Miracle-dz/UniFAR-FTUs huggingface dataset:
High-Throughput Screening Platform for Natural Product–Based Drug Discovery Against 3 Neglected Tropical Diseases

African trypanosomiasis, leishmaniasis, and Chagas disease are 3 neglected tropical diseases for which current therapeutic interventions are inadequate or toxic. There is an urgent need to find new lead compounds against these diseases. Most drug discovery strategies rely on high-throughput screening (HTS) of synthetic chemical libraries using phenotypic and target-based approaches. Combinatorial chemistry libraries contain hundreds of thousands of compounds; however, they lack the structural diversity required to find entirely novel chemotypes. Natural products, in contrast, are a highly underexplored pool of unique chemical diversity that can serve as excellent templates for the synthesis of novel, biologically active molecules. We report here a validated HTS platform for the screening of microbial extracts against the 3 diseases. We have used this platform in a pilot project to screen a subset (5976) of microbial extracts from the MEDINA Natural Products library. Tandem liquid chromatography–mass spectrometry showed that 48 extracts contain potentially new compounds that are currently undergoing de-replication for future isolation and characterization. Known active components included actinomycin D, bafilomycin B1, chromomycin A3, echinomycin, hygrolidin, and nonactins, among others. The report here is, to our knowledge, the first HTS of microbial natural product extracts against the above-mentioned kinetoplastid parasites.
Microbiomes of Unreactive and Pathologically Altered Ileocecal Lymph Nodes of Slaughter Pigs

ABSTRACT Microbe-laden dendritic cells are shifted to ileocecal lymph nodes (ICLNs), where microbes are concentrated and an adequate immune response is triggered. Hence, ICLNs are at a crucial position in immune anatomy and control processes of the local immune system. Pathological alterations in ICLNs, such as reactive hyperplasia, lymphadenitis purulenta, or granulomatosa, can harbor a multitude of pathogens and commensals, posing a potential zoonotic risk in animal production. The aim of this study was to characterize the microbial diversity of unreactive ICLNs of slaughter pigs and to investigate community shifts in reactive ICLNs altered by enlargement, purulence, or granulomatous formations. Pyrosequencing of 16S rRNA gene amplicons from 32 ICLNs yielded 175,313 sequences, clustering into 650 operational taxonomic units (OTUs). OTUs were assigned to 239 genera and 11 phyla. Besides a highly diverse bacterial community in ICLNs, we observed significant shifts in pathologically altered ICLNs. The relative abundances of Cloacibacterium- and Novosphingobium-associated OTUs and the genus Faecalibacterium were significantly higher in unreactive ICLNs than in pathologically altered ICLNs. Enlarged ICLNs harbored significantly more Lactobacillus- and Clostridium-associated sequences. Relative abundances of Mycoplasma, Bacteroides, Veillonella, and Variovorax OTUs were significantly increased in granulomatous ICLNs, whereas abundances of Pseudomonas, Escherichia, and Acinetobacter OTUs were significantly increased in purulent ICLNs (P < 0.05). Correlation-based networks revealed interactions among OTUs in all ICLN groups, and discriminant analyses depicted discrimination in response to pathological alterations. This study is the first community-based survey in ICLNs of livestock animals and will provide a basis to broaden the knowledge of microbe-host interactions in pigs.
How to screen for 222Rn in large buildings.

222Rn measurements have been made in over 10,000 ground-contact rooms in 908 federal buildings. These data were examined statistically to compare parametric distributions that might be useful in the design and execution of future surveys of indoor 222Rn in large buildings. In 152 of the 365 buildings with the most measurements per building, the log-normal distribution was acceptable. Many other distributions were observed in the other 213 buildings, including bi- and tri-modal distributions. In contrast, when data from entire facilities were examined, the data were usually described by a lognormal distribution. Because of the above observations, we propose that any future surveys of indoor 222Rn in large buildings be done in two phases, screening and assessment. During the screening phase, all facilities may be surveyed with a comparatively low sampling density, perhaps, one measurement per 465 m2 (5,000 ft2) of floor space. Based on the results presented here, it is expected that statistical analysis of the screening data will reveal any facilities with substantial evidence of a high incidence of rooms with elevated indoor 222Rn concentrations (e.g., above 150 Bq m-3). In the assessment phase, the identified facilities will be surveyed with a sampling density of one measurement for every ground-contact room or about one per 84 m2 (900 ft2). Using numerical simulation techniques, we have tested the proposed screening phase protocol against data from sixteen facilities. The results of the simulated screenings support the feasibility of a two-phased approach to the task of identifying facilities having rooms with elevated 222Rn concentrations.
Prenatal Diagnosis of Retroperitoneal Teratoma: A Case Report and Review of the Literature

We report a case of retroperitoneal teratoma diagnosed prenatally by serial sonographic examinations in the third trimester. A 29-year-old woman was referred for sonographic evaluation at 33 weeks’ gestation because of a fetal intra-abdominal mass. Our initial sonographic image suggested a neuroblastoma. Repeat ultrasound images demonstrated an increase in size of the tumor, while the content of the tumor became predominantly solid with areas of calcification. Teratoma should be considered on detection of any cystic or mixed semisolid mass, especially when calcification is present. The fetus was prenatally diagnosed with retroperitoneal teratoma. After birth at 39 weeks, the tumor was removed and histological analysis revealed an immature retroperitoneal teratoma. Intensive monitoring of the changes in ultrasound images of the tumor should provide ground for a precise antenatal diagnosis.
Childhood Sexual Abuse, HPA Axis Regulation, and Mental Health

Adults who experienced childhood sexual abuse (CSA) are at increased risk for major depressive disorder (MDD) and posttraumatic stress disorder (PTSD). Animal studies suggest that dysregulated biological stress systems are a potential mechanism, but there are multiple challenges involved in conducting translational studies in humans. The purpose of this integrative literature review was to determine the state of the science of hypothalamic–pituitary–adrenal (HPA) axis regulation in adults who experienced CSA, with a focus on the health outcomes of MDD and PTSD. A variety of methods for HPA axis measurement were used in the 10 reviewed studies. The results suggested that changes in HPA axis regulation are present in many adults who experienced CSA—with and without a current MDD or PTSD diagnosis. Further research is needed to verify these findings. The review results can help researchers determine research strategies that will optimize scarce subject and financial resources.
The dietary protein, IGF-I, skeletal health axis

Abstract Dietary protein represents an important nutrient for bone health and thereby for the prevention of osteoporosis. Besides its role as a brick provider for building the organic matrix of skeletal tissues, dietary protein stimulates the production of the anabolic bone trophic factor IGF-I (insulin-like growth factor I). The liver is the main source of circulating IGF-I. During growth, protein undernutrition results in reduced bone mass and strength. Genetic defect impairing the production of IGF-I markedly reduces bone development in both length and width. The serum level of IGF-I markedly increases and then decreases during pubertal maturation in parallel with the change in bone growth and standing height velocity. The impact of physical activity on bone structure and strength is enhanced by increased dietary protein consumption. This synergism between these two important environmental factors can be observed in prepubertal boys, thus modifying the genetically determined bone growth trajectory. In anorexia nervosa, IGF-I is low as well as bone mineral mass. In selective protein undernutrition, there is a resistance to the exogenous bone anabolic effect of IGF-I. A series of animal experiments and human clinical trials underscore the positive effect of increased dietary intake of protein on calcium-phosphate economy and bone balance. On the contrary, the dietary protein-induced acidosis hypothesis of osteoporosis is not supported by several experimental and clinical studies. There is a direct effect of amino acids on the local production of IGF-I by osteoblastic cells. IGF-I is likely the main mediator of the positive effect of parathyroid hormone (PTH) on bone formation, thus explaining the reduction in fragility fractures as observed in PTH-treated postmenopausal women. In elderly women and men, relatively high protein intake protects against spinal and femoral bone loss. In hip fracture patients, isocaloric correction of the relatively low protein intake results in: increased IGF-I serum level, significant attenuation of postsurgical bone loss, improved muscle strength, better recovery, and shortened hospital stay. Thus, dietary protein contributes to bone health from early childhood to old age. An adequate intake of protein should be recommended in the prevention and treatment of osteoporosis.
Histopathology of Mucosa-Associated Lymphoid Tissue

Mucosa-associated lymphoid tissue (MALT) is a generalized term incorporating a disseminated collection of lymphoid tissues in multiple sites throughout the body. MALT sites that have been/are primarily studied include bronchus-associated lymphoid tissue (BALT), gut-associated lymphoid tissue (GALT), and nasopharynx-associated lymphoid tissue (NALT). Since MALT sites are often under-sampled in conventional toxicity studies, MALT lesions have not been extensively documented in these lymphoid effector sites. Lesions of the nasopharyngeal lymphoid tissue and Peyer’s patches include degeneration, inflammation, and both primary and metastatic neoplasia.
Maternal high fat diet deficient in vitamin B12 influences long chain polyunsaturated fatty acid composition in rats

Abstract Objective: In India, there is a rise in non-communicable diseases due to diets deficient in vitamin B12, low in docosahexaenoic acid (DHA) and increased consumption of westernized diet. The present study aims to examine the effect of maternal high fat diet (HFD) in absence of vitamin B12 on pregnancy outcome and tissue fatty acid composition in dams. Methods: Pregnant Wistar rats were assigned to following diets: Control (C), HFD, High fat diet supplemented with omega-3 fatty acids (HFDO), 4) High fat diet deficient in vitamin B12 (HFBD), High fat deficient in vitamin B12 supplemented with omega-3 fatty acids (HFBDO). Results: There was no effect on pregnancy outcome as a consequence of different dietary treatments. The levels of DHA in HFBD group were lower (p < 0.05 for both) in placenta as compared to both control and HFD groups, which were improved by omega-3 fatty acid supplementation. Conclusion: This data suggests that maternal HFD (using dairy fat) did not adversely affect pregnancy outcome. However, maternal HFBD reduced levels of placental DHA. This may have implications for reduced fetal brain growth and development.
Inhibitory actions of indomethacin on electrical and mechanical responses produced by nerve stimulation in circular smooth muscle of the guinea-pig gastric fundus.

The effects of indomethacin on electrical and mechanical responses produced by transmural nerve stimulation (TNS) were investigated in isolated circular smooth muscle of the guinea-pig gastric fundus. TNS evoked a cholinergic excitatory junction potential (e.j.p.). The e.j.p.s were inhibited by 1-10 microM indomethacin, in a concentration-dependent manner, with no marked alteration of the resting membrane potential. Exogenously applied acetylcholine caused a depolarization of the membrane that was not altered by indomethacin. TNS evoked a cholinergic twitch contraction at low frequencies (0.1 Hz). A train of TNS's at high frequency (1 Hz) produced a transient contraction with a subsequent sustained relaxation. Indomethacin reduced the resting tension and inhibited these TNS-induced contractions. Application of Nomega-nitro-L-arginine (NOLA), an inhibitor of nitric oxide (NO) synthesis, increased the amplitude of twitch contractions, and altered transient contractions to tetanic contractions during TNS at a frequency of 1 Hz, also with an increased amplitude. In the presence of NOLA, indomethacin (5 microM) again reduced the resting tension and inhibited TNS-induced contractions. This inhibition was greater for twitch contractions than for tetanic contractions. Nifedipine reduced the TNS-induced contractions, while addition of indomethacin further reduced the amplitude of contractions. Contractions produced by low concentrations of acetylcholine (0.1 microM) were inhibited by indomethacin, while those produced by 1 microM were not. These results indicate that the inhibitory actions of indomethacin on TNS-induced contractions do not involve enhanced production of NO or selective inhibition of voltage-gated Ca-channels. Prejunctional autoregulatory mechanisms may also not be altered by indomethacin. As indomethacin inhibits the enzyme cyclooxygenase, it is speculated that endogenously produced prostaglandins exert excitatory actions on gastric smooth muscle, and act mainly postjunctionally to facilitate spontaneous and neurogenic electrical and mechanical activity.
Multispectral image visualization through first-order fusion

We present a new formalism for the treatment and understanding of multispectral images and multisensor imagery based on first-order contrast information. Although little attention has been paid to the utility of multispectral contrast, we develop a theory for multispectral contrast that enables us to produce an optimal grayscale visualization of the first-order contrast of an image with an arbitrary number of bands. We demonstrate how our technique can reveal significantly more interpretive information to an image analyst, who can use it in a number of image understanding algorithms. Existing grayscale visualization strategies are reviewed. A variety of experimental results are presented to support the performance of the new method.
Crosstalk and low frequency radiation in a coupled microstrip line with a top cover

In this work we use a full-wave method to analyze the propagation characteristics of a coupled microstrip transmission line with a metallic top cover. This metallic top cover may be present in a microstrip structure due to a circuit package. We show that an even leaky mode and an improper odd mode can be excited in this structure at low frequencies. As a consequence, effects as radiation, power loss, and interference, which are usually found in microstrip transmission lines at high frequencies, appear instead in this structure at low frequencies, thus compromising the signal integrity on the line. We provide numerical results to demonstrate that signal propagation and crosstalk for this line cannot be accurately predicted by a conventional analysis based upon a quasi-TEM approximation and transmission line theory even at frequencies such that the cross section of the line is much smaller than the wavelength.
CEO Political Ideology, Shareholder Primacy and Dividend Policy

We argue that CEOs have diﬀerent attitudes toward the ﬁrm’s stakeholders and that these diﬀerences in attitudes aﬀect the ﬁrm’s decision making. We hypothesize that these diﬀerences stem from diﬀerences in political ideology: Liberal CEOs, as compared to their conservative counterparts, pay less attention to shareholders and this is reﬂected in dividend policy. To test the validity of our hypothesis, we measure CEO ideology by political donations. We study the CEOs of S&amp;P 500 ﬁrms during 1997-2014 and ﬁnd that ﬁrms with liberal CEOs are less likely to pay dividends and have signiﬁcantly lower dividend payouts. In contrast, conservative CEOs pay more dividends, even if this requires redundancies.
Dissociation Between the Blood Flow Response of Transplanted Pancreatic Islets and that of the Implantation Organ

The aim of this study was to investigate if the blood flow of transplanted islets is affected by the implantation organ or regulated by the grafted islets themselves. For this purpose adult rats were partially depancreatized and islets were isolated from the excised pancreatic tissue, maintained in tissue culture for 7 days, and subsequently 500 islets were implanted into the same animal beneath the renal capsule. Four weeks after transplantation, the rats were given an I.V. injection of either saline or furosemide (7.5 mg/kg body weight). Fifteen minutes later the blood perfusion of the whole left kidney and its islet grafts were measured separately with a microsphere technique. Also, the blood flow values of the pancreatic remnant were determined. Rats that were partially pancreatectomized and transplanted showed a decreased whole pancreatic blood flow in the pancreatic remnant after furosemide injection, whereas the blood flow to the islets was not significantly affected. Furosemide also increased the blood flow to the kidney but had no effect on the blood perfusion of the pancreatic islets grafted into the same kidney. These results suggest that the blood flow of an islet graft does not necessarily change in concert with the blood flow of the implantation organ. This may reflect differences in the blood flow regulation between the grafted islets and the implantation organ. In addition, it could be that the vascular system developing in the transplanted islets originates from either the islets or the kidney capsule, rather than from the kidney parenchyma. This may account for a different blood flow regulation.
[Risks and health problems caused by the use of video terminals].

OBJECTIVE To evaluate the association between video display terminal (VDT) use and health hazards, occupational risks, and psychosocial factors, in newspaper workers. MATERIALS AND METHODS A cross-sectional study was conducted in 1998 in a representative sample (n = 68) drawn from a population of 218 VDT operators in Mexico City. Data were collected using a self-administered questionnaire. Data were confirmed by performing physical examinations. The research hypothesis was that both the current and cumulative use of VDT are associated with visual, musculoskeletal system, and skin illnesses, as well as with fatigue and mental or psychosomatic disorders. Occupational health hazards were assessed (visual problems, postural risks, sedentary work, computer mouse use, excessive heat, and overcrowding), as well as psychosocial factors related to work organization (psychological demands, work control, and social support). Prevalence ratios were adjusted for confounding variables like age, sex and schooling. RESULTS Women were more likely than men to have upper extremity musculoskeletal disorders (MSD), dermatitis, and seborrheic eczema. VDT use was associated with neuro-visual fatigue, upper extremity MSD, dermatitis, and seborrheic eczema. Computer mouse use and postural risks were significantly associated with health problems. Psychosocial factors were mainly associated with mental problems, psychosomatic disorders, and fatigue. CONCLUSIONS Intense use of video screens has been found to cause musculoskeletal disorders of the hand. The diversification of tasks and control of labor processes itself had a protective effect against psychosomatic disorders and pathological fatigue.
cAMP-dependent Protein Kinase Phosphorylation of EVL, a Mena/VASP Relative, Regulates Its Interaction with Actin and SH3 Domains*

Proteins of the Ena/VASP family are implicated in processes that require dynamic actin remodeling such as axon guidance and platelet activation. In this work, we explored some of the pathways that likely regulate actin dynamics in part via EVL (Ena/VASP-like protein). Two isoforms, EVL and EVL-I, were highly expressed in hematopoietic cells of thymus and spleen. In CD3-activated T-cells, EVL was found in F-actin-rich patches and at the distal tips of the microspikes that formed on the activated side of the T-cells. Like the other family members, EVL localized to focal adhesions and the leading edge of lamellipodia when expressed in fibroblasts. EVL was a substrate for the cAMP-dependent protein kinase, and this phosphorylation regulated several of the interactions between EVL and its ligands. Unlike VASP, EVL nucleated actin polymerization under physiological conditions, whereas phosphorylation of both EVL and VASP decreased their nucleating activity. EVL bound directly to the Abl, Lyn, and nSrc SH3 domains; the FE65 WW domain; and profilin, likely via its proline-rich core. Binding of Abl and nSrc SH3 domains, but not profilin or other SH3 domains, was abolished by cAMP-dependent protein kinase phosphorylation of EVL. We show strong cooperative binding of two profilin dimers on the polyproline sequence of EVL. Additionally, profilin competed with the SH3 domains for binding to partially overlapping binding sites. These data suggest that the function of EVL could be modulated in a complex manner by its interactions with multiple ligands and through phosphorylation by cyclic nucleotide dependent kinases.
Reciprocal interactions between oscillatory activities of different frequencies in the subthalamic region of patients with Parkinson's disease

Synchronization of neuronal activity evident in the local field potential (LFP) recorded in the subthalamic region of patients with Parkinson's disease occurs at low frequencies (< 30 Hz) and, in some patients following treatment with levodopa, at high frequencies between 65 and 85 Hz. Here we investigate the functional relationship between these different activities by determining whether spontaneous fluctuations in their strength are correlated across time. To this end, we analysed recordings of LFPs from macroelectrodes inserted in the subthalamic area of 16 patients with Parkinson's disease, after treatment with anti‐parkinsonian medication. Time‐evolving autospectra of LFPs with significant 65–85 Hz peaks (from 21 sides) were computed and correlations between frequency components determined over time. LFP activity in the 5–32 Hz band was significantly negatively correlated with that in the 65–85 Hz band in data averaged across all 21 sides, as well as in 15 (71%) of the individual records. Negative correlations were relatively selective for interactions between these frequency bands and occurred over time epochs of as little as 40 s. They occurred about 50 min after levodopa and were recorded concurrently with contralateral levodopa‐induced dyskinesias in all but four cases. Positive correlations were not seen between activities in the 5–32 Hz and 65–85 Hz bands. The spontaneous negative correlations suggest a reciprocal relationship between population synchrony in the high‐ and low‐frequency ranges, and raise the possibility that spontaneous fluctuations in the balance between these activities may contribute to levodopa‐induced dyskinesias.