bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultrastructural identification and molecular characterization of two new parabasalid species that naturally colonize laboratory mice,Tritrichomonas musculusandTritrichomonas casperi
Authors: Tuzlak Leila , Alves-Ferreira Eliza V.C. , Kennard Andrea , Shehata Christina , Schwartz Cindi L. , Grigg Michael E. 
Published: January 2023

ABSTRACTTritrichomonas murisis a flagellated protist isolated from the cecum of wild mice in the Czech Republic. This commensal protist has been shown previously to alter immune phenotypes in laboratory mice. Other trichomonads, previously referred to asTritrichomonas musculisandTritrichomonas rainier, also naturally colonize laboratory mice and cause immune alterations. This report formally describes two new trichomonads,Tritrichomonas musculusn. sp., andTritrichomonas casperin. sp., at the ultrastructural and molecular level. These two protists were isolated from laboratory mice, and were differentiated by their size and the structure of their undulating membrane and posterior flagellum. Analysis at the18S rRNAand trans-ITSgenetic loci supported their designation as distinct species, related toT. muris. To further assess the true extent of parabasalid diversity infecting laboratory mice, 135 mice were screened at the NIH using pan-parabasalid primers that amplify the trans-ITSregion. Forty-four percent of mice were positive for parabasalids, encompassing a total of 8 distinct sequence types.Tritrichomonas casperiandTrichomitus-like protists were dominant.T. musculusandT. rainierwere also detected, butT. muriswas not. Our work establishes a previously underappreciated diversity of commensal trichomonad protists that naturally colonize the enteric cavity of laboratory mice.
The intracellular symbiontWolbachiaaltersDrosophiladevelopment and metabolism to buffer against nutritional stress
Authors: Lindsey Amelia RI , Tennessen Jason M , Gelaw Michael A , Jones Megan W , Parish Audrey J , Newton Irene LG , Nemkov Travis , D’Alessandro Angelo , Rai Madhulika , Stark Nicole 
Published: January 2023

ABSTRACTThe intracellular bacteriumWolbachiais a common symbiont of many arthropods and nematodes, well studied for its impacts on host reproductive biology. However, its broad success as a vertically transmitted infection cannot be attributed to manipulations of host reproduction alone. Using theDrosophila melanogastermodel and their natively associatedWolbachiastrain “wMel”, we show thatWolbachiainfection supports fly development and buffers against nutritional stress.Wolbachiainfection across several fly genotypes and a range of nutrient conditions resulted in reduced pupal mortality, increased adult emergence, and larger size. We determined that the exogenous supplementation of pyrimidines partially rescued developmental phenotypes in theWolbachia-free flies, and thatWolbachiatiters were responsive to reduced gene expression of the fly’sde novopyrimidine synthesis pathway. In parallel, transcriptomic and metabolomic analyses indicated thatWolbachiaimpacts larval biology far beyond pyrimidine metabolism.Wolbachia-infected larvae had strong signatures of shifts in glutathione and mitochondrial metabolism, plus significant changes in the expression of key developmental regulators includingNotch, the insulin receptor (lnR), and the juvenile hormone receptorMethoprene-tolerant(Met). We propose thatWolbachiaacts as a beneficial symbiont to support fly development and enhance host fitness, especially during periods of nutrient stress.SIGNIFICANCEWolbachiais a bacterial symbiont of arthropods and nematodes, well described for its manipulations of arthropod reproduction. However, many have theorized there must be more to this symbiosis, even in well-studiedWolbachia-host relationships such as withDrosophila. Reproductive impacts alone cannot explain the success and ubiquity of this bacterium. Here, we useDrosophila melanogasterand their nativeWolbachiainfections to show thatWolbachiasupports fly development and significantly buffers flies against nutritional stress. These developmental advantages might help explain the ubiquity ofWolbachiainfections.
Base editing as a genetic treatment for spinal muscular atrophy
Authors: Alves Christiano R. R. , Ha Leillani L. , Yaworski Rebecca , Lazzarotto Cicera R. , Christie Kathleen A. , Reilly Aoife , Beauvais Ariane , Doll Roman M. , de la Cruz Demitri , Maguire Casey A. , Swoboda Kathryn J. , Tsai Shengdar Q. , Kothary Rashmi , Kleinstiver Benjamin P. 
Published: January 2023

AbstractSpinal muscular atrophy (SMA) is a devastating neuromuscular disease caused by mutations in theSMN1gene. Despite the development of various therapies, outcomes can remain suboptimal in SMA infants and the duration of such therapies are uncertain.SMN2is a paralogous gene that mainly differs fromSMN1by a C•G-to-T•A transition in exon 7, resulting in the skipping of exon 7 in mostSMN2transcripts and production of only low levels of survival motor neuron (SMN) protein. Genome editing technologies targeted to theSMN2exon 7 mutation could offer a therapeutic strategy to restore SMN protein expression to normal levels irrespective of the patientSMN1mutation. Here, we optimized a base editing approach to precisely editSMN2, reverting the exon 7 mutation via an A•T-to-G•C base edit. We tested a range of different adenosine base editors (ABEs) and Cas9 enzymes, resulting in up to 99% intended editing in SMA patient-derived fibroblasts with concomitant increases inSMN2exon 7 transcript expression and SMN protein levels. We generated and characterized ABEs fused to high-fidelity Cas9 variants which reduced potential off-target editing. Delivery of these optimized ABEs via dual adeno-associated virus (AAV) vectors resulted in preciseSMN2editingin vivoin an SMA mouse model. This base editing approach to correctSMN2should provide a long-lasting genetic treatment for SMA with advantages compared to current nucleic acid, small molecule, or exogenous gene replacement therapies. More broadly, our work highlights the potential of PAMless SpRY base editors to install edits efficiently and safely.
Structural preferences shape the entropic force of disordered protein ensembles
Authors: Yu Feng , Sukenik Shahar 
Published: January 2023

AbstractIntrinsically disordered protein regions (IDRs) make up over 30% of the human proteome and instead of a native, well-folded structure exist in a dynamic conformational ensemble. Tethering IDRs to a surface (for example, the surface of a well-folded region of the same protein) can reduce the number of accessible conformations in IDR ensembles. This reduces the ensemble’s conformational entropy, generating an effective entropic force that pulls away from the point of tethering. Recent experimental work has shown that this entropic force causes measurable, physiologically relevant changes to protein function, but how the magnitude of this force depends on the IDR sequence remains unexplored. Here we use all-atom simulations to analyze how structural preferences encoded in dozens of IDR ensembles contribute to the entropic force they exert upon tethering. We show that sequence-encoded structural preferences play an important role in determining the magnitude of this force and that compact, spherical ensembles generate an entropic force that can be several times higher than more extended ensembles. We further show that changes in the surrounding solution’s chemistry can modulate IDR entropic force strength. We propose that the entropic force is a sequence-dependent, environmentally tunable property of terminal IDR sequences.
Abnormal chondrocyte intercalation in a zebrafish model ofcblCsyndrome restored by an MMACHC cobalamin binding mutant
Authors: Paz David , Pinales Briana E. , Castellanos Barbara S. , Perez Isaiah , Gil Claudia B. , Jimenez Madrigal Lourdes , Reyes-Nava Nayeli G. , Castro Victoria L. , Sloan Jennifer L. , Quintana Anita M. 
Published: January 2023

AbstractVariants in theMMACHCgene cause combined methylmalonic acidemia and homocystinuriacblCtype, the most common inborn error of intracellular cobalamin (vitamin B12) metabolism.cblCis associated with neurodevelopmental, hematological, ocular, and biochemical abnormalities. In a subset of patients, mild craniofacial dysmorphia has also been described. Mouse models ofMmachcdeletion are embryonic lethal but cause severe craniofacial phenotypes such as facial clefts.MMACHCencodes an enzyme required for cobalamin processing and variants in this gene result in the accumulation of two metabolites: methylmalonic acid (MMA) and homocysteine (HC). Interestingly, other inborn errors of cobalamin metabolism, such ascblXsyndrome, are associated with mild facial phenotypes. However, the presence and severity of MMA and HC accumulation incblXsyndrome is not consistent with the presence or absence of facial phenotypes. Thus, the mechanisms by which mutation ofMMACHCcause craniofacial defects have not been completely elucidated. Here we have characterized the craniofacial phenotypes in a zebrafish model ofcblC(hg13) and performed restoration experiments with either wildtype or a cobalamin binding deficient MMACHC protein. Homozygous mutants did not display gross morphological defects in facial development, but did have abnormal chondrocyte intercalation, which was fully penetrant. Abnormal chondrocyte intercalation was not associated with defects in the expression/localization of neural crest specific markers,sox10orbarx1. Most importantly, chondrocyte organization was fully restored by wildtype MMACHC and a cobalamin binding deficient variant of MMACHC protein. Collectively, these data suggest that mutation ofMMACHCcauses mild to moderate craniofacial phenotypes that are independent of cobalamin binding.
High sensitivity proteome-scale search for crosslinked peptides using CRIMP 2.0
Authors: Crowder D. Alex , Sarpe Vladimir , Amaral Bruno C. , Brodie Nicholas I. , Michael Andrew R. M. , Schriemer David 
Published: January 2023

AbstractCrosslinking mass spectrometry (XL-MS) is a valuable technique for the generation of point-to-point distance measurements in protein space. Applications involvingin situchemical crosslinking have created the possibility of mapping whole protein interactomes with high spatial resolution. However, an XL-MS experiment carried out directly on cells requires highly efficient software that can detect crosslinked peptides with sensitivity and controlled error rates. Many algorithmic approaches invoke a filtering strategy designed to reduce the size of the database prior to mounting a search for crosslinks, but concern has been expressed over the possibility of reduced sensitivity with such strategies. Here we present a full upgrade to CRIMP, the crosslinking app in the Mass Spec Studio, which implements a new strategy for the detection of both component peptides in the MS2spectrum. Using several published datasets, we demonstrate that this pre-searching method is sensitive and fast, permitting whole proteome searches on a conventional desktop computer for both cleavable and noncleavable crosslinkers. We introduce a new strategy for scoring crosslinks, adapted from computer vision algorithms, that properly resolves conflicting XL hits from other crosslinking reaction products, and we present a method for enhancing the detection of protein-protein interactions that relies upon compositional data.
Netrin-1 binding to Unc5B regulates Blood-Retina Barrier integrity
Authors: Furtado Jessica , Geraldo Luiz Henrique , Leser Felipe Saceanu , Poulet Mathilde , Park Hyojin , Pibouin-Fragner Laurence , Eichmann Anne , Boyé Kevin 
Published: January 2023

ABSTRACTBackgroundThe blood brain barrier (BBB) preserves neuronal function in the central nervous system (CNS) by tightly controlling metabolite exchanges with the blood. In the eye, the retina is likewise protected by the blood-retina barrier (BRB) to maintain phototransduction. We showed that the secreted guidance cue Netrin-1 regulated BBB integrity, by binding to endothelial Unc5B and regulating canonical β-catenin dependent expression of BBB gene expressionObjectiveHere, we investigated if Netrin-1-binding to endothelial Unc5B also controlled BRB integrity, and if this process involved Norrin/β-catenin signaling, which is the major known driver of BRB development and maintenance.MethodsWe analyzed Tamoxifen-inducible loss- and gain-of-function alleles ofUnc5B, Ntn1andCtnnb1in conjunction with tracer injections and biochemical signaling studies.ResultsInducible endothelialUnc5Bdeletion, and inducible globalNtn1deletion in postnatal mice reduced phosphorylation of the Norrin receptor LRP5, leading to reduced β-catenin and LEF1 expression, conversion of retina endothelial cells from a barrier-competent Claudin-5+/PLVAP-state to a Claudin-5-/PLVAP+ leaky phenotype, and extravasation of injected low molecular weight tracers. InducibleCtnnb1gain of function rescued vascular leak inUnc5Bmutants, andNtn1overexpression induced BRB tightening. Unc5B expression in pericytes contributed to BRB permeability, via regulation of endothelial Unc5B. Mechanistically, Netrin-1-Unc5B signaling promoted β-catenin dependent BRB signaling by enhancing phosphorylation of the Norrin receptor LRP5 via the Discs large homologue 1 (Dlg1) intracellular scaffolding protein.ConclusionsThe data identify Netrin1-Unc5B as novel regulators of BRB integrity, with implications for diseases associated with BRB disruption.
Explaining reward crowdfunding backers' intentions and behavior
Authors: Baah-Peprah Prince 
Published: January 2023

PurposeEarlier research into crowdfunding adoption has drawn on social psychology, trust, signaling and well-being theories. Despite its wide appeal and use, the technology acceptance model (TAM) has received little attention in terms of explaining the adoption of crowdfunding platforms. The current study examines the applicability of two versions of this framework: the original TAM1 and the extended TAM2 frameworks.Design/methodology/approachData were collected through a survey distributed to the users of Finland's leading reward crowdfunding website, Mesenaatti, who have backed crowdfunding campaigns previously. The authors employed structural equation modelling (SEM–lavaan package) and conducted a series of quality tests to alleviate concerns with certain biases.FindingsAnalyses of 556 observations exhibit support for all hypotheses underlying both TAM frameworks, with two exceptions. Contrary to expectations, voluntariness does not moderate the effect of subjective norms on contribution intentions, and the effect of perceived ease-of-use is primarily mediated by perceived usefulness, rather than directly influencing intentions.Originality/valueFirst, the study extends the generalizability of TAM to the context of crowdfunding and with respect to financial contribution behavior. Second, it shows that backers' perceptions of platform usefulness and ease-of-use are important antecedents of crowdfunding contribution behavior, and that the former exerts greater influence than the latter. Third, it further clarifies the influences of relevant antecedents of crowdfunding backers' contribution intentions and behaviors. Specifically, the authors show that experience only weakly moderates the influence of subjective norms on contribution intentions, and voluntariness does not moderate this association. The authors discuss explanations for these findings and their implications for research and practice.
Cost prediction of building projects using the novel hybrid RA-ANN model
Authors: Wang Yali , Zuo Jian , Pan Min , Tu Bocun , Chang Rui-Dong , Liu Shicheng , Xiong Feng , Dong Na 
Published: January 2023

PurposeAccurate and timely cost prediction is critical to the success of construction projects which is still facing challenges especially at the early stage. In the context of rapid development of machine learning technology and the massive cost data from historical projects, this paper aims to propose a novel cost prediction model based on historical data with improved performance when only limited information about the new project is available.Design/methodology/approachThe proposed approach combines regression analysis (RA) and artificial neural network (ANN) to build a novel hybrid cost prediction model with the former as front-end prediction and the latter as back-end correction. Firstly, the main factors influencing the cost of building projects are identified through literature research and subsequently screened by principal component analysis (PCA). Secondly the optimal RA model is determined through multi-model comparison and used for front-end prediction. Finally, ANN is applied to construct the error correction model. The hybrid RA-ANN model was trained and tested with cost data from 128 completed construction projects in China.FindingsThe results show that the hybrid cost prediction model has the advantages of both RA and ANN whose prediction accuracy is higher than that of RA and ANN only with the information such as total floor area, height and number of floors.Originality/value(1) The most critical influencing factors of the buildings’ cost are found out by means of PCA on the historical data. (2) A novel hybrid RA-ANN model is proposed which proved to have the advantages of both RA and ANN with higher accuracy. (3) The comparison among different models has been carried out which is helpful to future model selection.
Decision making in human resources standard practices and change management innovation initiatives: the common destiny of being affected by biases
Authors: Palmucci Dario Natale 
Published: January 2023

PurposeThis work aims to shed light on the cognitive biases that may have an influence on the strategic decision-making process, with a particular focus on those impacting both human resources (HR) standard activities within organizations and new innovative change management initiatives critical for them to survive.Design/methodology/approachThis is a conceptual paper based on a literature review on cognitive biases and managerial decision-making. The conceptual approach is employed to outline how subjective cognitive barriers can undermine managerial decisions and, in particular, the objectivity of HR practices and change management initiatives.FindingsThe discussion emphasizes that cognitive biases are ever-present elements in the decision-making process of professionals, and they influence several areas of management including HR and change management.Research limitations/implicationsLimitations of the study concern the method adopted, as it is conceptual. The implications of the paper are relevant for supervisors and employees working in the HR and innovation/R&D departments in order to create awareness within the organizational contexts and limit the negative influence of these cognitive barriers during their daily activities.Originality/valueThe research contributes to the knowledge on HR management and decision-making process by combining literature findings with practical examples and tips suggesting how to avoid biases in the decision-making process regarding HR and change management.
Responding to the COVID-19 pandemic – catching up in the food industry through business model innovation
Authors: Münch Christopher , Hartmann Evi 
Published: January 2023

PurposeThe food supply chain worldwide has suffered severely due to the COVID-19 pandemic countermeasures. Previous research suggests that business model innovation (BMI) could be a viable solution for recovering from the pandemic and fostering organizational resilience. This study analyzes the capabilities that enable food companies to innovate their business model and thereby increase organizational resilience.Design/methodology/approachResults were obtained using a multiple-case study approach consisting of 15 companies along the entire food supply chain. Managers and decision-makers were interviewed, and the collected insights were enriched with additional material.FindingsThe results show several capabilities that enable companies to innovate their business model due to disruption. These capabilities are categorized into four phases based on the processual representation of BMIs.Originality/valueThis study contributes to the understanding of BMI in the food supply chain and provides empirical evidence on the potential for business recovery through BMI.
Knowledge trajectories in the internationalization of the firm
Authors: Barbosa Sylvio Leal , Rezende Sergio Fernando Loureiro , Versiani Angela , Galdino Katia M. 
Published: January 2023

PurposeThe purpose of this paper is to analyze how the internationalizing firm accumulates knowledge from different domains throughout time, during entry and post-entry moves in a foreign market. This paper focuses on market, institutional, internationalization and technological knowledge.Design/methodology/approachThe paper uses a comparative case study method, relying on three longitudinal cases of multinational firms' (MNEs) internationalization processes, particularly concerning MNEs' entry and post-entry moves in one foreign market (Brazil).FindingsThroughout the internationalization processes, the internationalizing firms unevenly developed experiential knowledge within Brazil. As a result, the market, internationalization, institutional and technological knowledge followed different accumulation patterns, distinguished based on precedence, simultaneity and speed. More specifically, (1) the market and institutional knowledge trajectories evolved simultaneously; (2) the market knowledge trajectory preceded that of technological knowledge and (3) the accumulation of internationalization knowledge happened faster than that of the market, institutional and technological knowledge.Originality/valueThis paper shows how knowledge accumulation in internationalization processes varies throughout time and according to the type of knowledge involved. While most of the literature relies on cross-sectional studies that discount the changing nature of knowledge, this paper shows that the internationalizing firm accumulates market, internationalization, institutional and technological knowledge following three temporal dimensions: precedence, simultaneity and speed.
Retail inventory policy under demand uncertainty and inventory-level-dependent demand
Authors: Srivastava Mohit , Mehta Peeyush , Swami Sanjeev 
Published: January 2023

PurposeThe purpose of this paper is to determine the inventory replenishment policies when demand rate is a function of the inventory space allocated to the products on retail shelves. Existing results on inventory policies with inventory-level-dependent demand (ILDD) assume deterministic functional forms of the demand rate. In this paper, the authors model the inventory decisions when demand is a function of shelf-space allocation and random uncertainty. The authors provide managerial insights of this paper's results.Design/methodology/approachThe demand rate is assumed to be a function of shelf-space allocation based on two settings in the literature. First, the authors model the demand rate as a function of initial shelf-space allocation. In the next setting, the authors assume that the demand rate is a function of instantaneous inventory level on shelves. In both the settings, the authors also model random demand uncertainty in addition to the shelf-space dependency of demand rate. The objective is to maximize the expected profit and determine the inventory parameters.FindingsIn addition to the demand uncertainty, the authors consider linear, power and exponential functional forms of demand rate. Inventory policy that maximizes expected profit is determined when demand rate is a function of initial allocation and displayed inventory level. The results are implementable for practitioners for optimizing the shelf-space allocation and related inventory policy.Originality/valueMost of the extant results on inventory policy with shelf-space-dependent demand do not model the demand uncertainty. The authors model a variety of functional forms of demand rate with ILDD in addition to the demand uncertainty. The results are a building block for more applications in inventory management for real-life applications.