bluuebunny/crossref_metadata_2025 huggingface dataset:
SPT6L, a newly discovered ancestral component of the plant RNA-directed DNA methylation pathway
Authors: Čermák Vojtěch , Kašpar Tomáš , Fischer Lukáš
Published: January 2024

RNA-directed DNA methylation (RdDM) is driven by small RNAs (sRNAs) complementary to the nascent transcript of RNA polymerase V (Pol V). sRNAs associated with ARGONAUTE (AGO) proteins are tethered to Pol V mainly by the AGO-hook domain of its subunit NRPE1. We found, byin silicoanalyses, that Pol V strongly colocalizes on chromatin with another AGO-hook protein, SPT6-like (SPT6L), which is a known essential transcription elongation factor of Pol II. Our phylogenetic analysis revealed that SPT6L acquired its AGO-binding capacity already in the most basal streptophyte algae, even before the emergence of Pol V, suggesting that SPT6L might be a driving force behind the RdDM evolution. Since its emergence, SPT6L with the AGO-hook represents the only conserved SPT6 homolog inViridiplantae, implying that the same protein is involved in both Pol II and Pol V complexes. To better understand the role of SPT6L in the Pol V complex, we characterized genomic loci where these two colocalize and uncovered that DNA methylation there is more dynamic, driven by higher levels of sRNAs often from non-canonical RdDM pathways and more dependent on chromatin modifying and remodeling proteins like MORC. Pol V loci with SPT6L are highly depleted in helitrons but enriched in gene promoters for which locally and temporally precise methylation is necessary. In view of these results, we discuss potential roles of multiple AGO-hook domains present in the Pol V complex and speculate that SPT6L mediatesde novomethylation of naïve loci by interconnecting Pol II and Pol V activities.
MoCHI: neural networks to fit interpretable models and quantify energies, energetic couplings, epistasis and allostery from deep mutational scanning data
Authors: Faure Andre J. , Lehner Ben
Published: January 2024

The massively parallel nature of deep mutational scanning (DMS) allows the quantification of the phenotypic effects of thousands of perturbations in a single experiment. We have developed MoCHI, a software tool that allows the parameterisation of arbitrarily complex models using DMS data. MoCHI simplifies the task of building custom models from measurements of mutant effects on any number of phenotypes. It allows the inference of free energy changes, as well as pairwise and higher-order interaction terms (energetic couplings) for specified biophysical models. When a suitable user-specified mechanistic model is not available, global nonlinearities (epistasis) can be estimated directly from the data. MoCHI also builds upon and leverages theory on ensemble (or background-averaged) epistasis to learn sparse predictive models that can incorporate higher-order epistatic terms and are informative of the genetic architecture of the underlying biological system. The combination of DMS and MoCHI allows biophysical measurements to be performed at scale, including the construction of complete allosteric maps of proteins. MoCHI is freely available (https://github.com/lehner-lab/MoCHI) and implemented as an easy-to-use python package relying on the PyTorch machine learning framework.
B-type plexins regulate mitosis via RanGTPase
Authors: Mukhwana Nicholus , Garg Ritu , Williamson Magali
Published: January 2024

Aberrant mitosis can result in aneuploidy and cancer. The small GTPase, Ran, is a key regulator of mitosis. B-type Plexins regulate Ran activity by acting as RanGTPase activating proteins (GAPs) and have been implicated in cancer progression. However, whether B-type plexins have a role in mitosis has not so far been investigated.

We show here that PlexinB1 functions in the control of mitosis. Depletion of PlexinB1 resulted in defects in chromosomal segregation, increasing cells with multipolar spindles and prolonging metaphase, while activation of PlexinB1/B2 with Sema4D produced aberrant spindles.

An increase in MAD1-positive kinetochores in PlexinB1/B2 depleted cells indicated application of spindle assembly checkpoint (SAC), possibly resulting from faulty spindle-microtubule assembly, and PlexinB1 depletion promoted regrowth of acentrosomal microtubules and defects in spindle pole refocussing. Depleted cells that had bypassed SAC possessed lagging chromosomes and chromosomal bridges.

The mitotic defects observed upon PlexinB1 depletion were rescued by an RCC1 inhibitor, indicating that PlexinB1 signals, at least in part, via Ran to affect mitosis.

These errors in mitosis generated multinucleate cells, and nuclei of altered morphology and abnormal karyotype. Furthermore, Sema4D-treatment increased the percentage of cells with micronuclei, precursors of chromothripsis. Defects in B-type plexins may contribute to the well-established role of plexins in cancer progression by inducing chromosomal instability.
Human IL-6 fosters long-term engraftment of patient derived disease-driving myeloma cells in immunodeficient mice
Authors: Hasanali Zainul S. , Garfall Alfred L. , Burzenski Lisa , Shultz Leonard D. , Tang Yan , Kadu Siddhant , Sheppard Neil C. , Dopkin Derek , Vogl Dan T. , Cohen Adam D. , Waxman Adam J. , Susanibar-Adaniya Sandra P. , Carroll Martin , Stadtmauer Edward A. , Allman David
Published: January 2024

Multiple myeloma is a largely incurable and life-threatening malignancy of antibody-secreting plasma cells. An effective and widely available animal model that recapitulates human myeloma and related plasma cell disorders is lacking. We show that busulfan-conditioned hIL-6 transgenic NSG mice (NSG+hIL6) reliably support the engraftment of malignant and pre-malignant human plasma cells including from patients diagnosed with monoclonal gammopathy of undetermined significance, pre- and post-relapse myeloma, plasma cell leukemia, and AL amyloidosis. Consistent with human disease, NSG+hIL6 mice engrafted with patient-derived myeloma cells, developed serum M spikes, and a majority developed anemia, hypercalcemia, and/or bone lesions. Single cell RNA sequencing showed non-malignant and malignant cell engraftment, the latter expressing a wide array of mRNAs associated with myeloma cell survival and proliferation. Myeloma engrafted mice given CAR T-cells targeting plasma cells or bortezomib experienced reduced tumor burden. Our results establish NSG+hIL6 mice as an effective patient derived xenograft model for study and preclinical drug development of multiple myeloma and related plasma cell disorders.
Med12 cooperates with multiple differentiation signals to facilitate efficient lineage transitions in embryonic stem cells
Authors: Fernkorn Max , Schröter Christian
Published: January 2024

Cell differentiation results from coordinated changes in gene transcription in response to combinations of signals. FGF, Wnt, and mTOR signals regulate the differentiation of pluripotent mammalian cells towards embryonic and extraembryonic lineages, but how these signals cooperate with general transcriptional regulators is not fully resolved. Here, we report a genome-wide CRISPR screen that reveals both signaling components and general transcriptional regulators for differentiation-associated gene expression in mESCs. Focusing on the Mediator subunitMed12as one of the strongest hits in the screen, we show that it regulates gene expression in parallel to FGF and mTOR signals. Loss ofMed12is compatible with differentiation along both the embryonic epiblast and the extraembryonic primitive endoderm lineage, but impairs pluripotency gene expression and slows down transitions between pluripotency states. These findings suggest thatMed12helps pluripotent cells to efficiently execute transcriptional changes during differentiation, thereby modulating the effects of a broad range of signals.
An optimized live imaging and growth analysis approach for Arabidopsis Sepals
Authors: Yadav Avilash Singh , Roeder Adrienne H.K.
Published: January 2024

Background

Arabidopsis thalianasepals are excellent models for analyzing growth of entire organs due to their relatively small size, which can be captured at a cellular resolution under a confocal microscope [1]. To investigate how growth of different tissue layers generates unique organ morphologies, it is necessary to live-image deep into the tissue. However, imaging deep cell layers of the sepal is practically challenging, as it is hindered by the presence of extracellular air spaces between mesophyll cells, among other factors which causes optical aberrations. Image processing is also difficult due to the low signal-to-noise ratio of the deeper tissue layers, an issue mainly associated with live imaging datasets. Addressing some of these challenges, we provide an optimized methodology for live imaging sepals and subsequent image processing. This helps us track the growth of individual cells on the outer and inner epidermal layers, which are the key drivers of sepal morphogenesis.

Results

For live imaging sepals across all tissue layers at early stages of development, we found that the use of a bright fluorescent membrane marker, coupled with increased laser intensity and an enhanced Z-resolution produces high-quality images suitable for downstream image processing. Our optimized parameters allowed us to image the bottommost cell layer of the sepal (inner epidermal layer) without compromising viability. We used a ‘voxel removal’ technique to visualize the inner epidermal layer in MorphoGraphX [2, 3] image processing software. Finally, we describe the process of optimizing the parameters for creating a 2.5D mesh surface for the inner epidermis. This allowed segmentation and parent tracking of individual cells through multiple time points, despite the weak signal of the inner epidermal cells.

Conclusion

We provide a robust pipeline for imaging and analyzing growth across inner and outer epidermal layers during early sepal development. Our approach can potentially be employed for analyzing growth of other internal cell layers of the sepals as well. For each of the steps, approaches, and parameters we used, we have provided in-depth explanations to help researchers understand the rationale and replicate our pipeline.
Transcriptomic interplay betweenAcinetobacter baumannii, human macrophage and polymyxin
Authors: Kho Zhi Ying , Azad Mohammad Abul Kalam , Zhu Yan , Han Mei-Ling , Zhou Qi (Tony) , Velkov Tony , Naderer Thomas , Li Jian
Published: January 2024

Optimization of antibiotic therapy has been hindered by our dearth of understanding on the mechanism of the host-pathogen-drug interactions. Here, we employed dual RNA-sequencing to examine transcriptomic perturbations in response to polymyxin B in a co-culture infection model ofAcinetobacter baumanniiand human macrophages. Our findings revealed that polymyxin B treatment induced significant transcriptomic response in macrophage-interactingA. baumannii, exacerbating bacterial oxidative stress, disrupting metal homeostasis, affecting osmoadaptation, triggering stringent stress response, and influencing pathogenic factors. Moreover, infected macrophages adapt heme catabolism, coagulation cascade, and hypoxia-inducible signaling to confront bacterial invasion. DisruptingrcnB,ompW, andtraR/dksAgenes inA. baumanniiimpairs metal homeostasis, osmotic stress defense and stringent responses, thereby enhancing antibacterial killing by polymyxin. These findings shed light on the global stress adaptations at the network level during host-pathogen-drug interactions, revealing promising therapeutic targets for further investigation.

IMPORTANCE

In the context of the development of bacterial resistance during the course of antibiotic therapy, the role of macrophages in shaping bacterial response to antibiotic killing remains enigmatic. Herein we employed dual RNA-sequencing and anin vitrotripartite model to delve into the unexplored transcriptional networks of theAcinetobacter baumannii-macrophage-polymyxin axis. Our findings uncovered the potential synergy between macrophages and polymyxin B which appear to act in co-operation to disrupt multiple stress tolerance mechanisms inA. baumannii. Notably, we discovered the critical roles of bacterial nickel/cobalt homeostasis (rcnBfamily), osmotic stress defense (ompWfamily), and stringent response regulator (traR/dksAC4-type zinc finger) in tolerating the last-line antibiotic polymyxin B. Our findings may lead to potential targets for the development of novel therapeutics against the problematic pathogenA. baumannii.
Elaboration of the Homer1 Recognition Landscape Reveals Incomplete Divergence of Paralogous EVH1 Domains
Authors: Singer Avinoam , Ramos Alejandra , Keating Amy E.
Published: January 2024

Short 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 Statement

Short 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.
TET3 regulates cellular terminal differentiation at the metabolic level
Authors: Mulet Isabel , Grueso-Cortina Carmen , Cortés-Cano Mireia , Gerovska Daniela , Wu Guangming , Jimenez-Blasco Daniel , Curtabbi Andrea , Hernansanz-Agustín Pablo , Manjarrés-Raza Israel , Bolaños Juan Pedro , Enríquez José Antonio , Araúzo-Bravo Marcos J. , Tapia Natalia
Published: January 2024

TET-family members play an essential role in cell fate commitment and their dysfunctions result in arrested differentiation. TET3 is ubiquitously expressed in differentiated cells and essential in postnatal development due to yet unknown reasons. To define TET3 function in cell differentiation, we profiled the intestinal epithelium at the single-cell level from wild-type andTet3knockout mice. Here we show that, in the absence of TET3, enterocytes exhibit an aberrant differentiation trajectory and do not acquire a physiological cell identity due to an impairment in oxidative phosphorylation, specifically due to an ATP synthase assembly deficiency. Furthermore, our analysis demonstrates that the loss of TET3 compromises mitochondrial metabolic maturation and leads to a metabolic profile enriched in glycolysis-dependent anabolic pathways similar to those observed in undifferentiated cells. Collectively, our study has revealed the molecular mechanism by which TET3 regulates terminal differentiation at the metabolic level.
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

Transthyretin (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

Norepinephrine (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

Widespread 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

Neurons 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

Purpose

Service 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/approach

This 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.

Findings

The 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/value

This 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

Purpose

Based 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/approach

Hypotheses are tested in an empirical study including 191 firms using partial least square structural equation modeling technique.

Findings

The 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/value

The 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

The 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

In 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

Aim

This 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).

Methods

We 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.

Results

We 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.

Conclusion

Maternal 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

Aim

The 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.

Methods

We 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.

Results

Six 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).

Conclusions

The 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

Background

Human leukocyte antigen (HLA) allele frequencies have a known association with the pathogenesis of various autoimmune diseases.

Methods

We 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.

Results

There 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).

Conclusion

Patients 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

This 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

Currently, 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.
Heat shocks during egg incubation led to developmental, morphological, and behavioral differences in Arctic charr (Salvelinus alpinus)
Authors: Lubin François‐Raphaël , Réalis‐Doyelle Emilie , Espinat Laurent , Guillard Jean , Raffard Allan
Published: January 2024

Temperature variation is affecting fish biodiversity worldwide, causing changes in geographic distribution, phenotypic structure, and even species extinction. Incubation is a critical stage for stenothermic species, which are vulnerable to large temperature fluctuations, and its effects on the phenotype at later developmental stages are understudied, despite the fact that the phenotype being essential for organism ecology and evolution. In this study, we tested the effects of heat shocks during the embryonic period on the phenotype of Arctic charr (Salvelinus alpinus). We repeatedly quantified multiple phenotypic traits, including morphology, development, and behavior, over a period of 4 months, from hatching to juvenile stage in individuals that had experienced heat shocks (+ 5°C on 24 h, seven times) during their embryonic stage and those that had not. We found that heat shocks led to smaller body size at hatching and a lower sociability. Interestingly, these effects weakened throughout the development of individuals and even reversed in the case of body size. We also found an accelerated growth rate and a higher body condition in the presence of heat shocks. Our study provides evidence that heat shocks experienced during incubation can have long‐lasting effects on an individual's phenotype. This highlights the importance of the incubation phase for the development of ectothermic organisms and suggests that temperature fluctuations may have significant ecological and evolutionary implications for Arctic charr. Given the predicted increase in extreme events and the unpredictability of temperature fluctuations, it is critical to further investigate their effects on development by examining fluctuations that vary in frequency and intensity.
Documenting the indication for antimicrobial prescribing: A retrospective observational study of long‐term care homes
Authors: Champaneria Kayuri , Langford Bradley J. , Allen Jean‐Paul , Brown Kevin , Daneman Nick , Schwartz Kevin , Leung Valerie
Published: January 2024

Background

Overuse of antimicrobials in residents of long‐term care homes is common and can result in harm. Antimicrobial stewardship interventions are needed in the long‐term care (LTC) homes setting to improve the appropriate use of antimicrobials. Previous literature has highlighted the importance of documenting antimicrobial indication as a strategy that contributes to improve antimicrobial use; however, there is a lack of evidence in LTC homes. This study examines the prevalence, clarity, and facility‐level variability of antibiotic indication documentation in this setting.

Methods

This is an observational retrospective study of oral antibiotic prescriptions dispensed to 218 homes between January 1, 2021 and December 31, 2022 in Ontario, Canada. Indication was obtained from reviewing antibiotic prescription data. Clarity was determined by comparing documented indication to the National Antimicrobial Prescribing Survey (NAPS). Descriptive analysis was performed to examine the prevalence and clarity of indication documentation. Funnel plots were generated to examine variability in prevalence of indication documentation and clarity at the home level.

Results

Overall, 22.9% (7998/34,867) of prescriptions had an indication documented. The proportion of indications that were clear was 37% (2984/7998). The most common indications were for urinary (45%), skin and soft tissue (19.9%) and respiratory infections (15.0%). At the home level, the median prevalence of indication was 19.6% (interquartile range [IQR]: 10.8%–31.4%) and median prevalence of clear indications was 35.1% (IQR: 23.8%–42.9%). Funnel plots revealed substantial variability in indication prevalence with 46.3% of homes falling outside of 99% limits but minimal variability in indication clarity between homes with only 8.7% of homes outside of 99% control limits.

Conclusions

There is an opportunity to increase both the prevalence and clarity of antibiotic prescriptions in LTC homes. Future work should focus on determining how best to support prescription indication documentation in this setting with consideration being given to prescription workflow and most common antibiotic prescription indications.
Assessing the potential of phytogenic feed additives: A comprehensive review on their effectiveness as a potent dietary enhancement for nonruminant in swine and poultry
Authors: Biswas Sarbani , Ahn Je M. , Kim In Ho
Published: January 2024

Phytogenic feed additives (PFAs) often referred to as phytobiotics or botanical feed additives, are natural compounds derived from various plants, herbs, spices and other botanical sources. These feed additives are intended to serve a variety of purposes, including an immune system regulator, an antimicrobial, an antimutagenic, an antioxidant and a growth promoter. They are composed of bioactive compounds extracted from plants, including essential oils, polyphenols, terpenoids and flavonoids. They are mostly utilized as substitute antibiotic growth promoters in nonruminant (swine and poultry) livestock production, owing to the prohibition of antibiotic usage in the feed industry. It has been thoroughly examined to ascertain their impact on intestinal health and activity, correlation with animals' effective health and well‐being, productivity, food security and environmental impact. The potential uses of these feed additives depend on the properties of herbs, the comprehension of their principal and secondary components, knowledge of their mechanisms of action, the safety of animals and the products they produce. They are gaining recognition as effective and sustainable tools for promoting animal health and performance while reducing the reliance on antibiotics in nonruminant nutrition. Their natural origins, multifaceted benefits and alignment with consumer preferences make them a valuable addition to modern animal farming process. However, because of their inconsistent effects and inadequate knowledge of the mechanisms of action, their usage as a feed additive has been limited. This review offers a comprehensive assessment of the applications of PFAs as an effective feed supplement in swine and poultry nutrition. In summary, this comprehensive review provides current knowledge, identifies gaps in research and emphasizes the potential of phytogenic additives to foster sustainable and healthier livestock production systems while addressing the global concerns associated with antibiotic use in livestock farming.
Yalla Nutbikh “Let's cook”: Negotiating emotions of belonging through food in heritage language classrooms
Authors: Elabdali Rima
Published: January 2024

Research on emotions and second language learning has recently expanded to heritage language education contexts. Influenced by a long tradition in psycholinguistics and second language acquisition, research on heritage language emotions has mainly focused on the statistical effects of emotions on language development rather than examining emotions that relate to social and interpersonal relations. This article responds to these research needs through a critical ethnographic exploration of how emotions of belonging are negotiated through the production and consumption of food at an Arabic heritage language school in the United States. Drawing on data from observations, interviews, and field notes collected during a 2‐year period, I argue that the production and consumption of Arabic food during cooking events and classes at the school afford students opportunities to negotiate emotions of belonging toward Arab culture as an embodied and nonessentialist practice, toward diverse religions and nationalities in the heritage school community, and toward the local majority community in the United States. This analysis foregrounds the affordances of occasions in which language learning and emotions are situated within the sociomaterial practices of heritage culture and highlights the need to establish interinstitutional connections with community schools to support the socioemotional well‐being and educational equity of immigrant and racialized youth.
CYP46A1-mediated cholesterol turnover induces sex-specific changes in cognition and counteracts memory loss in ovariectomized mice
Authors: Latorre-Leal María , Rodriguez-Rodriguez Patricia , Franchini Luca , Nikolidakis Orestis , Daniilidou Makrina , Delac Ljerka , Varshney Mukesh K. , Arroyo-García Luis E. , Eroli Francesca , Winblad Bengt , Blennow Kaj , Zetterberg Henrik , Kivipelto Miia , Pacciarini Manuela , Wang Yuqin , Griffiths William J. , Björkhem Ingemar , Matton Anna , Nalvarte Ivan , Merino-Serrais Paula , Cedazo-Minguez Angel , Maioli Silvia
Published: January 2024

The brain-specific enzyme CYP46A1 controls cholesterol turnover by converting cholesterol into 24
S
-hydroxycholesterol (24OH). Dysregulation of brain cholesterol turnover and reduced
CYP46A1
levels are observed in Alzheimer’s disease (AD). In this study, we report that
CYP46A1
overexpression in aged female mice leads to enhanced estrogen signaling in the hippocampus and improved cognitive functions. In contrast, age-matched
CYP46A1
overexpressing males show anxiety-like behavior, worsened memory, and elevated levels of 5α-dihydrotestosterone in the hippocampus. We report that, in neurons, 24OH contributes to these divergent effects by activating sex hormone signaling, including estrogen receptors.
CYP46A1
overexpression in female mice protects from memory impairments induced by ovariectomy while having no effects in gonadectomized males. Last, we measured cerebrospinal fluid levels of 24OH in a clinical cohort of patients with AD and found that 24OH negatively correlates with neurodegeneration markers only in women. We suggest that CYP46A1 activation is a valuable pharmacological target for enhancing estrogen signaling in women at risk of developing neurodegenerative diseases.