bluuebunny/crossref_metadata_2025_split huggingface dataset:
Female-biased population sex ratios caused by genetic rather than ecological mechanisms
Authors: Mao Xiaomeng , Cortés Andres J. , Rixen Christian , Karrenberg Sophie 
Published: December 2023

Abstract1. Biased sex ratios among reproductive individuals are common in plants, but the underlying mechanisms, as well as the evolutionary consequences, are not well understood. The classical theory of Düsing and Fisher predicts an equal primary sex ratio at seed production, based on the selective advantage of the rare sex. Biased sex ratios among reproductive plants can arise from sexual dimorphism in survival and flowering. Sex ratio biases can also be present from seed; in these cases, assumptions of Düsing’s and Fisher’s theory, for example, random mating or demographic equilibrium, were not met.2. We investigated mechanisms leading to female-biased sex ratios in the arctic-alpine dwarf willowSalix herbaceaL. We studied sex ratios in three natural populations over three years as well as in 29 crosses (full-sib families) under controlled conditions over four growth periods. We tested whether sex ratio was associated with germination, survival or flowering, and whether females and males differed in habitat, size or flowering.3. We detected a strong and consistent female bias, both in natural populations (sex ratio [proportion of females]: 0.71-0.82) and in our controlled experiment (overall sex ratio: 0.70-0-72). Our data did not support habitat segregation of the sexes or sexual dimorphism in size or flowering. Family sex ratios varied largely (from 0.25 to 1), including many female-biased families, but also unbiased families and two male-biased families. Families with lower germination, seedling establishment, survival or flowering did not have stronger female bias, indicating that intrinsically higher survival or flowering in females does not explain overall female bias.4. Synthesis. Our results suggest that sex ratio bias inS. herbaceais already present in seeds and does not arise through intrinsic differences between sexes. Candidate mechanisms that can lead to both overall female bias and variation in sex ratio among families are meiotic drive or cyto-nuclear interactions. The pioneer habit ofSalixmay lead to non-equilibrium population dynamics that allow for the long-term persistence of variable genetic sex ratio distortion systems that arise from genetic conflict.
Functional genetic characterization of stress tolerance and biofilm formation inNakaseomyces glabratavia a novel CRISPR activation system
Authors: Maroc Laetitia , Shaker Hajer , Shapiro Rebecca S. 
Published: December 2023

AbstractThe overexpression of genes frequently arises inNakaseomyces(formerlyCandida)glabratavia gain-of-function mutations, gene duplication or aneuploidies, with important consequences on pathogenesis traits and antifungal drug resistance. This highlights the need to develop specific genetic tools to mimic and study genetic amplification in this important fungal pathogen. Here, we report the development, validation, and applications of the first CRISPR activation (CRISPRa) system inN. glabratafor targeted genetic overexpression. Using this system, we demonstrate the ability of CRISPRa to drive high levels of gene expression inN. glabrata, and further assess optimal guide RNA targeting for robust overexpression. We demonstrate the applications of CRISPRa to overexpress genes involved in fungal pathogenesis and drug resistance, and detect corresponding phenotypic alterations in these key traits, including the characterization of novel phenotypes. Finally, we capture strain variation using our CRISPRa system in two commonly usedN. glabratagenetic backgrounds. Together, this tool will expand our capacity for functional genetic overexpression in this pathogen, with numerous possibilities for future applications.
Tight junction component protein claudin-1 deficiency in retinal pigment epithelium leads to early and intermediate age-related macular degeneration phenotypes in mice
Authors: Nakai Ayaka , Lee Deokho , Zhang Yan , Shoda Chiho , Imanishi Tetsu , Jeong Heonuk , Ikeda Shin-ichi , Negishi Kazuno , Nakashizuka Hiroyuki , Yamagami Satoru , Kubo Akiharu , Kurihara Toshihide 
Published: December 2023

AbstractThe early and intermediate age-related macular degeneration (AMD) is characterized by the presence of drusen and pigmentary abnormalities in the retinal pigment epithelial (RPE) cells which form the outer blood retinal barrier (oBRB). Fluid leakage through the disrupted oBRB from the choroid to the neural retina has been implicated in the pathogenesis of AMD, however; the molecular mechanisms still remain unclear. The family of four transmembrane proteins, claudins are known to form tight junctions (TJs) in the oBRB. Nonetheless, there are few reports showing how they function in the oBRBin vivo. We found that claudin-1 is dominantly expressed in TJs of the mouse RPE. To investigate the role of claudin-1 in the RPE, we generated RPE-specificCldn1conditional knockout mice (Best1-Cre+/-Cldn1flox/floxmice:Cldn1cKO mice). Deficiency ofCldn1led to age-related lipid deposits such as subretinal drusenoid deposits (SDD), increased lipid droplets in the RPE, basal lamellar deposits (BlamD) and membranous debris in the Bruch’s membrane. In addition, pigmentary abnormalities such as RPE hypertrophy, multilayered-RPE cells, and ectopic pigment granules outside the RPE were observed inCldn1cKO mice. Our study provides new insights into the possible association of the TJ protein claudin-1 with lipid metabolism and cellular ageing in the RPE contributing to the early onset of AMD.
DisDock: A Deep Learning Method for Metal Ion-Protein Redocking
Authors: Lin Menghan , Li Keqiao , Zhang Yuan , Pan Feng , Wu Wei , Zhang Jinfeng 
Published: December 2023

AbstractThe structures of metalloproteins are essential for comprehending their functions and interactions. The breakthrough of AlphaFold has made it possible to predict protein structures with experimental accuracy. However, the type of metal ion that a metalloprotein binds and the binding structure are still not readily available, even with the predicted protein structure. In this study, we present DisDock, a physics-driven deep learning method for predicting protein-metal docking. DisDock takes distogram of randomly initialized protein-ligand configuration as input and outputs the distogram of the predicted binding complex. It combines the U-net architecture with self-attention modules to enhance model performance. Taking inspiration from the physical principle that atoms in closer proximity display a stronger mutual attraction, this predictor capitalizes on geometric information to uncover latent characteristics indicative of atom interactions. To train our model, we employ a high-quality metalloprotein dataset sourced from the Mother of All Databases (MOAD). Experimental results demonstrate that our approach outperforms other existing methods in prediction accuracy for various types of metal ions.
Regional differences in synaptic degeneration are linked to alpha-synuclein burden and axonal damage in Parkinson’s disease and Dementia with Lewy bodies
Authors: Frigerio Irene , Bouwman Maud MA , Noordermeer Ruby TGMM , Podobnik Ema , Popovic Marko , Timmermans Evelien , Rozemuller Annemieke JM , van de Berg Wilma DJ , Jonkman Laura E 
Published: December 2023

AbstractRegional differences in synaptic degeneration may underlie differences in clinical presentation and neuropathological disease progression in Parkinson’s Disease (PD) and Dementia with Lewy bodies (DLB). Here, we mapped and quantified synaptic degeneration in cortical brain regions in PD, PD with dementia (PDD) and DLB, and assessed whether regional differences in synaptic loss are linked to axonal degeneration and neuropathological burden. We included a total of 47 brain donors, 9 PD, 12 PDD, 6 DLB and 20 non-neurological controls. Synaptophysin+and SV2A+puncta were quantified in eight cortical regions using a high throughput microscopy approach. Neurofilament light chain (NfL) immunoreactivity, Lewy body (LB) density, phosphorylated-tau and amyloid-β load were also quantified. Group differences in synaptic density, and associations with neuropathological markers and Clinical Dementia Rating (CDR) scores, were investigated using linear mixed models. We found significantly decreased synaptophysin and SV2A densities in the cortex of PD, PDD and DLB cases compared to controls. Specifically, synaptic density was decreased in cortical regions affected at Braak α-synuclein stage 5 in PD (middle temporal gyrus, anterior cingulate and insula), and was additionally decreased in cortical regions affected at Braak α-synuclein stage 4 in PDD and DLB compared to controls (entorhinal cortex, parahippocampal gyrus and fusiform gyrus). Synaptic loss associated with higher NfL immunoreactivity and LB density. Global synaptophysin loss associated with longer disease duration and higher CDR scores. Synaptic neurodegeneration occurred in temporal, cingulate and insular cortices in PD, as well as in parahippocampal regions in PDD and DLB. In addition, synaptic loss was linked to axonal damage and severe α-synuclein burden. These results, together with the association between synaptic loss and disease progression and cognitive impairment, indicate that regional synaptic loss may underlie clinical differences between PD and PDD/DLB. Our results might provide useful information for the interpretation of synaptic biomarkersin vivo.
A Fluorescence-Based Sensor for Calibrated Measurement of Protein Kinase Stability in Live Cells
Authors: Paul Joseph W. , Muratcioğlu Serena , Kuriyan John 
Published: December 2023

AbstractOncogenic mutations can destabilize signaling proteins, resulting in increased or unregulated activity. Thus, there is considerable interest in mapping the relationship between mutations and the stability of proteins, to better understand the consequences of oncogenic mutations and potentially inform the development of new therapeutics. Here, we develop a tool to study protein-kinase stability in live mammalian cells and the effects of the HSP90 chaperone system on the stability of these kinases. We monitor the fluorescence of kinases fused to a fluorescent protein relative to that of a co-expressed reference fluorescent protein. We used this tool to study the dependence of Src- and Raf-family kinases on the HSP90 system. We demonstrate that this sensor reports on destabilization induced by oncogenic mutations in these kinases. We also show that Src-homology 2 (SH2) and Src-homology 3 (SH3) domains, which are required for autoinhibition of Src-family kinases, stabilize these kinase domains in the cell. Our expression-calibrated sensor enables the facile characterization of the effects of mutations and small-molecule drugs on protein-kinase stability.
The role of Miocene-Pleistocene environmental change in diversification of the genusHypoclinemusChabanaud, 1928
Authors: Rodrigues Alan Erik S. , Ready Jonathan Stuart , Pereira da Silva Lucas Gabriel , Silva Kamila de Fátima , Ferreira Silva Derlan José , Sabaj Mark H. , Andrade Marcelo C. , Vasconcelos Santelmo , Sales João Bráullio L. 
Published: December 2023

AbstractThe Neotropical region stands out as one of the most taxonomically diverse areas on the planet, garnering significant attention in the context of marine incursions and their role in shaping this diversity. Among marine-derived taxa, pleuronectiform fishes exhibit distinctive morphological characteristics that have attracted significant scientific interest. However, the biogeography ofHypoclinemus mentalis, initially described asSolea mentalisand subsequently assigned to the genusAchirus, was eventually reclassified into its current monotypic genus due to its limited distribution in freshwater environments, in contrast to the species ofAchirus. The broad distribution of a single species across multiple South American river basins positionsH. mentalisas an ideal candidate for biogeographic studies within South America, with an emphasis on the detection of cryptic lineages associated with major drainage basins. In our study, we employed mitochondrial and nuclear markers to investigate the potential existence of such lineages within the broader context of a molecular phylogeny that encompasses all valid genera in the flatfish family Achiridae. Our findings reveal thatHypoclinemuscomprises seven operational taxonomic units (OTUs), as deduced from specimens collected across the majority of its documented range. Furthermore, our phylogeographic analyses support the hypothesis that colonization of freshwater habitats occurred through connections between the Caribbean Sea and Lake Pebas approximately 21.28 million years ago. Moreover, we observed that differentiation of lineages within theHypoclinemusgenus was significantly influenced by pronounced sea level fluctuations during the Plio-Pleistocene epoch, underscoring the impact of glaciations and interglacial periods on the biogeographic patterns.
Nuclear VANGL2 Inhibits Lactogenic Differentiation
Authors: Rubio Stefany , Molinuevo Rut , Sanz-Gomez Natalia , Zomorrodinia Talieh , Cockrum Chad S. , Luong Elina , Rivas Lucia , Cadle Kora , Menendez Julien , Hinck Lindsay 
Published: December 2023

ABSTRACTPlanar cell polarity (PCP) proteins coordinate tissue morphogenesis by governing cell patterning and polarity. Asymmetrically localized on the plasma membrane of cells, PCP proteins are also trafficked by endocytosis, suggesting they may have intracellular functions that are dependent or independent of their extracellular role, but whether these functions extend to transcriptional control remains unknown. Here, we show the nuclear localization of transmembrane, PCP protein, VANGL2, in undifferentiated, but not differentiated, HC11 cells, which serve as a model for mammary lactogenic differentiation. Loss ofVangl2function results in upregulation of pathways related to STAT5 signaling. We identify DNA binding sites and a nuclear localization signal in VANGL2, and use CUT&RUN to demonstrate direct binding of VANGL2 to specific DNA binding motifs, including one in theStat5apromoter. Knockdown (KD) ofVangl2in HC11 cells and primary mammary organoids results in upregulation ofStat5a,Ccnd1andCsn2, larger acini and organoids, and precocious differentiation; phenotypes rescued by overexpression ofVangl2, but notVangl2ΔNLS. Together, these results advance a paradigm whereby PCP proteins coordinate tissue morphogenesis by keeping transcriptional programs governing differentiation in check.
Shaping contexts through entrepreneurship: a micro-historical analysis of Hongbang entrepreneurs in China (1896-1949)
Authors: Xu Cheng , Zhou Haibo , Fan Bohong , Sun Yanqi 
Published: December 2023

Purpose
The purpose of this study is to address a significant gap in the understanding of entrepreneurship at the microfoundation level. It focuses on how individual entrepreneurs, specifically Hongbang entrepreneurs in China from 1896 to 1949, shape and transform their contexts. The aim is to provide a deeper understanding of the mechanisms that facilitate entrepreneurial success.

Design/methodology/approach
The study adopts a microhistorical approach, investigating the case of Hongbang entrepreneurs in China during 1896-1949. It involves an in-depth examination of historical records to explore the strategic interactions between these entrepreneurs and core stakeholders such as consumers, financial intermediaries, government regulators, and human resources. The research methodology emphasizes a process-oriented view, examining the evolution of personalized networks into extensive connections.

Findings
The research reveals that Hongbang entrepreneurs successfully reshaped their unfavorable embedded contexts by strategically collaborating with key stakeholders. They influenced consumer tastes, allied with financial intermediaries, negotiated with governments on regulation policies, and developed human resource stocks. The transformation was facilitated by the evolution of their networks from personalized to extensive connections. These findings highlight the localized strategies such as cronyism in resource acquisition within China’s private property development industry.

Originality/value
This study contributes to the field by offering insights into entrepreneurial contextualization and networking. It sheds light on the complex interplay between entrepreneurs and their contexts, providing a nuanced understanding of localized strategies in the Chinese context. The findings add value to the discourse on entrepreneurship by elucidating the strategic and processual acts through which entrepreneurs engage with stakeholders and reshape their environments.
Interactive effects of organizational resources on sustainable product design practices: a resource orchestration perspective
Authors: John-Mariadoss Babu , Pomirleanu Nadia , Chennamaneni Pavan R. , Ganesh Pillai Rajani , Zailani Suhaiza 
Published: December 2023

Purpose
The purpose of this study is to investigate the interactive effects of a firm’s strategic sustainability orientation (SSO) and customer relationship capital (CRC) on sustainable product design practices (SPDP).

Design/methodology/approach
The authors examine the interactive effects of two firm resources, namely, SSO and CRC, as they relate to SPDP, using survey data from 132 manufacturers in Malaysia.

Findings
The findings show that the effect of SSO on SPDP is stronger when CRC is low, than otherwise. The authors also find that the interactive effects of the firm-level resources stated above are stronger when customer pressures (CPs) are higher than when they are low.

Research limitations/implications
The authors contribute to the literature by studying the effects of firm-level strategic resources and their interactions as they relate to SPDP. An important limitation of this research is the usage of single-source data and single-period data.

Practical implications
Managerially, this research provides new insights into how organizations should respond to CPs while understanding the counterintuitive but disabling effects of customer relationship assets.

Social implications
The findings are important to society because most of the environmental impact arising from the production, consumption and disposal of products is a direct consequence of decisions made at the product design stage and an unintended consequence of the marketing decision-making processes that underlie marketing strategy formulation that fails to recognize ecosystems impact as a standard decision influence.

Originality/value
To the best of the authors’ knowledge, this research is the first to study the effects of firm-level strategic resources and their interactions as they relate to SPDP.
After COVID-19 lockdown: an exploratory study about the influence of mindfulness-feelings toward an individual’s outdoor lifestyle and empowerment
Authors: Borges Ana Pinto , Vieira Elvira Pacheco , Rodrigues Paula , Lopes de Almeida António , Sousa Ana 
Published: December 2023

PurposeThis study aimed to detect the relationships between mindfulness and events participation, and then between the later and psychological empowerment.Design/methodology/approachThe proposed model's underlying hypotheses were empirically tested with data collected through an online survey addressed to a convenience sample of frequent leisure participants (n = 199). The authors applied the structural equation model (SEM) to confirm the aforementioned relationships. To assess the adequacy of the psychometric properties of the measures, the authors performed a confirmatory factor analysis of the measurement model, with a maximum likelihood estimation method.FindingsUnder the effects of the lockdown period environment, the results express a positive relationship between a mindful state of mind – related to observation/attention – and the yearnings and perceptions about the participation in events. This relationship for consistency was proven to be moderated by the perception of the participation importance to the individual subjective well-being/mental health. Due to participation insights, there was a positive effect on psychological empowerment, supporting the relationship that had been hypothesized.Originality/valueThe authors propose and test a new model that contributes to the theory and examines how mindfulness behavior can effect more alluring and intense participation in events and what are the anticipated outcomes in terms of psychological empowerment.
Validation of sustainability indicators in the energy sector considering their relationship with the UN SDGs: analysis of an emerging economy country using the Lawshe method
Authors: Marinho Samille Souza , Rego Neto Armando Gomes , Fernandes Reimison Moreira , Silva Melo André Cristiano , Lourenço Bastos Leonardo dos Santos , Martins Vitor William Batista 
Published: December 2023

Purpose
This study aims to identify sustainability indicators in the energy sector through a literature review and validate them from the perspective and context of professionals working in the sector in an emerging economy country, Brazil, considering the relationship of these indicators with the achievement of the targets set by the United Nations sustainable development goals (UN SDGs).

Design/methodology/approach
To accomplish this, a literature review on sustainability indicators specific to the energy sector was conducted. Subsequently, a research instrument (questionnaire) based on the identified indicators was developed and a survey was administered to professionals in the field. The collected data were analyzed using the Lawshe method.

Findings
The results revealed 20 indicators, distributed across environmental, economic and social dimensions. Among these, nine indicators were validated, including global impacts, local impacts, renewable energy production as a percentage of total production, greenhouse gas emissions, access to electricity, investment in the energy sector, installed capacity in the electricity sector, energy prices in the end-use sector and energy distribution and conversion efficiency.

Originality/value
Consequently, it was possible to determine which SDGs are directly impacted and provide a foundation for future actions that can contribute to the sustainable advancement of the energy sector in emerging countries.