bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elaboration of the Homer1 Recognition Landscape Reveals Incomplete Divergence of Paralogous EVH1 Domains
Authors: Singer Avinoam , Ramos Alejandra , Keating Amy E. 
Published: January 2024

AbstractShort sequences that mediate interactions with modular binding domains are ubiquitous throughout eukaryotic proteomes. Networks of Short Linear Motifs (SLiMs) and their corresponding binding domains orchestrate many cellular processes, and the low mutational barrier to evolving novel interactions provides a way for biological systems to rapidly sample selectable phenotypes. Mapping SLiM binding specificity and the rules that govern SLiM evolution is fundamental to uncovering the pathways regulated by these networks and developing the tools to manipulate them. We used high-throughput screening of the human proteome to identify sequences that bind to the Enabled/VASP homology 1 (EVH1) domain of the postsynaptic density scaffolding protein Homer1. In doing so, we expanded current understanding of the determinants of Homer EVH1 binding preferences and defined a new motif that can facilitate the discovery of additional Homer-mediated interactions. Interestingly, the Homer1 EVH1 domain preferentially binds to sequences containing an N-terminally overlapping motif that is bound by the paralogous family of Ena/VASP actin polymerases, and many of these sequences can bind to EVH1 domains from both protein families. We provide evidence from orthologous EVH1 domains in pre-metazoan organisms that the overlap in human Ena/VASP and Homer binding preferences corresponds to an incomplete divergence from a common Ena/VASP ancestor. Given this overlap in binding profiles, promiscuous sequences that can be recognized by both families either achieve specificity through extrinsic regulatory strategies or may provide functional benefits via multi-specificity. This may explain why these paralogs incompletely diverged despite the accessibility of further diverged isoforms.Impact StatementShort linear motifs bind to structurally conserved domains to mediate many protein interactions. Current definitions of motifs, using regular expressions, are over simplified and do not capture what is required for binding. Unbiased proteome interaction screens can refine these definitions. For EVH1 domains considered in this work, screening elucidated Homer1 binding requirements and revealed a residual overlap of specificity of two anciently diverged families, highlighting both opportunities and challenges of multi-specificity in domain-motif interactions.
The conformational landscape of human transthyretin revealed by cryo-EM
Authors: Basanta Benjamin , Nugroho Karina , Yan Nicholas L. , Kline Gabriel M. , Powers Evan T. , Tsai Felix J. , Wu Mengyu , Hansel-Harris Althea , Chen Jason S. , Forli Stefano , Kelly Jeffrey W. , Lander Gabriel C. 
Published: January 2024

AbstractTransthyretin (TTR) is a natively tetrameric thyroxine transporter found in blood and cerebrospinal fluid whose misfolding and aggregation causes transthyretin amyloidosis. A rational drug design campaign identified the small molecule tafamidis (Vyndaqel/Vyndamax) as an effective stabilizer of the native TTR fold, and this aggregation inhibitor is regulatory agency-approved for the treatment of TTR amyloidosis. Despite 50 years of structural studies on TTR and this triumph of structure-based drug design, there remains a notable dearth of structural information available to understand ligand binding allostery and amyloidogenic TTR unfolding intermediates. We used single-particle cryo-electron microscopy (cryo-EM) to investigate the conformational landscape of this 55 kiloDalton tetramer in the absence and presence of one or two ligands, revealing inherent asymmetries in the tetrameric architecture and previously unobserved conformational states. These findings provide critical mechanistic insights into negatively cooperative ligand binding and the structural pathways responsible for TTR amyloidogenesis. This study underscores the capacity of cryo-EM to provide new insights into protein structures that have been historically considered too small to visualize and to identify pharmacological targets suppressed by the confines of the crystal lattice, opening uncharted territory in structure-based drug design.
Frontal noradrenergic and cholinergic transients exhibit distinct spatiotemporal dynamics during competitive decision-making
Authors: Wang Hongli , Ortega Heather K. , Kelly Emma B. , Indajang Jonathan , Feng Jiesi , Li Yulong , Kwan Alex C. 
Published: January 2024

AbstractNorepinephrine (NE) and acetylcholine (ACh) are neuromodulators that are crucial for learning and decision-making. In the cortex, NE and ACh are released at specific sites along neuromodulatory axons, which would constrain their spatiotemporal dynamics at the subcellular scale. However, how the fluctuating patterns of NE and ACh signaling may be linked to behavioral events is unknown. Here, leveraging genetically encoded NE and ACh indicators, we use two-photon microscopy to visualize neuromodulatory signals in the superficial layer of the mouse medial frontal cortex during decision-making. Head-fixed mice engage in a competitive game called matching pennies against a computer opponent. We show that both NE and ACh transients carry information about decision-related variables including choice, outcome, and reinforcer. However, the two neuromodulators differ in their spatiotemporal pattern of task-related activation. Spatially, NE signals are more segregated with choice and outcome encoded at distinct locations, whereas ACh signals can multiplex and reflect different behavioral correlates at the same site. Temporally, task-driven NE transients were more synchronized and peaked earlier than ACh transients. To test functional relevance, using optogenetics we found that evoked elevation of NE, but not ACh, in the medial frontal cortex increases the propensity of the animals to switch and explore alternate options. Taken together, the results reveal distinct spatiotemporal patterns of rapid ACh and NE transients at the subcellular scale during decision-making in mice, which may endow these neuromodulators with different ways to impact neural plasticity to mediate learning and adaptive behavior.
A nascent riboswitch helix orchestrates robust transcriptional regulation through signal integration
Authors: Chauvier Adrien , Dandpat Shiba , Romero Rosa , Walter Nils G. 
Published: January 2024

AbstractWidespread manganese-sensing transcriptional riboswitches effect the dependable gene regulation needed for bacterial manganese homeostasis in changing environments. Riboswitches – like most structured RNAs – are believed to fold co-transcriptionally, subject to both ligand binding and transcription events; yet how these processes are orchestrated for robust regulation is poorly understood. Through a combination of single molecule and bulk approaches, we discovered how a single Mn2+ion and the transcribing RNA polymerase (RNAP), paused immediately downstream by a DNA template sequence, are coordinated by the bridging switch helix P1.1 in the paradigmaticLactococcus lactisriboswitch. This coordination achieves a heretofore-overlooked semi-docked global conformation of the nascent RNA, P1.1 base pair stabilization, transcription factor NusA ejection, and RNAP pause extension, thereby enforcing transcription readthrough. Our work demonstrates how a central, adaptable RNA helix functions analogous to a molecular fulcrum of a first-class lever system to integrate disparate signals for finely balanced gene expression control.
Astrocytes tune neuronal excitability through the Ca2+-activated K+current sIAHP
Authors: Expósito Sara , Alberquilla Samuel , Martín Eduardo D. 
Published: January 2024

SUMMARYNeurons have the unique ability to integrate synaptic information by modulating the function of the voltage-gated membrane ion channels, which govern their excitability. Astrocytes play active roles in synaptic function, from synapse formation and maturation to plasticity processes. However, it remains elusive whether astrocytes can impact the neuronal activity by regulating membrane ion conductances that control the intrinsic firing properties. Here, we found that astrocytes, by releasing adenosine, enhance the slow Ca2+-activated K+current (sIAHP) in CA1 hippocampal pyramidal neurons. Remarkably, we showed that interneuron activity was involved in the astrocyte-mediated sIAHP modulation. Indeed, both synaptically activated and optogenetically stimulated hippocampal interneurons evoked coordinated signaling in astrocytes and pyramidal neurons, which relied on GABABand adenosine A1 receptors activation. In addition, the selective genetic ablation of GABABreceptors in CA1 astrocytes prevented the spike frequency adaptation in pyramidal cells after interneuron activation. Therefore, our data reveal the astrocyte capability to modulate the intrinsic membrane properties that dictate neuronal firing rate and hippocampal networks activity.
The effect of service recovery on socially distant third-party customers: an experimental research on emotions, forgiveness, repatronage intention and WoM
Authors: Çelik Süleyman , Özkan Tektaş Öznur , Kavak Bahtışen 
Published: January 2024

PurposeService failures usually occur in front of third-party customers. Third-party customers react emotionally and behaviorally to service failure and recovery efforts aimed at focal customers. However, there is a gap in the literature on how third-party customers react to a service failures incident and a recovery over another customer, depending on how socially close or distant they are from. This study investigates the effect of third-party customers' emotions on consumer forgiveness, negative word-of-mouth (WoM) and repatronage intentions in the service recovery process by comparing close and distant third-party customers.Design/methodology/approachThis study utilizes a 2 (social distance to the focal customer: close, distant) × 2 (service recovery: yes, no) between-subjects design. The authors used a scenario-based experiment to test the proposed hypotheses. A total of 576 respondents were involved in the study.FindingsThe results from the authors' scenario-based experimental study show that positive and negative emotions felt by distant third-party customers are higher than those of close third-party customers. In addition, the effect of positive emotions on customer forgiveness is more substantial for distant third-party customers. Third, moderated-mediation analysis indicates that social distance has a moderator effect only on the relationship between positive emotions and customer forgiveness.Originality/valueThis study contributes to the service literature by comparing socially close and socially distant third-party customers' reactions to service failure and recovery attempts.
Human resource analytics, creative problem-solving capabilities and firm performance: mediator moderator analysis using PLS-SEM
Authors: Thakur Shweta Jaiswal , Bhatnagar Jyotsna , Farndale Elaine , Aeron Prageet 
Published: January 2024

PurposeBased on resource-based and dynamic capabilities theorizing, this study explores how human resource analytics (HRA) can improve human resource management (HRM) performance and organizational performance, with creative problem-solving capability (CPSC) as an underlying mediator for creating value from HRA. It also explores how data quality and HRA personnel expertise act as moderators in this relationship.Design/methodology/approachHypotheses are tested in an empirical study including 191 firms using partial least square structural equation modeling technique.FindingsThe findings confirm the direct and indirect effect of HRA use and maturity on HRM and organizational performance, as well as the mediating role of CPSC. HRA personnel expertise was found to moderate the relationship between HRA and CPSC, data quality being an important factor.Originality/valueThe findings contribute to the sparse evidence of value creation from HRA use/maturity on HRM and organizational outcomes, providing a theoretical logic of resource-based view and dynamic capabilities view based on the underlying causal mechanism through which HRA creates value. The study identified complementary capabilities which when combined with HRA use/maturity and CPSC result in value creation.
Toward multidimensional information: A derivatization‐free UHPLC‐QqQ MS/MS method for amino acid components of fingerprint
Authors: Tian Shisi , Wang Yanyan , Liu Shuo , Liu Zhaolun , Zhao Ya‐Bin 
Published: January 2024

AbstractThe analysis of fingerprint chemical composition is a meaningful way to excavate the multidimensional information of fingerprint, including the donor profiling information and the age of a fingerprint, which broadens the evidential values of fingerprint, especially for the partial and distorted fingerprint. But the research remains still in the pilot phases or is ongoing. Amino acids are the dominant organic substances in latent sweat fingerprint and influenced by many donor factors. Hence, their content reflects personal information of donors. Forensic science will be revolutionized if suspects can be individualized by their amino acid content. The diverse nature, distinct physicochemical properties, and ultra‐micro levels of amino acids present in fingerprints make it hard to detect. A high sensitivity method for detecting and quantifying multiple amino acid components is required. UHPLC‐QqQ MS/MS offers high sensitivity, high separation, simultaneous multicomponents detection, and no derivatization, making it an ideal method for detecting and analyzing amino acids in fingerprints. Therefore, in this study, we propose and validate an efficient UHPLC‐QqQ MS/MS method for the extraction and analysis of 13 amino acids from fingerprint. We compared the results of amino acids of 10 different substrates and found that the inherent amino acids in most porous substrates would have been extracted along with the fingerprint amino acids, making them unsuitable for quantitative amino acid analysis. Instead, plastic sheets are ideal substrates for laboratory studies. Then, extensive experiments were conducted among 30 donors for multidimensional information analysis. The type of samples analyzed were eccrine‐rich fingerprints. A Binary Logistic Regression (BLR) model was developed, and the female and male donors were successfully differentiated by amino acids in fingerprints. Two other mathematical models were also developed to verify the accuracy, and all three different mathematical models were able to identify donors of different genders with over 90% accuracy. This demonstrates that amino acids have the potential to provide more information for donors as metabolic markers. In the future, we will conduct a series of experiments to analyze more multidimensional information for individual identification by amino acid content in the fingerprint.
The Duty of Water: Land, Labour, and the Racialisation of Waste in Colonial and Contemporary Punjab
Authors: Hayat Maira 
Published: January 2024

AbstractIn our present changing climate, water governance is fast becoming a matter of concern everywhere, but especially in the Global South, which has long been the object of (mis)understandings of state failure and dysfunction. A common characterisation of “bad” water governance calls attention to the waste of water. In this article I show how contemporary development discourse and practice around the waste of water articulate conceptions of bureaucratic labour, farmer capability, and the suitability of irrigation practices, recalling a prior moment in colonial water governance. Examining the development of the “duty of water” in the context of canal irrigation infrastructure in colonial Punjab, I argue that seemingly “technical” measures and metrics of water governance are rooted in a colonial grammar, and show how the duty of water articulated racialised classifications of natives as wasteful, their places as waste, and of their labour, both agricultural and bureaucratic. While the tendency has been to view colonial irrigation as a battle with nature, I emphasise it instead as a battle of British with native labour to contribute to conceptualisations of environment and bureaucracy inseparable from, and incomplete without, an understanding of racialised labour. Today, figurations of labour have changed, but the underlying view of labour impeding, not enabling, governance, continues.
Maternal biomarkers in predicting neonatal sepsis after preterm premature rupture of membranes in preterm infants
Authors: Grill Agnes , Goeral Katharina , Leitich Harald , Farr Alex , Berger Angelika , Rittenschober‐Boehm Judith 
Published: January 2024

AbstractAimThis retrospective cohort study aimed to assess the utility of maternal C‐reactive protein (CRP) and leukocyte levels in predicting neonatal sepsis after preterm premature rupture of membranes (pPROM).MethodsWe conducted a retrospective cohort study (2009–2021), encompassing preterm infants born ≤29 + 6 weeks of gestation following pPROM. The primary outcome was early‐onset neonatal sepsis within the initial 72 h of life.ResultsWe analysed data from 706 patients with a median gestational age at pPROM of 25.1 weeks and a median gestational age at birth of 26.4 weeks. Overall survival rate was 86.1%, with 65.7% survival without severe morbidities. These rates were significantly worse in preterm infants with sepsis. Maternal CRP and leukocyte levels correlated significantly with neonatal infection markers and sepsis. However, their predictive values, correlation coefficients, and area under the curve values were generally low. Using maternal CRP ≥2 mg/dL to predict neonatal sepsis yielded a positive predictive value of 18.5%, negative predictive value of 91.5%, AUC of 0.589, 45.5% sensitivity, and 74.5% specificity.ConclusionMaternal CRP and leukocyte levels were ineffective as a tool for predicting early‐onset neonatal sepsis following early pPROM. Consequently, these biomarkers lack the reliability required for clinical decision‐making in this context.
Patterns of long‐term care service use and multimorbidity in older Japanese adults: A cross‐sectional study of claim data
Authors: Sagawa Mieko , Noguchi‐Watanabe Maiko , Fukui Sakiko 
Published: January 2024

AimThe long‐term care (LTC) insurance system provides a combination of several services in Japan; therefore, it is important to clarify service utilization. Furthermore, it is important to consider multimorbidity among older adults, who frequently present several diseases. This study aimed to clarify LTC service utilization patterns, including those for newly added multifunctional services, and to describe the basic characteristics, including multimorbidity, of these patterns.MethodsWe included 37 419 older adults in care need levels 1–5, living at home, who used LTC services in October 2017. We used LTC and medical claims data that were linked using unique identifiers from the National Health Insurance, Advanced Elderly Medical Insurance, and LTC Insurance of Shizuoka Prefecture in Japan. LTC service utilization patterns were identified using cluster analysis based on service fees. Multimorbidity was analyzed using the Charlson Comorbidity Index (CCI) and compared characteristics in these patterns.ResultsSix LTC service utilization patterns were identified: light use (51.0%), intensive use of day care (33.7%), intensive use of short stay (6.3%), intensive use of home help (5.1%), multifunctional LTC in small‐group homes (MLS) use (3.7%), and MLS and home‐visiting nurses (MLSH) use (0.2%). MLSH use had the highest CCI (3.6 ± 2.3). Intensive use of day care and short stay had the lowest CCI (2.6 ± 1.9).ConclusionsThe characteristics of multimorbidity differed by LTC service utilization patterns. Our findings are useful for considering service utilization that takes into account the characteristics of older adults. Geriatr Gerontol Int 2024; 24: 283–289.
Major histocompatibility complex (MHC) gene frequency in acquired dermal macular hyperpigmentation: a case control study
Authors: Vinay Keshavamurthy , Kamat Divya , Narayan R Vignesh , Minz Ranjana W. , Singh Jagdeep , Bishnoi Anuradha , Chatterjee Debajyoti , Parsad Davinder , Kumaran Muthu S. 
Published: January 2024

AbstractBackgroundHuman leukocyte antigen (HLA) allele frequencies have a known association with the pathogenesis of various autoimmune diseases.MethodsWe recruited 31 Indian patients of acquired dermal macular hyperpigmentation (ADMH) and 60 unrelated, age‐and‐gender‐matched healthy controls. After history and clinical examination, 5 ml of blood in EDTA vials was collected. These samples were subjected to DNA extraction and the expression of HLA A, B, C, DR, DQ‐A, and DQ‐B was studied.ResultsThere was a predominance of females with a gender ratio of 23 : 8 and the most common phototype was Fitzpatrick type IV (83.9%). There was a significant association of HLA A*03:01 (OR: 5.8, CI: 1.7–17.0, P = 0.005), HLA B*07:02 (OR: 5.3, CI: 1.9–14.6, P = 0.003), HLA C*07:02 (OR: 4.3, CI: 1.8–9.6, P = 0.001), HLA DRB1*10:01 (OR: 7.6, CI: 1.7–38.00, P = 0.022), and HLA DRB1*15:02 (OR: 31.0, CI: 4.4–341.8, P < 0.001) with patients compared to controls, whereas HLA DQB*03:01 was less associated with patients compared to controls (OR: 0.2, CI: 0.0–0.6, P = 0.009).ConclusionPatients with ADMH are more likely to have the HLA A*03:01, HLA B 07*02, HLA C*07:02, HLA DRB1*10:01, HLA DRB1*15:02 and less likely to have the HLA DQB*03:01 allele. Larger cohort studies may thus be conducted studying these specific alleles.
A predictive multistage postdisaster damage assessment framework for drone routing
Authors: Adsanver Birce , Coban Elvin , Balcik Burcu 
Published: January 2024

AbstractThis study focuses on postdisaster damage assessment operations supported by a set of drones. We propose a multistage framework, consisting of two phases applied iteratively to rapidly gather damage information within an assessment period. In the initial phase, the problem involves determining areas to be scanned by each drone and the optimal sequence for visiting these selected areas. We have adapted an electric vehicle routing formulation and devised a variable neighborhood descent heuristic for this phase. In the second phase, information collected from the scanned areas is employed to predict the damage status of the unscanned areas. We have introduced a novel, fast, and easily implementable imputation policy for this purpose. To evaluate the performance of our approach in real‐life disasters, we develop a case study for the expected 7.5 magnitude earthquake in Istanbul, Turkey. Our numerical study demonstrates a significant improvement in response time and priority‐based metrics.
Non‐invasive medical imaging technology for the diagnosis of burn depth
Authors: Li Hang , Bu Qilong , Shi Xufeng , Xu Xiayu , Li Jing 
Published: January 2024

AbstractCurrently, the clinical diagnosis of burn depth primarily relies on physicians' judgements based on patients' symptoms and physical signs, particularly the morphological characteristics of the wound. This method highly depends on individual doctors' clinical experience, proving challenging for less experienced or primary care physicians, with results often varying from one practitioner to another. Therefore, scholars have been exploring an objective and quantitative auxiliary examination technique to enhance the accuracy and consistency of burn depth diagnosis. Non‐invasive medical imaging technology, with its significant advantages in examining tissue surface morphology, blood flow in deep and changes in structure and composition, has become a hot topic in burn diagnostic technology research in recent years. This paper reviews various non‐invasive medical imaging technologies that have shown potential in burn depth diagnosis. These technologies are summarized and synthesized in terms of imaging principles, current research status, advantages and limitations, aiming to provide a reference for clinical application or research for burn specialists.