bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Dsc ubiquitin ligase complex identifies transmembrane degrons to degrade orphaned proteins at the Golgi
Authors: Weyer Yannick , Schwabl Sinead Iduna , Tang Xuechen , Widerin Michael A. , Niedrist Veronika , Tettamanti Maria G. , Weys Sabine , Sarg Bettina , Kremser Leopold , Liedl Klaus R. , Schmidt Oliver , Teis David 
Published: March 2024

AbstractThe Golgi apparatus is essential for protein sorting, yet its quality control mechanisms are poorly understood. Here we show that the Dsc ubiquitin ligase complex, particularly the rhomboid pseudo-protease subunit, Dsc2, assesses the hydrophobic length of α-helical transmembrane domains (TMDs) at the Golgi. Thereby the Dsc complex interacts with orphaned ER and Golgi proteins that have shorter TMDs and ubiquitinates them for targeted degradation. Some Dsc substrates will be K63 polyubiquitinated for ESCRT dependent vacuolar degradation or K48 polyubiquitinated forendosome andGolgiassociated proteasomaldegradation (EGAD). Other Dsc substrates are exclusively extracted by Cdc48 for EGAD. The accumulation of Dsc substrates entails a specific increase in glycerophospholipids with shorter and asymmetric fatty acyl chains. Hence, the Dsc complex mediates the selective degradation of orphaned proteins at the sorting center of cells, which prevents their spreading across other organelles and thus preserves cellular membrane protein and lipid composition.
Protection from plague via single dose administration of antibody to neutralize the type I interferon response
Authors: Marks KD , Anderson DM 
Published: March 2024

AbstractYersinia pestisis a gram-negative bacterium and the causative agent for the plague.Yersinia spp. use effector proteins of the type III secretion system (T3SS) to skew the host immune response toward a bacterial advantage during infection. Previous work established that mice which lack the type I IFN receptor (IFNAR), exhibit resistance to pulmonary infection byY. pestis. In this work, we addressed the efficacy of a single dose administration of neutralizing antibody to IFNAR (MAR1) as a preventive treatment for plague. We show that single dose administration of MAR1 provides protection from mortality due to secondary septicemic plague where it appears to reduce the production of serum TNFα during the disease phase. We further demonstrate that the T3SS effector protein YopJ is necessary for MAR1-induced protection, however IFNAR-dependent serum TNFα was observed independent of YopJ. We further define tissue-specific anti-bacterial roles of IFNAR that are blocked by YopJ activity indicating that YopJ and IFNAR work in parallel to promote disease. The combined data suggest that therapeutic targeting of IFNAR signaling may reduce the hyper-inflammatory response associated with plague.
Human assembloid model of the ascending neural sensory pathway
Authors: Kim Ji-il , Imaizumi Kent , Thete Mayuri Vijay , Hudacova Zuzana , Jurjuţ Ovidiu , Amin Neal D. , Scherrer Grégory , Paşca Sergiu P. 
Published: March 2024

AbstractThe ascending somatosensory pathways convey crucial information about pain, touch, itch, and body part movement from peripheral organs to the central nervous system. Despite a significant need for effective therapeutics modulating pain and other somatosensory modalities, clinical translation remains challenging, which is likely related to species-specific features and the lack of in vitro models to directly probe and manipulate this polysynaptic pathway. Here, we established human ascending somatosensory assembloids (hASA)– a four-part assembloid completely generated from human pluripotent stem cells that integrates somatosensory, spinal, diencephalic, and cortical organoids to model the human ascending spinothalamic pathway. Transcriptomic profiling confirmed the presence of key cell types in this circuit. Rabies tracing and calcium imaging showed that sensory neurons connected with dorsal spinal cord projection neurons, which ascending axons further connected to thalamic neurons. Following noxious chemical stimulation, single neuron calcium imaging of intact hASA demonstrated coordinated response, while four-part concomitant extracellular recordings and calcium imaging revealed synchronized activity across the assembloid. Loss of the sodium channel SCN9A, which causes pain insensitivity in humans, disrupted synchrony across the four-part hASA. Taken together, these experiments demonstrate the ability to functionally assemble the essential components of the human sensory pathway. These findings could both accelerate our understanding of human sensory circuits and facilitate therapeutic development.
Controlling Drug Partitioning in Individual Protein Condensates through Laser-Induced Microscale Phase Transitions
Authors: Leppert Axel , Feng Jianhui , Railaite Vaida , Bohn Pessatti Tomas , Mörman Cecilia , Os-terholz Hannah , Maia Filipe R.N.C. , Linder Markus B. , Rising Anna , Landreh Michael 
Published: March 2024

ABSTRACTGelation of protein condensates formed by liquid-liquid phase separation (LLPS) occurs in a wide range of biological contexts, from the assembly of biomaterials to the formation of fibrillar aggregates and is therefore of interest for biomedical applications. Soluble-to-gel (sol-gel) transitions are controlled through macroscopic processes such as changes in temperature or buffer composition, resulting in bulk conversion of liquid droplets into microgels within minutes to hours. Using microscopy and mass spectrometry, we show that condensates of an engineered mini-spidroin (NT2repCTYF) undergo a spontaneous sol-gel transition resulting in the loss of exchange of proteins between the soluble and the condensed phase. We find that liquid spidroin condensates absorb visible light, which enables us to control sol-gel transitions of individual droplets through laser pulses. Fluorescence microscopy reveals that laser-induced gelation significantly alters the interactions between droplet proteins and small molecules, which allows us to load single droplets with an anticancer drug. In summary, our findings demonstrate direct control of phase transitions in individual condensates opening new avenues for functional and structural characterization.SYNOPSIS TOCThe liquid-to-solid transitions of phase-separated protein condensates are challenging to control. Leppertet al. show that condensates of engineered mini-spidroins gelate at slightly elevated temperatures. Using high-energy laser pulses at wavelengths that are absorbed by the droplets, the authors induce sol-gel transitions in single droplets. These gelated droplets are chemically stable and exhibit an increased ability to sequester drug molecules.
Regulatory Dynamics of Sch9 in Response to Cytosolic Acidification: From Spatial Reconfiguration to Cellular Adaptation to Stresses
Authors: Fujii Rui , Takeda Eigo , Itakura Eisuke , Matsuura Akira 
Published: March 2024

AbstractThe regulation of cellular metabolism in response to intracellular and extracellular conditions is critical for cell survival. InSaccharomyces cerevisiae, Sch9 is a well-established substrate of the target of rapamycin complex 1 (TORC1) and regulates metabolic pathways and stress responses. Sch9 is enriched on the vacuolar membrane through binding to PI(3,5)P2, and this localization is essential for TORC1-dependent phosphorylation. Previous studies have demonstrated that glucose starvation and oxidative stress cause the dissociation of Sch9 from the vacuolar membrane. However, the underlying mechanism and physiological significance of the change in Sch9 localization still require elucidation. In this study, we demonstrated that cytosolic pH is a regulator of Sch9 localization. We observed that multiple stress conditions that induce cytosolic acidification consistently led to the detachment of Sch9 from the vacuolar membrane. Furthermore, we confirmed that the affinity between Sch9 and PI(3,5)P2is pH-dependentin vitro. This pH-dependent localization switch of Sch9 is linked to selective regulation of the TORC1–Sch9 pathway. Impairment of the dissociation of Sch9 from the vacuolar membrane in response to cytosolic acidification resulted in deficient induction of the expression of the stress response gene and delayed the adaptive response to acetic acid stress. These findings indicate that the appropriate control of Sch9 localization is essential for metabolic reprogramming.
Syntheses, crystal structures and intermolecular interactions of six novel pyrimidin-2-yl-substituted triaryltriazoles
Authors: Song Huijie , Peng Ri , Zuo Yi , Wang Tao , Zhu Dunru 
Published: March 2024

Six new pyrimidin-2-yl-substituted triaryltriazoles, namely, 4-(4-R-phenyl)-3-(pyridin-2-yl)-5-(pyrimidin-2-yl)-1,2,4-triazoles [L1
: R = methoxy (OCH3); L2
: R = methyl (CH3); L3
: R = nil (H); L4
: R = bromo (Br); L5
: R = chloro (Cl); L6
: R = fluoro (F)] have been successfully synthesized with yields in the range 68.3–81.7%. Compounds L1–6
have been characterized by UV–Vis, FT–IR, 1H NMR and ESI–MS spectroscopy, and elemental analysis. In addition, the structures of L2–6
and the ethanol monosolvate of L2
(L2
·C2H5OH) have been determined by single-crystal X-ray diffraction. A combination of intermolecular O—H...N, C—H...O, C—H...N and C—H...π hydrogen bonds connects the components of L2
·C2H5OH into a three-dimensional (3D) framework. A combination of three intermolecular C—H...N hydrogen bonds links the molecules of L2
or L3
into two different 3D networks. Both L4
and L5
show a similar 3D net structure through two intermolecular C—H...N hydrogen bonds and one kind of C—H...π interaction. However, L6
displays a more complicated 3D net structure via three intermolecular C—H...N hydrogen bonds and one kind of C—H...π interaction. Notably, an interaction between the π-electrons and the lone-pair p-electrons of a halogen atom (Br, Cl and F) is observed in L4–6
, which will further stabilize the 3D networks. The intermolecular interactions in L2
·C2H5OH and L2–6
were further investigated by 3D Hirshfeld surface analyses and 2D fingerprint plots to show that the prominent interactions are H...H, N...H/H...N and C...H/H...C contacts.
Identifying the hospital logistics key performance indicators for public hospitals in remote areas of Thailand
Authors: Sirisawat Pornwasin , Rodbundith Tipavinee Suwanwong , Hasachoo Narat 
Published: March 2024

Purpose
This study aims to investigate and classify the hospital logistics key performance indicators (KPIs) using the context of public hospitals in remote areas.

Design/methodology/approach
The public hospitals in northern Thailand were selected for the case study. The questionnaire was developed and used to collect data from hospital logistics experts. Then, the analytic hierarchy process (AHP) method was used to evaluate the hospital logistics KPIs in each dimension.

Findings
This research found that the procurement management dimension is ranked highest. Information and technology management is the last rank in the hospital logistics KPIs used for public hospitals in remote areas.

Research limitations/implications
The public hospitals located in northern Thailand were selected for the case study. Fuzzy multi-criteria decision-making methods can be used to reduce the vagueness of the values.

Practical implications
The results from this study can be a guideline for hospitals to improve the efficiency of their logistics operations.

Social implications
The decision-makers in the hospital can use these results to improve the hospital’s logistics performance in the future, which could help increase the service level and the safety of the patients.

Originality/value
The hospital logistics KPIs were revised, and the crucial KPIs were prioritized for improving the hospital logistics using the AHP method.
ESD training for university teachers: which is more effective, the face-to-face or digital format? Results of an intervention study
Authors: Hemmer Ingrid , Koch Christoph , Peitz Anna 
Published: March 2024

Purpose
This paper aims to analyze the extent to which education for sustainable development (ESD) training enhances university teachers’ professional competence and whether it has the same effect in the digital as in the face-to-face format.

Design/methodology/approach
A training concept was developed based on the professional action competence model. Between 2018 and 2021, 19 training sessions were conducted with 183 university teachers: ten in face-to-face sessions and nine in the digital format. Questionnaires were administered before and after the training to determine its impact.

Findings
Overall, the training proved to be effective. There was a significant increase in professional knowledge and self-efficacy after the training, but there was no change in motivation. The face-to-face and digital formats proved to be equally effective.

Research limitations/implications
The long-term effect of the training could not be determined.

Practical implications
There should be regular ESD training and coaching for university teachers.

Originality/value
There has been little research on the effectiveness of ESD teacher training, and no comparison between the face-to-face and digital approaches exists. It has been possible to train a relatively large number of university teachers from a wide range of subject areas, about two-thirds of whom have had no previous ESD experience.
Social competence and SME performance: extending the nonfinancial perspective
Authors: John Elia 
Published: March 2024

PurposeThe purpose of this paper is to investigate the influence of entrepreneurs’ social competence (SC) on small and medium-sized enterprise (SME) performance.Design/methodology/approachPrimary data of 250 manufacturing SMEs were collected through a survey method. The influence of SC on performance was tested using structural equation modelling (SEM).FindingsOverall, the findings suggest that SC dimensions have a positive influence on SME performance in terms of nonfinancial perspective. More clearly, the findings show that out of five dimensions of SC, which include social adaptability, social perception, social expressiveness, persuasiveness and impression management; social perception, persuasiveness and impression management have direct effect on customer perspective; persuasiveness, social expressiveness and social adaptability have a direct influence on internal business processes and social adaptability, social perception, impression management and social expressiveness are directly related with learning and growth. Contrary to expectations though, social perception and social adaptability were significantly and negatively associated with internal business processes and customer perspective, respectively, while there was no significant correlation between social expressiveness, persuasiveness and impression management with customer perspective, business processes and learning and growth in that order.Practical implicationsThe current study affirms that SMEs managed by entrepreneurs and managers who possess high levels of SC, may have a better performance compared to those operated by entrepreneurs with low levels of SC. This justifies a need for SME entrepreneurs and managers to work hard to improve their SC capabilities.Originality/valueThis study is pertinent and unique because, it extensively examines each of the five dimensions of SC in relation to nonfinancial indicators of SME performance. Besides, the study also provides additional evidence of the impact of SC on SME performance by suggesting that entrepreneurs who are socially competent are more likely to own highly successful ventures.
How knowledge resources drive industrial chain carbon reduction: an analysis from the knowledge management perspective
Authors: Yang Yimin , Deng Xuhui , Wang Zilong , Yang Lulu 
Published: March 2024

Purpose
This paper aims to analyze the role and advantages of knowledge resources in the carbon emission reduction of the industrial chain, and how it can be used to promote the carbon emission reduction of the industrial chain, so that the industry can better achieve the saving of energy and the reduction of emission.

Design/methodology/approach
This paper argues that the traditional resource-plundering industrial chain production method can no longer meet the needs of sustainable development of the green and low-carbon industrial chain, and builds the coupling and coordination of knowledge technology innovation drive and industrial chain carbon emission reduction mechanism, in the four dimensions of industrial chain organization, government support, internet support and staff brainstorming, put forward suggestions for knowledge resources to drive carbon emission reduction in the industrial chain.

Findings
This paper holds that the use of knowledge resource advantages can better help industrial chain enterprises to carry out technological innovation, knowledge resource digital platform construction, knowledge resource overflow and transfer, application and management of network information technology, so as to reduce carbon emission in industrial chain.

Originality/value
This paper contributes to the discussion about the high-quality implementation of the revitalization strategy of the industrial chain and also deepens research on the knowledge resource-driven carbon emission reduction of the industrial chain. Further, this paper enriches the role of knowledge resources in the industrial industry, and the theoretical results support the advantages of knowledge resource in the field of chain carbon emission reduction.
Understanding the impact of technological flexibility at different decision levels to reap enterprise resource planning benefits
Authors: Ahmed Waqar , Najmi Arsalan , Majeed Sohail 
Published: March 2024

Purpose
This paper aims to provide a framework regarding Information Technology (IT) Flexibility in Supply Chain and its relationship with the benefits we could see from Enterprise Resource Planning (ERP) systems. Furthermore, this research explores the moderating effect of Process Integration Capability in the relationship between IT flexibility and ERP benefits.

Design/methodology/approach
This research model will help organizations get additional benefits from their ERP systems that incurred huge costs, time and multiple resources at their implementation. The technique used for analyzing data is structural equation modeling (SEM), and data is collected from 107 respondents through a questionnaire from Business and IT Professionals.

Findings
The study findings reveal a positive and significant relationship between IT flexibility and ERP systems benefits; moreover, results also confirmed that the organization's process integration capability significantly increased the benefits of ERP systems. The findings also highlight empirical evidence about the significance of the top-to-bottom approach investing in IT flexibility and the bottom-to-top approach during the implementation of IT systems for successful implementations.

Practical implications
This study has various implications for practitioners that help them successfully implement and long-term viability of their IT infrastructure.

Originality/value
This study's findings will help IT managers and strategists make effective decisions for creating IT flexibility in alignment with the strategic goals to realize the desired results expected from ERP systems and implementations of new IT systems.
Facilitating feedback generation and group skill development through assessment design
Authors: Selvaretnam Geethanjali 
Published: March 2024

PurposeLarge classes pose challenges in managing different types of skills (e.g. maths, subject-specific knowledge, writing, confidence and communication), facilitating interactions, enabling active learning and providing timely feedback. This paper shares a design of a set of assessments for a large undergraduate economics course consisting of students from diverse cultural backgrounds. The benefits, challenges and learning experiences of students are analysed.Design/methodology/approachStudents worked in groups to complete an assessment with several questions which would be useful as a revision for the individual assessment, the following week. Survey questionnaires with Likert-type questions and open-ended questions were used to analyse the learning and skill development that occurred because of the group work. Responses to the open-ended survey questions were coded and analysed by identifying the themes and categorising the various issues that emerged.FindingsThis assessment design developed group working skills, created opportunities to interact and enhanced learning. The analysis of the responses found that working with peers enabled the students to generate their own feedback, clear doubts and learn to solve problems. Effective communication, planning meetings and working around the diverse group members’ strengths and weaknesses are some graduate skills that are developed in this group assessment. The challenges were arranging meetings, finalising assessments, engagement of group members and unreliable technology. However, the students found ways to overcome these challenges.Originality/valueThis assessment design can be useful in higher education practice by introducing a mechanism for authentic collaborative practice. This paper adds to the literature on peer interactions and group work and enables effective learning at scale.
Platelet rich plasma alleviates endometritis induced by lipopolysaccharide in mice via inhibiting TLR4/NF‐κB signaling pathway
Authors: Liu Xiaoqiang , Wang Yuqing , Wen Xiaoyang , Hao Cuifang , Ma Jinlong , Yan Lei 
Published: March 2024

AbstractBackgroundEndometritis is an inflammatory reaction of the lining of uterus, leading to the occurrence of infertility. Platelet rich plasma (PRP) has been proven to exhibit extremely effective for the treatment of endometrium‐associated infertility, but the mechanism of its prevention for endometritis remains unclear.ObjectiveThe present study aimed to investigate the protective effect of PRP against endometritis induced by lipopolysaccharide (LPS) and elucidate the mechanism underlying these effects.MethodsMouse model of endometritis was established by intrauterine perfusion of LPS. PRP intrauterine infusion was administered at 24 h after LPS induction. After another 24 h, the uterine tissues were harvested to observe histopathological changes, production of proinflammatory cytokines, variation of the Toll‐like receptor 4/nuclear factor κB (TLR4/NF‐κB) signaling pathways, and validated the anti‐inflammatory effect of PRP. The myeloperoxidase (MPO) activity and concentration of nitric oxide (NO) were determined using assay kit. Proinflammatory chemokines (tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), and interleukin‐6 (IL‐6)) were measured by ELISA and Real‐Time PCR. The activity of TLR4/NF‐κB pathway in uterine tissues was measured by Western blotting.ResultsHematoxylin‐eosin staining (H&E) appeared that PRP remarkably relieved the impairment of uterine tissues. Detection of MPO activity and concentration of NO revealed that PRP treatment distinctly mitigated infiltration of inflammatory cells in mice with endometritis induced by LPS. PRP treatment significantly affected the expression of TNF‐α, IL‐1β, and IL‐6. PRP was also found to suppress LPS‐induced activation of TLR4/NF‐κB pathway.ConclusionPRP effectively alleviates LPS‐induced endometritis via restraining the signal pathway of TLR4/NF‐κB. These findings provide a solid foundation for PRP as a potential therapeutic agent for endometritis.