bluuebunny/crossref_metadata_2025_split huggingface dataset:
Notochord and axial progenitor generation by timely BMP and NODAL inhibition during vertebrate trunk formation
Authors: Rito Tiago , Libby Ashley R.G. , Demuth Madeleine , Briscoe James 
Published: February 2023

AbstractThe formation of the vertebrate body involves the coordinated and progressive production of trunk tissues from progenitors located in the posterior of the embryo. In vitro models based on pluripotent stem cells (PSCs) replicate aspects of this process, but they lack some tissue components normally present in the trunk. Most strikingly, the notochord, a hallmark of chordates and the source of midline signals that pattern surrounding tissues, is absent from current models of human trunk formation. To investigate how trunk tissue is formed, we performed single-cell transcriptomic analysis of chick embryos. This delineated molecularly discrete progenitor populations, which we spatially locate in the embryo, compare across species, and relate to signalling activity. Guided by this map, we determined how differentiating human PSCs develop a stereotypical spatial organization of tissue types. We found that LATS1/2 repression of YAP activity, in conjunction with FGF-mediated MAPK activation, induced the transcription factor Bra/TBXT and facilitated WNT signaling. In addition, inhibiting a WNT-induced NODAL and BMP signaling cascade at the appropriate time regulated the proportions of different tissue types produced, including notochordal cells. We used this information to create an integrated 3D model of human gastrulation undergoing morphogenetic movements to produce elongated structures with a notochord and spatially patterned neural tissue formation. Together the data provide insight into the mechanisms responsible for the formation of the tissues that comprise the vertebrate trunk and pave the way for future studies of patterning in a tissue-like environment.
Identification of pharmacological inducers of a reversible hypometabolic state for whole organ preservation
Authors: Sperry Megan M. , Charrez Berenice , Fotowat Haleh , Gardner Erica , Pilobello Kanoelani , Izadifar Zohreh , Lin Tiffany , Kuelker Abigail , Kaki Sahith , Lewandowski Michael , Lightbown Shanda , Martinez Ramses , Marquez Susan , Moore Joel , Plaza-Oliver Maria , Sesay Adama M. , Shcherbina Kostyantyn , Sheehan Katherine , Takeda Takako , Del Campo Daniela , Andrijauskaite Kristina , Cisneros Exal , Lopez Riley , Cano Isabella , Maxwell Zachary , Jessop Israel , Veraza Rafael J. , Bunegin Leon , Percival Thomas J. , Yracheta Jaclyn , Pena Jorge , Wood Diandra , Homas Zachary , Hinshaw Cody , Cox-Hinshaw Jennifer , Parry Olivia G. , Sleeter Justin J. , Weitzel Erik K. , Levin Michael , Super Michael , Novak Richard , Ingber Donald E. 
Published: February 2023

ABSTRACTDrugs that induce reversible slowing of metabolic and physiological processes would have great value for organ preservation, especially for organs with high susceptibility to hypoxia-reperfusion injury, such as the heart. Using whole-organism screening of metabolism, mobility, and development inXenopus, we identified an existing drug, SNC80, that rapidly and reversibly slows biochemical and metabolic activities while preserving cell and tissue viability. Although SNC80 was developed as a delta opioid receptor activator, we discovered that its ability to slow metabolism is independent of its opioid modulating activity as a novel SNC80 analog (WB3) with almost 1,000 times less delta opioid receptor binding activity is equally active. Metabolic suppression was also achieved using SNC80 in microfluidic human organs-on-chips, as well as in explanted whole porcine hearts and limbs, demonstrating the cross-species relevance of this approach and potential clinical relevance for surgical transplantation. Pharmacological induction of physiological slowing in combination with organ perfusion transport systems may offer a new therapeutic approach for tissue and organ preservation for transplantation, trauma management, and enhancing patient survival in remote and low-resource locations.
A molecularly defined NAcSh D1 subtype controls feeding and energy homeostasis
Authors: Liu Yiqiong , Wang Ying , Zhao Zheng-dong , Xie Guoguang , Zhang Chao , Chen Renchao , Zhang Yi 
Published: February 2023

AbstractOrchestrating complex behavioral states, such as approach and consumption of food, is critical for survival. In addition to hypothalamus neuronal circuits, the nucleus accumbens (NAc) also plays an important role in controlling appetite and satiety in responses to changing external stimuli. However, the specific neuronal subtypes of NAc involved as well as how the humoral and neuronal signals coordinate to regulate feeding remain incompletely understood. Here, we deciphered the spatial diversity of neuron subtypes of the NAc shell (NAcSh) and defined a dopamine receptor D1(Drd1)- andSerpinb2-expressing subtype located in NAcSh encoding food consumption. Chemogenetics- and optogenetics-mediated regulation ofSerpinb2+neurons bidirectionally regulates food seeking and consumption specifically. Circuitry stimulation revealed the NAcShSerpinb2→LHLepRprojection controls refeeding and can overcome leptin-mediated feeding suppression. Furthermore, NAcShSerpinb2+neuron ablation reduces food intake and upregulates energy expenditure resulting in body weight loss. Together, our study reveals a neural circuit consisted of molecularly distinct neuronal subtype that bidirectionally regulates energy homeostasis, which can serve as a potential therapeutic target for eating disorders.
Engineered Immunogens to Elicit Antibodies Against Conserved Coronavirus Epitopes
Authors: Kapingidza Brenda , Marston Daniel J. , Harris Caitlin , Wrapp Daniel , Winters Kaitlyn , Mielke Dieter , Xiaozhi Lu , Yin Qi , Foulger Andrew , Parks Rob , Barr Maggie , Newman Amanda , Schäfer Alexandra , Eaton Amanda , Flores Justine Mae , Harner Austin , Cantazaro Nicholas J , Mallory Michael L , Mattocks Melissa D , Beverly Christopher , Rhodes Brianna , Mansouri Katayoun , Itallie Elizabeth Van , Vure Pranay , Manness Brooke , Keyes Taylor , Stanfield-Oakley Sherry , Woods Christopher W. , Petzold Elizabeth A. , Walter Emmanuel B , Wiehe Kevin , Edwards Robert J. , Montefiori David , Ferrari Guido , Baric Ralph , Cain Derek W. , Saunders Kevin O. , Haynes Barton F. , Azoitei Mihai L. 
Published: February 2023

AbstractImmune responses to SARS-CoV-2 primarily target the receptor binding domain of the spike protein, which continually mutates to escape acquired immunity. Other regions in the spike S2 subunit, such as the stem helix and the segment encompassing residues 815-823 adjacent to the fusion peptide, are highly conserved across sarbecoviruses and are recognized by broadly reactive antibodies, providing hope that vaccines targeting these epitopes could offer protection against both current and emergent viruses. Here we employed computational modeling to design scaffolded immunogens that display the spike 815-823 peptide and the stem helix epitopes without the distracting and immunodominant RBD. These engineered proteins bound with high affinity and specificity to the mature and germline versions of previously identified broadly protective human antibodies. Epitope scaffolds interacted with both sera and isolated monoclonal antibodies with broadly reactivity from individuals with pre-existing SARS-CoV-2 immunity. When used as immunogens, epitope scaffolds elicited sera with broad betacoronavirus reactivity and protected as “boosts” against live virus challenge in mice, illustrating their potential as components of a future pancoronavirus vaccine.
Characterization of early white matter changes in CADASIL using microscopic diffusion imaging and relaxometry
Authors: Barrière David A. , Uszynski Ivy , Rajani Rikesh M. , Gueniot Florian , Domenga-Denier Valérie , Boumezbeur Fawzi , Poupon Cyril , Joutel Anne 
Published: February 2023

AbstractBackground and purposeCerebral small vessel diseases (SVDs) are characterized by early white matter (WM) changes, whose pathological underpinnings are yet poorly understood. CADASIL is a monogenic and archetypal SVD, providing an ideal model for investigating these changes. Here, we used multicompartment microscopic diffusion imaging and relaxometry to elucidate microstructural changes underlying early WM abnormalities in CADASIL.MethodsWe acquired diffusion MRI data with a multiple-shell Q-space sampling strategy, and relaxometry T1 and T2 data, with a 160 and 80-μm isotropic resolution respectively,ex vivo, in CADASIL and control mice. Diffusion datasets were computed with the Neurite Orientation Dispersion and Density Imaging model to extract the neurite density index, the extracellular free water and the orientation dispersion index. Relaxometry datasets were computed with a 3-compartment myelin water imaging model to extract the myelin content. MRI metrics were compared between CADASIL and control mice using voxel and WM tract-based analyses and with electron microscopy analysis.ResultsWM in CADASIL mice displayed a widespread reduction in general fractional anisotropy, a large increase in extracellular free water, a reduction in the myelin content, but no reduction in neurite density. Electron microscopy analysis showed a ∽2-fold increase in the extracellular spaces and an elevation of the g-ratio indicative of myelin sheath thinning in CADASIL WM.ConclusionOur findings suggest that accumulation of interstitial fluid and myelin damage are 2 major factors underlying early WM changes in CADASIL. Advanced diffusion MRI and relaxometry are promising approaches to decipher the underpinnings of WM alterations in SVDs.
Validation of Fourier transform infrared microspectroscopy for the evaluation of enzymatic cross-linking of bone collagen
Authors: Mieczkowska Aleksandra , Mabilleau Guillaume 
Published: February 2023

ABSTRACTEnzymatic cross-linking of the bone collagen is important to resist to crack growth and to increased flexural strength. In the present study, we proposed a new method for assessment of enzymatic cross-link based on FTIR microspectroscopy that takes into account secondary structure of type I collagen. Briefly, femurs were collected from sham or ovariectomized mice and subjected either to LC-MS or embedded in polymethylmethacrylate, cut and analyzed by FTIR microspectroscopy. FTIR acquisition were recorded before and after UV exposure or acid treatment. In addition, femurs from a second animal study were used to compare gene expression ofPlod2andLoxenzymes and enzymatic cross-links determined by FTIR microspectroscopy.We evidenced here that intensities and areas of subbands located at ∼1660 cm-1, ∼1680 cm-1and ∼1690 cm-1were positively and significantly associated with the concentration of pyridinoline (PYD), deoxypyridinoline (DPD) or immature dihydroxylysinonorleucine (DHLNL) / hydroxylysinonorleucine (HLNL) cross-links. Seventy-two hours exposure to UV light significantly reduced by ∼86% and ∼89% the intensity and area of the ∼1660 cm-1subband. Similarly, 24 hours of acid treatment significantly reduced by 78% and 76% the intensity and area of the ∼1690 cm-1subband.Plod2andLoxexpression were also positively associated to the signal of the ∼1660 cm-1and ∼1690 cm-1subbands.In conclusion, our study provided a new method for decomposing the amide I envelope of bone section that positively correlates with PYD and immature collagen cross-links. This method allows for investigation of tissue distribution of enzymatic cross-links in bone section.
Induction of viral mimicry upon loss of DHX9 and ADAR1 in breast cancer cells
Authors: Cottrell Kyle A. , Ryu Sua , Torres Luisangely Soto , Schab Angela M. , Weber Jason D. 
Published: February 2023

SummaryDetection of viral double-stranded RNA (dsRNA) is an important component of innate immunity. However, many endogenous RNAs containing double-stranded regions can be misrecognized and activate innate immunity. The interferon inducible ADAR1-p150 suppresses dsRNA sensing, an essential function for ADAR1 in many cancers, including breast. Although ADAR1-p150 has been well established in this role, the functions of the constitutively expressed ADAR1-p110 isoform are less understood. We used proximity labeling to identify putative ADAR1-p110 interacting proteins in breast cancer cell lines. Of the proteins identified, the RNA helicase DHX9 was of particular interest. Knockdown of DHX9 in ADAR1-dependent cell lines caused cell death and activation of the dsRNA sensor PKR. In ADAR1-independent cell lines, combined knockdown of DHX9 and ADAR1, but neither alone, caused activation of multiple dsRNA sensing pathways leading to a viral mimicry phenotype. Together, these results reveal an important role for DHX9 in suppressing dsRNA sensing by multiple pathways.
The antiphage defense system CBASS controls resistance and enables killing by antifolate antibiotics inVibrio cholerae
Authors: Brenzinger Susanne , Airoldi Martina , Ogunleye Adewale Joseph , Brochado Ana Rita 
Published: February 2023

SummaryToxic bacterial modules, in particular toxin-antitoxin (TA) systems, have been long sought-after for their antimicrobial potential, although with limited success1–6. Here we show that the cyclic-oligonucleotide-based antiphage signaling system (CBASS), another example of a toxic module, increases sensitivity to well-established antifolate antibiotics, interferes with their synergy, and ultimately enables bacterial lysis by antifolates - classic bacteriostatic antibiotics, inVibrio cholerae. We propose a molecular mechanism for the CBASS-antifolate interaction based on onset of cyclic-oligonucleotide production by the nucleotidyltransferase DncV upon folate depletion by antifolates. CBASS-antifolate interaction is specific to CBASS systems with closely related nucleotidyltransferases and similar folate binding. Altogether, our findings illustrate that toxic modules, such as the antiphage defense CBASS system, can dramatically impact antibiotic activity, and open the possibility that endogenous metabolites could also act as triggers/silencers of toxic modules under stress beyond antibiotic treatment, such as during phage infection, biofilm formation or disease environments.
A Conserved Requirement for RME-8/DNAJC13 in Neuronal Autolysosome Reformation
Authors: Swords Sierra , Jia Nuo , Norris Anne , Modi Jil , Cai Qian , Grant Barth D. 
Published: February 2023

ABSTRACTAutophagosomes fuse with lysosomes, forming autolysosomes that degrade engulfed cargo. To maintain lysosomal capacity, autolysosome reformation (ALR) must regenerate lysosomes from autolysosomes using a membrane tubule-based process. Maintaining lysosomal capacity is required to maintain proteostasis and cellular health, especially in neurons where lysosomal dysfunction has been repeatedly implicated in neurodegenerative disease. Cell biological studies have linked the DNA-J domain Hsc70 co-chaperone RME-8/DNAJC13 to endosomal coat protein regulation, while human genetics studies have linked RME-8/DNAJC13 to neurological disease, including Parkinsonism and Essential Tremor. We report new analysis of the requirements for the RME-8/DNAJC13 protein in neurons, focusing onC. elegansmechanosensory neurons in the intact animal, and in primary mouse cortical neurons in culture. We find that loss of RME-8/DNAJC13 in both systems results in accumulation of grossly elongated autolysosomal tubules. FurtherC. elegansanalysis revealed a similar autolysosome tubule accumulation defect in mutants known to be required for ALR in mammals, including bec-1/beclin and vps-15/PIK3R4/p150 that regulate type-III PI3-kinase VPS-34, and dyn-1/dynaminthat severs ALR tubules. Clathrin is also an important ALR regulator implicated in autolysosome tubule formation and release. InC. eleganswe found that loss of RME-8 causes severe depletion of clathrin from neuronal autolysosomes, a phenotype shared withbec-1andvps-15mutants. We conclude that RME-8/DNAJC13 plays a conserved but previously unrecognized role in autolysosome reformation, likely affecting ALR tubule initiation and/or severing. Additionally, in both systems, we found that loss of RME-8/DNAJC13 appeared to reduce autophagic flux, suggesting feedback regulation from ALR to autophagy. Our results connecting RME-8/DNAJC13 to ALR and autophagy provide a potential mechanism by which RME-8/DNAJC13 could influence neuronal health and the progression of neurodegenerative disease.
How to reach a joint decision with the smallest need for compromise
Authors: Holguin Sofia , Kosheleva Olga 
Published: February 2023

PurposeUsually, people's interests do not match perfectly. So when several people need to make a joint decision, they need to compromise. The more people one has to coordinate the decision with, the fewer chances that each person's preferences will be properly taken into account. Therefore, when a large group of people need to make a decision, it is desirable to make sure that this decision can be reached by dividing all the people into small-size groups so that this decision can reach a compromise between the members of each group. The study's objective is to analyze when such a compromise is possible.Design/methodology/approachIn this paper, the authors use a recent mathematical result about convex sets to analyze this problem and to come up with an optimal size of such groups.FindingsThe authors find the smallest group size for which a joint decision is possible. Specifically, the authors show that in situations where each alternative is characterized by n quantities, it is possible to have a joint decision if the participants are divided into groups of size n -- and, in general, no such decision is possible if the participants are divided into groups of size n -- 1.Originality/valueThe main novelty of this paper is that, first, it formulates the problem, which, to the best of the authors’ knowledge, was never formulated in this way before, and, second, that it provides a solution to this problem.
Adaptability of enterprise resource planning (ERP) systems for cost management of building construction projects in Sri Lanka
Authors: Jayamaha B.H.V.H. , Perera B.A.K.S. , Gimhani K.D.M. , Rodrigo M.N.N. 
Published: February 2023

Purpose
Enterprise resource planning (ERP) systems that are equipped with numerous features and functionalities help to improve the profitability of construction corporations around the world through enhancing the efficiency of the functions related to cost management. Thus, the purpose of this study was to investigate the applicability of ERP systems for cost management of building construction projects in Sri Lanka.

Design/methodology/approach
A qualitative technique was used in this study, which comprised two-round Delphi-based semistructured interviews. Purposive sampling was used to determine the interviewees. Content analysis was used to evaluate the collected data.

Findings
The findings of this study identified the ERP system as a strategic tool for gaining a competitive advantage for an organization while confirming 14 uses of ERP systems and 16 stages of the cost management process. Eighteen issues were finalized at the end of the interview rounds while categorizing the suitable ERP applications at each stage of the cost management process.

Originality/value
Even though there are numerous distinct studies conducted on cost management and ERP systems, there has been a lack of studies conducted on the synergy between these two areas that can be adapted for the building projects in the Sri Lankan context. Therefore, the findings of this study can bring a new paradigm to the Sri Lankan construction sector by influencing the adaption of correct ERP systems at numerous project stages by providing a competitive edge.
Urban night lighting evaluation system and case study: blending popular contemporary elements, cultural traditions and advanced lighting technologies
Authors: Lin Qingcheng , Zhang Chi , Cai Huiling , Li Xuefeng , Xiao Hui 
Published: February 2023

PurposeNight lighting reflects the prosperous development of economic and the increasingly rich and colorful cultural life. Currently, various technical standards, protocols and management specifications have been developed to build a safe, comfortable and economical lighting environment. However, prevailing evaluation systems focus on objective indexes of illumination and have ignored environmental characteristics and subjective feelings and lacked consideration of regional culture, economic benefit, management and maintenance. In this context, a lighting evaluation system combining subjective and objective is proposed for the first time in this study to explore approaches to guide the development of a healthy and comfortable urban night-time environment.Design/methodology/approachExisting research and relevant lighting standards are analyzed and an evaluation model with a logical hierarchy is constructed by combining with the evaluation theory that is set based on people and the environment. The index weights were scientifically determined on the basis of the analytic hierarchy process (AHP) and fuzzy comprehensive evaluation method. The rationality and validity of the proposed evaluation system is verified in accordance with field projects and case studies.FindingsTaking into account traditional and cultural factors, the evaluation model established has an acceptable accuracy. Evaluation based on subjective-objective combination can provide a scientific basis for the management and optimization of night lighting.Originality/valueThe proposed evaluation system can serve as a guiding reference for other areas of cultural identity and esthetic perspective.
Effects of coflow-jet active flow control on airfoil stall
Authors: Yazdani Shima , Salimipour Erfan , Salimipour Ayoob , Sheremet Mikhail A. , Ghalambaz Mohammad 
Published: February 2023

Purpose
Active flow control on the NACA 0024 airfoil defined as suction-injection jet at the chord-based Reynolds number of 1.5 × 1e + 5 is studied.

Design/methodology/approach
The three-dimensional incompressible unsteady Reynolds-averaged Navier–Stokes equations with the SST k-ω turbulence model are used to study the effects of coflow-jet (CFJ) on the dynamic and static stall phenomena. CFJ implementation is conducted with several momentum coefficients to investigate their turnover. Furthermore, the current work intends to analyze the CFJ performance by varying the Reynolds number and jet momentum coefficient and comparing all states to the baseline airfoil, which has not been studied in prior research investigations.

Findings
It is observed that at the momentum coefficient (Cµ) of 0.06, the lift coefficients at low attack angles (up to a = 15) dramatically increase. Furthermore, the dynamic stall at the given Reynolds number and with the lowered frequency of 0.15 is explored. In the instance of Cµ = 0.07, the lift coefficient curve does not show a noticeable stall feature compared to Cµ = 0.05, suggesting that a more powerful stronger jet can entirely control the dynamic stall.

Originality/value
Furthermore, the current work intends to analyze the CFJ performance by varying the jet momentum coefficient and comparing all states to the baseline airfoil, which has not been studied in prior research investigations.