bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of The Implementation of The Salam Agreement in The Marketplace: A Critical View of Buying Orders on Shopee
Authors: Khotimah Khusnul , Hadziq M. Fuad
Published: November 2023

The facts of online transactions, there are many differences in dissimilarity when ordering and suitability of goods received. This discrepancy caused problems afterwards with many complaints, the effect was not willing of each other.. This study aims to find out how online buying and selling transactions are carried out through Shopee, what are the advantages and disadvantages, whether online buying and selling transactions can be said to be a transition from system of salam contracts in the sharia context, and whether the activities buying and selling online at Shopee according to the greeting agreement or not. This research method uses qualitative methods, the source of the data obtained is primary data, researchers also use secondary data sources originating from literature related research. The results of the study show that buying and selling online at Shopee has the same concept as the implementation of the salam contract. Online buying and selling transactions have advantages and disadvantages for both sellers and buyers. Online buying and selling transactions can be said to be a transition from the implementation of the salam contract, provided that both parties understand the same in terms of responsibility and trust. By system, buying and selling transactions at Shopee are said to be in accordance with the salam contract.
Hindbrain rhombomere centers harbor a heterogenous population of dividing progenitors which rely on Notch signaling
Authors: Belmonte-Mateos Carla , Meister Lydvina , Pujades Cristina
Published: November 2023

Tissue growth and morphogenesis are interrelated processes, whose tight coordination is essential for the production of different cell fates and the timely precise allocation of stem cell capacities. The zebrafish embryonic brainstem, the hindbrain, exemplifies such coupling between spatiotemporal cell diversity acquisition and tissue growth as the neurogenic commitment is differentially distributed over time. Here, we combined cell lineage and in vivo imaging approaches to reveal the emergence of specific cell population properties within the rhombomeres. We studied the molecular identity of hindbrain rhombomere centers and showed that they harbor different progenitor capacities that change over time. By clonal analysis, we revealed that cells within the center of rhombomeres decrease the proliferative capacity to remain mainly in the G1 phase. Proliferating progenitors give rise to neurons by asymmetric and symmetric neurogenic divisions while maintaining the pool of progenitors. The proliferative capacity of these cells differs from their neighbors, and they are delayed in the onset of Notch activity. Through functional studies, we demonstrated that they rely on Notch3 signaling to be maintained as non-committed progenitors. In this study, we show that cells in rhombomere centers, despite the neurogenic asynchrony, might share steps of a similar program with the rhombomere counterparts, to ensure proper tissue growth.
Not all (cells) who wander are lost: Upstream migration as a pervasive mode of amoeboid cell motility
Authors: Buffone Alexander , Hammer Daniel A. , Kim Sarah Hyun Ji , Anderson Nicholas R. , Mochida Ai , Lee Dong-Hun , Guin Subham
Published: November 2023

Leukocytes possess the ability to migrate upstream—against the direction of flow—on surfaces of specific chemistry. Upstream migration was first characterized in vitro for T-cells on surfaces comprised of intracellular adhesion molecule-1 (ICAM-1). Upstream migration occurs when the integrin receptor αLβ2 (also known as lymphocyte function-associated antigen-1, or LFA-1) binds to ICAM-1. LFA-1/ICAM-1 interactions are ubiquitous and are widely found in leukocyte trafficking. Upstream migration would be employed after cells come to arrest on the apical surface of the endothelium and might confer an advantage for both trans-endothelial migration and tissue surveillance. It has now been shown that several other motile amoeboid cells which have the responsibility of trafficking from blood vessels into tissues, such as Marginal zone B cells, hematopoietic stem cells, and neutrophils (when macrophage-1 antigen, Mac-1, is blocked), can also migrate upstream on ICAM-1 surfaces. This review will summarize what is known about the basic mechanisms of upstream migration, which cells have displayed this phenomenon, and the possible role of upstream migration in physiology and tissue homeostasis.
Advances in cryopreservation of Syzygium maire (swamp maire, maire tawake) zygotic embryos, a critically endangered tree species endemic to New Zealand
Authors: van der Walt Karin , Nadarajan Jayanthi , Mathew Liya , Bettoni Jean C. , Souza Juliana A.
Published: November 2023

Introduction

Syzygium maire is a threatened Myrtaceae tree species endemic to New Zealand. Due to its highly recalcitrant seed, cryopreservation is the only viable long-term ex situ conservation option for this species. Our previous attempts to cryopreserve the embryonic axis (EAs) of S. maire were unsuccessful but did provide a better understanding of desiccation behavior, biochemical composition, oxidative status, and ultrastructural changes associated with desiccation in EAs.

Methods

We incorporated this knowledge with biophysical information to investigate two advanced cryopreservation technologies: a droplet vacuum infiltration vitrification (DVIV) method and a novel metal-mesh vacuum infiltration vitrification (MVIV) method using Plant Vitrification Solution 2 (PVS2) for cryopreservation of the EAs.

Results

The PVS2 treatment at room temperature (~20°C) proved phytotoxic with extended PVS2 incubation significantly reducing EA survival. No EAs survived cryopreservation using DVIV, however MVIV resulted in post-cryopreservation survival of up to 19% following PVS2 incubation for 20 min. Biophysical thermal analysis using Differential Scanning Calorimetry revealed a 15-fold reduction in ice crystallization following incubation in PVS2 for 20 min or more, with all freezable water removed after 60 min incubation.

Discussion

These results present a significant advance in being able to successfully cryopreserve S. maire EAs. The findings from this study will aid the development of cryopreservation protocols for other extremely recalcitrant seeded species, many of which are threatened with extinction due to climate change, plant pathogens, and habitat destruction.
Concepts of multi-level dynamical modelling: understanding mechanisms of squamous cell carcinoma development in Fanconi anemia
Authors: Velleuer Eunike , Domínguez-Hüttinger Elisa , Rodríguez Alfredo , Harris Leonard A. , Carlberg Carsten
Published: November 2023

Fanconi anemia (FA) is a rare disease (incidence of 1:300,000) primarily based on the inheritance of pathogenic variants in genes of the FA/BRCA (breast cancer) pathway. These variants ultimately reduce the functionality of different proteins involved in the repair of DNA interstrand crosslinks and DNA double-strand breaks. At birth, individuals with FA might present with typical malformations, particularly radial axis and renal malformations, as well as other physical abnormalities like skin pigmentation anomalies. During the first decade of life, FA mostly causes bone marrow failure due to reduced capacity and loss of the hematopoietic stem and progenitor cells. This often makes hematopoietic stem cell transplantation necessary, but this therapy increases the already intrinsic risk of developing squamous cell carcinoma (SCC) in early adult age. Due to the underlying genetic defect in FA, classical chemo-radiation-based treatment protocols cannot be applied. Therefore, detecting and treating the multi-step tumorigenesis process of SCC in an early stage, or even its progenitors, is the best option for prolonging the life of adult FA individuals. However, the small number of FA individuals makes classical evidence-based medicine approaches based on results from randomized clinical trials impossible. As an alternative, we introduce here the concept of multi-level dynamical modelling using large, longitudinally collected genome, proteome- and transcriptome-wide data sets from a small number of FA individuals. This mechanistic modelling approach is based on the “hallmarks of cancer in FA”, which we derive from our unique database of the clinical history of over 750 FA individuals. Multi-omic data from healthy and diseased tissue samples of FA individuals are to be used for training constituent models of a multi-level tumorigenesis model, which will then be used to make experimentally testable predictions. In this way, mechanistic models facilitate not only a descriptive but also a functional understanding of SCC in FA. This approach will provide the basis for detecting signatures of SCCs at early stages and their precursors so they can be efficiently treated or even prevented, leading to a better prognosis and quality of life for the FA individual.
The impact of Enabling Collaborative Situations in AR-assisted consignment tasks
Authors: Compan Nathan , Matias Jérémy , Lutz Matthieu , Rix-Lièvre Géraldine , Brissaud Daniel , Belletier Clément , Coutarel Fabien
Published: November 2023

The introduction of emerging technologies is often an opportunity to redesign the workstation. The Enabling Collaborative Situation (ECS) is a theoretical proposal that aims to deploy the operator’s activity in a collaborative situation with an emerging technology. This approach often seems to be neglected by designers. It is a practical tool for industrialists to guide the design of new work situations as well as for the evaluation of existing situations. An experiment was designed to reproduce a consignment operation. The initial situation corresponded to a classic situation with a paper-based operating procedure. The second situation was assisted by an augmented reality (AR) device and corresponded to either a good intensity of ECS or a low intensity of ECS (which is classically observed in a factory). This study has succeeded in creating an ECS, and it is well perceived as such by the subjects, but the different improvements are not perceived as important enough to make the overall experience better (satisfaction, comprehension, accessibility, performance, etc.). As it was a first attempt, the transformations of the situation were limited. This low intensity of change may explain some of the results of the experiment, but this first attempt also shows the originality and the interest of this work.
Acute irradiation causes a long-term disturbance in the heterogeneity and gene expression profile of medullary thymic epithelial cells
Authors: Horie Kenta , Namiki Kano , Kinoshita Kyouhei , Miyauchi Maki , Ishikawa Tatsuya , Hayama Mio , Maruyama Yuya , Hagiwara Naho , Miyao Takahisa , Murata Shigeo , Kobayashi Tetsuya J. , Akiyama Nobuko , Akiyama Taishin
Published: November 2023

The thymus has the ability to regenerate from acute injury caused by radiation, infection, and stressors. In addition to thymocytes, thymic epithelial cells in the medulla (mTECs), which are crucial for T cell self-tolerance by ectopically expressing and presenting thousands of tissue-specific antigens (TSAs), are damaged by these insults and recover thereafter. However, given recent discoveries on the high heterogeneity of mTECs, it remains to be determined whether the frequency and properties of mTEC subsets are restored during thymic recovery from radiation damage. Here we demonstrate that acute total body irradiation with a sublethal dose induces aftereffects on heterogeneity and gene expression of mTECs. Single-cell RNA-sequencing (scRNA-seq) analysis showed that irradiation reduces the frequency of mTECs expressing AIRE, which is a critical regulator of TSA expression, 15 days after irradiation. In contrast, transit-amplifying mTECs (TA-mTECs), which are progenitors of AIRE-expressing mTECs, and Ccl21a-expressing mTECs, were less affected. Interestingly, a detailed analysis of scRNA-seq data suggested that the proportion of a unique mTEC cluster expressing Ccl25 and a high level of TSAs was severely decreased by irradiation. In sum, we propose that the effects of acute irradiation disrupt the heterogeneity and properties of mTECs over an extended period, which potentially leads to an impairment of thymic T cell selection.
The implication of neutrophil extracellular traps in nonalcoholic fatty liver disease
Authors: Fa Pengyan , Ke Benjamin G. , Dupre Abigail , Tsung Allan , Zhang Hongji
Published: November 2023

Nonalcoholic fatty liver disease (NAFLD) is an expanding worldwide health concern, and the underlying mechanisms contributing to its progression still need further exploration. Neutrophil extracellular traps (NETs) are intricate formations comprised of nuclear constituents and diverse antimicrobial granules that are released into the extracellular milieu by activated neutrophils upon various triggers, which play a pivotal part in the onset and advancement of NAFLD. NETs actively participate in the genesis of NAFLD by fostering oxidative stress and inflammation, ultimately resulting in hepatic fat accumulation and the escalation of liver injury. Recent insights into the interaction with other hepatic immune populations and mediators, such as macrophages and T regulatory cells, have revealed several important mechanisms that can trigger further liver injury. In conclusion, the formation of NETs emerged as an important factor in the development of NAFLD, offering a promising target for innovative therapeutic approaches against this debilitating condition. This comprehensive review seeks to compile existing studies exploring the involvement of NETs in the genesis of NAFLD and their influence on the immune response throughout the progression of NAFLD.
Water mass mixing contributes dynamics of dissolved organic matter in Kuroshio-Oyashio confluence region
Authors: Wang Yasong , Liu Bilin , Wu Weichao , Liu Liang , Wang Yinghui , Xu Yunping
Published: November 2023

The Kuroshio-Oyashio confluence region (K/O region) plays a significant role in the global carbon cycle and climate change. In this study, we examined the concentration and composition of dissolved organic matter (DOM) in water samples collected from depths of 0 to 1000 meters between 2019 and 2021. The concentration of dissolved organic carbon (DOC) ranged from 30.54 to 113.21 μmol L-1, with higher concentrations observed in surface waters. The biological index (BIX) decreases with increasing depth, indicating decreasing in-situ production of plankton downwards. Additionally, the humification index (HIX) increased with depth, suggesting the transformation of labile to refractory DOC by bacteria. Using parallel factor analysis, we identified two humic-like (C1, C3) and one protein-like (C2) fluorescent components in 467 water samples. Water samples collected in 2020 exhibited significantly higher specific ultraviolet absorbance at 254 nm (SUVA254) (0.5 ± 0.2 L mg-1 m-1) and higher intensities of C1 (8.2 ± 2.69 *10-3 R.U.) and C3 (9.22 ± 4.39 *10-3 R.U.) compared to samples from 2019 and 2021. We found that water temperature had a positive correlation with C2 intensity (r = 0.33; p< 0.01), but negative correlations with C1 (r = −0.72; p< 0.01) and C3 intensity (r = −0.55; p< 0.01). Comparison of measured and theoretical values using a conservative physical mixing model revealed active biogeochemical processes of DOM during water mixing of the Kuroshio, Oyashio, and North Pacific Intermediate Water that change concentration and composition of DOM. Since the hydrology in the K/O region is sensitive for the ongoing climate warming, further investigation is needed to understand water mass mixing and associated DOM dynamics.
Otolith morphology as a tool for stock discrimination of three rockfish species in the East Sea of Korea
Authors: Park Joo Myun , Kang Min Gu , Kim Jong Hun , Jawad Laith A. , Majeed Samroz
Published: November 2023

The shape and structure of otoliths play a vital role in studying fish populations because otolith shape indices are often applied to discriminate fish species. This study focused on examining inter- and intra-specific variations in otolith shape and size among three species of rockfish (Sebastes inermis, Sebastiscus marmoratus, and Sebastes zonatus) collected from the Dokdo and Ulleungdo regions of the East Sea in Korea. A total of 35 S. inermis specimens, 19 S. marmoratus specimens, and 59 S. zonatus specimens were collected between April 2021 and August 2022. The otolith shape was visualized using wavelet coefficients in the shapeR package. Otolith size indices, such as length, width, perimeter, and area, and shape indices, including form factor, aspect ratio, ellipticity, circularity, roundness, rectangularity, and squareness, were calculated for each species. Otolith size and shape indices significantly differed among the three rockfish species (p< 0.05). Compared with the other two species, S. marmoratus possessed more elongated otoliths, whereas S. zonatus had the largest otolith area, perimeter, and length. Average shape analysis based on wavelet coefficients revealed significant differences in otolith shape, particularly on the rostrum and posterior sides. A canonical analysis of principal components (CAP) confirmed the complete separation of otolith shapes among the three rockfish species, with 92.5% of the variation explained by the first axis (CAP1). The findings of this study enhance our understanding of the fish species in the Korean East Sea.
Nationwide in-hospital mortality and morbidity analysis of COVID-19 in advanced chronic kidney disease, dialysis and kidney transplant recipients
Authors: He Mingyue , Wang Yichen , Li Si , Gillespie Avrum
Published: November 2023

Background

Patients with advanced chronic kidney disease (CKD), end-stage kidney disease (ESKD), and kidney transplants (KT) are at an elevated risk for COVID-19 infection, hospitalization, and mortality. A comprehensive comparison of morbidity and mortality between these populations with kidney disease and individuals without any kidney disease is lacking.

Methods

We analysed the 2020 Nationwide Inpatient Sample (NIS) database for non-elective adult COVID-19 hospitalizations, categorizing patients into advanced CKD, ESKD, KT, and kidney disease-free cohorts. Our analysis included a description of the distribution of comorbidities across the entire spectrum of CKD, ESKD, and KT. Additionally, we investigated in-hospital mortality, morbidity, and resource utilization, adjusting for potential confounders through multivariable regression models.

Results

The study included 1,018,915 adults hospitalized for COVID-19 in 2020. The incidence of advanced CKD, ESKD, and KT in this cohort was 5.8%, 3.8%, and 0.4%, respectively. Patients with advanced CKD, ESKD, and KT exhibited higher multimorbidity burdens, with 90.3%, 91.0%, and 75.2% of patients in each group having a Charlson comorbidity index (CCI) equal to or greater than 3. The all-cause in-hospital mortality ranged from 9.3% in kidney disease-free patients to 20.6% in advanced CKD, 19.4% in ESKD, and 12.4% in KT patients. After adjusting for potential confounders at both the patient and hospital levels, CKD stages 3–5; ESKD; and KT were found to be associated with increased odds of mortality, with adjusted odds ratios (aOR) of 1.34, 1.80, 2.66, 1.97, and 1.69, respectively.

Conclusion

Patients hospitalized for COVID-19 with advanced CKD, ESKD, or KT demonstrated a higher burden of comorbidities and increased mortality rates compared to those without kidney disease. After adjusting for confounders, CKD stages 3–5; ESKD; and KT were identified as independent risk factors for in-hospital mortality, illustrating a dose-response relationship between the odds of mortality and adverse outcomes as CKD progressed from stages 3 to 5. Our study highlights the necessity for enhanced management of comorbidities, targeted interventions, and vigorous vaccination efforts to mitigate the risk of adverse outcomes in the vulnerable populations of patients with CKD, ESKD, and KT.
Safety and efficacy of remimazolam for general anesthesia in elderly patients undergoing laparoscopic cholecystectomy: a randomized controlled trial
Authors: So Keum Young , Park Jihwan , Kim Sang Hun
Published: November 2023

Introduction

There is insufficient evidence regarding the efficacy and safety of remimazolam in elderly patients. Therefore, this study evaluated the differences in the anesthesia characteristics and perioperative hemodynamic profiles of elderly patients receiving total intravenous anesthesia with remimazolam or propofol.

Methods

Eighty-four patients aged >65 years with an American Society of Anesthesiologists physical status of I–III were randomly assigned to Group R (receiving remimazolam, n = 42) or Group P (receiving propofol, n = 42). In Group R, remimazolam was initiated at a rate of 6 mg/kg/h until loss of consciousness (LOC) was achieved and maintained at 1 mg/kg/h subsequently. In Group P, 1.0–1.5 mg/kg of propofol was injected for 1 min and maintained at 100 μg/kg/min subsequently. The maintenance infusion rate was adjusted to maintain an appropriate depth of anesthesia until the end of the surgery. The primary outcome was the time to LOC. The depth of anesthesia scores and hemodynamic profiles were recorded perioperatively.

Results

The time to LOC was significantly longer in Group R (120 s) than in Group P (60 s) (p < 0.001). The time to eye-opening (Group R, 10 min; Group P, 10 min; p = 0.056), the incidence of maintenance of hemodynamic changes within 20% of the peri-anesthetic values, and treatments for hemodynamic instability did not differ significantly between the groups. The depth of anesthesia scores did not differ significantly between the groups; however, the scores were higher in Group R than those in Group P before endotracheal intubation. The hemodynamic parameters did not differ significantly at any time point. The time to extubation was longer in Group R (12 min) than that in Group P (10 min) (p = 0.007). Similarly, the time to discharge from the operating room was significantly longer in Group R (15 min) compared to Group P (12 min) (p = 0.018).

Conclusion

Remimazolam does not exhibit a comparable effect to propofol in terms of anesthesia induction and recovery. However, it demonstrates a similar effect to propofol regarding intraoperative anesthesia depth and hemodynamic profile in elderly patients undergoing remifentanil-based total intravenous anesthesia.
Effects of the multidomain intervention with nutritional supplements on cognition and gut microbiome in early symptomatic Alzheimer’s disease: a randomized controlled trial
Authors: Lee Eun Hye , Kim Geon Ha , Park Hee Kyung , Kang Hae Jin , Park Yoo Kyoung , Lee Hye Ah , Hong Chang Hyung , Moon So Young , Kang Woorim , Oh Hyun-Seok , Yoon Hai-Jeon , Choi Seong Hye , Jeong Jee Hyang
Published: November 2023

Background

The SoUth Korean study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention in at-risk elderly people (SUPERBRAIN) is a part of the World-Wide Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (WW-FINGERS) network. This study aimed to demonstrate the effects of the SUPERBRAIN-based multidomain intervention with nutritional supplements in amyloid positive emission tomography (PET) proven early symptomatic Alzheimer’s disease patients.

Methods

Forty-six participants who were diagnosed with mild cognitive impairment or mild dementia and were positive in the amyloid PET study randomized into three groups: group A, the multidomain intervention with nutritional supplements; group B, nutritional supplements only; and a control group. The primary outcome was a change in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total scale index score after an 8-week intervention. Secondary outcomes, including gut microbiome data, were also analyzed.

Results

The RBANS total scale index score improved significantly in group A compared with group B (p < 0.032) and compared with the control group (p < 0.001). After intervention, beta diversity of the gut microbiome between group A and the control group increased, and patients in group A were more enriched with Bifidobacterium.

Conclusion

SUPERBRAIN-based multidomain intervention with nutritional supplements improves cognition and gut microbiota in patients with early symptomatic Alzheimer’s disease who were amyloid-positive by PET.
Electroacupuncture at HT5 + GB20 promotes brain remodeling and significantly improves swallowing function in patients with stroke
Authors: Fu Xuefeng , Li Hao , Yang Wen , Li Xuezheng , Lu Lijun , Guo Hua , Guo Kaifeng , Huang Zhen
Published: November 2023

Background

This study compared the differences in the degree of brain activation, and swallowing function scales in patients with post-stroke dysphagia after treatment. We explored the mechanism of cortical remodeling and the improvement effect of electroacupuncture on swallowing function in patients and provided a theoretical basis for the clinical application of electroacupuncture.

Methods

Fifty patients with post-stroke dysphagia were randomized to the control or electroacupuncture group. The control group underwent conventional swallowing rehabilitation for 30 min each time for 12 sessions. In the electroacupuncture group, electroacupuncture was performed based on conventional swallowing rehabilitation for 30 min each time for 12 sessions. Cortical activation tests and swallowing function assessments were performed before and after treatment. Statistical analyses were used to investigate the differences within and between the two groups to explore the treatment effects.

Results

There were no statistical differences in clinical characteristics and baseline data between the two groups before treatment. Cortical activation and swallowing function were improved to different degrees in both groups after treatment compared with before treatment. After treatment, the electroacupuncture group showed higher LPM (t = 4.0780, p < 0.001) and RPM (t = 4.4026, p < 0.0001) cortical activation and tighter functional connectivity between RS1 and LM1 (t = 2.5336, p < 0.05), RM1 and LPM (t = 3.5339, p < 0.001), RPM and LM1 (t = 2.5302, p < 0.05), and LM1 and LPM (t = 2.9254, p < 0.01) compared with the control group. Correspondingly, the improvement in swallowing function was stronger in the electroacupuncture group than in the control group (p < 0.05).

Conclusion

This study demonstrated that electroacupuncture based on conventional treatment activated more of the cerebral cortex associated with swallowing and promoted functional connectivity and remodeling of the brain. Accompanying the brain remodeling, patients in the electroacupuncture group also showed greater improvement in swallowing function.

Clinical trial registration

ClinicalTrials.gov, ChiCTR2300067457.
Interactions of amyloidogenic proteins with mitochondrial protein import machinery in aging-related neurodegenerative diseases
Authors: Reed Ashley L. , Mitchell Wayne , Alexandrescu Andrei T. , Alder Nathan N.
Published: November 2023

Most mitochondrial proteins are targeted to the organelle by N-terminal mitochondrial targeting sequences (MTSs, or “presequences”) that are recognized by the import machinery and subsequently cleaved to yield the mature protein. MTSs do not have conserved amino acid compositions, but share common physicochemical properties, including the ability to form amphipathic α-helical structures enriched with basic and hydrophobic residues on alternating faces. The lack of strict sequence conservation implies that some polypeptides can be mistargeted to mitochondria, especially under cellular stress. The pathogenic accumulation of proteins within mitochondria is implicated in many aging-related neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and Huntington’s diseases. Mechanistically, these diseases may originate in part from mitochondrial interactions with amyloid-β precursor protein (APP) or its cleavage product amyloid-β (Aβ), α-synuclein (α-syn), and mutant forms of huntingtin (mHtt), respectively, that are mediated in part through their associations with the mitochondrial protein import machinery. Emerging evidence suggests that these amyloidogenic proteins may present cryptic targeting signals that act as MTS mimetics and can be recognized by mitochondrial import receptors and transported into different mitochondrial compartments. Accumulation of these mistargeted proteins could overwhelm the import machinery and its associated quality control mechanisms, thereby contributing to neurological disease progression. Alternatively, the uptake of amyloidogenic proteins into mitochondria may be part of a protein quality control mechanism for clearance of cytotoxic proteins. Here we review the pathomechanisms of these diseases as they relate to mitochondrial protein import and effects on mitochondrial function, what features of APP/Aβ, α-syn and mHtt make them suitable substrates for the import machinery, and how this information can be leveraged for the development of therapeutic interventions.
Construction of heat stress regulation networks based on Illumina and SMRT sequencing data in potato
Authors: Shang Lina , Zhou Yonghong , Wen Shiqi , Wang Ke , Li Yang , Zhang Meihua , Jian Hongju , Lyu Dianqiu
Published: November 2023

Potato (Solanum tuberosum L.) is one of the most important tuber food crops in the world; however, the cultivated potatoes are susceptible to high temperature, by which potato production is adversely affected. Understanding the coping mechanism of potato to heat stress is essential to secure yield and expand adaptability under environmental conditions with rising temperature. However, the lack of heat-related information has significantly limited the identification and application of core genes. To gain deeper insights into heat tolerance genes, next-generation sequencing and single-molecule real-time sequencing were used to learn the transcriptional response of potato to heat stress and 13,159 differentially expressed genes (DEGs) were identified in this study. All DEGs were grouped into 12 clusters using the K-means clustering algorithm. Gene Ontology enrichment analysis revealed that they were involved in temperature signaling, phytohormone, and protein modification. Among them, there were 950 differentially expressed transcription factors (DETFs). According to the network analysis of DETFs at the sixth hour under heat stress, we found some genes that were previously reported to be associated with photoperiodic tuberization, StCO (CONSTANS), tuber formation, StBEL11 (BEL1-LIKE 11), and earliness in potato, StCDF1 (CYCLING DOF FACTOR 1) responding to temperature. Furthermore, we verified the relative expression levels using quantitative real-time polymerase chain reaction, and the results were consistent with the inferences from transcriptomes. In addition, there were 22,125 alternative splicing events and 2,048 long non-coding RNAs. The database and network established in this study will extend our understanding of potato response to heat stress. It ultimately provided valuable resources for molecular analysis of heat stress response in potato and cultivation of potato varieties with heat tolerance.
Telomere-to-telomere and haplotype-resolved genome assembly of the Chinese cork oak (Quercus variabilis)
Authors: Wang Longxin , Li Lei-Lei , Chen Li , Zhang Ren-Gang , Zhao Shi-Wei , Yan Han , Gao Jie , Chen Xue , Si Yu-Jun , Chen Zhe , Liu Haibo , Xie Xiao-Man , Zhao Wei , Han Biao , Qin Xiaochun , Jia Kai-Hua
Published: November 2023

The Quercus variabilis, a deciduous broadleaved tree species, holds significant ecological and economical value. While a chromosome-level genome for this species has been made available, it remains riddled with unanchored sequences and gaps. In this study, we present a nearly complete comprehensive telomere-to-telomere (T2T) and haplotype-resolved reference genome for Q. variabilis. This was achieved through the integration of ONT ultra-long reads, PacBio HiFi long reads, and Hi-C data. The resultant two haplotype genomes measure 789 Mb and 768 Mb in length, with a contig N50 of 65 Mb and 56 Mb, and were anchored to 12 allelic chromosomes. Within this T2T haplotype-resolved assembly, we predicted 36,830 and 36,370 protein-coding genes, with 95.9% and 96.0% functional annotation for each haplotype genome. The availability of the T2T and haplotype-resolved reference genome lays a solid foundation, not only for illustrating genome structure and functional genomics studies but also to inform and facilitate genetic breeding and improvement of cultivated Quercus species.
Preventing leaders' autocratic entrenchment by exponential super-majority threshold escalators
Authors: Shapira Reuven
Published: November 2023

This article focuses on alternatives to leaders' constitutional term limits which failed to protect democracy in innumerable countries as they did not reduce incumbency advantages in re-election contests. Such a reduction can achieve a super-majority thresholds escalator for incumbents' re-election. Research has found that setting super-majority thresholds for leadership offices improves the quality of leadership. However, leaders' autocratic entrenchment poses the worse problem of democratic leadership quality. Setting escalating super-majority thresholds for an incumbent's re-election would bar autocratic entrenchment by reducing her/his incumbency advantages in re-election contests. Both ordinal and exponential escalator versions prolong the tenure of successful high-moral effective leaders beyond two terms, allowing them to use accumulated trust credit to advance radical changes, while incumbents who fail to achieve a super-majority threshold are replaced. However, the ordinal version lacks a terminal term, thus it may not prevent autocratic entrenchment, while the exponential version with its terminal term that ensures succession while escalating super-majority thresholds mitigates the exponential growth of leaders' power resources with tenure. After an incumbent fails to re-elect, a second voting round without her/him will give the winner a clear mandate to rule. Suggestions for further study of barring leaders' entrenchment by exponential escalating super-majority thresholds are offered.

JEL classification

D02; D70; K16; Z13; Z18.
The agency domain and behavioral interactions: assessing positive animal welfare using the Five Domains Model
Authors: Littlewood Katherine E. , Heslop Morgan V. , Cobb Mia L.
Published: November 2023

Animal welfare denotes how an animal experiences their life. It represents the overall mental experiences of an animal and is a subjective concept that cannot be directly measured. Instead, welfare indicators are used to cautiously infer mental experiences from resource provisions, management factors, and animal-based measures. The Five Domains Model is a holistic and structured framework for collating these indicators and assessing animal welfare. Contemporary approaches to animal welfare management consider how animals can be given opportunities to have positive experiences. However, the uncertainty surrounding positive mental experiences that can be inferred has resulted in risk-averse animal welfare scientists returning to the relative safety of positivism. This has meant that aspects of positive welfare are often referred to as animal ‘wants’. Agency is a concept that straddles the positivist-affective divide and represents a way forward for discussions about positive welfare. Agency is the capacity of individual animals to engage in voluntary, self-generated, and goal-directed behavior that they are motivated to perform. Discrete positive emotions are cautiously inferred from these agentic experiences based on available knowledge about the animal’s motivation for engaging in the behavior. Competence-building agency can be used to evaluate the potential for positive welfare and is represented by the Behavioral Interactions domain of the Five Domains Model. In 2020, The Model was updated to, amongst other things, include consideration of human-animal interactions. The most important aspect of this update was the renaming of Domain 4 from “Behavior” to “Behavioral Interactions” and the additional detail added to allow this domain’s purpose to be clearly understood to represent an animal’s opportunities to exercise agency. We illustrate how the Behavioral Interactions domain of The Model can be used to assess animals’ competence-building agency and positive welfare. In this article, we use the examples of sugar gliders housed in captivity and greyhounds that race to illustrate how the agentic qualities of choice, control, and challenge can be used to assess opportunities for animals to exercise agency and experience positive affective engagement.
Metabolome and Transcriptome Analyses Provide Insights into Glucosinolate Accumulation in the Novel Vegetable Crop Cardamine violifolia
Authors: Rao Shen , Gong Jue , Liu Haodong , Liu Xiaomeng , Cheng Shuiyuan , Cheng Hua , Cong Xin
Published: November 2023

Cardamine violifolia, a species belonging to the Brassicaceae family, is a novel vegetable crop that is rich in glucosinolates. However, the specific glucosinolate profiles in this species remain unknown. In the present study, four parts of C. violifolia were collected including central leaves (CLs), outer leaves (OLs), petiole (P), and root (R). The highest level of total glucosinolate was observed in the R. A total of 19 glucosinolates were found in C. violifolia. The predominant glucosinolate compounds were 3-methylbutyl glucosinolate, 6-methylsulfinylhexyl glucosinolate, Indol-3-ylmethyl glucosinolate, 4-methoxyglucobrassicin, and neoglucobrassicin. A transcriptome analysis showed that 16 genes, including BCAT1, BCAT3-6, CYP79A2, CYP79B2-3, CYP83A1, CYP83B1, and SOT17-18, and nine metabolites, such as valine, tryptophan, and 1-methylpropyl glucosinolate, were enriched in the glucosinolate biosynthesis pathway. These genes may be involved in the regulation of glucosinolate accumulation among the four parts. A weighted gene co-expression analysis showed that five genes were predicted to regulate glucosinolate accumulation, including ABC transporter G family member 19, 3-ketoacyl-CoA synthase 19, and pyruvate decarboxylase 1. This study deepens our understanding of the nutrient quality of C. violifolia and provides insights into the regulatory mechanism of glucosinolate accumulation in C. violifolia.
A Delphi Study to Determine International and National Equestrian Expert Opinions on Domains and Sub-Domains Essential to Managing Sporthorse Health and Welfare in the Olympic Disciplines
Authors: Williams Jane M. , Berg Lise C. , Clayton Hilary M. , Kirsch Katharina , Marlin David , Randle Hayley , Roepstroff Lars , Oldruitenborgh-Oosterbaan Marianne Sloet van , Weishaupt Michael A. , Munsters Carolien
Published: November 2023

The public is increasingly questioning equestrianism’s social license to operate. While the focus historically centered on horseracing, increased scrutiny is now being placed on how dressage, showjumping, and eventing are addressing equine management and welfare concerns. Nominated equestrian federation and equestrian organization experts (n = 104) directly involved in international and/or national-level horse sports took part in a four-stage, iterative Delphi to obtain consensus on what factors should be considered essential to manage sporthorse health and welfare. Five core domains were agreed as essential: training management, competition management, young horse management, health status and veterinary management, and the horse–human relationship. Two further domains: stable and environmental management, and welfare assessment were rated as important but not essential, as most respondents felt that these areas were already managed well. Participants felt increased education and guidance combined with further policy development and regulation are needed to support stakeholders to optimize sporthorse management. An appetite to engage with research to generate evidence that promotes sporthorse welfare was evident. The development of a sporthorse welfare charter and evidence-based guidelines to inform the management and monitoring of sporthorses’ health and welfare are recommended to provide horses with a good life and to safeguard the future of equestrian sports.
Effect of Spirulina platensis Supplementation on Reproductive Parameters of Sahrawi and Jabbali Goat Bucks
Authors: Al-Yahyaey Fahad , Stephen Cyril , Al-Shukaili Yasir , Al-Bulushi Samir , Shaat Ihab , Bush Russell
Published: November 2023

Spirulina platensis (SP) is a protein-rich dietary supplement that improves animal reproductive traits. This study investigated the effect of SP supplementation on puberty onset, semen characteristics, scrotal circumference (SC), libido, and hormone concentrations in Sahrawi and Jabbali bucks. The study was conducted in 36 bucks, divided into three groups (n = 6/group), for 70 days. The rations included the following: (1) Control feed (Con) with 14% crude protein and 11.97% MJ/kg DM energy; (2) Con with 2 g SP/head/day SP treatment (T1) and (3) Con with 4 g SP/head/day treatment (T2). The mean (±SEM) SC of both SP groups in the Sahrawi breed was significantly higher (p ≤ 0.05) compared to the Con. The mean of the semen volume significantly increased (p ≤ 0.05) in the SP group than in the Con group in both breeds. SP groups vs. Con groups had increased sperm concentration in Sahrawi bucks than Jabbali bucks. Mean serum luteinizing hormone (LH) and testosterone (Tes) concentrations in Jabbali bucks were significantly higher (p ≤ 0.05) in the SP groups compared to Sahrawi bucks. SP improved the SC, semen quality, libido, sperm concentration, and LH and Tes concentrations in both breeds. The results of the current study suggest that adding SP to the diet may have the ability to improve the semen quality of the local Omani bucks.
A Technical Report on the Potential Effects of Heat Stress on Antioxidant Enzymes Activities, Performance and Small Intestinal Morphology in Broiler Chickens Administered Probiotic and Ascorbic Acid during the Hot Summer Season
Authors: Sumanu Victory Osirimade , Naidoo Vinny , Oosthuizen Marinda , Chamunorwa Joseph Panashe
Published: November 2023

Oxidative stress negatively affects the welfare of broiler chickens leading to poor productivity and even death. This study examined the negative effect of heat stress on antioxidant enzyme activities, small intestinal morphology and performance in broiler chickens administered probiotic and ascorbic acid during the hot summer season, under otherwise controlled conditions. The study made use of 56 broiler chickens; which were divided into control; probiotic (1 g/kg); ascorbic acid (200 mg/kg) and probiotic + ascorbic acid (1 g/kg and 200 mg/kg, respectively). All administrations were given via feed from D1 to D35 of this study. Superoxide dismutase, glutathione peroxidase and catalase activities were highly significant (p < 0.0001) in the treatment groups compared to the control. Performance indicators (water intake and body weight gain) were significantly higher (p < 0.05) in the probiotic and probiotic + ascorbic acid group. The height of duodenal, jejunal and ileal villi, and goblet cell counts of broiler chickens were significantly different in the treatment groups. In conclusion, the study showed that heat stress negatively affects the levels of endogenous antioxidant enzymes, performance and the morphology of small intestinal epithelium, while the antioxidants were efficacious in ameliorating these adverse effects.
Evaluation of Two Tests for the Rapid Detection of CTX-M Producers Directly in Urine Samples
Authors: Tang Forrest , Lee Chung-Ho , Li Xin , Jiang Shuo , Chow Kin-Hung , Tse Cindy Wing-Sze , Ho Pak-Leung
Published: November 2023

Infections caused by extended-spectrum β-lactamase-producing Enterobacterales have increased rapidly and are mainly attributed to the production of CTX-M enzymes. This study evaluated the NG-Test® CTX-M MULTI lateral flow assay (CTX-M LFA) and the Rapid ESBL NP® test (ESBL NP test) for rapid detection of CTX-M-producing Enterobacterales directly in midstream urine (MSU) samples. Testing was performed on 277 clinical MSU samples in a hospital microbiology laboratory from November 2022 to January 2023; 60 of these samples (30 positive for ESBL producers and 30 positive for non-ESBL producers) were tested retrospectively after the identification and susceptibility results were obtained, and 217 samples were tested prospectively immediately after a Gram stain showing the presence of Gram-negative bacilli. The results were compared against phenotypic detection of ESBL and molecular testing as the reference methods. Overall, 67 of the 277 samples were culture-positive for ESBL-producing Enterobacterales. PCR for the blaCTX-M gene was positive for all ESBL-producing Enterobacterales isolates. All CTX-M LFA results were interpretable, while three of the ESBL NP test results were noninterpretable. The sensitivity of the CTX-M LFA (100%, 95% CI 94.6–100%) was higher than that of the ESBL NP test (86.6%, 95% CI 76.0–93.7%). Both tests had high specificities (CTX-M LFA, 99.1%, 95% CI 96.6–99.9% and ESBL NP test, 100%, 95% CI 98.2–100%). In conclusion, both the CTX-M LFA and the ESBL NP test can deliver rapid results that could improve antimicrobial stewardship for urinary tract infections.
Distribution of Antibiotic Resistance in a Mixed-Use Watershed and the Impact of Wastewater Treatment Plants on Antibiotic Resistance in Surface Water
Authors: Cho Sohyun , Hiott Lari M. , Read Quentin D. , Damashek Julian , Westrich Jason , Edwards Martinique , Seim Roland F. , Glinski Donna A. , Bateman McDonald Jacob M. , Ottesen Elizabeth A. , Lipp Erin K. , Henderson William Matthew , Jackson Charlene R. , Frye Jonathan G.
Published: November 2023

The aquatic environment has been recognized as a source of antibiotic resistance (AR) that factors into the One Health approach to combat AR. To provide much needed data on AR in the environment, a comprehensive survey of antibiotic-resistant bacteria (ARB), antibiotic resistance genes (ARGs), and antibiotic residues was conducted in a mixed-use watershed and wastewater treatment plants (WWTPs) within the watershed to evaluate these contaminants in surface water. A culture-based approach was used to determine prevalence and diversity of ARB in surface water. Low levels of AR Salmonella (9.6%) and Escherichia coli (6.5%) were detected, while all Enterococcus were resistant to at least one tested antibiotic. Fewer than 20% of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae (17.3%) and carbapenem-resistant Enterobacteriaceae (CRE) (7.7%) were recovered. Six ARGs were detected using qPCR, primarily the erythromycin-resistance gene, ermB. Of the 26 antibiotics measured, almost all water samples (98.7%) had detectable levels of antibiotics. Analysis of wastewater samples from three WWTPs showed that WWTPs did not completely remove AR contaminants. ARGs and antibiotics were detected in all the WWTP effluent discharges, indicating that WWTPs are the source of AR contaminants in receiving water. However, no significant difference in ARGs and antibiotics between the upstream and downstream water suggests that there are other sources of AR contamination. The widespread occurrence and abundance of medically important antibiotics, bacteria resistant to antibiotics used for human and veterinary purposes, and the genes associated with resistance to these antibiotics, may potentially pose risks to the local populations exposed to these water sources.