Miracle-dz/UniFAR-FTUs huggingface dataset:
The Role of HDAC6 in TDP-43-Induced Neurotoxicity and UPS Impairment

Transactive response DNA-binding protein 43 (TDP-43)-induced neurotoxicity is currently well recognized as a contributor to the pathology of amyotrophic lateral sclerosis (ALS), and the deposition of TDP-43 has been linked to other neurodegenerative diseases, such as frontotemporal lobar degeneration (FTLD) and Alzheimer’s disease (AD). Recent studies also suggest that TDP-43-induced neurotoxicity is associated with ubiquitin-proteasome system (UPS) impairment. Histone deacetylase 6 (HDAC6) is a well-known cytosolic deacetylase enzyme that suppresses the toxicity of UPS impairment. However, the role of HDAC6 in TDP-43-induced neurodegeneration is largely unknown. In this study, we found that HDAC6 overexpression decreased the levels of insoluble and cytosolic TDP-43 protein in TDP-43-overexpressing N2a cells. In addition, TDP-43 overexpression upregulated HDAC6 protein and mRNA levels, and knockdown of Hdac6 elevated the total protein level of TDP-43. We further found that HDAC6 modulates TDP-43-induced UPS impairment via the autophagy-lysosome pathway (ALP). We also showed that TDP-43 promoted a short lifespan in flies and that the accumulation of ubiquitin aggregates and climbing defects were significantly rescued by overexpression of HDAC6 in flies. Taken together, these findings suggest that HDAC6 overexpression can mitigate neuronal toxicity caused by TDP-43-induced UPS impairment, which may represent a novel therapeutic approach for ALS.
Cell-Specific Suppression of 4-Coumarate-CoA Ligase Gene Reveals Differential Effect of Lignin on Cell Physiological Function in Populus

Lignin is a main component of the secondary cell wall in vessels and fibers of xylem tissue. However, the significance of lignin in cell physiology during plant growth is unclear. In this study, we generated lignin-modified Populus via cell-specific downregulation of the 4-coumarate-CoA ligase gene (4CL). The transgenic plants with selective lignin modification in vessel elements or fiber cells allowed us to investigate how lignin affects the physiology of vessel or fiber cells in relation to plant growth. Results showed that vessel-specific suppression of lignin biosynthesis resulted in deformed vessels and normal fibers, while fiber-specific suppression of lignin biosynthesis led to less-lignified fibers and normal vessels. Further analyses revealed that the efficiency of long distance water transport was severely affected in transgenics with vessel-specific lignin modification, while minimal effect was detected in transgenics with fiber-specific lignin modification. Vessel-specific lignin reduction led to high susceptibility to drought stress and poor growth in field, likely due to vessel defects in long distance transport of water. The distinct physiological significance of lignin in different cell types provides insights into the selective modification of lignin for improvement of lignocellulosic biomass utilization.
Ocean Acidification and Warming Lead to Increased Growth and Altered Chloroplast Morphology in the Thermo-Tolerant Alga Symbiochlorum hainanensis

Ocean acidification and warming affect the growth and predominance of algae. However, the effects of ocean acidification and warming on the growth and gene transcription of thermo-tolerant algae are poorly understood. Here we determined the effects of elevated temperature (H) and acidification (A) on a recently discovered coral-associated thermo-tolerant alga Symbiochlorum hainanensis by culturing it under two temperature settings (26.0 and 32.0°C) crossed with two pH levels (8.16 and 7.81). The results showed that the growth of S. hainanensis was positively affected by H, A, and the combined treatment (AH). However, no superimposition effect of H and A on the growth of S. hainanensis was observed under AH. The analysis of chlorophyll fluorescence, pigment content, and subcellular morphology indicated that the chloroplast morphogenesis (enlargement) along with the increase of chlorophyll fluorescence and pigment content of S. hainanensis might be a universal mechanism for promoting the growth of S. hainanensis. Transcriptomic profiles revealed the effect of elevated temperature on the response of S. hainanensis to acidification involved in the down-regulation of photosynthesis- and carbohydrate metabolism-related genes but not the up-regulation of genes related to antioxidant and ubiquitination processes. Overall, this study firstly reports the growth, morphology, and molecular response of the thermo-tolerant alga S. hainanensis to future climate changes, suggesting the predominance of S. hainanensis in its associated corals and/or coral reefs in the future.
Establishment and Application of Multiplex PCR for Simultaneously Detecting Escherichia coli, Salmonella, Klebsiella pneumoniae, and Staphylococcus aureus in Minks

To establish a multiplex PCR for simultaneous detection of Escherichia coli (E. coli), Salmonella, Klebsiella pneumoniae (K. pneumoniae), and Staphylococcus aureus (S. aureus), four pairs of specific primers were designed according to the conservative regions of phoA gene for E. coli, invA gene for Salmonella, khe gene for K. pneumoniae, nuc gene for S. aureus. The quadruple PCR system was established through optimization of multiplex PCR and detection of specificity, sensitivity, and stability. The results showed that target gene bands of E. coli (622 bp), Salmonella (801 bp), K. pneumoniae (303 bp), and S. aureus (464 bp) could be amplified by this method specifically and simultaneously from the same sample containing the four pathogens, with a detection sensitivity of 100 pg/μL. Meanwhile, no bands of common clinical bacteria, including Clostridium perfringens, Pseudomonas aeruginosa, Pasteurella multocida, Streptococcus pneumoniae, Streptococcus pneumoniae, Proteus mirabilis, Staphylococcus sciuri, Staphylococcus pseudintermedius, Acinetobacter baumannii, Enterococcus faecalis, and Bacillus subtilis were amplified. In addition, 380 tissue samples were detected by multiplex and single PCR established in current study, respectively. Among the 368 carcass samples, positive detection rates of E. coli, K. pneumoniae, Salmonella, and S. aureus were 33.7, 12.0, 10.6, and 13.9%. Among the 12 visceral tissue samples, positive detection rates of E. coli, K. pneumoniae, Salmonella, and S. aureus were 41.7, 25.0, 16.7, and 8.3%, respectively. Positive detection rates of multiplex PCR were consistent with that of single PCR. Compared with single PCR, the multiplex PCR method had the advantages of time-saving, high specificity and high sensitivity. The results showed that the minks in these farms had mixed infection of these four pathogens, and the method established in this study could be applied to the rapid and accurate detection and identification of these four bacteria. In conclusion, the multiplex PCR method has stable detection results, good repeatability, and short detection time. It is suitable for the rapid and accurate detection of four kinds of bacteria above the carcass of fur animals, which could be suitable in microbial epidemiology investigation. It can provide a reliable technical reference for rapid clinical diagnosis and detection.
Broad Virus Detection and Variant Discovery in Fecal Samples of Hematopoietic Transplant Recipients Using Targeted Sequence Capture Metagenomics

Pediatric allogeneic hematopoietic stem cell transplantation (HSCT) patients often suffer from gastro-intestinal (GI) disease caused by viruses, Graft-versus-Host Disease (GVHD) or a combination of the two. Currently, the GI eukaryotic virome of HSCT recipients remains relatively understudied, which complicates the understanding of its role in GVHD pathogenicity. As decisions regarding immunosuppressive therapy in the treatment of virus infection or GVHD, respectively, can be completely contradicting, it is crucial to better understand the prevalence and relevance of viruses in the GI tract in the HSCT setting. A real time PCR panel for a set of specific viruses widely used to diagnose the most common causes of GI viral gastroenteritis is possibly insufficient to grasp the full extent of viruses present. Therefore, we applied the targeted sequence capture method ViroCap to residual fecal samples of 11 pediatric allogeneic HSCT recipients with GI symptoms and a suspicion of GVHD, to enrich for nucleic acids of viruses that are known to infect vertebrate hosts. After enrichment, NGS was applied to broadly detect viral sequences. Using ViroCap, we were able to detect viruses such as norovirus and adenovirus (ADV), that had been previously detected using clinical diagnostic PCR on the same sample. In addition, multiple, some of which clinically relevant viruses were detected, including ADV, human rhinovirus (HRV) and BK polyomavirus (BKV). Interestingly, in samples in which specific PCR testing for regular viral GI pathogens did not result in a diagnosis, the ViroCap pipeline led to the detection of viral sequences of human herpesvirus (HHV)-7, BKV, HRV, KI polyomavirus and astrovirus. The latter was an only recently described variant and showed extensive sequence mismatches with the applied real time PCR primers and would therefore not have been detected if tested. Our results indicate that target enrichment of viral nucleic acids through ViroCap leads to sensitive and broad possibly clinically relevant virus detection, including the detection of newer variants in clinical HSCT recipient samples. As such, ViroCap could be a useful detection tool clinically, but also in studying the associations between viral presence and GVHD.
School-Based Prevention in Very Remote Settings: A Feasibility Trial of Methods and Measures for the Evaluation of a Social Emotional Learning Program for Indigenous Students in Remote Northern Australia

Purpose: Skills for Life (SFL) is a social-emotional curriculum for Indigenous middle school students that was co-developed with educators and community members in a remote community of northern Australia. This preliminary study aimed to test the feasibility of processes and methods of data-gathering, the reliability of youth self-report measures, and to identify the direction of effects for an evaluation of a longer-term pilot of the curriculum. Design/Methodology/Approach: Indigenous Students in years 7–9 of a remote school participated in SFL over 2 years. The Strengths and Difficulties Questionnaire (SDQ), Kessler 6 (K6), and a purpose-designed Connected Self Scale (CSS) were administered to 63 students pre- and post-program. Findings: Only the K6, Prosocial behavior (SDQ), and two CSS subscales showed sufficient internal consistency for analysis. Change was positive but non-significant for SDQ and CSS. There was evidence of a dosage effect: students receiving the intervention over 2 years showed greater reduction in psychological distress than other students. There was no evidence of iatrogenic effects. Conclusions: The feasibility pilot is a critically important phase in the development of evaluation design and cjhoice of evaluation measures for challenging remote settings. This study found that evaluation of SFL with culturally and linguistically distinct Indigenous middle school students using self-report measures is feasible. However, the SDQ may not be suitable for this project. High levels of psychological distress suggest the need to investigate sources of life stress and potential supports for adolescent resilience in this context. This preliminary pilot aimed to trial methods and measures for evaluation of a social-emotional curriculum developed specifically for remote Australian Indigenous students who are at risk of poor psychosocial outcomes. No studies have examined the appropriateness of standardized self-report measures for evaluation of SEL with this student population in remote school settings.
MNL-Network: A Multi-Scale Non-local Network for Epilepsy Detection From EEG Signals

Epilepsy is a prevalent neurological disorder that threatens human health in the world. The most commonly used method to detect epilepsy is using the electroencephalogram (EEG). However, epilepsy detection from the EEG is time-consuming and error-prone work because of the varying levels of experience we find in physicians. To tackle this challenge, in this paper, we propose a multi-scale non-local (MNL) network to achieve automatic EEG signal detection. Our MNL-Network is based on 1D convolution neural network involving two specific layers to improve the classification performance. One layer is named the signal pooling layer which incorporates three different sizes of 1D max-pooling layers to learn the multi-scale features from the EEG signal. The other one is called a multi-scale non-local layer, which calculates the correlation of different multi-scale extracted features and outputs the correlative encoded features to further enhance the classification performance. To evaluate the effectiveness of our model, we conduct experiments on the Bonn dataset. The experimental results demonstrate that our MNL-Network could achieve competitive results in the EEG classification task.
“Birthday-Banding” as a Strategy to Moderate the Relative Age Effect: A Case Study Into the England Squash Talent Pathway

The relative age effect (RAE) is almost pervasive throughout youth sports, whereby relatively older athletes are consistently overrepresented compared to their relatively younger peers. Although researchers regularly cite the need for sports programs to incorporate strategies to moderate the RAE, organizational structures often continue to adopt a one-dimensional (bi)annual-age group approach. In an effort to combat this issue, England Squash implemented a “birthday-banding” strategy in its talent pathway, whereby young athletes move up to their next age group on their birthday, with the aim to remove particular selection time points and fixed chronological bandings. Thus, the purpose of this study was to examine the potential effects of the birthday-banding strategy on birth quarter (BQ) distributions throughout the England Squash talent pathway. Three mixed-gender groups were populated and analyzed: (a) ASPIRE athletes (n = 250), (b) Development and Potential athletes (n = 52), and (c) Senior team and Academy athletes (n = 26). Chi-square analysis and odds ratios were used to test BQ distributions against national norms and between quartiles, respectively. Results reveal no significant difference between BQ distributions within all three groups (P > 0.05). In contrast to most studies examining the RAE within athlete development settings, there appears to be no RAE throughout the England Squash talent pathway. These findings suggest that the birthday-banding strategy may be a useful tool to moderate RAE in youth sports.
Association of Blood Pressure at Successful Recanalization and Parenchymal Hemorrhage After Mechanical Thrombectomy With General Anesthesia

Background: This study aims to investigate the association between blood pressure (BP) at the time of recanalization and hemorrhagic transformation in large vessel occlusion (LVO) patients following mechanical thrombectomy (MT) with general anesthesia. Methods: We retrospectively reviewed our data base for patients with acute ischemic stroke acute ischemic stroke (AIS) who received MT between January 2018 and December 2019. The BP at two adjacent time points immediately after successful recanalization was recorded for subsequent calculation of mean BP (BPmean), maximum BP (BPmax), minimum BP (BPmin), range of BP (BPrange), and standard deviation of SP (BPSD). Hemorrhagic transformation was identified on 24-h computerized tomography images according to the European Cooperative Acute Stroke Study (ECASS) III trial. We used binary logistic regression analysis to investigate the association of BP parameters and the incidence of parenchymal hemorrhage (PH) and PH-2. Results: A total of 124 patients with anterior circulation LVO were finally included for analyses. After controlling for intravenous thrombolysis, procedure duration of mechanical thrombectomy, baseline National institutes of Health Stroke Scale (NIHSS), baseline ASPECTS, and number of device passes, the results showed that every increment of 10 mmHg in SBPrange (OR 1.559; 95% CI 1.027–2.365; P = 0.037) and SBPSD (OR 1.998; 95% CI 1.017–3.925; P = 0.045) were independently associated with PH. After adjustment for intravenous thrombolysis, procedure duration of mechanical thrombectomy, baseline NIHSS, the results showed that every increment of 10 mmHg in SBPmean (OR 1.973; 95% CI 1.190–3.271; P = 0.008), SBPmax (OR 1.838; 95% CI 1.199 to 2.815; P = 0.005), SBPrange (OR 1.908; 95% CI 1.161–3.136; P = 0.011) and SBPSD (OR 2.573; 95% CI 1.170–5.675; P = 0.019) were independently associated with PH-2. Conclusion: Patients with higher systolic BP and variability at the time of successful recanalization were more likely to have PH-2 in LVO patients following MT with general anesthesia.
Rhetoric by Accident

abstract:This essay presents a concept of rhetoric by accident, which understands accidents in regard to the materiality of affection (i.e., the condition of being affected) and in regard to the unconditioned rhetoricity of affectability. The concept of accidental rhetoric put forth depends on the ontological condition of openness, so first affect is stipulated in relation to the porousness of material life to explain the inevitability of affection and provide the basis for understanding rhetoric by accident. Then the accident is defined in alignment with material openness. Rather than consider accidents in terms of human control over contingencies, accidents are defined by the contingency of purposiveness to affection. That affect occurs without purpose means that beings experience rhetoric without a plan (i.e., by accident). The essay then considers how rhetoric by accident is part of any particular rhetoric’s existence, namely as a horizon of evolution and diversification for rhetoric.
Toward New Modalities in VEP-Based BCI Applications Using Dynamical Stimuli: Introducing Quasi-Periodic and Chaotic VEP-Based BCI

Visual evoked potentials (VEPs) to periodic stimuli are commonly used in brain computer interfaces for their favorable properties such as high target identification accuracy, less training time, and low surrounding target interference. Conventional periodic stimuli can lead to subjective visual fatigue due to continuous and high contrast stimulation. In this study, we compared quasi-periodic and chaotic complex stimuli to common periodic stimuli for use with VEP-based brain computer interfaces (BCIs). Canonical correlation analysis (CCA) and coherence methods were used to evaluate the performance of the three stimulus groups. Subjective fatigue caused by the presented stimuli was evaluated by the Visual Analogue Scale (VAS). Using CCA with the M2 template approach, target identification accuracy was highest for the chaotic stimuli (M = 86.8, SE = 1.8) compared to the quasi-periodic (M = 78.1, SE = 2.6, p = 0.008) and periodic (M = 64.3, SE = 1.9, p = 0.0001) stimulus groups. The evaluation of fatigue rates revealed that the chaotic stimuli caused less fatigue compared to the quasi-periodic (p = 0.001) and periodic (p = 0.0001) stimulus groups. In addition, the quasi-periodic stimuli led to lower fatigue rates compared to the periodic stimuli (p = 0.011). We conclude that the target identification results were better for the chaotic group compared to the other two stimulus groups with CCA. In addition, the chaotic stimuli led to a less subjective visual fatigue compared to the periodic and quasi-periodic stimuli and can be suitable for designing new comfortable VEP-based BCIs.
Single Nucleotide Polymorphisms Associated With Gut Homeostasis Influence Risk and Age-at-Onset of Parkinson's Disease

Research is increasingly focusing on gut inflammation as a contributor to Parkinson's disease (PD). Such gut inflammation is proposed to arise from a complex interaction between various genetic, environmental, and lifestyle factors, however these factors are under-characterized. This study investigated the association between PD and single-nucleotide polymorphisms (SNPs) in genes responsible for binding of bacterial metabolites and intestinal homeostasis, which have been implicated in intestinal infections or inflammatory bowel disease. A case-control analysis was performed utilizing the following cohorts: (i) patients from the Australian Parkinson's Disease Registry (APDR) (n = 212); (ii) a Caucasian subset of the Parkinson's Progression Markers Initiative (PPMI) cohort (n = 376); (iii) a combined control group (n = 404). The following SNPs were analyzed: PGLYRP2 rs892145, PGLYRP4 rs10888557, TLR1 rs4833095, TLR2 rs3804099, TLR4 rs7873784, CD14 rs2569190, MUC1 rs4072037, MUC2 rs11825977, CLDN2 rs12008279 and rs12014762, and CLDN4 rs8629. PD risk was significantly associated with PGLYRP4 rs10888557 genotype in both cohorts. PGLYRP2 rs892145 and TLR1 rs4833095 were also associated with disease risk in the APDR cohort, and TLR2 rs3804099 and MUC2 rs11825977 genotypes in the PPMI cohort. Interactive risk effects between PGLYRP2/PGLYRP4 and PGLYRP4/TLR2 were evident in the APDR and PPMI cohorts, respectively. In the APDR cohort, the PGLYRP4 GC genotype was significantly associated with age of symptom onset, independently of gender, toxin exposure or smoking status. This study demonstrates that genetic variation in the bacterial receptor PGLYRP4 may modulate risk and age-of-onset in idiopathic PD, while variants in PGLYRP2, TLR1/2, and MUC2 may also influence PD risk. Overall, this study provides evidence to support the role of dysregulated host-microbiome signaling and gut inflammation in PD, and further investigation of these SNPs and proteins may help identify people at risk of developing PD or increase understanding of early disease mechanisms.
Occlusal Fissures in Equine Cheek Teeth: A Prospective Longitudinal in vivo Study

Background: It has been suggested that fissures of the occlusal surface of equine cheek teeth may develop into crown fractures. Objectives: To examine the evolution of fissures present on the occlusal surface of cheek teeth. Furthermore, to investigate the presence of a fissure as a risk factor for the development of a subsequent crown fracture. Study Design: Observational longitudinal study. Methods: Bi-annual dental examinations were performed on 36 horses for 3 years. Video-recordings were made to evaluate the evolution of detected fissures. The effect of possible predictors on the development of tooth fractures was investigated by regression analysis. Results: The evolution of 785 fissures (467 type 1a, 271 type 1b, 47 type 2) was recorded. Fissure characteristics were observed to remain unchanged, disappear, become longer, shorter, change in configuration or change in color. Partial crown fractures (22 maxillary, 50 mandibular) were recorded in 52 cheek teeth in 22/36 horses. Fifty-nine of these fractures evolved from previously observed fissures (24 type 1a, 29 type 1b, 6 type 2). All fissure types proved to be a significant risk factor for the development of a crown fracture (p < 0.001), with the highest odds for type 2 fissures (OR = 14.27; 95% CI = 4.88–41.71). Other significant risk factors were the time of follow-up (p < 0.001), mandibular teeth (p < 0.001) and the lingual side of a tooth (p < 0.001). All fractures were non-complicated. Main Limitations: Some horses were prematurely lost for follow-up, which perhaps influenced the results. A longer follow-up period would have also allowed an evaluation of the risk for pulp disease on the long term subsequent to partial crown fractures. Conclusions: The presence of a fissure of any type, mandibular cheek teeth, the lingual side of cheek teeth, and time of follow-up proved to be significant risk factors for development of a cheek tooth crown fracture. Type 2 fissures showed the highest odds followed by type 1b fissures. The observed partial crown fractures demonstrated a low clinical impact whereby no tooth showed signs of development of endodontal disease.