Miracle-dz/UniFAR-FTUs huggingface dataset:
Fusarium species associated with medicinal plants of Lamiaceae and Asteraceae

The purpose of this study was to identify the Fusarium species associated with selected medicinal plant species of Lamiaceae and Asteraceae in Kerman, the second-largest province of Iran. The plants showing wilting/rotting symptoms as well as asymptomatic plants were collected from main medicinal plants reservoirs and production areas. Fusarium species were identified based on morphological characteristics as well as subsequent sequencing of the translation elongation factor 1-alpha (TEF1-α gene. The following species were identified: F. oxysporum, F. solani and F. nygamai from Achillea wilhelmsii (Asteraceae); F. solani, F. proliferatum and species of F. tricinctum species complex from Teucrium polium (Lamiaceae); F. solani, F. proliferatum and species of F. tricinctum species complex from Ziziphora tenuior (Lamiaceae); F. solani and a species of F. tricinctum species complex from Thymus carmanicus (Lamiaceae); F. redolens, F. brachygibbosum, F. proliferatum, F. tricinctum species complex, F. compactum and F. equiseti from Mentha piperita (Lamiaceae); and F. solani and F. proliferatum from Ziziphora cliniopodiodes (Lamiaceae). For the first time, the pathogenicity of Fusarium nygamai on Achillea wilhelmsii as well as F. redolens and F. brachygibbosum on Mentha piperita were confirmed in this study.
Disrupting HIV-1 capsid formation causes cGAS sensing of viral DNA

Detection of viral DNA by cyclic GMP-AMP synthase (cGAS) is a first line of defence leading to the production of type-I interferon (IFN). As HIV-1 is not a strong inducer of IFN we have hypothesised that its capsid cloaks viral DNA from cGAS. To test this we generated defective viral particles by treatment with HIV-1 protease inhibitors or by genetic manipulation of gag. These viruses had defective Gag cleavage, reduced infectivity and diminished capacity to saturate TRIM5α. Importantly, unlike wild-type HIV-1, infection with cleavage defective HIV-1 triggered an IFN response in THP-1 cells and primary human macrophages that was dependent on viral DNA and cGAS. Infection in the presence of the capsid destabilising small molecule PF-74 also induced a cGAS-dependent IFN response. These data demonstrate a protective role for capsid and suggest that antiviral activity of capsid- and protease-targeting antivirals may benefit from enhanced innate and adaptive immunity in vivo.
Animal experiment on spinal cord ischemia with evoked potentials by transcranial electrical stimulation

大動脈遮断に伴う脊髄障害をモニターする上で,経 頭蓋電気刺激による下行性脊髄誘発電位 (MEP)の 有用性を検討した. 雑 種幼犬30頭 を用いた. 実験1:15頭 を用い,開 胸後大動脈血流を第6胸 椎前方で2時 間遮断した. MEPはLevyの 方 法に準じて第10胸 椎レベルで8チ ャンネルのマッピング電極を用いて経時的に記録した. 局 所 脊髄血流量はレーザードップラー血流計を用いて脊髄背側より経時的に記録した. 実験2:15頭 を用い,実 験1と 同様の条件で行い,遮 断時間は1時間とした. さ らに24時 間後 の後肢運動機能を観察し,そ の後脊髄の組織学的検索を行った. 結果:実 験1で は5頭 でMEPの 振幅が50%以 下に減少した. こ れら5頭の局所脊髄血流量は 20%以 下に減少 した. 他 の10頭 では振幅が50%以 上を維持し,局 所脊髄血流量も25%以 上で あった. 実 験(2では4頭 でMEPの 振幅が50%以 下に減少し,う ち2頭 では減少は急速であり, 後肢運動麻痺を生じた. 他 の2頭 では麻痺を認めなかった. 麻 痺を認めた上記の2頭 の脊髄組織 学的所見では,灰 自質の後角から前角にかけて壊死巣があり,反 応性細胞浸潤および核の変性を 認めた. 麻 痺のなかった2頭でも後角に限局する壊死巣を認めた. MEPの 振幅が50%を 維持し たもの11頭 では,局 所脊髄血流量は20%以 上に維持されており,後 肢の運動麻痺はなく,組 織 学的には灰臼質に軽度のうっ血と出血が認められたのみであった. 以上の結果より,脊 髄虚血によって脊髄麻痺が生ずる臨界点は,局 所脊髄血流量が20%以 下 に減少した状態であり,MEP振 幅の50%以 上の急速な減少がこの状態を反映していると考えら れ,MEPの 脊髄虚血状態モニターとしての有用性が証明された. キーワー ド:脊髄モニタリング,脊 髄誘発電位,脊 髄虚血,脊 髄血流量測定
DeepSide: A Deep Learning Framework for Drug Side Effect Prediction

Drug failures due to unforeseen adverse effects at clinical trials pose health risks for the participants and lead to substantial financial losses. Side effect prediction algorithms have the potential to guide the drug design process. LINCS L1000 dataset provides a vast resource of cell line gene expression data perturbed by different drugs and creates a knowledge base for context specific features. The state-of-the-art approach that aims at using context specific information relies on only the high-quality experiments in LINCS L1000 and discards a large portion of the experiments. In this study, our goal is to boost the prediction performance by utilizing this data to its full extent. We experiment with 5 deep learning architectures. We find that a multi-modal architecture produces the best predictive performance among multi-layer perceptron-based architectures when drug chemical structure (CS), and the full set of drug perturbed gene expression profiles (GEX) are used as modalities. Overall, we observe that the CS is more informative than the GEX. A convolutional neural network-based model that uses only SMILES string representation of the drugs achieves the best results and provides 13.0% macro-AUC and 3.1% micro-AUC improvements over the state-of-the-art. We also show that the model is able to predict side effect-drug pairs that are reported in the literature but was missing in the ground truth side effect dataset. DeepSide is available at http://github.com/OnurUner/DeepSide.
The Effects of Sperm Number and Insemination Interval on the Fertility and Hatchability of Sentul Hens

Sexually mature Indonesian native hens (Sentul hens) were housed singly in laying cages and artificially inseminated with combination of three different levels of diluted pooled semen (50 million sperm/0.05 ml; 100 million sperm/0.1 ml; and 150 million sperm/0.15 ml) and at either of three different intervals (every 3, 6 and 9 days). The results show that the sperm number and Insemination intervals had no significant interaction (P>0.05) on % fertility and hatchability. The best fertility around 90 %; P<0.05 was obtained by inseminating interval 6 days with sperm number 100 million/0.1 ml of diluted semen.
Divergence and support among slightly suboptimal likelihood gene trees

Contemporary phylogenomic studies frequently incorporate two‐step coalescent analyses wherein the first step is to infer individual‐gene trees, generally using maximum‐likelihood implemented in the popular programs PhyML or RAxML. Four concerns with this approach are that these programs only present a single fully resolved gene tree to the user despite potential for ambiguous support, insufficient phylogenetic signal to fully resolve each gene tree, inexact computer arithmetic affecting the reported likelihood of gene trees, and an exclusive focus on the most likely tree while ignoring trees that are only slightly suboptimal or within the error tolerance. Taken together, these four concerns are sufficient for RAxML and PhyML users to be suspicious of the resulting (perhaps over‐resolved) gene‐tree topologies and (perhaps unjustifiably high) bootstrap support for individual clades. In this study, we sought to determine how frequently these concerns apply in practice to contemporary phylogenomic studies that use RAxML for gene‐tree inference. We did so by re‐analyzing 100 genes from each of ten studies that, taken together, are representative of many empirical phylogenomic studies. Our seven findings are as follows. First, the few search replicates that are frequently applied in phylogenomic studies are generally insufficient to find the optimal gene‐tree topology. Second, there is often more topological variation among slightly suboptimal gene trees relative to the best‐reported tree than can be safely ignored. Third, the Shimodaira–Hasegawa‐like approximate likelihood ratio test is highly effective at identifying dubiously supported clades and outperforms the alternative approaches of relying on bootstrap support or collapsing minimum‐length branches. Fourth, the bootstrap can, but rarely does, indicate high support for clades that are not supported amongst slightly suboptimal trees. Fifth, increasing the accuracy by which RAxML optimizes model‐parameter values generally has a nominal effect on selection of optimal trees. Sixth, tree searches using the GTRCAT model were generally less effective at finding optimal known trees than those using the GTRGAMMA model. Seventh, choice of gene‐tree sampling strategy can affect inferred coalescent branch lengths, species‐tree topology and branch support.
Experimental Control of Macrophage Pro-Inflammatory Dynamics Using Predictive Models

Macrophage activity is a major component of the healthy response to infection and injury that consists of tightly regulated early pro-inflammatory activation followed by anti-inflammatory and regenerative activity. In numerous diseases, however, macrophage polarization becomes dysregulated and can not only impair recovery, but can also promote further injury and pathogenesis, e.g. after injury, in diabetes, or in Alzheimer’s disease. Dysregulated macrophages may either fail to polarize or become chronically polarized, resulting in increased production of cytotoxic factors, diminished capacity to clear pathogens, or failure to promote tissue regeneration. In these cases, a method of predicting and dynamically controlling macrophage polarization will enable a new strategy for treating diverse inflammatory diseases. In this work, we developed a model-predictive control framework to temporally regulate macrophage polarization. Using RAW 264.7 macrophages as a model system, we enabled temporal control by identifying transfer function models relating the polarization marker iNOS to exogenous pro- and anti-inflammatory stimuli. These stimuli-to-iNOS response models were identified using linear autoregressive with exogenous input terms (ARX) equations and were coupled with nonlinear elements to account for experimentally identified supra-additive and hysteretic effects. Using this model architecture, we were able to reproduce experimentally observed temporal iNOS dynamics induced with lipopolysaccharides (LPS) and interferon gamma (IFN-γ). Moreover, the identified model enabled the design of time-varying input trajectories to experimentally sustain the duration and magnitude of iNOS expression. By designing transfer function models with the intent to predict cell behavior, we were able to predict and experimentally obtain temporal regulation of iNOS expression using LPS and IFN-γ from both naïve and non-naïve initial states. Moreover, our data driven models revealed decaying magnitude of iNOS response to LPS stimulation over time that could be recovered using combined treatment with both LPS and IFN-γ. Given the importance of dynamic tissue macrophage polarization and overall inflammatory regulation to a broad number of diseases, the temporal control methodology presented here will have numerous applications for regulating immune activity dynamics in chronic inflammatory diseases.
Experimental determination of the force of malaria infection reveals a non-linear relationship to mosquito sporozoite loads

Plasmodium sporozoites are the infective stage of the malaria parasite. Though this is a bottleneck for the parasite, the quantitative dynamics of transmission, from mosquito inoculation of sporozoites to patent blood-stage infection in the mammalian host, are poorly understood. Here we utilize a rodent model to determine the probability of malaria infection after infectious mosquito bite, and consider the impact of mosquito parasite load, blood-meal acquisition, probe-time, and probe location, on infection probability. We found that infection likelihood correlates with mosquito sporozoite load and, to a lesser degree, the duration of probing, and is not dependent upon the mosquito’s ability to find blood. The relationship between sporozoite load and infection probability is non-linear and can be described by a set of models that include a threshold, with mosquitoes harboring over 10,000 salivary gland sporozoites being 7.5 times more likely to initiate a malaria infection. Overall, our data suggest that the small subset of highly infected mosquitoes may contribute disproportionally to malaria transmission in the field and that quantifying mosquito sporozoite loads could aid in predicting the force of infection in different transmission settings. Author Summary Malaria is a leading cause of death in many parts of the world. Infection is initiated when infected Anopheles mosquitoes inject sporozoites as they look for blood. Though transmission is a bottleneck for the parasite and thus a good point for intervention, many aspects of transmission remain poorly understood. In this study, using a rodent model of malaria, we found that less than 20% of infectious bites result in disease, demonstrating that the majority of infective bites do not result in malaria infection. Furthermore, we found that the bites of mosquitoes with heavy parasite burdens are 7.5 times more likely to result in disease. These data have important implications for designing interventions targeting transmission stages of the malaria parasite as they suggest that reducing parasite loads, even without completely eliminating them, could be effective against disease spread. We also found that mosquitoes that probe but do not succeed in finding blood are equally likely to initiate infection, an important finding for human vaccine trials. Together, this work adds to our understanding of malaria transmission dynamics and our capacity to develop malaria elimination strategies.
A MAP of tumor-host interactions in glioma at single cell resolution

Single-cell RNA sequencing is the reference technique to characterize the heterogeneity of tumor microenvironment and can be efficiently used to discover cross-talk mechanisms between immune cells and cancer cells. We present a novel method, single cell Tumor-Host Interaction tool (scTHI), to identify significantly activated ligand-receptor interactions across clusters of cells from single-cell RNA sequencing data. We apply our approach to uncover the ligand-receptor interactions in glioma using six publicly available human glioma datasets encompassing 71 patients. We provide a comprehensive map of the signalling mechanisms between malignant cells and non-malignant cells in glioma uncovering potential novel therapeutic targets.
Hubs of long-distance co-alteration in brain pathology

The exact mechanisms at the root of pathologic anatomical covariances are still unknown. It is nonetheless becoming clearer that the impact of brain diseases is more convincingly represented in terms of co-alterations rather than in terms of localization of alterations. According to this view, neurological and psychiatric conditions might be seen as whole-brain patterns of modifications. In this context, the physical distance between two co-altered areas may provide insightful information about how pathology develops across the brain, assuming that long-range co-alterations might be relevant features of pathological networks. To demonstrate this hypothesis, we calculated the probability of co-alteration between brain areas across a large database of voxel-based morphometry studies of psychiatric and neurological disorders, and we investigated the physical (Euclidean) distance of the edges of the resulting network. Such analysis produced a series of observations relevant for the understanding of pathology, which range from unanticipated results to the recognition of regions of well-known functional and clinical relevance. For instance, it emphasizes the importance of the anterior and dorsal prefrontal cortices in the distribution of the disease-related alterations, as well as a specular asymmetry of gray matter decreases and increases between the hemispheres. Also, the analyses of schizophrenia and Alzheimer’s disease show that long-distance co-alterations are able to identify areas involved in pathology and symptomatology. Moreover, the good concordance between the measure of the mean physical distance and that of functional degree centrality suggests that co-alterations and connectivity are intimately related. These findings highlight the importance of analyzing the physical distance in pathology, as the areas characterized by a long mean distance may be considered as hubs with a crucial role in the systems of alterations induced by brain diseases.
Acta Botanica Brasilica

The relationship between plants and frugivorous animals is modulated by morphological and nutritional characteristics of fruits, as well as their seasonal availability across habitats. We evaluated fruiting phenology, fruit morphology and nutritional characteristics of 35 abundant plant species from 15 families associated with frugivorous birds from distinct habitats in the Cerrado (savanna, forest, and palm swamp). For a subset of 16 plant species, we also evaluated the overlap in interactions with frugivorous birds using data from the literature. Open-habitat plants had their fruiting peak during the rainy season, while fruiting of forest species was evenly distributed across the year. Plants of the same family exhibited similar fruit morphology and nutritional characteristics. Most plants had fruits with more sugars than lipids, while all species with higher lipid content were from savanna habitats and produced fruits during the rainy season, the peak reproductive season for birds. Assemblages of frugivorous birds exhibited considerable overlap, irrespective of habitat or fruiting season of plants. The complementarity found among habitats, considering seasonal availability and nutritional profile of fruits for frugivorous birds, is relevant for community maintenance and regeneration. Therefore, this landscape level complexity should always be considered in conservation and restoration policies for the Cerrado.
Natural evolvement of lung tumors induced by N-ethyl-N-nitrosourea (ENU) and the impact of a high sucrose-high fat diet on tumor evolvement assessed by tumor histology in inbred BALB/c and C57BL/6J mice.

Background The model of lung tumors transplacentally induced by N-ethyl-N-nitrosourea (ENU) in inbred BALB/c and C57BL/6J mice was used to investigate the impact of a high sucrose-high fat (HSHF) diet on lung tumorigenesis. Methods The offspring was separated by gender and randomly divided into 2 subgroups in both ENU- and buffer-treated groups at the time of weaning. One subgroup was put on the standard diet and the other on the HSHF diet from weaning to the age of 24 weeks. The entire lungs went through a standard process of paraffin-embedded blocks. Every lung block was cut in serial sections but one in every five sections was saved to generate step sections that were stained by hematoxylin and eosin. The tumor histology was assessed on the step sections. Results At 24-week checkpoint, a spectrum of histological changes was observed in the mice on both diets. Specifically, they presented as alveolar hyperplasia, adenomas and adenomas with nuclear dysplasia at various degrees. Those tumors were actually at different developmental stages. Lung adenocarcinomas were developed in mice on the HSHF diet. A cluster of tumor cells with wide foamy or clear or signet-ring shaped cytoplasm (fatty changes) appeared in a low frequency on the HSHF diet. Conclusions The observed histological changes indicated that lung tumors were developed at different times and evolved at different paces. The HSHF diet accelerated the course of tumor evolvement. Tumor cells with fatty changes might be induced by the HSHF diet.
Selective K-ATP channel-dependent loss of pacemaking in vulnerable nigrostriatal dopamine neurons by α-synuclein aggregates

Parkinson disease (PD), one of the most common neurodegenerative disorder, is believed to be driven by toxic α-synuclein aggregates eventually resulting in selective loss of vulnerable neuron populations, prominent among them, nigrostriatal dopamine (DA) neurons in the lateral substantia nigra (l-SN). How α-synuclein aggregates initiate a pathophysiological cascade selectively in vulnerable neurons is still unclear. Here, we show that the exposure to low nanomolar concentrations of α-synuclein aggregates (i.e. fibrils) but not its monomeric forms acutely and selectively disrupted the electrical pacemaker function of the DA subpopulation most vulnerable in PD. This implies that only dorsolateral striatum projecting l-SN DA neurons were electrically silenced by α-synuclein aggregates, while the activity of neither neighboring DA neurons in medial SN projecting to dorsomedial striatum nor mesolimbic DA neurons in the ventral tegmental area (VTA) were affected. Moreover, we demonstrate functional K-ATP channels comprised of Kir6.2 subunit in DA neurons to be necessary to mediate this acute pacemaker disruption by α-synuclein aggregates. Our study thus identifies a molecularly defined target that quickly translates the presence of α-synuclein aggregates into an immediate impairment of essential neuronal function. This constitutes a novel candidate process how a protein-aggregation-driven sequence in PD is initiated that might eventually lead to selective neurodegeneration.
Impaired phagocytic function in CX3CR1+ tissue-resident skeletal muscle macrophages prevents muscle recovery after influenza A virus-induced pneumonia in aged mice

Skeletal muscle dysfunction in survivors of pneumonia is a major cause of lasting morbidity that disproportionately affects older individuals. We found that skeletal muscle recovery was impaired in aged compared with young mice after influenza A virus-induced pneumonia. In young mice, recovery of muscle loss was associated with expansion of tissue-resident skeletal muscle macrophages and downregulation of MHC II expression, followed by a proliferation of muscle satellite cells. These findings were absent in aged mice and in mice deficient in Cx3cr1. Transcriptomic profiling of tissue-resident skeletal muscle macrophages from aged compared with young mice showed downregulation of pathways associated with phagocytosis and proteostasis, and persistent upregulation of inflammatory pathways. Consistently, skeletal muscle macrophages from aged mice failed to downregulate MHCII expression during recovery from influenza A virus induced pneumonia and showed impaired phagocytic function in vitro. Like aged animals, mice deficient in the phagocytic receptor Mertk showed no macrophage expansion, MHCII downregulation or satellite cell proliferation and failed to recover skeletal muscle function after influenza A pneumonia. Our data suggest that a loss of phagocytic function in a CX3CR1+ tissue-resident skeletal muscle macrophage population in aged mice precludes satellite cell proliferation and recovery of skeletal muscle function after influenza A pneumonia.
Fat food exacerbates post-prandial hypothalamic inflammation involving GFAP+ cells and microglia

In humans, obesity was associated with brain inflammation and glial cell proliferation. Studies in rodents showed that glial cell proliferation occurs within 24 hours of high-fat diet (HFD) consumption, before obesity development. This proliferation was mainly observed in the hypothalamus (HT), a crucial brain structure for controlling body weight. Therefore, we sought to characterize the post-prandial HT inflammatory response to 1-3-6 hours exposure to a standard diet and HFD. HFD exposure increased gene expression of astrocyte and microglial marker (GFAP and Iba1) compare to standard treated mice and induced morphological modifications of microglial cells in HT. This remodeling was associated with higher expression of inflammatory genes and differential activation of hypothalamic neuropeptides involved in energy balance regulation. DREADD and PLX5622 technologies, used to modulate GFAP-positive or microglial cells activity respectively, showed that both glial cell types are involved in hypothalamic post-prandial inflammation, but in a different time frame and with a diet specificity Thus, an exacerbated post-prandial inflammation in brain might predispose individuals to obesity and needs to be characterized to address this worldwide crisis.