bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional Regulators of theGolli/Myelin Basic ProteinLocus Integrate Additive and Stealth Activities
Authors: Bagheri Hooman , Friedman Hana , Siminovitch Kathy , Peterson Alan 
Published: April 2020

ABSTRACTMyelin is composed of plasma membrane spirally wrapped around axons and compacted into dense sheaths by myelin associated proteins. In the central nervous system (CNS), myelin is elaborated by neuroepithelial derived oligodendrocytes and in the peripheral nervous system (PNS) by neural crest derived Schwann cells. While some myelin proteins are unique to only one lineage,myelin basic protein(Mbp) is expressed in both. Overlapping theMbpgene isGolli, a transcriptional unit that is expressed widely both within and beyond the nervous system. A super-enhancer domain within theGolli/Mbplocus contains multiple enhancers shown previously to drive reporter construct expression specifically in oligodendrocytes or Schwann cells. In order to determine the contribution of each enhancer to theGolli/Mbpexpression program and examine if interactions among these enhancers occur, we derived mouse lines in which enhancers were deleted, either singly or in different combinations, and relative mRNA accumulation was measured at key stages of development. Although super-enhancers have been shown to facilitate interaction among their component enhancers, the enhancers investigated here demonstrated functions that were largely additive. However, enhancers demonstrating autonomous activity strictly in one cell lineage, when missing, were found to significantly reduce output in the other thus revealing cryptic “stealth” activity. Further,Golliaccumulation in all cell types investigated was markedly and uniformly attenuated by the absence of a key oligodendrocyte enhancer. Our observations expose a novel level of enhancer interaction and are consistent with a model in which enhancer-mediated DNA looping underlies higher-orderGolli/Mbpregulatory organization.AUTHOR SUMMARYThe control of transcription is mediated through regulatory sequences that engage in a lineage and developmentally contextual manner. TheGolli/Mbplocus gives rise to several mRNAs and whileMbpmRNAs accumulate exclusively in the two glial cell types that elaborate myelin,GollimRNAs accumulate in diverse cell types both within and beyond the nervous system. To determine how the differentGolli/Mbpenhancers distribute their activities and to reveal if they operate as autonomous agents or have functionally significant interactions with each other we derived multiple enhancer knock-out lines. Comparing the developmental accumulation ofMbpandGollimRNAs revealed that the autonomous targeting capacity of multiple enhancers accurately predicted their in-situ contributions. Also, they acted in a largely additive manner indicating significant individual autonomy that can be accounted for by a simple chromatin looping model. Unexpectedly, we also uncovered cryptic “stealth” activity emanating from these same enhancers in lineages where they show no autonomous targeting capacity thus providing new insight into the control of lineage specific gene expression.
PhANNs, a fast and accurate tool and web server to classify phage structural proteins
Authors: Cantu Vito Adrian , Salamon Peter , Seguritan Victor , Redfield Jackson , Salamon David , Edwards Robert A. , Segall Anca M. 
Published: April 2020

AbstractFor any given bacteriophage genome or phage sequences in metagenomic data sets, we are unable to assign a function to 50-90% of genes. Structural protein-encoding genes constitute a large fraction of the average phage genome and are among the most divergent and difficult-to-identify genes using homology-based methods. To understand the functions encoded by phages, their contributions to their environments, and to help gauge their utility as potential phage therapy agents, we have developed a new approach to classify phage ORFs into ten major classes of structural proteins or into an “other” category. The resulting tool is named PhANNs (Phage Artificial Neural Networks). We built a database of 538,213 manually curated phage protein sequences that we split into eleven subsets (10 for cross-validation, one for testing) using a novel clustering method that ensures there are no homologous proteins between sets yet maintains the maximum sequence diversity for training. An Artificial Neural Network ensemble trained on features extracted from those sets reached a test F1-score of 0.875 and test accuracy of 86.2%. PhANNs can rapidly classify proteins into one of the ten classes, and non-phage proteins are classified as “other”, providing a new approach for functional annotation of phage proteins. PhANNs is open source and can be run from our web server or installed locally.Author SummaryBacteriophages (phages, viruses that infect bacteria) are the most abundant biological entity on Earth. They outnumber bacteria by a factor of ten. As phages are very different within them and from bacteria, and we have comparatively few phage genes in our database, we are unable to assign function to 50%-90% of phage genes. In this work, we developed PhANNs, a machine learning tool that can classify a phage gene as one of ten structural roles, or “other”. This approach does not require a similar gene to be known.
Cytotoxicity of the effector protein BteA was attenuated in Bordetella pertussis by insertion of an alanine residue
Authors: Bayram Jan , Malcova Ivana , Sinkovec Larisa , Holubova Jana , Streparola Gaia , Jurnecka David , Kucera Jan , Sedlacek Radislav , Sebo Peter , Kamanova Jana 
Published: April 2020

AbstractBordetella bronchisepticaandBordetella pertussisare closely related respiratory pathogens that evolved from a common bacterial ancestor. WhileB. bronchisepticahas an environmental reservoir and mostly establishes chronic infections in a broad range of mammals,B. pertussisis a human-specific pathogen causing acute pulmonary pertussis in infants and whooping cough illness in older humans. Both species employ a type III secretion system (T3SS) to inject a cytotoxic BteA effector protein into host cells. However, compared to the high BteA-mediated cytotoxicity ofB. bronchiseptica, the cytotoxicity induced byB. pertussisBteA (BpBteA) appears to be quite low and this has been attributed to the reduced T3SS gene expression inB. pertussis. We show that presence of an alanine residue inserted at position 503 (A503) ofBpBteA accounts for its strongly attenuated cytotoxic potency. Deletion of A503 fromBpBteA greatly enhanced the cytotoxic activity ofB. pertussisB1917 on mammalian HeLa cells and expression ofBpBteAΔA503 was highly toxic toSaccharomyces cerevisiaecells.Vice versa, insertion of A503 intoB. bronchisepticaBteA (BbBteA) strongly decreased its cytotoxicity to yeast and HeLa cells. Moreover, production ofBpBteAΔA503 increased virulence ofB. pertussisB1917 in the mouse model of intranasal infection (reduced LD50) but yielded less inflammatory pathology in infected mouse lungs at sublethal infectious doses. This suggests that A503 insertion in the T3SS effectorBpBteA may represent an evolutionary adaptation that fine-tunesB. pertussisvirulence and host immune response.Author summaryPertussis remains the least-controlled vaccine-preventable infectious disease and the mechanisms by whichBordetella pertussissubverts defense mechanisms of human airway mucosa remain poorly understood. We found thatB. pertussishad the cytotoxic activity of its type III secretion system-delivered effector BteA strongly attenuated by insertion of an alanine residue at position 503 as compared to the BteA homologue of the animal pathogenB. bronchiseptica. This functional adaptation reduced the capacity ofB. pertussisto suppress host inflammatory response and may contribute to an acute course of the pulmonary form of human infant pertussis.
LCM-seq identifies robust markers of vulnerable and resistant human midbrain dopamine neurons
Authors: Aguila Julio , Cheng Shangli , Kee Nigel , Cao Ming , Deng Qiaolin , Hedlund Eva 
Published: April 2020

ABSTRACTDefining transcriptional profiles of substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) dopamine neurons in human is critical to understanding their differential vulnerability in Parkinson Disease. However, reported marker profiles for these neuron populations are derived predominantly from rodents, utilize small sample sizes and display extensive variability between studies. Here, we map selective expression profiles of dopamine neurons in an extensive collection of human SNc and VTA using laser capture microdissection coupled with Smart-seq2 RNA sequencing (LCM-seq). By applying a bootstrapping strategy as sample input to DESeq2, we identify 33 differentially expressed SNc- or VTA-specific markers and we also compute the minimal cohort size required to identify differentially expressed genes (DEGs) that are concordant regardless of cohort size. Among the identified DEGs,ZCCHC12, CDH13andSERPINE2, are minimally required to distinguish SNc or VTA dopamine neurons in both human and mouse. In summary, our study identifies novel markers, besides previously identified ones, which will be instrumentsal for future studies aiming to modulate dopamine neuron resilience as well as validate cell identity of stem cell-derived dopamine neurons.
Proteins and Ions Compete for Membrane Interaction: the case of Lactadherin
Authors: De Lio A. M. , Paul D. , Jain R. , Morrissey J. H. , Pogorelov T. V. 
Published: April 2020

ABSTRACTCharged molecular species, such as ions, play a vital role in the life of the cell. In particular, divalent calcium ions (Ca2+) are critical for activating cellular membranes. Interactions between Ca2+and anionic phosphatidylserine (PS) lipids result in structural changes of the plasma membrane and are vital for many signaling pathways, such as the tightly regulated blood coagulation cascade. Upon cell damage, PS lipids are externalized to the outer leaflet, where they are not only exposed to Ca2+, but also to proteins. Lactadherin is a glycoprotein, important for cell-adhesion, that can act as an anticoagulant. While a number of experimental studies have been performed on lactadherin’s C2 domain’s (LactC2) binding affinity for PS molecules, an atomistic description of LactC2 interactions with PS lipids in the plasma membrane is lacking. We performed extensive all-atom molecular dynamics simulations of mixed lipid bilayers and experimental characterization of LactC2-membrane interactions in the presence and absence of Ca2+and characterized PS-Ca2+and PS-LactC2 interactions to guide our understanding of how these interactions initiate and impede blood coagulation, respectively. The captured spontaneously formed long-lived PS-Ca2+and PS-LactC2 complexes revealed that the protein side chains involved in PS-LactC2 interactions appear to be affected by the presence of Ca2+. The degree of LactC2 insertion into the lipid bilayer also appears to be dependent on the presence of Ca2+. Characterizing the interactions between Ca2+and LactC2 with PS lipids can lead to a greater understanding of the activation and regulation of the blood coagulation cascade and of the basis of charged species interactions with the lipid membrane.STATEMENT OF SIGNIFICANCELactadherin plays an important role in cellular signaling including blood coagulation. Many of these processes involve lactadherin interacting with the lipids of the cell plasma membrane. Lactadherin acts as an anticoagulant and contributes to a number of health issues. Understanding the interactions that drive lactadherin’s anticoagulant properties can lead to potential new drug targets.
Understanding cloud ERP continuance intention and individual performance: a TTF-driven perspective
Authors: Cheng Yung-Ming 
Published: April 2020

PurposeThis study's purpose is to propose a hybrid model based on expectation-confirmation model (ECM) and technology acceptance model (TAM) to examine whether organizational users' perceived task-technology fit (TTF) in cloud enterprise resource planning (ERP) as an antecedent to user beliefs can directly and indirectly affect their continuance intention of cloud ERP and individual performance.Design/methodology/approachSample data for this study were collected from end users of cloud ERP working in companies in Taiwan. A total of 500 questionnaires were distributed in the 50 sample companies, and 355 (71.0%) usable questionnaires were analyzed using structural equation modeling in this study.FindingsThis study showed that organizational users' perceived TTF contributed positively to their perceived usefulness, confirmation and perceived ease of use of cloud ERP, which in turn directly and indirectly led to their satisfaction with cloud ERP, continuance intention of cloud ERP and individual performance; that is, this study's findings strongly supported the research model integrating ECM, TAM and TTF model with all hypothesized links being significant.Originality/valueThis study contributes to an understanding of the TTF model in explaining organizational users' cloud ERP continuance intention that is difficult to explain with only their utilitarian perceptions of cloud ERP. Further, it is especially worth mentioning that this study places considerably more emphasis upon organizational users' individual performance greatly driven by their perceived TTF in cloud ERP and continuance intention of cloud ERP. Thus, this study's empirical evidence on incorporating ECM, TAM and TTF model can significantly enhance better understanding of the outcomes for cloud ERP continuance intention and shed light on the possible formulation of a richer post-adoption model.
Towards successful strategies to overcome BPR implementation issues: case of Sri Lanka
Authors: Fasna M.F.F. , Gunatilake Sachie 
Published: April 2020

PurposeCurrently, most of the organisations that undertake business process reengineering (BPR) projects with the intention of enhancing their business performance are encountering several issues throughout their endeavours. As these BPR implementation issues are perceived as one of the key contributory factors leading to BPR project failures, it is crucial to adopt timely strategies to overcome these issues. Hence, this study is focused on identifying the strategies to be adopted to overcome BPR implementation issues.Design/methodology/approachFour case studies were conducted in organisations that have successfully implemented BPR projects within last five years. In total, 14 semi-structured interviews were conducted among the different stakeholders who got involved in the selected BPR projects for identifying the issues faced and the strategies that they have adopted during their project implementation.FindingsStudy derived twenty-seven issues faced by the Sri Lankan organisations during different phases of BPR projects, and forty-five unique strategies to deal with these derived BPR implementation issues.Originality/valueThis study contributes to the field by exploring the issues in implementing BPR projects that should be given enough consideration to ensure the success of BPR projects in the Sri Lankan context along with the strategies to overcome the issues encountered throughout them. It is expected that the findings of this study would be useful in ensuring the success of future BPR projects.
Internationalisation business processes in an under-supported policy contexts: evidence from Italian SMEs
Authors: Jafari-Sadeghi Vahid , Dutta Dev K. , Ferraris Alberto , Del Giudice Manlio 
Published: April 2020

PurposeThe main objective of this research was to identify the key critical determinants of internationalisation business processes that entrepreneurs adopted in under-supported policy contexts.Design/methodology/approachThis research utilised a case-study design, incorporating multiple case examples, applying non-probability purposive selection criteria. A total of five in-depth, structured 90-min to two-hour case interviews were conducted with Italian entrepreneurs, in which four out of the five cases selected are goods-oriented, and one is services oriented.FindingsRegarding internal entrepreneurial motives, four crucial determinants were recognised: (1) Making more profit, (2) Expanding market, (3) Personal tendency to export and (4) Obtaining social respect. Regarding external networking capabilities, two key factors were identified: (1) Developing relationships with an international partner or representative and (2) Maintaining relationships with industry-relevant authorities.Research limitations/implicationsThe data gathered for this paper depends on self-announcing, expanding the likelihood of being one-sided for social desirability answers. The sample of research is also limited to small and medium businesses and has covered a limited number of companies.Originality/valueAn under-supported policy context forces international entrepreneurs to make their own arrangements and tailor their business process through personal initiative and interactions with network partners. Taking advantage of field-based data, this paper is probably one of the earliest research studies to identify several internal and external factors impacting on firm internationalisation business processes in the low policy support context for entrepreneurship.
Numerical simulation of Fisher's type equation via a collocation technique based on re-defined quintic B-splines
Authors: Dhiman Neeraj , Chauhan Amit , Tamsir Mohammad , Chauhan Anand 
Published: April 2020

PurposeA collocation technique based on re-defined quintic B-splines over Crank-Nicolson is presented to solve the Fisher's type equation. We take three cases of aforesaid equation. The stability analysis and rate of convergence are also done.Design/methodology/approachThe quintic B-splines are re-defined which are used for space integration. Taylor series expansion is applied for linearization of the nonlinear terms. The discretization of the problem gives up linear system of equations. A Gaussian elimination method is used to solve these systems.FindingsThree examples are taken for analysis. The analysis gives guarantee that the present method provides much better results than previously presented methods in literature. The stability analysis and rate of convergence show that the method is unconditionally stable and quadratic convergent for Fisher's type equation. Moreover, the present method is simple and easy to implement, so it may be considered as an alternative method to solve PDEs.Originality/valueThis work is the original work of authors which is neither published nor submitted anywhere else for publication.
Proteomic analysis of CHIKV‐infected human fibroblast‐like synoviocytes: Identification of host factors potentially associated with CHIKV replication and cellular pathogenesis
Authors: Sukkaew Apamas , Suksatu Ampa , Roytrakul Sittiruk , Smith Duncan R. , Ubol Sukathida 
Published: April 2020

AbstractChikungunya virus (CHIKV) is a mosquito‐borne virus that causes arthralgic fever. Fibroblast‐like synoviocytes play a key role in joint damage in inflammatory arthritides and can additionally serve as target cells for CHIKV infection. To gain a better understanding of CHIKV‐induced arthralgia, the interaction between CHIKV and synoviocytes was investigated at the protein level. A gel‐enhanced liquid chromatography‐mass spectrometry (GeLC‐MS/MS) approach was used to examine protein expression from primary human fibroblast‐like synoviocytes (HFLS) infected with clinical isolates of CHIKV at 12 and 24 hr post infection. Our analysis identified 259 and 241 proteins of known function that were differentially expressed (>1.5 or <−1.5 fold change) following CHIKV infection at 12 and 24 hpi, respectively. These proteins are involved in cellular homeostasis, including cellular trafficking, cytoskeletal organization, immune response, metabolic process, and protein modification. Some of these proteins have previously been reported to participate in arthralgia/arthritis and the death of infected cells. Our results provide information on the CHIKV‐induced modulation of cellular proteins of HFLS at an early stage of infection, as well as highlighting biological processes associated with CHIKV infection in the main target cells of the joint.
Responses and resilience of tallgrass prairie streams to patch‐burn grazing
Authors: Fulgoni Jessica N. , Whiles Matt R. , Dodds Walter K. , Larson Danelle M. , Jackson Karen E. , Grudzinski Bartosz P. 
Published: April 2020

Abstract

Patch‐burn grazing (PBG) can promote terrestrial heterogeneity and biodiversity, but can temporarily increase stream nutrients and ecosystem metabolism, and alter macroinvertebrate assemblages. The impacts of grazing on stream channel morphology and post‐PBG recovery patterns are unclear.

We assessed the influence of grazing in PBG managed grassland streams in Missouri, USA, and subsequent recovery when grazing ceased for 2 years. We hypothesized that grazing would degrade water quality, stream biotic integrity and channel morphology, but that riparian fencing would mitigate these effects. We predicted that biological and chemical variables in unfenced streams would return to pre‐PBG levels within 2 years after grazing ceased, but channel morphology would not.

Six small headwater streams (two in ungrazed control watersheds, two in PBG watersheds with 10 m fenced riparian zones and two in PBG unfenced) were sampled over 7 years; 2 years before PBG, 3 years during PBG and 2 years post‐PBG. We sampled macroinvertebrates and water chemistry monthly when water was present and surveyed channel morphology at least once each study period.

During grazing, unfenced watersheds showed the greatest changes in channel width, depth and area. During the post‐PBG period, one of the two unfenced watersheds showed partial recovery of channel morphology. Although grazing increased concentrations of nutrients and chlorophyll‐a, concentrations returned to pre‐PBG conditions after grazing ceased, indicating recovery. Very fine organic sediments increased in the unfenced watersheds compared to the control during grazing but recovered afterwards. Contributions of Chironomidae to total invertebrate abundance increased in the unfenced watersheds during grazing, and then decreased during the post‐PBG period.

Riparian fencing mostly mitigated effects of grazing on the streams. Unfenced streams were resilient to effects of grazing in a PBG managed grassland, with most metrics recovering within 2 years after grazing ceased, except for channel morphology.

Synthesis and applications. Grazing in a patch‐burn grazed managed grassland coupled with riparian fencing could be an effective conservation tool for land managers of prairies, with relatively modest influences on stream water quality and biotic integrity. Persistent changes in stream channel morphology and effects of longer periods of grazing deserve further research.