Miracle-dz/UniFAR-FTUs huggingface dataset:
Training the brain: could it improve multiple sclerosis treatment?

Abstract Multiple sclerosis (MS) is a neurological disease characterized by neuroinflammation, demyelination and axonal degeneration along with loss of function in the central nervous system. For many years, research in MS has focused on the efficacy of pharmacological treatments. However, during the last years, many publications have been dedicated to the study of the efficacy of non-pharmacological strategies, such as physical exercise and cognitive training. Beneficial effects of the combination of both strategies on cognitive function have been described in both ageing adults and patients with neurodegenerative diseases, such as MS. The analysis of combining both physical and cognitive stimulation can be summarized by the environmental enrichment (EE) experiments, which are more suitable for animal models. EE refers to housing conditions consisting of exercise and cognitive and social stimulation. In this review, we will summarize the available studies that describe the influence of EE in both MS patients and MS animal models.
Produção de anticorpos policlonais anti-ricina

A ricina e uma proteina bastante toxica presente nas sementes de mamona que impossibilita o uso da torta de mamona "in natura", como racao. A torta de mamona destoxificada necessita ainda de metodos de analise que garantam a ausencia de tracos dessa proteina. Objetivou-se, neste trabalho, produzir e avaliar a sensibilidade e especificidade de anticorpos policlonais anti-ricina, para serem empregados como possiveis componentes de metodos sorologicos na deteccao de ricina em torta de mamona destoxificada. Foram avaliadas tres doses da proteina: 400, 180 e 100 µg cada uma dividida em duas aplicacoes em coelhos. A primeira dose foi injetada no animal no inicio do experimento e a segunda apos 21 dias. O metodo de ELISA indicou que as duas doses menores (100 e 180 µg) induziram respostas imunologicas primaria e secundaria com producao de anticorpos especificos. Enquanto a dose maior (400 µg) de ricina apresentou uma resposta primaria com elevacao dos titulos de anticorpos, seguida de uma supressao da resposta. Esse perfil e sugestivo de tolerância imunologica. Pela tecnica de Western blotting verificou-se que os anticorpos policlonais produzidos sao bastante especificos para a ricina, no entanto, por detectarem ricina na forma nativa e desnaturada nao sao recomendados para o monitoramento de ricina em torta de mamona destoxificada por tratamento termico.
Capillaria hepatica (Nematode) in rodents of the Lahore Metropolis Corporation-Pakistan.

A total of 3600rodentswere live-trapped from three different localities (1200 each)of the Lahore Metropolitan sAllama Iqbal Town, Walled City andRailway Station and adjacent areas, and scanned for the prevalence of Capillaria hepatica . In each of these f ourtypes ofstructureswere sampled for rats and miceresidential houses (RH), flour mills (FM), fruit/vegetable shops (F/VS) and departmental store s/grocery shops (DS/GS) . Majority ofthetrappedrodents includedhouse ratsRattus rattus(n = 3190)witha fewhouse miceMus musculus(n = 410). Hepatic capillari asis was recorded in7.0% of the rodentsin Lahore city . Theprevalencewas statistically higherin females thaninmales and in adultsthan younganimals. A significant difference was found in the infection rate between rats and mice . Similarly t he infection rate varied significantly both monthly andseasonallyand thepeak prevalence was recor dedduringsummer (10.8%). Inter-structure infection rate was non-significant.
Haramonas viridissp. nov. (Raphidophyceae, Heterokontophyta), a new sand‐dwelling raphidophyte from cold temperate waters

A new, marine, sand‐dwelling raphidophyte from Sylt, Germany, Haramonas viridis Horiguchi et Hoppenrath sp. nov. is described. This represents a second species in the previously monotypic genus Haramonas, which was originally described from a sand sample from a mangrove river mouth in tropical Australia, based on the type species, H. dimorpha. This new species from a cold temperate region: (i) possesses a tubular invagi‐nation in the posterior part of the cell; (ii) produces copious amounts of mucilage in culture; (iii) possesses both motile and non‐motile stages in its life cycle; and (iv) has overlapping discoidal chloroplasts, all of which are diagnostic features of the genus Haramonas. Therefore, it is indisputable that this species belongs to this genus. However, the species from Sylt differs from the type species of the genus in: (i) having a larger cell size; (ii) possessing a larger number of chloroplasts; and (iii) being greenish in color. The ultrastructural study revealed that the structure of the tubular invagi‐nation was the same as that of the type species.
pKa calculations of calbindin D9k: Effects of Ca2+ binding, protein dielectric constant, and ionic strength

Calbindin is a small (75 residues) helix‐loop‐helix (“EF‐hand”) calcium‐binding protein belonging to the calmodulin superfamily. It binds two Ca2+ ions. Continuum electrostatics in combination with the boundary element method was employed for the calculation of the acid‐dissociation constants Ka (pKa = −log Ka) values of all titratable residues in the protein. The objectives were to determine quantitatively the effects of divalent ion binding and small ion‐induced structural changes on predicted pKa's. Computations were carried out for the apo and holo form of calbindin, for which both X‐ray and NMR structures were available. Comparison was made with several sets of experimental pKa values determined by NMR spectroscopy. Different choices of the dielectric constant (ranging from 4 to 78.5) for calbindin and variations in ionic strength (from 0 to 0.3 M) were investigated in a systematic fashion. Removal of the two bound Ca2+ ions increases the pKa values of all residues if no conformational changes were allowed. If conformational differences between the apo and holo were accounted for, shifts in either direction were observed. Titrating groups that are directly involved in Ca2+ binding (Asp and Glu) required a dielectric constant of 78.5 for the holo structure to obtain a reasonable estimate of their pKa's. For the apo structure, passable values for the pKa's of these ligating groups could be determined if the structure was allowed to relax upon ion removal. Proteins 2000;41:554–567. © 2000 Wiley‐Liss, Inc.
Chloroquine in fighting COVID-19: good, bad, or both?

ABSTRACT Coronavirus disease 2019 (COVID-19) has attracted worldwide attention due to its speed of progression and elevated mortality rate. Amid the rush to develop treatments, recent hopes have focused on the anti-malarial drug chloroquine or the derivative hydroxychloroquine. Here, we briefly discuss the evidence for the potential use of these drugs with regard to the current pandemic.
Liparis funingensis (Orchidaceae; Epidendroideae; Malaxidae), a new species from Yunnan, China: evidence from morphology and DNA

A new orchid species, Liparis funingensis, from Yunnan, China, is described and illustrated in this study based on morphological and molecular analyses. A detailed comparison between the newly discovered orchid and other members of Liparis was performed. This new plant is characterized by an obovate lip and is trilobed. The sidelobes are semiorbicular and fleshy, and the midlobe is short and bilobed with triangular lobes. The disc has a deeply bilobed basal callus and two longitudinal lamellae from the base extending to above the middle. There are four pollinia in two pairs, with each pair exhibiting long caudicles without a viscidium. The rostellum also has a bursa synovialis. These features distinguish this new orchid from all other known species of Liparis. A phylogenetic analysis was subsequently performed to determine the systematic position of this enigmatic species. A molecular study based on nuclear ribosomal ITS and plastid matK DNA sequence data indicates that L. funingensis is a member of L. layardii subclade.
Identification of the distinct genomic features in gastroesophageal junction adenocarcinoma and its Siewert subtypes

Rates of gastroesophageal junction adenocarcinomas (GEJAs) have shown an alarming increase; however, the genetic background of GEJA and its Siewert classification have yet to be uncovered. Here, 60 paired tumor and normal DNA samples from GEJA patients were analyzed by whole‐exome sequencing. Among them, 13 were Siewert type I, 14 were type II, and 33 were type III. A predominance of C/G>T/A substitutions was discovered in GEJA, followed by C/G>A/T substitutions. Notably, Siewert type I and type II/III display distinct sets of driver genes, mutational spectrum, and recurrently disrupted pathways. Siewert type I showed similarity to esophageal adenocarcinomas (EACs) and the chromosomal instability subtype of stomach adenocarcinomas, while Siewert type II/III showed similarity to the genomic stable subtype of stomach adenocarcinoma. We also found that mutation of FBXW7, a driver gene of GEJA, was enriched in Siewert type I. Our data identify differences between GEJA and stomach/EACs at the genomic level and provide evidence for differential treatment based on Siewert classification of GEJA. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Critical Analysis of Image Descriptors

: Image description is a sub field of image processing. Local features or nearby elements and their descriptors are robust and compact vector representations of their neighborhood, and building squares of numerous computer vision applications. Descriptors are picking up prominence for getting correspondence between two pictures, and seeking and finding the required picture from dataset. This paper presents the detailed comparison & experimental analysis of different existing image description techniques such as Speeded up Robust Features,Binary Robust Invariant Scalable Keypoints, and Fast Retina Keypoint. Their performance is analyzed on MATLAB (2015a). In this research study three image descriptor algorithms are analyzed in terms of their detected feature points, considering two scenarios (Scenario 1: simple image and Scenario 2: cluttered scene) and two cases (Case 1: Rotation and Case 2: Scaling) along with the image correspondence computation in three cases (Simple, Rotation and Scaling).
Hypergraphes : clustering, réduction et marches aléatoires orientées pour la segmentation d'images et de vidéo

Graphs have been successfully used in Pattern Recognition and Computer Vision domains for a number of years, due to their ability to represent relational patterns. However, their main limitation comes from the fact that they are only able to model pairwise affinities between elements of interest. In this work, we focus on exploiting the advantages of hypergraphs, which generalize the graph concept by providing the possibility to model relationships of higher dimension, in the domain of image analysis and more particularly image processing such as image or video segmentation. This thesis mainly focused on how we can represent the image data into a hypergraph-based model, and how we can handle such a representation in a particular application. In many of these applications the problem can be formulated as a partitioning of the underlying hypergraph structure, and consequently we developed a novel hypergraph partitioning and clustering approach (RHC), based on the reduction of the hypergraph structure. Two novel hypergraph reduction algorithms (HR-IH and HR-MST) have been designed for this purpose. The RHC framework has been exploited in different computer vision problems (image segmentation, object-based video segmentation and superpixels generation), for which appropriate hypergraph-based models have been designed. Finally, the notion of directed hypergraph has been introduced in the computer vision domain, by proposing both a directed hypergraph-based representation of the image content (DINH), and an interactive image segmentation algorithm by semi-supervised learning on such a DINH. The latter is formulated in terms of Markov random walks on directed hypergraphs, for which an appropriate transition matrix and important mathematical properties have been developed. Extensive experiments have shown that hypergraphs can in general provide a richer image representation model thangraphs, and that the proposed algorithms are efficient both in terms of segmentation quality and complexity. It has also been shown that using directed hypergraphs can provide an improvement to undirected hypergraphbased structures.
Cationic Covalent-Organic Framework as Efficient Redox Motor for High-Performance Lithium-Sulfur Batteries.

The shuttle effect of soluble lithium polysulfides (LiPSs) leads to the rapid decay of sulfur cathode, severely hindering the practical applications of lithium-sulfur (Li-S) batteries. To this point, a covalent-organic framework (COF) with proper cationic sites, which can be utilized as the cathode host of high-performance Li-S batteries, is reported. The chemical sulfur anchoring within micropores effectively suppresses the dissolution of LiPSs into the electrolyte. During the discharge step, the cationic sites can accept electrons from anode and deliver them to polysulfides to facilitate the polysulfides' disintegration. Meanwhile, the cationic sites can receive electrons from polysulfides and then send them to the anode during the charge process, which promotes the polysulfides oxidation. Thus, both experiments and computational modeling show that the cationic COF can effectively inhibit the shuttle effect of LiPSs and improve the batteries' performances. Compared with electrically neutral COFs, the cationic COF-based batteries show much better cycling stability even at high current density, for instance, a high specific capacity of 468 mA h g-1 is retained after 300 cycles at a current density of 4.0 C.
Garcinia cambogia suppresses adipogenesis in 3T3‐L1 cells by inhibiting p90RSK and Stat3 activation during mitotic clonal expansion

Obesity is associated with an increase in adipose tissue, which is mediated by hyperplasia and hypertrophy. Therefore, inhibiting cell proliferation during mitotic clonal expansion (MCE) is one of the major strategies for preventing obesity. The antagonistic effects of Garcinia cambogia (G. cambogia) on obesity have been studied in animal experimental models. However, the effects of G. cambogia extract on MCE, and the underlying molecular mechanisms, are poorly understood. In this study, 3T3‐L1 cells were used to investigate whether G. cambogia extract affected cell proliferation during MCE and to identify target molecules for any anti‐adipogenic activity. G. cambogia extract suppressed isobutylmethylxanthine and dexamethasone‐and‐insulin (MDI)‐induced adipogenesis at an early stage by attenuating MCE. In G. cambogia extract‐treated preadipocytes, MDI‐induced cell proliferation and cell cycle progression were inhibited by G0/G1 arrest due to an increase in p21 and p27 expression, and inhibition of cyclin‐dependent kinase 2, cyclin E1 expression, and retinoblastoma (Rb) phosphorylation. In addition, the MDI‐induced phosphorylation and subsequent translocation into the nucleus of p90 ribosomal S6 kinase (p90RSK) and signal transducer and activator of transcription (Stat) 3 were suppressed. Specific inhibitors of p90RSK (FMK) and Stat3 (stattic) regulated cell proliferation and adipogenesis. In conclusion, this study demonstrated that G. cambogia extract inhibited MCE by regulating p90RSK, Stat3, and cell cycle proteins, leading to G0/G1 arrest. These findings provide new insight into the mechanism by which G. cambogia suppresses adipocyte differentiation and show that p90RSK is critical for adipogenesis as a new molecular target.
Designing novel inhibitors against cyclopropane mycolic acid synthase 3 (PcaA): targeting dormant state of Mycobacterium tuberculosis

Abstract Mycobacterium tuberculosis can sustain inside the host in dormant (non-replicating) state for years. It suppresses the host immune system by residing in the host alveolar macrophage, resulting in the development of latent tuberculosis. Despite many antibiotics available for the treatment of tuberculosis, the major hurdle in complete elimination is the ability of the bacilli to undergo dormancy and develop resistance against the existing drugs. Cyclopropanation of mycolic acids present in the cell wall of mycobacteria is required for its persistence and virulence. Cyclopropane synthases such as PcaA, CmaA1 and CmaA2, introduce site-specific modifications in mycolic acids. PcaA expression levels are high during dormancy and the gene mutants fails to persist, showing reduced survival in host macrophage. Hence, PcaA appears as a potential target to develop inhibitors against the dormant bacilli. In this study, we have identified compounds with maximum binding affinity against PcaA by in-silico virtual screening of anti-tuberculosis compounds and their structural analogues. In-silico docking followed molecular dynamic simulations and free energy calculations of the compounds with highest docking score in their respective libraries. This study reports novel inhibitors that can act as better anti-tuberculosis compounds targeting PcaA. Communicated by Ramaswamy H. Sarma
The use of patient‐derived breast tissue explants to study macrophage polarization and the effects of environmental chemical exposure

Ex vivo mammary explant systems are an excellent model to study interactions between epithelium and stromal cell types because they contain physiologically relevant heterotypic interactions in the background of genetically diverse patients. The intact human mammary tissue, termed patient‐derived explant (PDE), can be used to investigate cellular responses to a wide variety of external stimuli in situ. For this study, we examined the impact of cytokines or environmental chemicals on macrophage phenotypes. We demonstrate that we can polarize macrophages within human breast tissue PDEs toward M1 or M2 through the addition of interferon‐γ (IFNγ) + lipopolysaccharide (LPS) or interleukin (IL)‐4 + IL‐13, respectively. Elevated expression levels of M(IFNγ + LPS) markers (HLADRA and CXCL10) or M(IL‐4 + IL‐13) markers (CD209 and CCL18) were observed in cytokine‐treated tissues. We also examined the impact of the endocrine‐disrupting chemical, benzophenone‐3, on PDEs and measured significant, yet varying effects on macrophage polarization. Furthermore, a subset of the PDEs respond to IL‐4 + IL‐13 through downregulation of E‐cadherin and upregulation of vimentin which is reminiscent of epithelial‐to‐mesenchymal transition (EMT) changes. Finally, we were able to show immortalized nonmalignant breast epithelial cells can exhibit EMT characteristics when exposed to growth factors secreted by M(IL‐4 + IL‐13) macrophages. Taken together, the PDE model system is an outstanding preclinical model to study early tissue‐resident immune responses and effects on epithelial and stromal responses to stimuli found both endogenously in the breast and exogenously as a result of exposures.
Scouting around 1,2,3,4‐Tetrahydrochromeno[3,2‐c]pyridin‐10‐ones for Single‐ and Multitarget Ligands Directed towards Relevant Alzheimer's Targets

A number of 1,2,3,4‐tetrahydrochromeno[3,2‐c]pyridin‐10‐one derivatives have been synthesized and screened against different targets involved in the onset and progression of Alzheimer's disease (AD), such as acetyl‐ and butyrylcholinesterase (AChE and BChE), monoamine oxidases A and B (MAO A and B), aggregation of β‐amyloid (Aβ) and reactive oxygen species (ROS) production. Derivatives 1 c, 3 b, 4 and 5 a showed multifaceted profiles of promising anti‐AD features and returned well‐balanced multitargeting inhibitory activities. Moreover, compound 1 f, a potent and selective human MAO B inhibitor (IC50=0.89 μM), proved to be a safe neuroprotectant in a human neuroblastoma cell line (SH‐SY5Y) by improving viability impaired by Aβ1–42 and pro‐oxidant insult. Furthermore, structure–activity relationships (SARs) and docking models were derived in order to assist further hit‐to‐lead optimization stage.
Validity evidence and norms of the Spanish versión of the Hurlbert Index of Sexual Fantasy.

BACKGROUND Sexual fantasies are described as thoughts or mental images with sexual content. The Hurlbert Index of Sexual Fantasy (HISF) evaluates the positive attitude towards sexual fantasies. The objective of this study was to provide validity evidence of the Spanish version of the HISF and to present its standard scores. METHOD The sample was composed of 3,458 adults from the general Spanish population (1,641 men; 1,817 women), distributed across age groups (18-34, 35-49, and over 50 years old). RESULTS The unifactorial structure of the Spanish version of the HISF showed strict measurement invariance across sex, age range, and education level. Positive attitudes towards sexual fantasies significantly correlated with erotophilia, sexual assertiveness, sexual desire, and sexual functioning. Also, the scale was useful for differentiating between individuals with sexual functioning difficulties and individuals with no difficulties. Finally, the standard scores were obtained based on sex and age range. CONCLUSIONS The Spanish version of the HISF is a reliable, valid, and invariant scale for assessing a positive attitude towards sexual fantasies in people with different sociodemographic characteristics.
NRF2 mediates γ-globin gene regulation through epigenetic modifications in a β-YAC transgenic mouse model

NRF2 is the master regulator for the cellular oxidative stress response and regulates γ-globin gene expression in human erythroid progenitors and sickle cell disease mice. To explore NRF2 function, we established a human β-globin locus yeast artificial chromosome transgenic/NRF2 knockout (β-YAC/NRF2−/−) mouse model. NRF2 loss reduced γ-globin gene expression during erythropoiesis and abolished the ability of dimethyl fumarate, an NRF2 activator, to enhance γ-globin transcription. We observed decreased H3K4Me1 and H3K4Me3 chromatin marks and association of TATA-binding protein and RNA polymerase II at the β-locus control region (LCR) and γ-globin gene promoters in β-YAC/NRF2−/− mice. As a result, long-range chromatin interaction between the LCR DNase I hypersensitive sites and γ-globin gene was decreased, while interaction with the β-globin was not affected. Further, NRF2 loss silenced the expression of DNA methylcytosine dioxygenases TET1, TET2, and TET3 and inhibited γ-globin gene DNA hydroxymethylation. Subsequently, protein-protein interaction between NRF2 and TET3 was demonstrated. These data support the ability of NRF2 to mediate γ-globin gene regulation through epigenetic DNA and histone modifications. Impact statement Sickle cell disease is an inherited hemoglobin disorder that affects over 100,000 people in the United States causing high morbidity and early mortality. Although new treatments were recently approved by the FDA, only one drug Hydroxyurea induces fetal hemoglobin expression to inhibit sickle hemoglobin polymerization in red blood cells. Our laboratory previously demonstrated the ability of the NRF2 activator, dimethyl fumarate to induce fetal hemoglobin in the sickle cell mouse model. In this study, we investigated molecular mechanisms of γ-globin gene activation by NRF2. We observed the ability of NRF2 to modulate chromatin structure in the human β-like globin gene locus of β-YAC transgenic mice during development. Furthermore, an NRF2/TET3 interaction regulates γ-globin gene DNA methylation. These findings provide potential new molecular targets for small molecule drug developed for treating sickle cell disease.