Miracle-dz/UniFAR-FTUs huggingface dataset:
Cell-free DNA Methylation and Transcriptomic Signature Prediction of Pregnancies with Adverse Outcomes

ABSTRACT Although analysis of maternal plasma cell-free content has been employed for screening of genetic abnormalities within a pregnancy, limited attention has been paid to its use for the detection of adverse pregnancy outcomes (APOs) based on placental function. Here we investigated cell-free DNA and RNA content of 102 maternal and 25 cord plasma samples. Employing a novel deconvolution methodology, we found that during the first trimester, placenta-specific DNA increased prior to the subsequent development of gestational diabetes with no change in patients with preeclampsia while decreasing with maternal obesity. Moreover, using cell-free RNA sequencing, APOs revealed 71 differentially expressed genes early in pregnancy. We noticed the upregulation of S100A8, MS4A3, and MMP8 that have been already associated with APOs but also the upregulation of BCL2L15 and the downregulation of ALPL that have never been associated with APOs. We constructed a classifier with a positive predictive ability (AUC) of 0.91 for APOs, 0.86 for preeclampsia alone and 0.64 for GDM. We conclude that placenta-specific cell-free nucleic acids during early gestation provide the possibility of predicting APOs prior to the emergence of characteristic clinical features.
Disparate Effects of Metformin on Mycobacterium tuberculosis Infection in Diabetic and Nondiabetic Mice

Comorbid type 2 diabetes poses a great challenge to the global control of tuberculosis. Here, we assessed the efficacy of metformin (MET), an antidiabetic drug, in mice infected with a very low dose of Mycobacterium tuberculosis. In contrast to diabetic mice, infected nondiabetic mice that received the same therapeutic concentration of MET presented with significantly higher disease burden. This warrants further studies to investigate the disparate efficacy of MET against tuberculosis in diabetic and nondiabetic individuals. ABSTRACT Comorbid type 2 diabetes poses a great challenge to the global control of tuberculosis. Here, we assessed the efficacy of metformin (MET), an antidiabetic drug, in mice infected with a very low dose of Mycobacterium tuberculosis. In contrast to diabetic mice, infected nondiabetic mice that received the same therapeutic concentration of MET presented with significantly higher disease burden. This warrants further studies to investigate the disparate efficacy of MET against tuberculosis in diabetic and nondiabetic individuals.
Changes in the composition of poultry farm excreta (PFE) by the cumulative influence of the age of birds, feed and climatic conditions and a simple mean for minimizing the environmental hazard

Constant growth of poultry industries impose environmental burden due to the release of numerous noxious volatiles from the Poultry Farm Excreta (PFE). Development of suitable waste management practices depend on the understanding of the factors involved particularly by the cumulative influence of the age of the birds, climatic conditions and nature of feed used. The study highlights the degree of changes in the composition of PFE due to the cumulative actions of these factors. Furthermore, the accumulation of PFE also promoted the loss of various nutrients. It is demonstrated that, in­situ drying in on­farm shadow condition itself minimize the loss of nutrients and hence the intensity of environmental hazards.
Identifying Sensitive Measures of Cognitive Decline at Different Clinical Stages of Alzheimer’s Disease

Abstract Objective: Alzheimer’s disease (AD) studies are increasingly targeting earlier (pre)clinical populations, in which the expected degree of observable cognitive decline over a certain time interval is reduced as compared to the dementia stage. Consequently, endpoints to capture early cognitive changes require refinement. We aimed to determine the sensitivity to decline of widely applied neuropsychological tests at different clinical stages of AD as outlined in the National Institute on Aging – Alzheimer’s Association (NIA-AA) research framework. Method: Amyloid-positive individuals (as determined by positron emission tomography or cerebrospinal fluid) with longitudinal neuropsychological assessments available were included from four well-defined study cohorts and subsequently classified among the NIA-AA stages. For each stage, we investigated the sensitivity to decline of 17 individual neuropsychological tests using linear mixed models. Results: 1103 participants (age = 70.54 ± 8.7, 47% female) were included: n = 120 Stage 1, n = 206 Stage 2, n = 467 Stage 3 and n = 309 Stage 4. Neuropsychological tests were differentially sensitive to decline across stages. For example, Category Fluency captured significant 1-year decline as early as Stage 1 (β = −.58, p < .001). Word List Delayed Recall (β = −.22, p < .05) and Trail Making Test (β = 6.2, p < .05) became sensitive to 1-year decline in Stage 2, whereas the Mini-Mental State Examination did not capture 1-year decline until Stage 3 (β = −1.13, p < .001) and 4 (β = −2.23, p < .001). Conclusions: We demonstrated that commonly used neuropsychological tests differ in their ability to capture decline depending on clinical stage within the AD continuum (preclinical to dementia). This implies that stage-specific cognitive endpoints are needed to accurately assess disease progression and increase the chance of successful treatment evaluation in AD.
Nanosponges Encapsulated Phytochemicals for Targeting Cancer: A Review.

Cancer is the most ruinous disease globally. Natural products have impressive characteristics, such as excep-tional chemical versatility, chemical and biological properties of macromolecular specificity and less toxicity which make them good leads in finding novel drugs. The phytochemicals not only help to prevent but also treat chronic cancerous conditions. The present review attempts to put forth some selected anticancer phytochemicals that had reported omics char-acteristic and specifically suppressed cancer with in vitro and in vivo activity. Certain issues pertaining to anticancer phy-tochemicals like delivery to target site in the body and achieving controlled release in order to prevent overdoses havelong been a concern for medical researchers worldwide. The most conventional chemotherapy protocols for the treatment of cancer lead to adverse effects that limit biological efficacy and compromise patient outcomes. In order to defeat incompe-tency of current and upcoming natural anticancer agents and to attain targeted drug delivery with good efficacy and fewer side effects, there is a special focus on novel nanostructured particles and nano approaches consisting of carrier system. Recent studies have led to the discovery of mesoporous and nanoporous drug delivery mechanisms, such as inorganic or organic-based nanosponges. The metal based inorganic systems have exhibited toxicity and non-biodegradable character in vivo. As a result of problems related to inorganic systems, major shift of research from inorganic to organic nanosystems has occurred. About decades ago, researchers have developed organic nanosponges to control the limitation of drug delivery and cancer therapies. This review article discusses the development and application of nanosponges encapsulated phyto-chemicals for cancer therapy.
RANDOM LOSS OF X CHROMOSOME AT MALE DETERMINATION IN AN APHID, SITOBION NEAR FRAGARIAE, DETECTED USING AN X-LINKED POLYMORPHIC MICROSATELLITE MARKER

This paper reports the first direct molecular evidence that X chromosome loss during determination of male aphids (XO) is random. Clonal and sexual females, and males, of the species Sitobion near fragariae were screened using three polymorphic microsatellite loci. Two loci, Sm10 and Sm17, showed the same heterozygous genotypes in all three aphid morphs. The third, Sm11, was heterozygous for the same two alleles in clonal and sexual females, but of the 25 males screened 11 showed the ‘160’ allele and 14 showed the ‘156’ allele. This result indicates X-linkage of locus Sm11, with random loss of the X chromosome during the formation of male embryos. The possible implications of this result are discussed with respect to aphid sex determination, recombination and chromosome evolution.
Physiologische und anatomische Korrelate einer Lärmschwerhörigkeit in subcortikalen Strukturen des zentralen auditorischen Systems in der Maus (Mus musculus)

neurodegenerative Prozesse bedingt sein. Summary In the present study, noise-induced physiological and anatomical changes in subcortical structures of the central auditory system were investigated at different posttraumatic stages. Thus, it should be distinguished between acute (TTS group) and long-term (PTS group) effects of noise damage. Normal hearing mice were exposed to a band noise (5-20 kHz) for 3 hours at 115 dB SPL. Auditory brainstem responses were measured to determine the produced hearing loss. A significant threshold shift was detectable in the TTS as well as in the PTS group. This effect was greater in TTS animals. To investigate central changes, neuronal spontaneous activities were recorded from single units in brain slices. Further, cell densities were determined by histological techniques. In addition, calcium dependent activity was measured using manganese enhanced MRI. Investigations were carried out in central auditory structures of the cochlear nucleus (CN), the inferior colliculus (IC) and the medial geniculate body (MGB). The results demonstrate a difference in acute and long-term effects of noise exposure. In the TTS group, only the CN in the brainstem was affected, indicating a direct noise impact leading to acute excitotoxicity. In the PTS group, physiological and anatomical changes could also be observed in higher structures of the auditory pathway. The effects can be related to long-lasting noise damage as well as neural plasticity caused by deprivation of auditory input. The results show a dramatic cell loss within the investigated structures. Further, there is an increase in calcium dependent activity in several auditory brain regions which can be caused by changes in neuronal activity patterns, neuroplasticity and neurodegenerative processes.
ANÁLISIS DE SECUENCIAS DE GENES DE Coffea arabica VAR. CATURRA

Currently at Cenicafe molecular studies of coffee Coffea arabica are being carried out with the purpose of identifying genes of agronomic importance. In this work, cDNA libraries of three different tissues (leaf, flower and fruit) from C. arabica var. Caturra were developed with the objective of obtaining data about the genes expressed in these tissues. A total of 1,824 unique transcripts (unigenes) was obtained out of the 3,029 sequences analyzed for the three cDNA libraries, 60% of them showed similarity with sequences reported for C. canephora. The analysis of the identified clones showed a broad diversity of genes involved in different metabolic functions. The main categories include proteins involved in cell organization and biogenesis, metabolism, protein synthesis, transport, transcription, signal transduction and response to pathogens or pests. These results agree with some studies made in tomato and Arabidopsis and can represent a general tendency in plants. Transcripts involved in response to pathogens, plagues and abiotic stress could be used in laboratory tests to confirm their function and to determine their potential use in coffee genetic improvement programs.
A role for Fibroblast Growth Factor Receptor 1 in the pathogenesis of Neisseria meningitidis

Neisseria meningitidis remains an important cause of human disease. It is highly adapted to the human host – its only known reservoir. Adaptations to the host environment include many specific interactions with human molecules including iron-binding proteins, components of the innate and adaptive immune systems, and cell surface receptors such as the Epidermal Growth Factor Receptor (EGFR). Interaction of the meningococcus with EGFR has been elucidated in some detail and leads to intracellular signalling and cytoskeletal changes contributing to the pathogenesis of the organism. Here, we show that the meningococcus also recruits Fibroblast Growth Factor Receptor 1 (FGFR1) onto the surface of human blood microvascular epithelial cells (HBMECs). Furthermore, meningococci internalised into these cells recruit the activated form of this receptor, and that expression and activation of FGFR1 is necessary for efficient internalisation of meningococci into HBMECs. We show that Neisseria meningitidis interacts specifically with the IIIc isoform of FGFR1.
Material and regenerative properties of an osteon-mimetic cortical bone-like scaffold

Abstract The objective of this work was to fabricate a rigid, resorbable and osteoconductive scaffold by mimicking the hierarchical structure of the cortical bone. Aligned peptide-functionalize nanofiber microsheets were generated with calcium phosphate (CaP) content similar to that of the natural cortical bone. Next, the CaP-rich fibrous microsheets were wrapped around a microneedle to form a laminated microtube mimicking the structure of an osteon. Then, a set of the osteon-mimetic microtubes were assembled around a solid rod and the assembly was annealed to fuse the microtubes and form a shell. Next, an array of circular microholes were drilled on the outer surface of the shell to generate a cortical bone-like scaffold with an interconnected network of Haversian- and Volkmann-like microcanals. The CaP content, porosity and density of the bone-mimetic microsheets were 240 wt%, 8% and 1.9 g/ml, respectively, which were close to that of natural cortical bone. The interconnected network of microcanals in the fused microtubes increased permeability of a model protein in the scaffold. The cortical scaffold induced osteogenesis and vasculogenesis in the absence of bone morphogenetic proteins upon seeding with human mesenchymal stem cells and endothelial colony-forming cells. The localized and timed-release of morphogenetic factors significantly increased the extent of osteogenic and vasculogenic differentiation of human mesenchymal stem cells and endothelial colony-forming cells in the cortical scaffold. The cortical bone-mimetic nature of the cellular construct provided balanced rigidity, resorption rate, osteoconductivity and nutrient diffusivity to support vascularization and osteogenesis.
Níveis de anticorpos anti- Babesia bigemina e Babesia bovis , em bezerros da raça Nelore, Ibagé e cruzamentos de Nelore

Foram analisados pela tecnica de anticorpos fluorescentes, os soros dos bezerros da raca Nelore, Ibage e cruzamentos de Nelore x Fleckvieh, Nelore x Chianina e Nelore x Charoles, do nascimento ao desmame, com a finalidade de determinar os niveis de imunoglobulinas anti-Babesia bigemina e Babesia bovis . No periodo de tres a quatorze dias de vida, foi observada correlacao positiva e significante entre os niveis de imunoglobulinas circulantes das vacas e os anticorpos sericos dos bezerros contra B. bigemina e/ou B. bovis , em algumas racas e cruzamentos. A media do titulo sorologico dos grupos experimentais apresentou um decrescimo nos niveis de anticorpos colostrais entre 28 e 56 dias de idade contra B. bigemina e entre 56 e 84 dias anti - B. bovis . A producao ativa de anticorpos contra B. bigemina foi observada aos 84 dias e aos 112 contra B. bovis . Em geral, os niveis de anticorpos contra B. bigemina foram mais elevados que o da B. bovis e houve maior semelhanca na curva de anticorpos dos bezerros da raca Nelore e seus cruzamentos que os da raca lbage. Embora a regiao seja considerada area de estabilidade enzootica, conclui-se que existe um periodo critico de baixa resistencia humoral, no qual podem ocorrer casos clinicos de babesiose.
Chemogenetic Manipulation of Dopamine Neurons Dictates Cocaine Potency at Distal Dopamine Transporters

The reinforcing efficacy of cocaine is largely determined by its capacity to inhibit the dopamine transporter (DAT), and emerging evidence suggests that differences in cocaine potency are linked to several symptoms of cocaine use disorder. Despite this evidence, the neural processes that govern cocaine potency in vivo remain unclear. In male rats, we used chemogenetics with intra-VTA microinfusions of the agonist clozapine-n-oxide to bidirectionally modulate dopamine neurons. Using ex vivo fast scan cyclic voltammetry, pharmacological probes of the DAT, biochemical assessments of DAT membrane availability and phosphorylation, and cocaine self-administration, we tested the effects of chemogenetic manipulations on cocaine potency at distal DATs in the nucleus accumbens as well as the behavioral economics of cocaine self-administration. We discovered that chemogenetic manipulation of dopamine neurons produced rapid, bidirectional modulation of cocaine potency at DATs in the nucleus accumbens. We then provided evidence that changes in cocaine potency are associated with alterations in DAT affinity for cocaine and demonstrated that this change in affinity coincides with DAT conformation biases and changes in DAT phosphorylation state. Finally, we showed that chemogenetic manipulation of dopamine neurons alters cocaine consumption in a manner consistent with changes in cocaine potency at distal DATs. Based on the spatial and temporal constraints inherent to our experimental design, we posit that changes in cocaine potency are driven by alterations in dopamine neuron activity. When considered together, these observations provide a novel mechanism through which GPCRs regulate cocaine's pharmacological and behavioral effects. SIGNIFICANCE STATEMENT Differences in the pharmacological effects of cocaine are believed to influence the development and progression of cocaine use disorder. However, the biological and physiological processes that determine sensitivity to cocaine remain unclear. In this work, we use a combination of chemogenetics, fast scan cyclic voltammetry, pharmacology, biochemistry, and cocaine self-administration with economic demand analysis to demonstrate a novel mechanism by which cocaine potency is determined in vivo. These studies identify a novel process by which the pharmacodynamics of cocaine are derived in vivo, and thus this work has widespread implications for understanding the mechanisms that regulate cocaine consumption across stages of addiction.
Conceptual and historical evolution of psychiatric nosology

Abstract Psychiatric taxonomies exist within conceptual frameworks which presuppose certain conceptions of psychiatric distress and offer guiding principles. This article provides an overview of the historical development of psychiatric classifications with an emphasis on their methodological assumptions. After identifying roots of scientific psychiatric classifications in the works of Sydenham and Linnaeus and discussing early classification systems, our survey focuses on the Kahlbaum-Hecker-Kraepelin paradigm (with its emphasis on longitudinal course of illness), the Wernicke-Kleist-Leonhard tradition (with its emphasis on neural systems), the development of the ICD and the DSM classifications (with their roots in medical statistics, their pragmatic nature, and their emphasis on descriptive and operationalized criteria), psychodynamic and idiographic perspectives (e.g. the Psychodynamic Diagnostic Manual), and transdiagnostic approaches (e.g. Research Domain Criteria). The central philosophical questions of nosology (descriptive vs aetiological, symptoms vs course of illness, idiographic vs nomothetic, categorical vs dimensional, etc.) have appeared and reappeared throughout this evolution. Ongoing controversies reflect the epistemological and ontological difficulties inherent in defining and classifying mental illness. It may be that no single taxonomy can satisfy all clinical, research, and administrative needs, and that, echoing the ideas of Aubrey Lewis, multiple systems may be required to serve different needs.
Testicular Growth and Comb and Wattles Development in Three Italian Chicken Genotypes Reared Under Free-Range Conditions

Male chickens belonging to three Italian purebreds – Ermellinata di Rovigo (ER), Robusta lionata (RL) and Robusta maculata (RM) – were studied. All the birds were reared under the same rearing conditions (from May until autumn). Chickens were reared under infra-red lamps from birth until 4 weeks of age with a 24L:0D photoperiod. Then they were kept outdoor: the photoperiod changed according to the season (from 16L:8D to 12L:12D). At 138 and 168 days of age 20 birds/breed were weighed and then slaughtered. Testicular samples were collected, after evisceration, processed and embedded in paraffine wax. Sections were stained for morphological observations, observed with light microscope, and then classified according to the testis maturation stage. Ermellinata di Rovigo chickens showed the lowest (P<0.01) body weight and the highest (P<0.01) testes weight; testes maturity was higher (P<0.01) in ER than in RL, whereas RM was intermediate. For each genotype testes weight and testes maturity did not significantly differ with aging. Correlations between testes weight and body, comb, and wattles weight, according to the breed, were calculated at 168 days of age. For ER no significant correlation was found, whereas RL showed a significant (P<0.01) positive relationship between testes weight and body weight, and sexual secondary characters. Robusta maculata showed a significant correlation between testes weight and comb (P<0.01) and wattles weight (P<0.10). Our results suggest that under the studied environmental conditions ER showed the highest testes development according to its more precocious achievement of adult body weight, whereas RL was the least precocious purebred.
Biocompatibility and corrosion resistance of metallic biomaterials

Abstract Biomaterials play a significant role in revolutionizing human life in terms of implants and medical devices. These materials essentially need to be highly biocompatible and inert to the human physiological conditions. This paper provides an in-depth, critical and analytical review on the previous research work and studies conducted in the field of metals and alloys used as implant materials including stainless steel, titanium and its alloys, cobalt chromium and others. Since the manufacturing of medical implants relies on selected grades of biomaterials, metals play a significant role in biomaterials market. This paper focuses on highlighting some basic principles of manufacturing implant materials underlying composition, structure and properties of these materials. Finally, attention is also given to the role of these implant materials on the betterment of human life in terms of their failures by critically analysing these materials.