Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural Model for Self-Limiting β-strand Arrangement Within an Alzheimer’s Amyloid-β Oligomer

Previous reports revealed that sodium dodecyl sulfate near its critical micelle concentration can drive the assembly of Aβ42 along an oligomeric pathway. This pathway produces a 150 kDa peptide oligomer (approximately 32 peptide molecules or protomers) that does not aggregate further into amyloid fibrils. Solid-state nuclear magnetic resonance (NMR) spectroscopy revealed structural features distinguishing the 150 kDa oligomer from fibrils. A puzzling feature was the coexistence of parallel and antiparallel β-sheets within the oligomer structure. Here we present new atomic-level structural constraints obtained via solid-state NMR spectroscopy, benefitting from improved resolution via sample concentration by ultracentrifugation. In addition, two-dimensional cryo-electron microscopy (cryo-EM) reconstruction revealed a 4-fold symmetric shape. We propose a structural model to rationalize the solid-sate NMR- and cryo-EM-derived structural constraints. This model has a hollow square cylinder shape, with antiparallel β-sheets formed by residues 33-39 lining the inner walls and parallel β-sheets formed by residues 11-22 lining the outer walls. Within successive layers, the outer β-strands on each side of the square cylinder alternate between two forms: one within a U-shaped protomer and another within L-shaped protomer. Molecular dynamics simulations show that, when the oligomer model is embedded in a lipid membrane, ions permeate through the central pore, with cation selectivity. The model further motivates an assembly pathway-based interpretation that may explain why the 150 kDa oligomer does not undergo further aggregation into amyloid fibrils. Significance Statement Aβ oligomers are thought to be the most toxic species in Alzheimer’s disease. Their sizes range from 2 to ∼50 protomers. Most published experimental data on Aβ oligomers indicate that they, like fibrils, are composed of β-sheets, but it is a mystery why any β-sheet aggregate would exist as a stable oligomer without undergoing further aggregation into fibrils. Here, structural constraints from solid-state NMR and cryo-EM led us to an oligomer model with a hollow square cylinder shape capable of conducting ions when embedded in a lipid membrane. Based on the model, we argue that geometric frustration may distinguish the assembly pathway that produces this oligomer from fibril-forming assembly pathways.
Exciton lifetimes in GaN and GaInN

Results from temperature dependent photoluminescence (PL) transient measurements on metalorganic vapor phase epitaxy grown epitaxial layers of GaN and GaInN are reported. In sufficiently pure GaN layers the free‐exciton PL dominates even at the lowest temperatures (2 K), and the intrinsic excitonic lifetimes can be obtained. We report a value of about 125 ps for the radiative lifetime of the free exciton in GaN at 2 K, as obtained from the PL transients of a 3 μm buried undoped GaN layer sandwiched between AlN and GaInN. The PL decay time in the ternary alloy GaInN, which is dominated by localized excitons at low temperatures, is much longer, about 500 ps.
Thymic macrophages consist of two populations with distinct 1 localization and origin 2 3

Institute of Microbiology and Immunology, National Yang Ming Chiao Tung University, Taipei, 7 Taiwan 8 Bioinformatics Program, Taiwan International Graduate Program, Institute of Information 9 Science, Academia Sinica, Taipei, Taiwan 10 Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, 11 Taipei, Taiwan 12 Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan 13 Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, 14 University of California, Berkeley, CA, United States 15 Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, 16 Taiwan 17 18
Unleashing the power within short-read RNA-seq for plant research: Beyond differential expression analysis and toward regulomics

RNA-seq has become a state-of-the-art technique for transcriptomic studies. Advances in both RNA-seq techniques and the corresponding analysis tools and pipelines have unprecedently shaped our understanding in almost every aspects of plant sciences. Notably, the integration of huge amount of RNA-seq with other omic data sets in the model plants and major crop species have facilitated plant regulomics, while the RNA-seq analysis has still been primarily used for differential expression analysis in many less-studied plant species. To unleash the analytical power of RNA-seq in plant species, especially less-studied species and biomass crops, we summarize recent achievements of RNA-seq analysis in the major plant species and representative tools in the four types of application: (1) transcriptome assembly, (2) construction of expression atlas, (3) network analysis, and (4) structural alteration. We emphasize the importance of expression atlas, coexpression networks and predictions of gene regulatory relationships in moving plant transcriptomes toward regulomics, an omic view of genome-wide transcription regulation. We highlight what can be achieved in plant research with RNA-seq by introducing a list of representative RNA-seq analysis tools and resources that are developed for certain minor species or suitable for the analysis without species limitation. In summary, we provide an updated digest on RNA-seq tools, resources and the diverse applications for plant research, and our perspective on the power and challenges of short-read RNA-seq analysis from a regulomic point view. A full utilization of these fruitful RNA-seq resources will promote plant omic research to a higher level, especially in those less studied species.
ggMOB: Elucidation of genomic conjugative features and associated cargo genes across bacterial genera using genus-genus mobilization networks

Horizontal gene transfer mediated by conjugation is considered an important evolutionary mechanism of bacteria. It allows organisms to quickly evolve new phenotypic properties including antimicrobial resistance (AMR) and virulence. The frequency of conjugation-mediated cargo gene exchange has not yet been comprehensively studied within and between bacterial taxa. We developed a frequency-based network of genus-genus conjugation features and candidate cargo genes from whole-genome sequence data of over 180,000 bacterial genomes, representing 1,345 genera. Using our method, which we refer to as ggMOB, we revealed that over half of the bacterial genomes contained one or more known conjugation features that matched exactly to at least one other genome. Moreover, the proportion of genomes containing these conjugation features varied substantially by genus and conjugation feature. These results and the genus-level network structure can be viewed interactively in the ggMOB interface, which allows for user-defined filtering of conjugation features and candidate cargo genes. Using the network data, we observed that the ratio of AMR gene representation in conjugative versus non-conjugative genomes exceeded 5:1, confirming that conjugation is a critical force for AMR spread across genera. Finally, we demonstrated that clustering genomes by conjugation profile sometimes correlated well with classical phylogenetic structuring; but that in some cases the clustering was highly discordant, suggesting that the importance of the accessory genome in driving bacterial evolution may be highly variable across both time and taxonomy. These results can advance scientific understanding of bacterial evolution, and can be used as a starting point for probing genus-genus gene exchange within complex microbial communities that include unculturable bacteria. ggMOB is publicly available under the GNU licence at https://ruiz-hci-lab.github. io/ggMOB/
Unraveling site fidelity and residency patterns of sperm whales in the insular oceanic waters of Macaronesia

Knowledge of the distribution and residency of pelagic marine megafauna, particularly deep-diving species, is scarce due to their high mobility over difficult-to-access oceanic areas and long periods underwater. However, the threatened status of many of these species, such as the sperm whale Physeter macrocephalus, increases the need to obtain quantitative data to support conservation measures. In the warm temperate waters of Macaronesia (Eastern North Atlantic), sperm whales occur year-round in a set of island systems (the Azores, Madeira, and the Canaries), mainly in social groups of females and juveniles with the occasional visits of mature males. Although it is known that they perform inter-archipelago movements, information on site fidelity and residency times is still scarce. Here, based on photographic-identification data, site fidelity and residency times of sperm whales were estimated for subareas of the Azores and the Madeira archipelagos, with a preliminary assessment for a subarea of the Canaries. The Azores and Madeira subareas presented similar proportions of individuals with recaptures (~25%), mainly inter-annual, while in the subarea of the Canaries, only <10% of the individuals were recaptured. Standardized Site Fidelity Indexes showed very low values (<0.01) for both the Azores and Madeira subareas. Lagged identification rates based on models including emigration and reimmigration estimated that an average of 44.8 individuals (SE=4.9) spent 12.9 days (SE=1.5) in the Azores before leaving for 99.1 days (SE=12.5), while 8.4 individuals (SE=16.1) spent 0.8 day (SE=6.6) in Madeira before leaving for 8.6 days (SE=6.9), with a very low mortality rate. This study i) indicates a degree of residency of about ¼ of the identified individuals for the Azores and Madeira subareas and ii) supports that these oceanic archipelagos constitute an important habitat for a Vulnerable species in the Atlantic. Moreover, it also highlights the importance of combining data from opportunistic and dedicated surveys and joint national and international efforts toward the conservation of marine megafauna.
Time-locked auditory cortical responses in the high-gamma band: A window into primary auditory cortex

Primary auditory cortex is a critical stage in the human auditory pathway, a gateway between subcortical and higher-level cortical areas. Receiving the output of all subcortical processing, it sends its output on to higher-level cortex. Non-invasive physiological recordings of primary auditory cortex using electroencephalography (EEG) and magnetoencephalography (MEG), however, may not have sufficient specificity to separate responses generated in primary auditory cortex from those generated in underlying subcortical areas or neighboring cortical areas. This limitation is important for investigations of effects of top-down processing (e.g., selective-attention-based) on primary auditory cortex: higher-level areas are known to be strongly influenced by top-down processes, but subcortical areas are often assumed to perform strictly bottom-up processing. Fortunately, recent advances have made it easier to isolate the neural activity of primary auditory cortex from other areas. In this perspective, we focus on time-locked responses to stimulus features in the high gamma band (70–150 Hz) and with early cortical latency (∼40 ms), intermediate between subcortical and higher-level areas. We review recent findings from physiological studies employing either repeated simple sounds or continuous speech, obtaining either a frequency following response (FFR) or temporal response function (TRF). The potential roles of top-down processing are underscored, and comparisons with invasive intracranial EEG (iEEG) and animal model recordings are made. We argue that MEG studies employing continuous speech stimuli may offer particular benefits, in that only a few minutes of speech generates robust high gamma responses from bilateral primary auditory cortex, and without measurable interference from subcortical or higher-level areas.
Physical ability, cervical function, and walking plantar pressure in frail and pre-frail older adults: An attentional focus approach

Aging and increased vulnerability define the clinical condition of frailty. However, while the cervical function is recognized as a determinant of balance and walking performance, no study simultaneously physical ability, cervical function, balance, and plantar pressure distribution in walking in nursing house population. Thus, the present study aimed to compare these parameters between Frail and Pre-Frail aged people. Thirty-one (12 men and 19 women) institutionalized participants (age: 89.45 ± 5.27 years, weight: 61.54 ± 9.99 kg, height: 160.34 ± 7.93 cm) were recruited and divided into Pre-Frail and Frail groups according to SPPB (Short Physical Performance Battery) score (Frail <6, Pre–Frail ≥6). Participants performed the Timed Up and Go Test (TUGT) and a static balance evaluation. The cervical range of motion (COM), knee extensor strength, and walking plantar pressure distribution have been measured. The Pre-Frail group showed a higher gait speed (ES = 0.78, p ≤ 0.001) and a better TUGT, as well as higher knee extensor strength (ES = 0.4, p = 0.04). Furthermore, the Pre-Frail group presented a center of pressure (COP) displacement velocity on the sagittal axis (ES = 0.43, p = 0.02) and a more COP projection on this axis (ES = 0.43, p = 0.02). No significant difference has been observed between the two groups concerning the total contact time and most of the plantar pressure parameters except for the rear foot relative contact time which was lower in the Pre-Frail group. The Pre-Frail group also showed better cervical tilt mobility (ES = 0.35, p = 0.04). This study highlights the influence of some new parameters on frailty in older people, such as cervical mobility and plantar pressure distribution in walking.
The Shank3Venus/Venus knock in mouse enables isoform-specific functional studies of Shank3a

Background Shank3 is a scaffolding protein essential for the organization and function of the glutamatergic postsynapse. Monogenic mutations in SHANK3 gene are among the leading genetic causes of Autism Spectrum Disorders (ASD). The multiplicity of Shank3 isoforms seems to generate as much functional diversity and yet, there are no tools to study endogenous Shank3 proteins in an isoform-specific manner. Methods In this study, we created a novel transgenic mouse line, the Shank3Venus/Venus knock in mouse, which allows to monitor the endogenous expression of the major Shank3 isoform in the brain, the full-length Shank3a isoform. Results We show that the endogenous Venus-Shank3a protein is localized in spines and is mainly expressed in the striatum, hippocampus and cortex of the developing and adult brain. We show that Shank3Venus/+ and Shank3Venus/Venus mice have no behavioral deficiency. We further crossed Shank3Venus/Venus mice with Shank3ΔC/ΔC mice, a model of ASD, to track the Venus-tagged wild-type copy of Shank3a in physiological (Shank3Venus/+) and pathological (Shank3Venus/ΔC) conditions. We report a developmental delay in brain expression of the Venus-Shank3a isoform in Shank3Venus/ΔC mice, compared to Shank3Venus/+ control mice. Conclusion Altogether, our results show that the Shank3Venus/Venus mouse line is a powerful tool to study endogenous Shank3a expression, in physiological conditions and in ASD.
The autonomic nervous system: A potential link to the efficacy of acupuncture

The autonomic nervous system (ANS) is a diffuse network that regulates physiological systems to maintain body homeostasis by integrating inputs from the internal and external environment, including the sympathetic, parasympathetic, and enteric nervous systems (ENS). Recent evidence suggests that ANS is one of the key neural pathways for acupuncture signal transduction, which has attracted worldwide attention in the acupuncture field. Here, we reviewed the basic and clinical research published in PubMed over the past 20 years on the effects of acupuncture on ANS regulation and homeostasis maintenance. It was found that acupuncture effectively alleviates ANS dysfunction-associated symptoms in its indications, such as migraine, depression, insomnia, functional dyspepsia, functional constipation. Acupuncture stimulation on some specific acupoints activates sensory nerve fibers, the spinal cord, and the brain. Using information integration and efferents from a complex network of autonomic nuclei of the brain, such as the insular cortex (IC), prefrontal cortex, anterior cingulate cortex (ACC), amygdala (AMG), hypothalamus, periaqueductal gray (PAG), nucleus tractus solitarius (NTS), ventrolateral medulla (VLM), nucleus ambiguus (AMB), acupuncture alleviates visceral dysfunction, inflammation via efferent autonomic nerves, and relieves pain and pain affect. The modulating pattern of sympathetic and parasympathetic nerves is associated with acupuncture stimulation on specific acupoints, intervention parameters, and disease models, and the relationships among them require further exploration. In conclusion, ANS is one of the therapeutic targets for acupuncture and mediates acupuncture’s actions, which restores homeostasis. A systemic study is needed to determine the rules and mechanisms underlying the effects of acupoint stimulation on corresponding organs mediated by specific central nervous networks and the efferent ANS.
Comparison between Lactobacillus rhamnosus GG and LuxS-deficient strain in regulating gut barrier function and inflammation in early-weaned piglets

Background Early weaning-induced stress impairs the intestinal barrier function and adversely affects the health of piglet. Probiotics can be used to prevent and treat various intestinal diseases. Lactobacillus rhamnosus GG (LGG) has an LuxS/AI-2 quorum sensing (QS) system that senses environmental changes through chemical signaling molecules. The aim of the study was to explore whether luxS mutant affects the protective role of LGG in the gut barrier of weaned piglets by comparing the luxS mutant (ΔluxS) with its wild-type (WT). Methods Newborn piglets were orally administered with WT and ΔluxS at dosage of 109 CFU, respectively. Accordingly, newborn piglets in the Con group were orally administered with PBS. Piglets were weaned on day 21 and euthanized on day 24, three days following weaning. Results Supplementation of ΔluxS in advance significantly boosted the relative abundances of healthy microbes (including Catenibacterium, Eubacterium, Lachnospiraceae and Bifidobacterium). WT and ΔluxS maintain intestinal barrier function mainly by promoting intestinal villus to crypt ratio (VCR), occludin protein expression and mucus secretion (P<0.05). Furthermore, LGG reduces pro-inflammatory mediators by inhibiting TLR4 and MAPK signal transduction (P<0.05). Conclusion Both WT and ΔluxS were shown to resist weaning stress by enhancing the intestinal barrier function of piglets. It has to be said that the ability of ΔluxS to maintain intestinal tissue morphology and promote mucus secretion significantly decreased compared with that of WT.
Anthropogenic disturbance promotes the diversification of antibiotic resistance genes and virulence factors in the gut of plateau pikas (Ochotona curzoniae)

The prevalence and transmission of antibiotic resistance genes (ARGs) and virulence factors (VFs) pose a great threat to public health. The importance of pollution in determining the occurrence of ARGs and VFs in wildlife is poorly understood. Using a metagenomic approach, this study investigates the composition and functional pathways of bacteria, ARGs, and VFs in the gut microbiome of Plateau pikas in regions of medical pollution (MPR), heavy tourist traffic (HTR), and no contamination (NCR). We found that the abundance of probiotic genera (Clostridium, Eubacterium, Faecalibacterium, and Roseburia) were significantly lower in the HTR. The metabolic pathways of replication and repair in the endocrine and nervous systems were significantly enriched in the MPR, whereas endocrine and metabolic diseases were significantly enriched in the NCR. The Shannon and Gini–Simpson α-diversity indices of ARGs were highest in the HTR, and there were significant differences in β-diversity among the three regions. The resistance of ARGs to glycopeptide antibiotics increased significantly in the MPR, whereas the ARGs for aminocoumarins increased significantly in the HTR. The diversity of mobile genetic elements (MGEs) was significantly higher in the MPR than in other regions. We observed a strong positive correlation between ARGs and pathogenic bacteria, and the network structure was the most complex in the MPR. There were significant differences in the β-diversity of VFs among the three regions. Medical pollution led to significant enrichment of fibronectin-binding protein and PhoP, whereas tourism-related pollution (in the HTR) led to significant enrichment of LPS and LplA1. Our study indicates that environmental pollution can affect the structure and function of gut microbes and disseminate ARGs and VFs via horizontal transmission, thereby posing a threat to the health of wild animals.
The effects of three weight management methods on body composition and serum lipids of overweight and obese people

Introduction Obesity has become a major health problem worldwide. Diet management is an important means of weight loss. The aim of this study was to explore the improvement effect of a calorie-restricted diet (CRD), 5 + 2 intermittent fasting (5 + 2 IF), and high protein diet (HPD) on weight composition and serum lipid level of overweight and obese people in a short period (3 months). Methods Fifty-three participants aged 18–60 years and with body mass index (BMI) ranging from 24 to 35 kg/m2 were screened for inclusion and exclusion criteria and were randomly divided into three groups, i.e., CRD, 5 + 2 IF, and HPD. Basic information, body composition, and venous blood samples were collected at baseline and after 3 months of intervention. Body composition was measured using a body composition analyzer (SK-V9), and serum lipids were assayed using the Roche Cobas e702 automatic biochemistry analysis system. The generalized estimating equation (GEE) was used to analyze and compare the repeated measurements of body composition and levels of serum lipids. Results The results showed that total weight, BMI, body fat mass, muscle mass, visceral fat index, and waist and hip circumferences had significantly decreased in all three groups after 3 months of intervention, and the average weight loss was 3.3 ± 1.14, 4.12 ± 0.05, and 2.62 ± 0.13 kg in CRD, 5 + 2 IF, and HPD groups, respectively. The results of the GEE model indicated that compared with the CRD group, the 5 + 2 IF group showed a more significant decrease in weight (β = −0.272, P < 0.001), BMI (β = −0.091, P < 0.001), body fat mass (β = −0.172, P < 0.001), muscle (β = −0.043, P < 0.001), and visceral fat index (β = −0.019, P < 0.001), however, HPD has more advantages in visceral fat index loss (β = −0.011, P < 0.001) and lean body mass preserve (β = 0.229, P < 0.001). Conclusion Our findings showed that the 5 + 2 IF may be more effective in reducing total weight and body fat, and HPD may be more helpful in preventing lean body mass loss during a short-term weight loss intervention.