally, it obtains influential nodes from the candidate nodes. Experiment results show FAIMCS is faster than current algorithms and provides a high level of accuracy for large social networks.
A novel mouse model for liver metastasis of prostate cancer reveals dynamic tumour‐immune cell communication
Authors: Liu Kaiyuan , Jing Na , Wang Deng , Xu Penghui , Wang Jinming , Chen Xinyu , Cheng Chaping , Xin Zhixiang , He Yuman , Zhao Huifang , Ji ZhongZhong , Zhang Pengcheng , Gao Wei‐Qiang , Zhu Helen He , Zhang Kai 
Published: May 2021

AbstractObjectivesIn contrast to extensive studies on bone metastasis in advanced prostate cancer (PCa), liver metastasis has been under‐researched so far. In order to decipher molecular and cellular mechanisms underpinning liver metastasis of advanced PCa, we develop a rapid and immune sufficient mouse model for liver metastasis of PCa via orthotopic injection of organoids from PbCre+; rb1f/f;p53f/f mice.Materials and MethodsPbCre+;rb1f/f;p53f/f and PbCre+;ptenf/f;p53f/f mice were used to generate PCa organoid cultures in vitro. Immune sufficient liver metastasis models were established via orthotopic transplantation of organoids into the prostate of C57BL/6 mice. Immunofluorescent and immunohistochemical staining were performed to characterize the lineage profile in primary tumour and organoid‐derived tumour (ODT). The growth of niche‐labelling reporter infected ODT can be visualized by bioluminescent imaging system. Immune cells that communicated with tumour cells in the liver metastatic niche were determined by flow cytometry.ResultsA PCa liver metastasis model with full penetrance is established in immune‐intact mouse. This model reconstitutes the histological and lineage features of original tumours and reveals dynamic tumour‐immune cell communication in liver metastatic foci. Our results suggest that a lack of CD8+ T cell and an enrichment of CD163+ M2‐like macrophage as well as PD1+CD4+ T cell contribute to an immuno‐suppressive microenvironment of PCa liver metastasis.ConclusionsOur model can be served as a reliable tool for analysis of the molecular pathogenesis and tumour‐immune cell crosstalk in liver metastasis of PCa, and might be used as a valuable in vivo model for therapy development.
Genome stabilization by RAD51‐stimulatory compound 1 enhances efficiency of somatic cell nuclear transfer‐mediated reprogramming and full‐term development of cloned mouse embryos
Authors: Lee Ah Reum , Park Ji‐Hoon , Shim Sung Han , Hong Kwonho , La Hyeonwoo , Park Kyung‐Soon , Lee Dong Ryul 
Published: May 2021

AbstractObjectivesThe genetic instability and DNA damage arise during transcription factor‐mediated reprogramming of somatic cells, and its efficiency may be reduced due to abnormal chromatin remodelling. The efficiency in somatic cell nuclear transfer (SCNT)‐mediated reprogramming is also very low, and it is caused by development arrest of most reconstituted embryos.Materials and MethodsWhether the repair of genetic instability or double‐strand breaks (DSBs) during SCNT reprogramming may play an important role in embryonic development, we observed and analysed the effect of Rad 51, a key modulator of DNA damage response (DDR) in SCNT‐derived embryos.ResultsHere, we observed that the activity of Rad 51 is lower in SCNT eggs than in conventional IVF and found a significantly lower level of DSBs in SCNT embryos during reprogramming. To address this difference, supplementation with RS‐1, an activator of Rad51, during the activation of SCNT embryos can increase RAD51 expression and DSB foci and thereby increased the efficiency of SCNT reprogramming. Through subsequent single‐cell RNA‐seq analysis, we observed the reactivation of a large number of genes that were not expressed in SCNT‐2‐cell embryos by the upregulation of DDR, which may be related to overcoming the developmental block. Additionally, there may be an independent pathway involving histone demethylase that can reduce reprograming‐resistance regions.ConclusionsThis technology can contribute to the production of comparable cell sources for regenerative medicine.
A call to assess the impacts of electromagnetic fields from subsea cables on the movement ecology of marine migrants
Authors: Klimley A. Peter , Putman Nathan F. , Keller Bryan, A. , Noakes David 
Published: May 2021

AbstractThe number of subsea cables in the marine environment is likely to grow substantially in the near future. Arrays of energy‐generating windmills or wave power generators are planned for installation in the coastal waters of many countries worldwide. The electricity generated by these and other marine energy sources will be transported to shore through cables with the current and voltage creating electromagnetic fields (EMFs). Furthermore, there are also plans for the installation of undersea cables to interconnect countries and islands for the purpose of sharing power and communications. These also will generate EMFs in the marine environment. While shielding can negate the presence of direct electric fields, induced electric and magnetic fields readily penetrate into the water column. Cables carrying electric current produce anomalies in the earth's main field, which could have the potential for disrupting the migrations of fishes and diverse marine animals that rely on magnetic cues for orientation or navigation. Studies designed to test how these anthropogenic magnetic fields disrupt magnetic orientation have only recently started to be conducted. Given the cultural, economic, and conservation value of many of the species potentially at risk, such work should be immediately prioritized.
Identifying gaps in protected areas to expand integrated riverine ecosystem conservation
Authors: Major James , Perry Denielle , Aslan Clare , McManamay Ryan 
Published: May 2021

AbstractAs demand for water in the arid southwest increases, pressure is mounting on many aquatic and riparian species that rely on riverine habitat for survival. Some of these riverine areas are managed as private, state, or federal lands with differing levels of mandated protections; however, few efforts have explored the potential of filling gaps in riverine protection afforded by designation under the protection of the Wild and Scenic Rivers Act (WSRA) of 1968. Here, we examine how inclusion of eligible rivers, specifically the Nationwide Rivers Inventory (NRI), could fill gaps in protection for a species of high conservation need. A gap analysis overlapping the predicted species range with human disturbances and the level of protection identifies where sufficient protections for a species exist and where there are shortcomings, that is, gaps, potentially addressed by elevating NRI reaches to WSRA protection. This study uses the narrow‐headed garter snake as an indicator species for riverine ecosystem health of free‐flowing perennial reaches within the Arizona/New Mexico Mountains EPA Level III ecoregion. Over a quarter of NRI‐eligible reaches within the ecoregion are within the protection gap for the narrow‐headed garter snake. If designated Wild and Scenic, these reaches could offer needed protection for this species.
Aberrant cytoplasmic connexin43 expression as a helpful marker in vascular neoplasms
Authors: Frings Verena Gerlinde , Goebeler Matthias , Schilling Bastian , Kneitz Hermann 
Published: May 2021

AbstractBackgroundGap junctions consisting of connexins (Cx) are fundamental in controlling cell proliferation, differentiation, and cell death. Cx43 is the most broadly expressed Cx in humans and is attributed an important role in skin tumor development. Its role in cutaneous vascular neoplasms is yet unknown.MethodsFifteen cases each of cutaneous angiosarcoma (cAS), Kaposi sarcoma (KS), and cherry hemangioma (CH) were assessed by immunohistochemistry for expression of Cx43. Expression pattern, intensity, and percentage of positively stained cells were analyzed. Solid basal cell carcinomas served as positive and healthy skin as negative controls.ResultsMost cases of cAS presented with a strong Cx43 staining of almost all tumor cells, whereas endothelia of KS showed medium expression and CH showed mostly weak expression. In comparison with KS or cAS, the staining intensity of CH was significantly lower (P ≤ 0.001). All tissue sections of both cAS and KS were characterized by a mostly diffuse, cytoplasmic staining pattern of the vascular endothelia. None of those showed nuclear staining.ConclusionThe high‐to‐intermediate expression of Cx43 observed in all cases of cAS and KS suggests that this Cx may play a role in the development of malignant vascular neoplasms and serve as a helpful diagnostic marker.
Uncertainty in the modelled mortality of two tree species (Fraxinus) under novel climatic regimes
Authors: Steiner Kim C. , Graboski Lake E. , Berkebile Jennifer L. , Fei Songlin , Leites Laura P. 
Published: May 2021

AbstractAimBased upon species distribution models (SDMs), many studies have predicted that climate change will cause regional extinctions of tree species within the next 50–100 years. SDM‐based predictions have been challenged on procedural and theoretical grounds, but for tree species they are largely beyond the practical reach of direct experimental validation. Here we report the experimental consequences of moving seedlings from ~50 natural populations of each of two ash (Fraxinus) species to experimental sites spanning a range of 10°C colder to 10°C warmer (mean annual temperature) than home environments.LocationEastern North America.MethodsWe measured population‐by‐test‐site survival percentages and mean trunk diameters at an average age of 35 years. We then used linear, mixed‐effect models to develop transfer functions for each species and predict survival and mean annual growth as functions of fixed and random effects including, especially, the climatic distance (CD) between test site and home environment.ResultsSurvival and growth were highest at CD ≈ 0 and declined as populations were moved to warmer or colder environments, indicating that survival and growth were optimal when populations were in home‐like climates. However, variance around the model fit was substantial, and we could not statistically detect, even at α = .50, elevated mortality following displacements into environments 3.5°C (white ash) and 4.1°C (green ash) warmer in mean annual temperature. Survival rates of 80%–100% were common even within populations subjected to warming conditions greater than those predicted to cause meso‐scale extinctions in this century. We show that within‐population genetic variance, phenotypic plasticity and idiosyncratic aspects of the non‐climatic environment and its interaction with genotype each likely contributed to these unexpected responses to climatic displacement.Main conclusionsResults emphasize the uncertainty that underlies predictions of climate‐induced extinctions of long‐lived woody plants over time frames of 50 to perhaps 100 years into the future.
Acoustic stimulation increases implicit adaptation in sensorimotor adaptation
Authors: Leow Li‐Ann , Tresilian James R. , Uchida Aya , Koester Dirk , Spingler Tamara , Riek Stephan , Marinovic Welber 
Published: May 2021

AbstractSensorimotor adaptation is an important part of our ability to perform novel motor tasks (i.e., learning of motor skills). Efforts to improve adaptation in healthy and clinical patients using non‐invasive brain stimulation methods have been hindered by inter‐individual and intra‐individual variability in brain susceptibility to stimulation. Here, we explore unpredictable loud acoustic stimulation as an alternative method of modulating brain excitability to improve sensorimotor adaptation. In two experiments, participants moved a cursor towards targets, and adapted to a 30º rotation of cursor feedback, either with or without unpredictable acoustic stimulation. Acoustic stimulation improved initial adaptation to sensory prediction errors in Study 1, and improved overnight retention of adaptation in Study 2. Unpredictable loud acoustic stimulation might thus be a potent method of modulating sensorimotor adaptation in healthy adults.
The effects of psychosocial stress on item, cued‐pair and emotional memory
Authors: McManus Elizabeth , Talmi Deborah , Haroon Hamied , Muhlert Nils 
Published: May 2021

AbstractPhysical stress, such as from the cold‐pressor test, has been robustly associated with altered memory retrieval, but it is less clear whether the same happens following psychosocial stress. Studies using psychosocial stressors report mixed effects on memory, leading to uncertainty about the common cognitive impact of both forms of stress. The current study uses a series of four carefully designed experiments, each differing by only a single critical factor to determine the effects of psychosocial stress on specific aspects of episodic memory. In three experiments, we induced psychosocial stress after participants encoded words, then assessed retrieval of those words after a prolonged delay. These experiments found no effect of post‐encoding stress on recognition of neutral words or cued recall of word‐pairs, but a small effect on recollection of semantically related words. There were, however, positive relationships within the stress group between measures of stress (cortisol in experiment 1 and self‐reported‐anxiety in experiment 3) and recollection of single word stimuli. In the fourth experiment, we found that psychosocial stress immediately before retrieval did not influence word recognition. Recollection, particularly for semantically related stimuli, may therefore be more susceptible to the effects of psychosocial stress, and future studies can assess how this relates to other forms of stress. Overall, our findings suggest that the effects of psychosocial stress on episodic memory may be more subtle than expected, warranting further exploration in larger studies.