Miracle-dz/UniFAR-FTUs huggingface dataset:
Decoding and recoding phase behavior of TDP43 reveals that phase separation is not required for splicing function

Intrinsically disordered regions (IDRs) often are fast evolving protein domains of low sequence complexity that can drive phase transitions and are commonly found in many proteins associated with neurodegenerative diseases, including the RNA processing factor TDP43. Yet, how phase separation contributes to the physiological functions of TDP43 in cells remains enigmatic. We combined systematic mutagenesis guided by evolutionary sequence analysis with a live-cell reporter assay of TDP43 phase dynamics to identify regularly-spaced hydrophobic motifs separated by flexible, hydrophilic segments in the IDR as a key determinant of TDP43 phase properties. This heuristic framework allowed us to customize the material properties of TDP43 condensates to determine effects on splicing function. Remarkably, mutants with increased or decreased phase dynamics, and even mutants that failed to phase separate, could mediate the splicing of a quantitative, single-cell splicing reporter and endogenous targets. We conclude that phase separation is not required for the function of TDP43 in splicing.
Threshold elemental ratios and the temperature dependence of herbivory in fishes

Herbivorous ectothermic vertebrates are more diverse and abundant at lower latitudes. While thermal constraints may drive this pattern, its underlying cause remains unclear. We hypothesized that this constraint stems from an inability to meet the elevated phosphorus demands of bony vertebrates feeding on P‐poor plant material at cooler temperatures because low gross growth efficiency at warmer temperatures facilitates higher P ingestion rates. We predicted that dietary carbon:phosphorus (C:P) should exceed the threshold elemental ratio between carbon and P‐limited growth (TERC:P) for herbivores feeding at cooler temperatures, thereby limiting the range of herbivorous ectothermic vertebrates facing P‐limited growth. We tested this hypothesis using the Andean suckermouth catfishes Astroblepus and Chaetostoma. Astroblepus are invertivores that inhabit relatively cool, high‐elevation streams while Chaetostoma are grazers that inhabit relatively warm, low‐elevation streams. We calculated TERC:P for each genus across its elevational range and compared these values to measured values of food quality over an elevational gradient in the Andes. We also broadly summarized measurements of TERC:P across diverse groups of fishes. Supporting our hypothesis, we found that dietary C:P was predicted to exceed the TERC:P for the grazer Chaetostoma near the highest elevation where this genus has been recorded. Conversely, the TERC:P for the invertivore Astroblepus was consistently higher than that of Chaetostoma and thus its dietary C:P never approached the TERC:P. We found that, among all fishes, omnivores had higher average TERC:P than invertivores, and TERC:P did not vary with temperature. Our results suggest that, at least for Andean suckermouth catfishes, cool temperatures constrain herbivory at higher elevations. Increased gross growth efficiency at cooler temperatures evidently restricts the ability of P‐limited consumers to meet P demand. However, our survey of fish TERC:P estimates suggests that some fishes are able to circumvent this constraint through behavioural and life‐history adaptations that reduce P demand or increase P use efficiency. The physiological trade‐offs underlying these functional shifts reveal that geographic dietary patterns can be predicted by stoichiometric theory, but variation in food quality and consumer traits that reduce P demand and/or increase P efficiency can create exceptions to these patterns. A plain language summary is available for this article.
Neuronal L-Type Calcium Channel Signaling to the Nucleus Requires a Novel CaMKIIα-Shank3 Interaction

The activation of neuronal plasma membrane Ca2+ channels stimulates many intracellular responses. Scaffolding proteins can preferentially couple specific Ca2+ channels to distinct downstream outputs, such as increased gene expression, but the molecular mechanisms that underlie the exquisite specificity of these signaling pathways are incompletely understood. The activation of neuronal plasma membrane Ca2+ channels stimulates many intracellular responses. Scaffolding proteins can preferentially couple specific Ca2+ channels to distinct downstream outputs, such as increased gene expression, but the molecular mechanisms that underlie the exquisite specificity of these signaling pathways are incompletely understood. Here, we show that complexes containing CaMKII and Shank3, a postsynaptic scaffolding protein known to interact with L-type calcium channels (LTCCs), can be specifically coimmunoprecipitated from mouse forebrain extracts. Activated purified CaMKIIα also directly binds Shank3 between residues 829 and 1130. Mutation of Shank3 residues 949Arg-Arg-Lys951 to three alanines disrupts CaMKII binding in vitro and CaMKII association with Shank3 in heterologous cells. Our shRNA/rescue studies revealed that Shank3 binding to both CaMKII and LTCCs is important for increased phosphorylation of the nuclear CREB transcription factor and expression of c-Fos induced by depolarization of cultured hippocampal neurons. Thus, this novel CaMKII-Shank3 interaction is essential for the initiation of a specific long-range signal from LTCCs in the plasma membrane to the nucleus that is required for activity-dependent changes in neuronal gene expression during learning and memory. SIGNIFICANCE STATEMENT Precise neuronal expression of genes is essential for normal brain function. Proteins involved in signaling pathways that underlie activity-dependent gene expression, such as CaMKII, Shank3, and L-type calcium channels, are often mutated in multiple neuropsychiatric disorders. Shank3 and CaMKII were previously shown to bind L-type calcium channels, and we show here that Shank3 also binds to CaMKII. Our data show that each of these interactions is required for depolarization-induced phosphorylation of the CREB nuclear transcription factor, which stimulates the expression of c-Fos, a neuronal immediate early gene with key roles in synaptic plasticity, brain development, and behavior.
Evaluation of Acute Toxicity of the Ethanolic Leaf Extract of Brachystegia eurycoma in Albino Wistar Rats

Aims: The acute oral toxicity of ethanol extract of Brachystegia eurycoma was evaluated in Wistar albino rats. Study Design: Sixteen male Wistar albino rats were assigned in four groups of four rats each. Group 1 served as control while groups 2, 3 and 4 were treated with a single dose of 2000, 3500 and 5000 mg/kg bd. wt of extract respectively and observed for fourteen days. Place and Duration of Study: Department of Biochemistry, University of Port Harcourt, Choba, Rivers State, Nigeria, from 1 st of April 2018 to 15 th of April, 2018. Methodology: Healthy wistar albino rats weighing 120 – 180 g were fasted over-night prior to dosing. The animals were observed physically for toxic effect for the first twenty four (24) hours and once daily for the next thirteen (13) days for delayed toxicity. On the 14 th day, the rats were anesthetized, blood samples were collected for biochemical analyses while internal organs (kidney, heart, liver and spleen) were excised for histopathological examination. Original Research Article Ududua et al.; JOCAMR, 7(1): 1-7, 2019; Article no.JOCAMR. 46623 2 Results: No mortality was observed at all doses of the extract. 2000 and 3500 mg/kg of the extract showed no toxic effect. A significant (p˂0.05) increase in alkaline phosphatase (240.0 ± 5.00 to 296.67 ± 7.57 IU/L units), serum albumin (19.46 ± 1.36 to 28.89 ± 2.50 g/dl units), total bilirubin (5.07 ± 0.15 to 5.73 ± 0.29 μmol/L units) and serum creatinine (68.23 ± 0.25 to 72.06 ± 1.90 μmol/L units) was observed at 5000 mg/kg of the extract with the presence of distorted tubules, lobulated glomerulus in the kidney and inflammatory cells in liver sinusoid. Conclusion: Ethanol leaf extract B. eurycoma may possess nephrotoxic and hepatotoxic potentials at very high dose.
Scalable and Accurate Drug–target Prediction Based on Heterogeneous Bio-linked Network Mining

Motivation Despite the existing classification- and inference-based machine learning methods that show promising results in drug-target prediction, these methods possess inevitable limitations, where: 1) results are often biased as it lacks negative samples in the classification-based methods, and 2) novel drug-target associations with new (or isolated) drugs/targets cannot be explored by inference-based methods. As big data continues to boom, there is a need to study a scalable, robust, and accurate solution that can process large heterogeneous datasets and yield valuable predictions. Results We introduce a drug-target prediction method that improved our previously proposed method from the three aspects: 1) we constructed a heterogeneous network which incorporates 12 repositories and includes 7 types of biomedical entities (#20,119 entities, # 194,296 associations), 2) we enhanced the feature learning method with Node2Vec, a scalable state-of-art feature learning method, 3) we integrate the originally proposed inference-based model with a classification model, which is further fine-tuned by a negative sample selection algorithm. The proposed method shows a better result for drug–target association prediction: 95.3% AUC ROC score compared to the existing methods in the 10-fold cross-validation tests. We studied the biased learning/testing in the network-based pairwise prediction, and conclude a best training strategy. Finally, we conducted a disease specific prediction task based on 20 diseases. New drug-target associations were successfully predicted with AUC ROC in average, 97.2% (validated based on the DrugBank 5.1.0). The experiments showed the reliability of the proposed method in predicting novel drug-target associations for the disease treatment.
RumimiR: a detailed microRNA database focused on ruminant species

In recent years, the increasing use of Next Generation Sequencing technologies to explore the genome has generated large quantities of data. For microRNAs, more and more publications have described several thousand sequences, all species included. In order to obtain a detailed description of microRNAs from the literature for three ruminant species (bovine, caprine and ovine), a new database has been created: RumimiR. To date, 2,887, 2,733 and 5,095 unique microRNAs of bovine, caprine and ovine species, respectively, have been included. In addition to the most recent reference genomic position and sequence of each microRNA, this database contains details on the animals, tissue origins and experimental conditions available from the publications. Identity with human or mouse microRNA is mentioned. The RumimiR database enables data filtering, the selection of microRNAs being based on defined criteria such as animal status or tissue origin. For ruminant studies, RumimiR supplements the widely used miRBase database by browsing and filtering using complementary criteria, and the integration of all published sequences described as novel. The principal goal of this database is to provide easy access to all ruminant microRNAs described in the literature.
BIOCATALISADORES VEGETAIS NA REDUÇÃO DE ACETOFENONAS PRÓ-QUIRAIS E SUAS CONTRIBUIÇÕES PARA A QUÍMICA VERDE

The present work aimed to investigate the biocatalytic potential of plant residues in the reduction of acetophenone. The pineapple peels have formed different products, such as 1-phenylethanol, 2-phenylethanol, 1-phenylethyl acetate and 2-phenylethyl acetate, as well as pumpkin seeds and almonds of mango, 1-phenylethanol, 2-hydroxyacetophenone and 1-phenyl1,2-ethanol, showing low chemical selectivity, a desired result, but good conversion yields. Shells of banana, passion fruit, sugarcane bagasse and corn sabugo formed only 2-phenylethanol, the first three being more effective, with a conversion ranging from 21.7% to 80.0%. The studies to optimize the reaction conditions with banana and passion fruit, through the monitoring of conversion and enantiomeric excess, allowed to optimize the reaction time, pH and amount of biocatalyst. The best conditions found for the banana were 36 hours, 15 g and pH 7,0, while for passion fruit were 48 hours, 15 g and pH 7,6. Using the optimized conditions, the bioreductive potential of banana and passion fruit against acetophenone derivatives 2-bromoacetophenone, 3-bromoacetophenone, 4-bromoacetophenone, 1-phenyl-2,2,2-trifluoroethanone, 3-fluoracetophenone, 4fluoracetophenone and 2-nitroacetophenone. Among the derivatives tested 1-phenyl-2,2,2-trifluorethanone was the most reactive in yield> 99%.
Organizational commitment and work-related implementation of enterprise social networks (ESNs): the mediating roles of employees' organizational concern and prosocial values

PurposeThis study, based on the cognitive dissonance and commitment theories, aims to show that employees with high organizational commitment take more advantage of enterprise social networks (ESNs) due to work-related motivations. Furthermore, this study used the tricomponent attitude model to show that the employees' organizational concern and prosocial values mediate the impact of the organizational commitment on the work-related use of an ESN.Design/methodology/approachIn all, 361 employees from seven Iranian companies using different ESN software packages were surveyed. The validity of the hypotheses was evaluated using partial least square–structural equation modeling (PLS-SEM). FindingsThe results of this study confirm that the employees' organizational commitment has a positive impact on their work-related use of the relevant ESN directly and through the mediating roles of their organizational concern and prosocial values.Originality/valuePrevious studies have carefully addressed the role of organizational commitment in the implementation of conventional information systems. However, this is among the few studies addressing the role of commitment in the work-related implementation of ESNs. The results of this study shed light on how employees with a high level of commitment toward the organizations for which they work take advantage of ESNs due to a work-related motivation for the accomplishment of their duties, for bringing benefits into the organization and for helping their coworkers.
Identifying and Characterizing Non-Coding RNAs in the Dinoflagellate Karenia brevis

IDENTIFYING AND CHARACTERIZING NON-CODING RNAS IN THE DINOFLAGELLATE KAREN/A BREVIS by Helen Namataka December 2012 When algal cells proliferate and accumulate in marine and fresh water systems, they form algal blo'oms. The majority of these blooms are beneficial, but a significant number are detrimental and are known as harmful algal blooms (HABs). A number of negative effects, including closing of recreational beaches and economic loss, are observed during HABs. Predictably, the longer a bloom persists, the greater its effects on human, environmental and economic health. Karenia brevis, a mixotrophic dinoflagellate, forms HABs, and blooms caused by this organism have been known to remain several months after formation. For these reasons, research has been conducted to discover those factors that are responsible for the formation, maintenance and terminations of K.brevis blooms. These factors, whether man-made (e.g. eutrophication) or naturally occurring (e.g. aquatic fronts), have been and continue to be extensively investigated. As part of an effort to find molecular or genetic determinants that control K. brevis biology, it was discovered that these cells express a number of anti-sense RN As. For the first time in K.brevis, I have confirmed the expression of targeted anti-sense RNAs (asRNAs) and characterized their sequences.
Principals’ identity – developing and validating an analysis instrument in the Swedish context

ABSTRACT The aim of this article is to develop and validate an analysis instrument of principal’ identity in the Swedish context. A point of departure is taken in the work of Crow, Day, and Møller (2017) and three dimensions of the concept: professional, personal, and situated or socially located. The article builds on a survey on Swedish principals covering questions of the three identity dimensions. The survey reached approximately 3,000 out of the 3,600 Swedish principals, generating 1,286 replies (n = 1,286). The analyses identified questions with strong and weak correlation with the three dimensions. Thus, the findings provide components for a more refined analysis instrument to analyze how principals’ identity is formed and negotiated in different contexts without overlooking the fact that construction of identity is situated in time, space, and place. These findings also contribute to a more comprehensive image of principal’s professional identity. Additional studies, however, are requested for a more in-depth understanding of the concept of identity in various leadership contexts.
IGF TYPE I RECEPTOR LOCALIZATION AND TRAFFICKING IN OLIGODENDROCYTE PROGENITOR CELLS: REGULATION OF THE PI-3 KINASE/AKT PATHWAY

Insulin-like growth factor (IGF)-I is required for the survival of cells within the central nervous system (CNS), including oligodendrocytes (OLs) and their progenitors (OPs). Previously we demonstrated that IGF-I mediates long-term survival of OPs via sustained phosphorylation and activity of Akt, with concomitant stability and activity of the IGF type-I receptor (IGF-IR). The mechanism by which IGF-I regulates sustained Akt phosphorylation, however, is currently undefined. In this dissertation, we investigate the role of IGF-IR trafficking and subcellular localization in sustained Akt phosphorylation in OPs. We report that there are no change in total IGF-IR protein levels during IGF-I stimulation; however, there is maximal loss of surface receptors at 30 min and recovery of receptors at the cell surface by 120 min. To determine the role of IGF-IR surface loss we used dansylcadaverine, an inhibitor of receptor clustering and internalization. Dansylcadaverine blocked the clustering of biotin-conjugated IGF-I at the cell surface and prevented the internalization of the IGF-IR. In addition, dansylcadaverine blocked IGF-I mediated Akt phosphorylation. To determine the source of IGF-IR surface recovery at 120 min we used monensin, an inhibitor of endosomal trafficking, and cycloheximide, an inhibitor of protein translation. Whereas monensin attenuated IGF-I mediated Akt phosphorylation and blocked surface recovery of the IGF-IR, cycloheximide had no effect on Akt phosphorylation or on total IGF-IR protein levels. We also show that the IGF-IR co-localized with markers for the recycling endosome, including the transferrin receptor (TfR) and Rab11. Together, the results of these studies suggest that IGF-IR clustering and internalization are required to promote Akt
Developmental Biology: Frontiers for Clinical Genetics

Blackwell Munksgaard, 2007Hydatidiform mole (HM) is a human pregnancy with no embryo butcystic degeneration of chorionic villi. The common form of this conditionoccurs in 1 in every 1500 pregnancies in western societies and at a higherincidence in some geographic regions and populations. Recurrent molesaccount for 2% of all molar cases and a few of them occur in more thanone family member. By studying a familial form of recurrent moles,a recessive maternal locus responsible for this condition was mapped to19q13.4 and causative mutations identified. The defective protein,NALP7, is part of the CATERPILLAR protein family with roles inpathogen-induced inflammation and apoptosis. The exact role of NALP7in the pathophysiology of molar pregnancies is unknown yet. NALP7could have a role either in oogenesis or in the endometrium duringtrophoblast invasion and decidualization. In this review, we outlinedrecent advances in the field of HMs and reviewed the literature in thelight of the new data.
Breeding Low-Cadmium Wheat: Progress and Perspectives

Farmland cadmium (Cd) contamination has adverse impacts on both wheat grain yield and people’s well-being through food consumption. Safe farming using low-Cd cultivars has been proposed as a promising approach to address the farmland Cd pollution problem. To date, several dozen low-Cd wheat cultivars have been screened worldwide based on a Cd inhibition test, representing candidates for wheat Cd minimization. Unfortunately, the breeding of low-Cd wheat cultivars with desired traits or enhanced Cd exclusion has not been extensively explored. Moreover, the wheat Cd inhibition test for variety screening and conventional breeding is expensive and time-consuming. As an alternative, low-Cd wheat cultivars that were developed with molecular genetics and breeding approaches can be promising, typically by the association of marker-assisted selection (MAS) with conventional breeding practices. In this review, we provide a synthetics view of the background and knowledge basis for the breeding of low-Cd wheat cultivars.
Influence of Surface Reflection (Albedo) in Simulating the Sun Drying of Paddy Rice

The sun drying of agricultural products is a complicated process involving heat transfer, mass transfer, and variable weather conditions. Surface reflection (albedo), a crop’s radiative property, plays an essential role in energy balance, and understanding its contribution can improve the thermal analysis. In this study, field experiments were conducted in the Philippines to explore the influence of surface albedo on the sun drying of paddy rice. First, we implemented energy and mass balance equations in a transient model with the surroundings using a graphical programming language in Matlab/Simulink®. Second, we identified the influence of albedo on the sun drying model by using a sensitivity analysis. Third, we investigated the relationship of paddy rice albedo and the solar zenith angle. Lastly, we integrated the albedo function into the sun drying model. The simulation outputs were validated with field experiments. A better estimation of the measured exit temperature and instantaneous mass were obtained when a variable albedo was applied. This study makes clear that introducing a variable albedo has a positive impact on model improvement. This information is important for application in solar drying technologies, so that the drying process can be better assessed.
Grand Canonical Rate Theory for Electrochemical and Electrocatalytic Systems I: General Formulation and Proton-coupled Electron Transfer Reactions

A generally valid rate theory at fixed potentials is developed to treat electrochemical and electrocatalytic potential-dependent electron, proton, and proton-coupled electron reactions. Both classical and quantum reactions in adiabatic and non-adiabatic limits are treated. The applicability and new information obtained from the theory is demonstrated for the gold catalyzed acidic Volmer reaction.