Miracle-dz/UniFAR-FTUs huggingface dataset:
Selective inhibition of histone deacetylase 1 and 3 improves motor phenotype and alleviates transcriptional dysregulation in Huntington’s disease mice

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease characterized by a late clinical onset of psychiatric, cognitive, and motor symptoms. Transcriptional dysregulation is an early and central disease mechanism which is accompanied by epigenetic alterations in HD. Previous studies demonstrated that targeting transcriptional changes by inhibition of histone deacetylases (HDACs), especially the class I HDACs, provides therapeutic effects. Yet, their exact mechanisms of action and the features of HD pathology, on which these inhibitors act remain to be elucidated. Here, using transcriptional profiling, we found that selective inhibition of HDAC1 and HDAC3 by RGFP109 repaired the expression of a number of genes, including the transcription factor genes Neurod2 and Nr4a2, and 43% of the gene sets that were dysregulated by mutant Huntingtin expression in the striatum and improved motor skill learning deficit in the R6/1 mouse model of HD. RGFP109-treated R6/1 mice showed improved coordination on the RotaRod over four consecutive trials, while vehicle-treated R6/1 animals displayed no improvement in coordination skills and fell 50 seconds earlier off the rod in the fourth trial. We also found, by volumetric MRI, a widespread brain atrophy in the R6/1 mice at the symptomatic disease stage, on which RGFP109 showed a modest effect. Collectively, our combined work presents new evidence for specific HDAC1 and HDAC3 inhibition as a therapeutic strategy for alleviating the phenotypic and molecular features of HD.
Cryo-EM structural studies of the agonist complexed human TRPV4 ion-channel reveals novel structural rearrangements resulting in an open-conformation

The human transient receptor potential vanilloid 4 (hTRPV4) ion channel plays a critical role in a variety of biological processes. Whilst the activation of hTRPV4 gating properties has been reported for a broad spectrum of stimuli, including synthetic 4α-phorbols, the molecular basis of the activation is poorly understood. Here we report the novel cryo-EM structure of the hTRPV4 determined in the presence of the archetypical phorbol acid agonist, 4α-PDD. Complementary mutagenesis experiments support the EM-identified binding site as well as allowing rationalization of disruptive mutants located outside of the 4α-PDD binding site. This work represents the first structural information of hTRPV4 in a ligand-induced open conformation. Together, our data reveal the underlying molecular mechanisms resulting in the opening of the central pore and ion-channel activation and provide a structural template for designing inhibitors targeting the open-state conformation of hTRPV4.
Kidney injury molecule-1 is a potential receptor for SARS-CoV-2

COVID-19 patients present high incidence of kidney abnormalities, which are associated with poor prognosis and high mortality. Identification of SARS-CoV-2 in kidney of COVID-19 patients suggests renal tropism and direct infection. Presently, it is generally recognized that SARS-CoV-2 initiates invasion through binding of receptor-binding domain (RBD) of spike protein to host cell-membrane receptor ACE2, however, whether there is additional target of SARS-CoV-2 in kidney remains unclear. Kidney injury molecule-1 (KIM1) is a transmembrane protein that drastically up-regulated after renal injury. Here, binding between SARS-CoV2-RBD and the extracellular Ig V domain of KIM1 was identified by molecular simulations and co-immunoprecipitation, which was comparable in affinity to that of ACE2 to SARS-CoV-2. Moreover, KIM1 facilitated cell entry of SARS-CoV2-RBD, which was potently blockaded by a rationally designed KIM1-derived polypeptide. Together, the findings suggest KIM1 may mediate and exacerbate SARS-CoV-2 infection in a ‘vicious cycle’, and KIM1 could be further explored as a therapeutic target.
Mutagenicity, antioxidant activity and nutritional content of long-life tomato = Mutagenicidade, atividade antioxidante e conteúdo nutricional de tomate longa vida

The increasing tomato demand for the food market motivates improvements and the use of new biotechnologies in this fruit’s production. The hybrid crop stands out for fruit production resistant to rot and postharvest wilt (long-life crops). Within this context, consumption of genetically modified food deserves attention regarding the safety and nutritional aspects due to the fact that inclusion and/or overexpression of genetic traits can cause harm to human health in the short or long term. In this scenario, this study aimed to evaluate genotoxicity and mutagenicity from different varieties of long-life tomatoes obtained by genetic breeding and also determines main bioactive compounds and antioxidant activity. The genotoxicity and mutagenicity were analyzed via the micronucleus test and the evaluation of chromosome aberrations in mice bone marrow respectively. We have also analyzed carotene, beta-carotene, lycopene, total phenol and flavonoid contents via spectrophotometry and antioxidant activity via DPPH radical scavenging assay. Considering the results obtained, it is possible to conclude that despite the absence of significant genotoxic activity among the evaluated samples, the antioxidant activity and the differences found in composition seems to be ruled by genetic factors, possibly due to the genetic breeding.
Structural investigation of ACE2 dependent disassembly of the trimeric SARS-CoV-2 Spike glycoprotein

The human membrane protein Angiotensin-converting enzyme 2 (hACE2) acts as the main receptor for host cells invasion of the new coronavirus SARS-CoV-2. The viral surface glycoprotein Spike binds to hACE2, which triggers virus entry into cells. As of today, the role of hACE2 for virus fusion is not well understood. Blocking the transition of Spike from its prefusion to post-fusion state might be a strategy to prevent or treat COVID-19. Here we report a single particle cryo-electron microscopy analysis of SARS-CoV-2 trimeric Spike in presence of the human ACE2 ectodomain. The binding of purified hACE2 ectodomain to Spike induces the disassembly of the trimeric form of Spike and a structural rearrangement of its S1 domain to form a stable, monomeric complex with hACE2. This observed hACE2 dependent dissociation of the Spike trimer suggests a mechanism for the therapeutic role of recombinant soluble hACE2 for treatment of COVID-19.
Drp1 is required for AgRP neuronal activity and feeding

The hypothalamic orexigenic Agouti-related peptide (AgRP)-expressing neurons are crucial for the regulation of whole-body energy homeostasis. Here, we show that fasting-induced AgRP neuronal activation is associated with dynamin-related peptide 1 (Drp1)-mediated mitochondrial fission and mitochondrial fatty acid utilization in AgRP neurons. In line with this, mice lacking Drp1 in adult AgRP neurons (Drp1AgRPKO) show decrease in fasting-or ghrelin-induced AgRP neuronal activity and feeding and exhibited a significant decrease in body weight, fat mass, and feeding accompanied by a significant increase in energy expenditure. In support of the role for mitochondrial fission and fatty acids oxidation, Drp1AgRPKO mice showed attenuated palmitic acid-induced mitochondrial respiration. Altogether, our data revealed that mitochondrial dynamics and fatty acids oxidation in hypothalamic AgRP neurons is a critical mechanism for AgRP neuronal function and associated behavior.
Spatial and temporal changes in male gypsy moth wing morphology reflect host tree phenology and habitat quality

The size of adult gypsy moths, (Lymantria dispar L.), a capitalbreeder, is correlated with environmental conditions experienced as larvae. Proxies for adult size such as wing length may provide information about habitat quality and population density. We used male gypsy moths collected from pheromone traps at intervals through the flight season to assess phenological change in wing length. Consistent with a previous study conducted at our reference site, we found that wing length declines seasonally, likely resulting from phenological reduction in host foliage quality. This pattern was evident at our reference site over 8 years, and at our experimental sites with low‐density populations in 3 years. We assessed forest quality using two unique metrics, basal area of red oak (Quercus rubra), a high quality host tree, and a composite value generated from a published ranking of tree species quality for gypsy moth. We did not find a relationship between these metrics and wing length, although we found that the mean size of males was larger in stands with oak. Mean wing length in outbreak populations was significantly smaller reflecting density related processes such as intraspecific competition, although there was no significant seasonal effect on wing length.
Learning, visualizing and exploring 16S rRNA structure using an attention-based deep neural network

Recurrent neural networks (RNNs) with memory (e.g. LSTMs) and attention mechanisms are widely used in natural language processing because they can capture short and long term sequential information for diverse tasks. We propose an integrated deep learning model for microbial DNA sequence data, which exploits convolutional networks, recurrent neural networks, and attention mechanisms to perform sample-associated attribute prediction—phenotype prediction—and extract interesting features, such as informative taxa and predictive k-mer context. In this paper, we develop this novel deep learning approach and evaluate its application to amplicon sequences. We focus on typically short DNA reads of 16s ribosomal RNA (rRNA) marker genes, which identify the heterogeneity of a microbial community sample. Our deep learning approach enables sample-level attribute and taxonomic prediction, with the aim of aiding biological research and supporting medical diagnosis. We demonstrate that our implementation of a novel attention-based deep network architecture, Read2Pheno, achieves read-level phenotypic prediction and, in turn, that aggregating read-level information can robustly predict microbial community properties, host phenotype, and taxonomic classification, with performance comparable to conventional approaches. Most importantly, as a further result of the training process, the network architecture will encode sequences (reads) into dense, meaningful representations: learned embedded vectors output on the intermediate layer of the network model, which can provide biological insight when visualized. Finally, we demonstrate that a model with an attention layer can automatically identify informative regions in sequences/reads which are particularly informative for classification tasks. An implementation of the attention-based deep learning network is available at https://github.com/EESI/sequence_attention.
BMP signalling facilitates transit amplification in the developing chick and human cerebellum

The external granule layer (EGL) is a transient proliferative layer that gives rise to cerebellar granule cell neurons. Extensive EGL proliferation characterises the foliated structure of amniote cerebella, but the factors that regulate EGL formation, amplification within it, and differentiation from it, are incompletely understood. Here, we characterise bone morphogenic protein (BMP) signalling during cerebellar development in chick and human and show that while in chick BMP signalling correlates with external granule layer formation, in humans BMP signalling is maintained throughout the external granule layer after the onset of foliation. We also show via Immunohistochemical labelling of phosphorylated Smad1/5/9, that the spatiotemporal activity of BMP signalling is conserved between chick and human. Using in ovo electroporation in chick, we demonstrate that BMP signalling is necessary for subpial migration of granule cell precursors and hence the formation of the external granule layer (EGL) prior to transit amplification. However, altering BMP signalling does not block the formation of mature granule neurons but significantly disrupts that pattern of morphological transitions that accompany transit amplification. Our results elucidate two key, temporally distinct roles for BMP signalling in vivo in organising first the assembly of the EGL from the rhombic lip and subsequently the tempo of granule neuron production within the EGL. Significance statement Improper development of cerebellar granule neurons can manifest in a plethora of neurodevelopmental disorders, including but not limited to medulloblastoma and autism. Medulloblastoma can be a consequence of uncontrolled proliferation of granule cell progenitors, with BMP overexpression being a potential therapeutic avenue to inhibit this proliferation. Many studies have sought to understand the role of developmental signalling pathways in granule cell neurogenesis, using genetic manipulation in transgenic mice. To complement these insights, we have used comparative assessment of BMP signalling during development in chick and human embryos and in vivo manipulation of the chick to understand and segregate the spatiotemporal roles of BMP signalling, yielding important insights on evolution and in consideration of future therapeutic avenues that target BMP signalling.
Adaptive management plans rooted in quantitative ecological predictions of ecosystem processes: putting monitoring data to practical use

It is demonstrated how a hierarchical structural equation model that is fitted to temporal ecological monitoring data from a number of sites may be used to generate local ecological predictions and how these local ecological predictions may form the basis of adaptive management plans. Local ecological predictions will be made for the cover of cross-leaved heath on Danish wet heathlands, which is one of the indicators that determine the conservation status of wet heathlands under different management scenarios. Based on a realistic example, the model predictions concludes that grazing by domestic herbivores on wet heathlands with a relatively low cover cross-leaved heath cannot be recommended as the only management practice. Generally, it is recommended to use ecological monitoring data to generate quantitative and credible local adaptive management plans where the uncertainty is taken into account.
Defocus-dependent Thon-ring fading

The brightness of modern Schottky field-emission guns can produce electron beams that have very high spatial coherence, especially for the weak-illumination conditions that are used for single-particle electron cryo-microscopy in structural biology. Even so, many users have observed defocus-dependent Thon-ring fading that has led them to restrict their data collection strategy to imaging with relatively small defocus values. In this paper, we reproduce the observation of defocus-dependent Thon-ring fading and produce a quantitative analysis and clear explanation of its causes. We demonstrate that a major cause is the delocalization of high-resolution Fourier components outside the field of view of the camera. We also show that it is important to make a correction for linear magnification anisotropy, even if it is quite small, before circular averaging of the Thon rings, as is also true before merging data from particles in many orientations. Under the conditions used in this paper, which are typical of those used in single-particle electron cryomicroscopy, fading of the Thon rings due to source coherence is negligible. The principal conclusion is that much higher values of defocus can be used than is currently thought to be possible. This increased understanding should give electron microscopists the confidence to use higher amounts of defocus to allow, for example, better visibility of their particles and Ewald sphere correction.
Synthesis, structure, Hirshfeld analysis and fluorescence properties of a new asymmetric salamo-based ligand and its Cu(II) complex involving oxime oxygen coordination

Abstract A new asymmetric salamo-based ligand (H2L) was synthesized and upon reaction with Cu(ClO4)2 an extremely rare dinuclear Cu(II) complex [Cu2(L)2] was formed and characterized by elemental analyses, infrared spectroscopy, UV–vis absorption spectroscopy, X-ray single crystal diffraction and Hirshfeld surface analyses. The Cu(II) complex consists of two Cu(II) ions and two fully deprotonated ligand (L)2– units. The Cu(II) is coordinated with the N2O2 cavity (N1, N2, O1 and O4) of L2– and the oxime oxygen (O3) of another L2– unit to form a uncommon dinuclear structure. The Cu(II) is five-coordinated, τ = 0.02, and has a configuration of slightly twisted tetragonal pyramidal geometry. The comparison between H2L and its Cu(II) complex through Hirshfeld surface analyses shows that the interaction of O-H/H-O is reduced, indicating that deprotonation of phenolic hydroxyl group and the coordination of Cu(II) forms a stable complex. In addition, fluorescence quenching of the Cu(II) complex compared to H2L further confirms the above experimental results. GRAPHICAL ABSTRACT
A protocol for in vitro propagation of ber (Ziziphus jujuba)

A protocol for micropropagation of Ziziphus jujuba was developed by using nodal explants in different media compositions. Various morphogenic responses of explants have been observed by using different media, viz. MS, B 5 and N 6 . MS basal medium was found to be the best among them for shoot proliferation (93.75 %). Shoot development was initiated within a week. No callus development was observed. In order to enhance the shoot regenerative potential, explants were cultured on MS medium supplemented with various cytokinins, viz. BAP, kinetin and TDZ. MS medium supplemented with BAP (1.78 μM) was found to be ideal for shoot development. Among various auxins used, 2.69 μM NAA proved to be the best to induce healthy roots with minimum callused thickening, resulting in maximum survival of plants (80 %) in the field.
Pacific warm pool subsurface heat sequestration modulated Walker circulation and ENSO activity during the Holocene

Orbitally driven warm pool upper-water temperature regulates the equatorial Pacific climate change over the past 25,000 years. Dynamics driving the El Niño–Southern Oscillation (ENSO) over longer-than-interannual time scales are poorly understood. Here, we compile thermocline temperature records of the Indo-Pacific warm pool over the past 25,000 years, which reveal a major warming in the Early Holocene and a secondary warming in the Middle Holocene. We suggest that the first thermocline warming corresponds to heat transport of southern Pacific shallow overturning circulation driven by June (austral winter) insolation maximum. The second thermocline warming follows equatorial September insolation maximum, which may have caused a steeper west-east upper-ocean thermal gradient and an intensified Walker circulation in the equatorial Pacific. We propose that the warm pool thermocline warming ultimately reduced the interannual ENSO activity in the Early to Middle Holocene. Thus, a substantially increased oceanic heat content of the warm pool, acting as a negative feedback for ENSO in the past, may play its role in the ongoing global warming.
Selecting elite tomato genotypes through a modified analytical hierarchy process

Abstract. Plant genetic improvement may be done traditionally by selecting the most appropriate genotypes based on heritability, stability, genetic distance and other genetic parameters. In this paper, the analytical hierarchy process (AHP) with some modifications was used as a new multivariate method for determining the capability of elite tomato (Solanum lycopersicum L.) genotypes to form the next-generation breeding population. Modified AHP is performed in three steps: (i) aligning traits and genotypes, (ii) calculating weights of traits, and (iii) calculating weights of genotypes. Fruit quality and yield were evaluated in 20 F2 tomato families cultured along with their parents in a randomised complete block design with three replications in the research field. The traits fruit yield, plant cluster number and fruit number per plant were identified as the most effective for ordering genotypes. Four families were identified as the best (selection among families), and the best individuals selected from a total of 60 individuals (selection within families) almost all belonged to these four families. Because of the use of genetic parameters in modified AHP, the selected genotypes were the best choices with respect to fruit yield, lycopene content and capability to create a breeding population.
Reactive Video: Adaptive Video Playback Based on User Motion for Supporting Physical Activity

Videos are a convenient platform to begin, maintain, or improve a fitness program or physical activity. Traditional video systems allow users to manipulate videos through specific user interface actions such as button clicks or mouse drags, but have no model of what the user is doing and are unable to adapt in useful ways. We present adaptive video playback, which seamlessly synchronises video playback with the user's movements, building upon the principle of direct manipulation video navigation. We implement adaptive video playback in Reactive Video, a vision-based system which supports users learning or practising a physical skill. The use of pre-existing videos removes the need to create bespoke content or specially authored videos, and the system can provide real-time guidance and feedback to better support users when learning new movements. Adaptive video playback using a discrete Bayes and particle filter are evaluated on a data set collected of participants performing tai chi and radio exercises. Results show that both approaches can accurately adapt to the user's movements, however reversing playback can be problematic.
Long-term Feeding of the Yellowtail Seriola quinqueradiata with Soy Protein Concentrate-based Non-fishmeal Diet Supplemented with Taurine

Previous studies have shown that the growth performance of the yellowtail Seriola quinqueradiata fed non-fishmeal (non-FM) diets was improved by supplementing with dietary taurine. However, it has not been determined whether yellowtail can be reared from juveniles to adults on non-FM diets supplemented with taurine. The present study evaluated the growth performance of yellowtail fed a soy protein concentrate (SPC)-based non-FM diet supplemented with taurine for 65 weeks from juveniles to adults. Juvenile fish (initial body weight, 470 g) were fed with the taurinesupplemented SPC-based non-FM (TS) diet or an FM diet. The TS group could be reared for 65 weeks. However, the growth rate of the TS group was markedly lower than that of the FM group; the hemochemical indices, condition factor, and hepatosomatic index of the TS group were lower than those of the FM group because the lipid content of the TS diet was too low for yellowtail to grow sufficiently. These results show that yellowtail can be reared from juveniles to adults on an SPC-based non-FM diet by supplementing with taurine, suggesting that the growth performance and physiological conditions of yellowtail fed a TS diet could be improved by increasing the dietary lipid content.