Miracle-dz/UniFAR-FTUs huggingface dataset:
Hoxa 5 : A Key Player in Development and Disease

A critical position in the developmental hierarchy is occupied by the Hox genes, which encode transcription factors. Hox genes are crucial in specifying regional identity along the embryonic axes and in regulating morphogenesis. In mouse, targeted mutations of Hox genes cause skeletal transformations and organ defects that can impair viability. Here, we present the current knowledge about the Hoxa5 gene, a paradigm for the function and the regulation of Hox genes. The phenotypic survey of Hoxa5 ́/ ́ mice has unveiled its critical role in the regional specification of the skeleton and in organogenesis. Most Hoxa5 ́/ ́ mice die at birth from respiratory distress due to tracheal and lung dysmorphogenesis and impaired diaphragm innervation. The severity of the phenotype establishes that Hoxa5 plays a predominant role in lung organogenesis versus other Hox genes. Hoxa5 also governs digestive tract morphogenesis, thyroid and mammary glands development, and ovary homeostasis. Deregulated Hoxa5 expression is reported in cancers, indicating Hoxa5 involvement in tumor predisposition and progression. The dynamic Hoxa5 expression profile is under the transcriptional control of multiple cis-acting sequences and trans-acting regulators. It is also modulated by epigenetic mechanisms, implicating chromatin modifications and microRNAs. Finally, lncRNAs originating from alternative splicing and distal promoters encompass the Hoxa5 locus.
Acetylcholine and Alzheimer's Disease

The hypothesis that cognitive impairment in Alzheimer's disease is related to cholinergic degeneration in the brain is still, a decade after its formulation, subject to critical evaluation. In marked contrast to the monoamine hypotheses of affective disorders or schizophrenia – based primarily on the mechanisms of action of therapeutic drugs, and yet lacking convincing pathological data on the human brain itself – the cholinergic hypothesis of Alzheimer's disease currently rests largely on evidence of neurochemical pathology in affected tissue, but still depends on effective therapy for its ultimate validation. The urgent need for a means of countering cognitive impairment in degenerative dementias such as Alzheimer's disease (probably the most important cause of intellectual decline in old age) hardly needs emphasising. In this annotation, a number of key questions specifically relating to the cholinergic involvement in Alzheimer's disease are considered. These questions are already being answered both within and, as so often in the history of biological psychiatry, outside the immediate area of investigation.
Synaptic vesicle exocytosis-endocytosis at central synapses

At nerve terminals, neurotransmitter release is mediated by exocytosis of synaptic vesicles at active zone. After exocytosis, vesicular components are efficiently retrieved by endocytosis. Tight coupling between synaptic vesicle exocytosis and endocytosis is critical for the maintenance of neurotransmission at central synapses. Recently, we have developed a new fluorescent pH reporter that permits us to examine exocytosis-endocytosis coupling at the level of individual synaptic vesicles at hippocampal synapses.1 To our surprise, we observed that the tight coupling of exocytosis and endocytosis broke down at very low stimulation frequencies, resulting in the generation of two endocytic vesicles per single exocytic fusion event. As stimulation frequency increased, exocytosis-endocytic coupling was restored with one endocytic vesicle generated for each vesicle exocytosed. Further studies revealed that the dissimilar patterns of exocytosis-endocytic coupling at different stimulation frequencies were mediated by two pathways of endocytosis that are orchestrated during differential patterns of neuronal activity.1 Here, we summarize our observations and further discuss their possible implications.
Recognition of CpG Island Chromatin by KDM2A Requires Direct and Specific Interaction with Linker DNA

ABSTRACT Up to 70% of human genes are associated with regions of nonmethylated DNA called CpG islands (S. Saxonov, P. Berg, and D. L. Brutlag, Proc. Natl. Acad. Sci. U. S. A. 103:1412–1417, 2006). Usually associated with the 5′ end of genes, CpG islands are thought to impact gene expression. We previously demonstrated that the histone demethylase KDM2A is specifically recruited to CpG islands to define a unique chromatin architecture and highlight gene regulatory regions in large and complex mammalian genomes. This targeting relies on a zinc finger CXXC DNA binding domain (ZF-CXXC), but how this demethylase interfaces with CpG island chromatin in vivo remains unknown. Here we demonstrate, using defined chromatin templates in vitro and chromatin profiling in vivo, that nucleosomes are a major barrier to KDM2A binding and that CpG islands are directly interpreted by the ZF-CXXC domain through specific interaction with linker DNA. Furthermore, KDM2A appears to be constrained to CpG islands not only by their nonmethylated state but also by a combination of methylated DNA and nucleosome occlusion elsewhere in the genome. Our observations suggest that both DNA sequence and chromatin structure are defining factors in interpreting CpG island chromatin and translation of the CpG signal. More generally, these features of CpG island recognition suggest that chromatin structure and accessibility play a major role in defining how transcription factors recognize DNA and regulatory elements genome-wide.
A New Suction Device for Microsurgery

A new suction device for microsurgical procedures is presented. This device is made of soft, compliant PVC, which enables all fluids to be evacuated from the surgical field without damaging the surrounding soft tissue. The device is designed with front and radial ports that allow placement onto the blood vessel or nerve while the anastomosis is being performed. There is a tapered end providing the surgeon with fine control of the suction. Unlike other bulky suction devices, this one readily fits into the operative field without inhibiting operative procedures. It also readily fits varying sizes of conventional Frazier-type tips. The device has been used in over 100 microsurgical procedures and it has served well.
Modification of the Ferret Model for Pneumonia From Seasonal Human Influenza A Virus Infection

The primary complication of seasonal influenza in humans is viral pneumonia. A conventional animal model—intranasal inoculation of ferrets with 106 median tissue culture infectious dose of virus—results in disease that is neither consistent nor comparable with severe viral pneumonia in humans. Therefore, the authors modified the experimental procedures by increasing the median tissue culture infectious dose to 109 and by inoculating via the intratracheal route, testing these procedures with H1N1 strains (A/Bilthoven/3075/1978 and A/Netherlands/26/2007) and H3N2 strains (A/Bilthoven/16190/1968 and A/Netherlands/177/2008) of seasonal influenza virus. The ferrets of all groups (n = 3 per virus strain) had clinical signs, increased body temperature, virus excretion from day 1, loss of body weight, and increased relative lung weight at 4 days postinoculation. All ferrets had severe pulmonary consolidation, and histologic examination revealed moderate to severe necrotizing bronchointerstitial pneumonia with severe edema, necrosis of alveolar epithelium, inflammatory infiltrates in alveolar septa and lumina, epithelial regeneration, and perivascular and peribronchiolar inflammatory infiltrates. The lesions were associated with the presence of influenza virus antigen in respiratory epithelium by immunohistochemistry. Although all 4 virus strains caused pulmonary lesions of comparable severity, virus isolation in the lungs, trachea, nasal concha, and tonsils showed higher mean virus titers in the H1/07 and H3/68 groups than in the H1/78 and H3/08 groups. In conclusion, the above H1N1 and H3N2 strains cause severe pneumonia in ferrets by use of the modified experimental procedures and provide a good model for pneumonia caused by seasonal influenza A virus infection in humans.
A Framework for Robot Programming in Cobotic Environments: First User Experiments

The increasing presence of robots in industries has not gone unnoticed. Large industrial players have incorporated them into their production lines, but smaller companies hesitate due to high initial costs and the lack of programming expertise. In this work we introduce a framework that combines two disciplines, Programming by Demonstration and Automated Planning, to allow users without any programming knowledge to program a robot. The user teaches the robot atomic actions together with their semantic meaning and represents them in terms of preconditions and effects. Using these atomic actions the robot can generate action sequences autonomously to reach any goal given by the user. We evaluated the usability of our framework in terms of user experiments with a Baxter Research Robot and showed that it is well-adapted to users without any programming experience.
Influence of ambient air pollutant sources on clinical encounters for infant bronchiolitis.

RATIONALE Data regarding the influence of ambient air pollution on infant bronchiolitis are few. OBJECTIVES We evaluated the impact of several air pollutants and their sources on infant bronchiolitis. METHODS Infants in the Georgia Air Basin of British Columbia with an inpatient or outpatient clinical encounter for bronchiolitis (n = 11,675) were matched on day of birth to as many as 10 control subjects. Exposure to particulate matter with a diameter of 2.5 mum or less (PM(2.5)), PM(10), NO(2)/NO, SO(2), CO, and O(3) were assessed on the basis of a regional monitoring network. Traffic exposure was assessed using regionally developed land use regression (LUR) models of NO(2), NO, PM(2.5), and black carbon as well as proximity to highways. Exposure to wood smoke and industrial emissions was also evaluated. Risk estimates were derived using conditional logistic regression and adjusted for infant sex and First Nations (Canadian government term for recognized aboriginal groups) status and for maternal education, age, income-level, parity, smoking during pregnancy, and initiation of breastfeeding. MEASUREMENTS AND MAIN RESULTS An interquartile increase in lifetime exposure to NO(2), NO, SO(2), CO, wood-smoke exposure days, and point source emissions score was associated with increased risk of bronchiolitis (e.g., adjusted odds ratio [OR(adj)] NO(2), 95% confidence interval [CI], 1.12, 1.09-1.16; OR(adj) wood smoke, 95% CI, 1.08, 1.04-1.11). Infants who lived within 50 meters of a major highway had a 6% higher risk (1.06, 0.97-1.17). No adverse effect of increased exposure to PM(10), PM(2.5), or black carbon, was observed. Ozone exposure was negatively correlated with the other pollutants and negatively associated with the risk of bronchiolitis. CONCLUSIONS Air pollutants from several sources may increase infant bronchiolitis requiring clinical care. Traffic, local point source emissions, and wood smoke may contribute to this disease.
Microthrombocytosis and Platelet Fragmentation Associated with Idiopathic/Autoimmune Thrombocytopenic Purpura

Platelet volume distribution curves were obtained in 20 control subjects and in 21 patients with idiopathic/autoimmune thrombocytopenic purpura. A striking increase in microthrombocytes as well as megathrombocytes was noted in 86% of patients on one or more occasions, particularly in the presence of severe thrombocytopenia. The entire spectrum of platelet volume distribution curves noted in patients could be reproduced experimentally in rabbits following intravenous injection of anti‐platelet antibody. Differential centrifugation studies with control subjects revealed that microthrombocytes were light platelets and megathrombocytes were heavy platelets. Electron microscopy in patients with thrombocytopenia revealed that microthrombocytes were composed of intact small platelets as well as platelet fragments. It is concluded that severe peripheral destruction of platelets is associated with an increase in microthrombocytes as well as megathrombocytes.
Concavity Approximation Based Power Allocation in Millimeter-Wave MIMO Systems

This paper investigates the power allocation in millimeter-wave multiple-input multiple-output systems. The asymptotic concavity of the sum rate of the system is utilized to form the proposed power allocation approach. In contrast to the traditional approaches, the proposed approach utilizes a channel asymptotic orthogonality-based approximation which is more suitable, thus achieves higher spectral efficiency. The analysis demonstrates that the sum rate of the system increases as the number of antennas increases. Numerical results verify the analysis and show that the proposed approach can perform better than those traditional approaches.
Human growth, nutrition, and health status in Sub-Saharan Africa.

Sub-Saharan Africa (SSA) has the greatest population growth rates, the highest levels of infant and child mortality, and the poorest economies in the world. The physical quality of life index for developed countries is 80, yet for 33 SSA countries it ranges from 20.5-66. Routine monitoring of growth and nutritional status of children demonstrates their health status. The proportion of low birth weight infants is high in SSA with most countries having levels 10-20% . Further even though average birth weight consistently rose during the 1980s in SSA, the range of smallest to largest mean birth weights is lower than the medians for developed counties. Moreover 40% of 5 year olds are mild or moderately malnourished as evidenced by growth retardation and some biochemical changes, yet they exhibit or clinical signs and symptoms. Besides diarrhea often exacerbates malnutrition. Through childhood and adolescence, growth patterns (particularly among the rural Turkana pastoralists) steadily deviate from the 50th centile of US norms. Thus almost 50% of early adolescents in rural areas are below the 5th centile. Studies have found that pastoralist children tend to begin being slightly above the 5th centile of US norms and gradually fall below it. Further peak growth velocities among SSA children are low, but postpeak velocities are higher than equal velocities for children in developed countries. Thus adult heights are only between the 5th-50th centiles. Throughout childhood and adolescence, US Blacks have higher absolute levels of subcutaneous fat than children in SSA. Yet the main centralized patterning of fat in SSA children basically equals that of US Blacks, but invariably less marginal than in Whites. In conclusion, adverse socioeconomic conditions in SSA result in low levels of health at all growth phases thereby confounding their genetic potential.
Multi –omics and metabolic modelling pipelines: challenges and tools for systems microbiology

Integrated -omics approaches are quickly spreading across microbiology research labs, leading to i) the possibility of detecting previously hidden features of microbial cells like multi-scale spatial organisation and ii) tracing molecular components across multiple cellular functional states. This promises to reduce the knowledge gap between genotype and phenotype and poses new challenges for computational microbiologists. We underline how the capability to unravel the complexity of microbial life will strongly depend on the integration of the huge and diverse amount of information that can be derived today from - omics experiments. In this work, we present opportunities and challenges of multi –omics data integration in current systems biology pipelines. We here discuss which layers of biological information are important for biotechnological and clinical purposes, with a special focus on bacterial metabolism and modelling procedures. A general review of the most recent computational tools for performing large-scale datasets integration is also presented, together with a possible framework to guide the design of systems biology experiments by microbiologists.
Virologic and Immunologic Events in Hilar Lymph Nodes During Simian Immunodeficiency Virus Infection Development of Polarized Inflammation

Lymphoid tissues are sites of soluble and cell-associated antigen sampling of peripheral tissues, and they are key compartments for the generation of cellular and humoral immune responses. Hilar lymph nodes (HiLNs), which drain the lungs, were examined to understand the effects of simian immunodeficiency virus (SIV) infection on this compartment of the immune system. Histologic and messenger RNA (mRNA) expression profiling approaches were used to determine the numbers, types, and distributions of SIV viral RNA cells and to identify differentially expressed genes in HiLNs during SIV infection. SIV RNA cells were found to be primarily CD68 and localized to paracortical and medullary regions early in infection, whereas they resided mainly in paracortex during AIDS. As SIV infection progressed, CXCL9, CXCL10, interferon-g, and Toll-like receptor 3 levels all increased. In contrast, CCL19 increased early in infection but decreased during AIDS, whereas CCL21 decreased progressively throughout infection. Finally, local levels of cellular activation were increased throughout infection. Taken together, these findings indicate that SIV infection leads to an inflammatory environment in lung-draining lymph nodes that is characterized by type 1 cytokines and chemokines and likely has an impact on the nature and strength of immune responses to pulmonary pathogens.
Self-interaction correction in multiple scattering theory

We propose a simplified version of self-interaction corrected local spin-density (SIC-LSD) approximation, based on multiple scattering theory, which implements self-interaction correction locally, within the KKR method. The multiple scattering aspect of this new SIC-LSD method allows for the description of crystal potentials which vary from site to site in a random fashion and the calculation of physical quantities averaged over ensembles of such potentials using the coherent potential approximation (CPA). This facilitates applications of the SIC to alloys and pseudoalloys which could describe disordered local moment systems, as well as intermediate valences. As a demonstration of the method, we study the well-known $\alpha$-$\gamma$ phase transition in Ce, where we also explain how SIC operates in terms of multiple scattering theory.
Dermoscopy as an auxiliary tool in the differentiation of the main types of erythroderma due to dermatological disorders

Dermoscopy as an auxiliary tool in the differentiation of the main types of erythroderma due to dermatological disorders Most cases of erythroderma are due to inflammatory and lymphoproliferative skin disorders, mainly including psoriasis, eczematous diseases, pityriasis rubra pilaris, and mycosis fungoides. Even though the clinical history or presence of specific cutaneous/nail lesions may be useful in assisting the differential diagnosis of erythrodermas caused by the aforementioned dermatoses, their distinction is often challenging for both dermatologists and pathologists. We here report the dermoscopic pattern of four instances of chronic erythroderma in patients with a definitive diagnosis of the above-mentioned dermatological conditions (dermoscopy was always carried out with DermLite DL3; 3Gen, San Juan Capistrano, CA, USA). Case 1 (erythroderma due to psoriasis; Fig. 1a) has a monomorphous pattern with diffusely distributed whitish scales and regularly arranged dotted vessels on a fairly homogeneous reddish background (Fig. 2a). Case 2 (erythroderma due to atopic dermatitis; Fig. 1b) has yellowish scales/serocrusts, sparse whitish scales, and patchily distributed dotted vessels on a pinkish background (Fig. 2b). Case 3 (erythroderma due to mycosis fungoides; Fig. 1c) has a monomorphous aspect consisting of sparse whitish scales ass.ociated with widespread dotted vessels and some peculiar
Serum tryptase correlates with the KIT D816V mutation burden in adults with indolent systemic mastocytosis

Systemic mastocytosis (SM) is characterized by the growth of neoplastic mast cells (MCs). Most adults with indolent SM carry the KIT D816V mutation. We recently introduced the D816V+ allele fraction as a disease marker in SM using a sensitive and quantitative KIT D816V mutation analysis that consistently allows mutation detection in peripheral blood (PB) and bone marrow (BM). The D816V+ allele fraction represents a quantitative measure which allows KIT D816V‐positivity to be analyzed as a continuous variable instead of a categorical variable (negative/positive) as previously described. Serum tryptase represents an established disease marker in SM, and it remains to be tested whether tryptase and the D816V+ allele fraction are associated or represent independent disease markers. In this study, correlation analysis between serum tryptase, the D816V+ allele fraction in PB and BM, and the MC fraction was performed in 57 indolent systemic mastocytosis (ISM) patients. We detected significant correlations between the D816V+ allele fraction, the mature neoplastic MC fraction, and serum tryptase which represent three different biological measures of disease burden. Mutation analysis was performed in two or more PB samples in 39 patients, and the results demonstrated high stability with no overall tendency to increasing D816V+ allele fractions over time. Considerable variation was nevertheless observed in the correlation analyses. Serum tryptase reflects the mature MC load, whereas the D816V+ allele fraction includes cells other than mature MCs to a variable extent. We conclude that tryptase and the D816V+ allele fraction represent different, although correlated, measures of disease status in SM.
Coronal sealing ability of a new root canal filling material.

BACKGROUND AND OBJECTIVE To date, many different materials have been proposed for root canal fillings, but gutta-percha (used with various types of sealers) has remained the material of choice for over a century. A new root canal obturation system, the Epiphany endodontic obturation system, has been developed to replace gutta-percha and traditional sealers for root canal obturation. The purpose of this study was to evaluate the coronal sealing ability of the new endodontic obturation system. MATERIALS AND METHODS Seventy-two maxillary and mandibular single-rooted human teeth extracted for periodontal reasons were used. The root canals were instrumented using the step-back technique and were irrigated with 5.25% sodium hypochlorite. The smear layer was removed by washing in 10 mL of 17% ethylenediamine tetra-acetic acid (EDTA). The specimens were randomly divided into 3 groups (group 1 to be filled with gutta-percha and AH 26 sealer, group 2 with gutta-percha and AH plus sealer, and group 3 with Epiphany self-etch sealer and Resilon obturating material) and obturated by lateral condensation. Teeth were centrifuged at 30 g for 5 minutes in 2% methylene blue dye solution to allow evaluation of any coronal leakage. The tooth roots were longitudinally grooved with a diamond disk and split with a chisel. Dye penetration was measured from the coronal to the apical part of the root canal using a stereomicroscope with ocular micrometer, and the mean leakage value for each group was calculated and recorded. RESULTS The 6 positive control specimens had total dye penetration of the root canal system, whereas the 6 negative control teeth had no dye penetration into the roots. All of the experimental groups demonstrated some degree of coronal leakage. Coronal leakage was greatest in the teeth filled with gutta-percha and AH 26 sealer and least in teeth treated with Epiphany sealer and Resilon core material. These differences in coronal leakage were statistically significant (p < 0.05). CONCLUSION All of the root canal filling materials tested in this evaluation yielded a satisfactory seal; however, the Epiphany root canal filling system exhibited the least coronal leakage.