Miracle-dz/UniFAR-FTUs huggingface dataset:
Ascl1 phospho-site mutations enhance neuronal conversion of adult cortical astrocytes in vivo

Direct neuronal reprogramming, the process whereby a terminally differentiated cell is converted into an induced neuron without traversing a pluripotent state, has tremendous therapeutic potential for a host of neurodegenerative diseases. While there is strong evidence for astrocyte-to-neuron conversion in vitro, in vivo studies in the adult brain are less supportive or controversial. Here, we set out to enhance the efficacy of neuronal conversion of adult astrocytes in vivo by optimizing the neurogenic capacity of a driver transcription factor encoded by the proneural gene Ascl1. Specifically, we mutated six serine phospho-acceptor sites in Ascl1 to alanines (Ascl1SA6) to prevent phosphorylation by proline-directed serine/threonine kinases. Native Ascl1 or Ascl1SA6 were expressed in adult, murine cortical astrocytes under the control of a glial fibrillary acidic protein (GFAP) promoter using adeno-associated viruses (AAVs). When targeted to the cerebral cortex in vivo, mCherry+ cells transduced with AAV8-GFAP-Ascl1SA6-mCherry or AAV8-GFAP-Ascl1-mCherry expressed neuronal markers within 14 days post-transduction, with Ascl1SA6 promoting the formation of more mature dendritic arbors compared to Ascl1. However, mCherry expression disappeared by 2-months post-transduction of the AAV8-GFAP-mCherry control-vector. To circumvent reporter issues, AAV-GFAP-iCre (control) and AAV-GFAP-Ascl1 (or Ascl1SA6)-iCre constructs were generated and injected into the cerebral cortex of Rosa reporter mice. In all comparisons of AAV capsids (AAV5 and AAV8), GFAP promoters (long and short), and reporter mice (Rosa-zsGreen and Rosa-tdtomato), Ascl1SA6 transduced cells more frequently expressed early- (Dcx) and late- (NeuN) neuronal markers. Furthermore, Ascl1SA6 repressed the expression of astrocytic markers Sox9 and GFAP more efficiently than Ascl1. Finally, we co-transduced an AAV expressing ChR2-(H134R)-YFP, an optogenetic actuator. After channelrhodopsin photostimulation, we found that Ascl1SA6 co-transduced astrocytes exhibited a significantly faster decay of evoked potentials to baseline, a neuronal feature, when compared to iCre control cells. Taken together, our findings support an enhanced neuronal conversion efficiency of Ascl1SA6 vs. Ascl1, and position Ascl1SA6 as a critical transcription factor for future studies aimed at converting adult brain astrocytes to mature neurons to treat disease.
Compensatory movement strategies differentially affect attention allocation and gait parameters in persons with Parkinson’s disease

Persons with Parkinson’s disease (PwP) are advised to use compensatory strategies such as external cues or cognitive movement strategies to overcome gait disturbances. It is suggested that external cues involve the processing of sensory stimulation, while cognitive-movement strategies use attention allocation. This study aimed to compare over time changes in attention allocation in PwP between prolonged walking with cognitive movement strategy and external cues; to compare the effect of cognitive movement strategies and external cues on gait parameters; and evaluate whether these changes depend on cognitive function. Eleven PwP participated in a single-group pilot study. Participants walked for 10 min under each of three conditions: natural walking, using external cuing, using a cognitive movement strategy. Attention and gait variables were extracted from a single-channel electroencephalogram and accelerometers recordings, respectively. Attention allocation was assessed by the% of Brain Engagement Index (BEI) signals within an attentive engagement range. Cognitive function was assessed using a neuropsychological battery. The walk was divided into 2-min time segments, and the results from each 2-min segment were used to determine the effects of time and condition. Associations between cognitive function and BEI signals were tested. Findings show that in the cognitive movement strategy condition, there was a reduction in the % of BEI signals within the attentive engagement range after the first 2 min of walking. Despite this reduction the BEI did not consistently differ from natural and metronome walking. Spatiotemporal gait variables were better in the cognitive movement strategy condition relative to the other conditions. Global cognitive and information processing scores were significantly associated with the BEI only when the cognitive movement strategy was applied. In conclusion, the study shows that a cognitive movement strategy has positive effects on gait variables but may impose a higher attentional load. Furthermore, when walking using a cognitive movement strategy, persons with higher cognitive function showed elevated attentive engagement. The findings support the idea that cognitive and attentional resources are required for cognitive movement strategies in PwP. Additionally, this study provides support for using single-channel EEG to explore mechanistic aspects of clinical interventions.
Immune checkpoint inhibitors for PD-1/PD-L1 axis in combination with other immunotherapies and targeted therapies for non-small cell lung cancer

It has been widely acknowledged that the use of immune checkpoint inhibitors (ICI) is an effective therapeutic treatment in many late-stage cancers. However, not all patients could benefit from ICI therapy. Several biomarkers, such as high expression of PD-L1, high mutational burden, and higher number of tumor infiltration lymphocytes have shown to predict clinical benefit from immune checkpoint therapies. One approach using ICI in combination with other immunotherapies and targeted therapies is now being investigated to enhance the efficacy of ICI alone. In this review, we summarized the use of other promising immunotherapies and targeted therapies in combination with ICI in treatment of lung cancers. The results from multiple animals and clinical trials were reviewed. We also briefly discussed the possible outlooks for future treatment.
Metode Reduksi Ukuran Pada Masalah Penugasan Kuadratik Simetris (Size Reduction Method Over Simmetric Quadratic Assignment Problem (Sqap))

Masalah penugasan kuadratik simetris (SQAP) merupakan suatu optimisasi masalah penugasan N fasilitas ke N lokasi, dengan setiap (i , k ) fasilitas akan ditugaskan pada ( j , n) lokasi, i, j , k , n ∈ B + , i, j , k , n ≤ N , dan masing‐masing hanya melaksanakan satu tugas. Masalah SQAP adalah masalah menentukan total biaya penugasan seekonomis mungkin. Dalam paper ini akan didiskusikan suatu metode yang mereduksi matriks biaya berukuran N × N menjadi berukuran ( N − 1) × ( N − 1) . Kata‐kata kunci: masalah penugasan kuadratik simetris, metode reduksi ukuran.
Hormetic effect of 17α-ethynylestradiol on activated sludge microbial community response

Synthetic estrogen analogues are among the most potent estrogenic contaminants in effluents from wastewater treatment plants. Although its effects have been well elucidated in the feminization of male fish and interference with the endocrine systems in humans, it has not been fully explored in the activated sludge (AS) microbiome, particularly EE2 (17α-ethynylestradiol). Therefore, in this study, the bacterial community shift in a 6-day laboratory-scale reactor in environmental (0, 5, 10, and 100 ng/L) and predictive elevated concentrations (5, 10, and 100 mg/L) of EE2 was investigated using culture-based and metagenomics approaches. Results showed significant changes (t-test, all p < 0.05) between initial and final physicochemical parameters (pH, DO, and EC). Although environmental concentrations showed a slight decrease in microbial counts (5.6 × 106 to 4.6 × 106 CFU/ml) after a 24-h incubation for the culturable approach, the predictive elevated concentrations (5 to 100 mg/L) revealed a drastic microbial counts reduction (5.6 × 106 to 8 × 102 CFU/ml). The metagenomic data analysis uncovered that bacterial communities in the control sample were dominated by Proteobacteria, followed by Bacteroidetes and Firmicutes. The taxonomic classification after exposure of microbial communities in various concentrations revealed significant differences in community composition between environmental concentration (Shannon indices between 2.58 to 3.68) and predictive elevated concentrations (Shannon indices between 2.24 and 2.84; t-test, all p < 0.05). The EE2 enriched seven OTUs were Novosphingobium, Cloacibacterium, Stenotrophomonas, Enterobacteriaceae_unclassified, Stenotrophomonas, Enterobacteriaceae_unclassified and Rhodobacteraceae_unclassified. These results were supported by a dehydrogenase activity (DHA) test, which demonstrated less (about 40%) DHA in predictive elevated concentrations than in environmental concentrations. Notwithstanding, these findings suggest that EE2 may possess potent hormetic effect as evidenced by promotion of microbiome richness and dehydrogenase activity of AS in lower EE2 doses.
Editorial: Emerging and re-emerging viral zoonoses

COPYRIGHT © 2022 Kumar, Uversky, Tomar, Li, Chappell and Lau. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Editorial: Emerging and re-emerging viral zoonoses
Small RNA-based plant protection against diseases

Plant diseases cause significant decreases in yield and quality of crops and consequently pose a very substantial threat to food security. In the continuous search for environmentally friendly crop protection, exploitation of RNA interferance machinery is showing promising results. It is well established that small RNAs (sRNAs) including microRNA (miRNA) and small interfering RNA (siRNA) are involved in the regulation of gene expression via both transcriptional and post-transcriptional RNA silencing. sRNAs from host plants can enter into pathogen cells during invasion and silence pathogen genes. This process has been exploited through Host-Induced Gene Silencing (HIGS), in which plant transgenes that produce sRNAs are engineered to silence pest and pathogen genes. Similarly, exogenously applied sRNAs can enter pest and pathogen cells, either directly or via the hosts, and silence target genes. This process has been exploited in Spray-Induced Gene Silencing (SIGS). Here, we focus on the role of sRNAs and review how they have recently been used against various plant pathogens through HIGS or SIGS-based methods and discuss advantages and drawbacks of these approaches.
How does workplace ostracism affect employee innovation behavior: An analysis of chain mediating effect

This study seeks to examine the relationship between workplace ostracism and innovation behavior while considering the mediating role of knowledge hiding and organizational identification. The study also tests the moderating role of task interdependence in these relationships. The study collected data through structured questionnaires from 409 participants (i.e., employees) working in the small to medium-sized enterprise of big cities of China. The study adopted a structured equation modeling technique for data analysis. Significantly, the study results suggest that workplace ostracism is negatively associated with innovation behavior, both directly and indirectly via knowledge hiding and organizational identification. We also find that task interdependence weakens the positive relationship between workplace ostracism and knowledge hiding. Current study has tested the negative relationship between workplace ostracism and innovation behavior unlike most of the previous investigations that have focused on positive factors. Our study from a rational perspective to explore the influence mechanism between workplace ostracism and innovation behavior is addition to the previous research and the rich, in revelation managers motivate employees to implement knowledge sharing activities at the same time, pay attention to take measures to restrain negative knowledge such as knowledge hidden activities, to activate the creativity of organization staff of intellectual resources. This paper contributes to innovation behavior literature which is an important part of innovation management based on both conservation of resources theory and social network theory.
Bringing the local back in. The role of territories in the “biological” transition process toward circular economy: A perspective of analysis

As widely evidenced in the past decades, the level of “humanity's metabolism” is unsustainable and must be reduced. It is especially related to issues, such as availability of resources, impacts of transportation, waste management, and external costs that could adversely affect the economic and environmental scenario at a global level. In the transition to circular economy (CE), moving from the insights of industrial ecology (IE) and the related “biological paradigm”, it has been suggested that the meso scale is the one in which great efficiencies can be achieved; the focus is on territories in which networks of economic actors' express significant potential in terms of synergistic and efficient use of resources and wastes. This perspective article aims to propose a detailed methodological viewpoint of this issue, moving from the scientific and empirical experience gained in a long-term research project conducted by the author on the themes of IE, CE, and their development in local contexts. The first phase of the research was characterized by theoretical-methodological in-depth analysis, case studies, and pilot tests, including different operating local contexts to evaluate their potential for the development of IE-based approaches. The results obtained and the experiences gained in the first phase have been used to develop an interpretative framework for assessing the role of external factors in influencing the process of development. Currently, the research is aimed at developing an analytical model capable of representing both the structural and operational characteristics of such contexts and the relative factors of influence in view of the adoption of circular strategies for the territory in which they are located.
Continuous theta burst stimulation for drug-resistant epilepsy

Introduction Repetitive transcranial magnetic stimulation (rTMS) may have anti-epileptic effects, especially in patients with neocortical lesions. Initial clinical trials demonstrated that the duration of the seizure reducing effect is relatively short-lived. In the context of a chronic condition like epilepsy, theta burst stimulation (TBS) may represent a potential solution in optimizing treatment practicality and durability as it was demonstrated to be associated with longer-lasting after-effects. TBS has been studied extensively in diverse neuropsychiatric conditions, but a therapeutic TBS protocol has not previously been applied in epilepsy patients. Materials and methods We performed a prospective open-label pilot study of 4-day accelerated continuous TBS (cTBS) treatment in patients with neocortical drug-resistant epilepsy (DRE). A treatment session consisted of 5 cTBS trains, each comprising 600 pulses presented in 50 Hz triplet bursts every 200 ms, delivered at 10-min intertrain-intervals, targeted over the epileptic focus (EF) using a neuronavigation-guided figure-of-8 coil. Safety and feasibility, and seizure frequency were assessed as primary and secondary endpoints, respectively, over a 4-week baseline period, a 1-week treatment period and a 7-week follow-up period, using adverse event logging, electro-encephalography, cognitive, and psychological questionnaires and a seizure diary kept by the patients and/or caregivers. Results Seven subjects (4M:3F; median age 48, interquartile ranges 25) underwent the treatment protocol. Adverse events were reported in all subjects but were mild and transient. No clinical or electrographic seizures were evoked during or immediately following stimulation. No deterioration was found in cognition nor in psycho-emotional well-being following treatment. Treatment burden was acceptable, but seems to depend on clinical effect, duration of ongoing effect and stimulation site. Median weekly seizure frequency and ratio of seizure-free weeks did not change significantly in this small patient cohort. Conclusion We report the results of the first ever trial of cTBS as a treatment for neocortical DRE. A 4-day accelerated cTBS protocol over the EF appears safe and feasible. Although the design and sample size of this open-label pilot study is unfit to reliably identify a therapeutic effect, results encourage further exploration of cTBS as an anti-epileptic treatment and potential optimization compared to conventional rTMS in a dedicated randomized controlled trial. (clinicaltrials.gov: NCT02635633).
Use of 3D modeling to refine predictions of canopy light utilization: A comparative study on canopy photosynthesis models with different dimensions

Canopy photosynthesis integrates leaf functional and structural traits in space and time and correlates positively with yield formation. Many models with different levels of architectural details ranging from zero-dimensional (0D) to three-dimensional (3D) have been developed to simulate canopy light interception and photosynthesis. Based on these models, a crop growth model can be used to assess crop yield in response to genetic improvement, optimized practices, and environmental change. However, to what extent do architectural details influence light interception, photosynthetic production, and grain yield remains unknown. Here, we show that a crop growth model with high-resolution upscaling approach in space reduces the departure of predicted yield from actual yield and refines the simulation of canopy photosynthetic production. We found crop yield predictions decreased by 12.0–48.5% with increasing the resolution of light simulation, suggesting that a crop growth model without architectural details may result in a considerable departure from the actual photosynthetic production. A dramatic difference in light interception and photosynthetic production of canopy between cultivars was captured by the proposed 3D model rather than the 0D, 1D, and 2D models. Furthermore, we found that the overestimation of crop yield by the 0D model is caused by the overestimation of canopy photosynthetically active radiation (PAR) interception and the RUE and that by the 1D and 2D model is caused by the overestimated canopy photosynthesis rate that is possibly related to higher predicted PAR and fraction of sunlit leaves. Overall, this study confirms the necessity of taking detailed architecture traits into consideration when evaluating the strategies of genetic improvement and canopy configuration in improving crop yield by crop modeling.
Modularity and the Politics of Emotion Categorisation

: Empirically-informed approaches to emotion often construe our emotions as modules: systems hardwired into our brains by evolution and purpose-built to generate certain coordinated patterns of expressive, physiological, behavioural and phenomenological responses. In ‘Against Modularity’ (2008), de Sousa argues that we shouldn’t think of our emotions in terms of a limited number of modules because this conflicts with our aspirations for a life of greater emotional richness. My aim in this paper is to defend de Sousa’s critique of modular emotion taxonomies from some obvious rejoinders, and to develop his positive proposal as to how we might reconcile the evidence for emotional modularity with an attitude of disapproval towards rigid emotion taxonomies.
Thirteen dubious ways to detect conserved structural RNAs

Covariation induced by compensatory base substitutions in RNA alignments is a great way to deduce conserved RNA structure, in principle. In practice, success depends on many factors, importantly the quality and depth of the alignment and the choice of covariation statistic. Measuring covariation between pairs of aligned positions is easy. However, using covariation to infer evolutionarily conserved RNA structure is complicated by other extraneous sources of covariation such as that resulting from homologous sequences having evolved from a common ancestor. In order to provide evidence of evolutionarily conserved RNA structure, a method to distinguish covariation due to sources other than RNA structure is necessary. Moreover, there are several sorts of artifactually generated covariation signals that can further confound the analysis. Additionally, some covariation signal is difficult to detect due to incomplete comparative data. Here, we investigate and critically discuss the practice of inferring conserved RNA structure by comparative sequence analysis. We provide new methods on how to approach and decide which of the numerous long non‐coding RNAs (lncRNAs) have biologically relevant structures.
What Is Hidden Behind The Gender Differences Of Carotid Atherosclerosis?

This review article reveals possible causes that may underlie gender differences of carotid atherosclerosis: vascular anatomy, localization and morphology of atherosclerotic plaques, different effects and prevalence of known risk factors between genders (arterial hypertension, hypercholesterolemia, obesity, smoking, alcohol consumption, depression / stress). A separate place in the review is given to markers of inflammation and the protective effect of female sex hormones.
Graph-Assisted Tensor Disaggregation

Consider a multi-aspect tensor dataset which is only observed in multiple complementary aggregated versions, each one at a lower resolution than the highest available one. Recent work [2] has demonstrated that given two such tensors, which have been aggregated in lower resolutions in complementary dimensions, we can pose and solve the disaggregation as an instance of a coupled tensor decomposition. In this work, we are exploring the scenario in which, in addition to the two complementary aggregated views, we also have access to a graph where nodes correspond to samples of the tensor mode that has not been aggregated. Given this graph, we propose a graph-assisted tensor disaggregation method. In our experimental evaluation, we demonstrate that our proposed method performs on par with the state of the art when the rank of the underlying coupled tensor decomposition is low, and significantly outperforms the state of the art in cases where the rank increases, producing more robust and higher-quality disaggregation.
The Genetic Stability, Replication Kinetics and Cytopathogenicity of Recombinant Avian Coronaviruses with a T16A or an A26F Mutation within the E Protein Is Cell-Type Dependent

The envelope (E) protein of the avian coronavirus infectious bronchitis virus (IBV) is a small-membrane protein present in two forms during infection: a monomer and a pentameric ion channel. Each form has an independent role during replication; the monomer disrupts the secretory pathway, and the pentamer facilitates virion production. The presence of a T16A or A26F mutation within E exclusively generates the pentameric or monomeric form, respectively. We generated two recombinant IBVs (rIBVs) based on the apathogenic molecular clone Beau-R, containing either a T16A or A26F mutation, denoted as BeauR-T16A and BeauR-A26F. The replication and genetic stability of the rIBVs were assessed in several different cell types, including primary and continuous cells, ex vivo tracheal organ cultures (TOCs) and in ovo. Different replication profiles were observed between cell cultures of different origins. BeauR-A26F replicated to a lower level than Beau-R in Vero cells and in ovo but not in DF1, primary chicken kidney (CK) cells or TOCs. Genetic stability and cytopathic effects were found to differ depending on the cell system. The effect of the T16A and A26F mutations appear to be cell-type dependent, which, therefore, highlights the importance of cell type in the investigation of the IBV E protein.