Miracle-dz/UniFAR-FTUs huggingface dataset:
Early Onset of Puberty: Tracking Genetic and Environmental Factors

Under physiological conditions, factors affecting the genetic control of hypothalamic functions are predominant in determining the individual variations in timing of pubertal onset. In pathological conditions, however, these variations can involve different genetic susceptibility and the interaction of environmental factors. The high incidence of precocious puberty in foreign children migrating to Belgium and the detection in their plasma of a long-lasting 1,1,1-trichloro-2,2-bis(4-chlorophenyl) ethane (DDT) residue suggest the potential role of environmental endocrine disrupting chemicals in the early onset of puberty. This hypothesis was confirmed by experimental data showing that temporary exposure of immature female rats to DDT in vivo results in early onset of puberty. We compared the gene expression profile of hypothalamic hamartoma associated or not with precocious puberty in order to identify gene networks responsible for both hamartoma-dependent sexual precocity and the onset of normal human puberty. In conclusion, pathological variations in the timing of puberty may provide unique information about the interactions of either environmental conditions or genetic susceptibility with the hypothalamic mechanism controlling the onset of sexual maturation, as shown by examples of precocious puberty following exposure to endocrine disrupters or due to hypothalamic hamartoma.
Description of Study Population and Analysis of Factors Influencing Adherence in the Observational Italian Study “Evaluation of Pharmacotherapy Adherence in Bipolar Disorder” (EPHAR)

Background: In patients with bipolar disorder, medication is effective in preventing relapses. Unfortunately, adherence to treatment in bipolar disorder, as in other chronic or recurrent conditions, is not optimal. Estimates of nonadherence to prescribed treatment range from 30% to 60% in epidemiological studies, and are at around 30% in clinical trials. Adherence to treatment is a potent predictor of effectiveness, both in clinical trials and cohort studies, therefore is a very relevant area of investigation. This study will try to show a picture of the real life care where adherence is influenced by a wide range of variables. Methods: Prospective, observational, multicenter study in 650 adult patients with bipolar disorder, who had to initiate or change their treatment regimen, observed for 1 year. Adherence was measured by the Simplified Medication Adherence Questionnaire (SMAQ). Additional variables: Symptom severity, Montgomery‐Åsberg Depression Rating Scale (MADRS), Young Mania Rating Scale (YMRS), Clinical Global Impression–Bipolar Disorder (CGI‐BD), the Drug Attitude Inventory score (DAI‐30), and quality of life (EuroQoL 5 Dimensions). The variables were recorded every 3 months for the next year. Results: Most subjects were out‐patients (77.1%), female (58.8%), aged 31–50 years (50.1%) and overweight (41.8%) or obese (28.7%); 67.4% had type I bipolar disorder and 66.8% had depressive or mixed symptoms. Adherence was 39.9% at baseline (and increased up to 67.0% at completion. The main predictors of nonadherence were alcohol consumption, severe bipolar symptoms, young age at time of first treatment, negative attitude towards treatment. Conclusions: The patient population of this observational trial was representative of the patients changing their therapy for bipolar disorder seen in clinical practice in Italy. Lack of adherence to pharmacotherapy for bipolar disorder is a serious issue, which is more likely to arise in alcohol users and patients with severe symptoms, negative attitude towards medication and/or initiation of treatment early in life. The findings could lead to a more adequate approach of adherence in patients with bipolar disorders.
Adrenergic signalling between rat taste receptor cells

In taste buds, synaptic transmission is traditionally thought to occur from taste receptor cells to the afferent nerve. This communication reports the novel observation that taste receptor cells respond to adrenergic stimulation. Noradrenaline application inhibited outward potassium currents in a dose‐dependent manner. This inhibition was mimicked by the β agonist isoproterenol and blocked by the β antagonist propranolol. The α agonists clonidine and phenylephrine both inhibited the potassium currents and elevated intracellular calcium levels. Inwardly rectifying potassium currents were unaffected by adrenergic stimulation. Experiments using the RT‐PCR technique demonstrate that lingual epithelium expresses multiple α (α1a, α1b, α1c, α1d, α2a, α2b, α2c) and β (β1, β2) subtypes of adrenergic receptors, and immunocytochemistry localized noradrenaline to a subset of taste receptor cells. Collectively, these data imply strongly that adrenergic transmission within the taste bud may play a paracrine role in taste physiology.
Electron Partitioning between the Cytochrome and Alternative Pathways in Plant Mitochondria

The contribution of the cyanide-resistant, alternative pathway to plant mitochondrial electron transport has been studied using a modified aqueous phase on-line mass spectrometry-gas chromatography system. This technique permits direct measurement of the partitioning of electrons between the cytochrome and alternative pathways in the absence of added inhibitors. We demonstrate that in mitochondria isolated from soybean (Glycine max L. cv Ransom) cotyledons, the alternative pathway contributes significantly to oxygen uptake under state 4 conditions, when succinate is used as a substrate. However, when NADH is the substrate, addition of pyruvate, an allosteric activator of the alternative pathway, is required to achieve the same level of alternative pathway activity. Under state 3 conditions, when the reduction state of the ubiquinone pool is low, the addition of pyruvate allows the alternative pathway to compete with the cytochrome pathway for electrons from the ubiquinone pool when the cytochrome pathway is not saturated. These results provide direct experimental verification of the kinetics consequences of pyruvate addition on the partitioning of electron flow between the two respiratory pathways. This distribution of electrons between the two unsaturated pathways could not be measured using conventional oxygen electrode methods and illustrates a clear advantage of the mass spectrometry technique. These results have significant ramifications for studies of plant respiration using the oxygen electrode, particularly those studies involving intact tissues.
First record of epizootic ulcerative syndrome from the Upper Congo catchment: An outbreak in the Bangweulu swamps, Zambia.

We report on the first outbreak of epizootic ulcerative syndrome (EUS) amongst wild fish populations in the Bangweulu swamps, an inland delta, in the north of Zambia during 2014. The area supports a large and diverse fish fauna related to, but distinct from, that of the Zambezi River system where EUS outbreaks have occurred since 2006. A sizeable artisanal fishery, based on extensive fish weirs, is sustained by the annual flooding of the swamps, and observations of the disease outbreak by fishermen were recorded. Signs typical of infection with Aphanomyces invadans were observed in a number of species. Clinical observations, histology and molecular diagnostic methods were used to confirm infection with A. invadans in two of the most commonly and severely affected species. Several features of the wetland may have contributed to the outbreak and the annual recurrence of the disease. Modes by which the disease may have been introduced into the swamps are discussed. The outbreak is of great significance as the Bangweulu swamps drain into the Congo River in neighbouring Democratic Republic of Congo, Africa's largest drainage system with an extensive and diverse fish fauna previously unaffected by EUS.
Rapid adaptation of harmful cyanobacteria to rising CO2

Significance Cyanobacterial blooms pose a major threat to the water quality of many eutrophic lakes and reservoirs. Cyanobacteria are thought to be very effective competitors when CO2 levels are depleted during dense blooms. Their response to elevated CO2 is less understood, however. We study competition among cyanobacteria, and find both laboratory and field evidence for natural selection of strains with different carbon uptake systems at different CO2 levels. Our results demonstrate that changes in inorganic carbon availability act as an important selective factor in cyanobacterial communities and suggest that future harmful cyanobacterial blooms will have a genotype composition that differs from contemporary blooms and will be tuned to the high-CO2 conditions. Rising atmospheric CO2 concentrations are likely to affect many ecosystems worldwide. However, to what extent elevated CO2 will induce evolutionary changes in photosynthetic organisms is still a major open question. Here, we show rapid microevolutionary adaptation of a harmful cyanobacterium to changes in inorganic carbon (Ci) availability. We studied the cyanobacterium Microcystis, a notorious genus that can develop toxic cyanobacterial blooms in many eutrophic lakes and reservoirs worldwide. Microcystis displays genetic variation in the Ci uptake systems BicA and SbtA, where BicA has a low affinity for bicarbonate but high flux rate, and SbtA has a high affinity but low flux rate. Our laboratory competition experiments show that bicA + sbtA genotypes were favored by natural selection at low CO2 levels, but were partially replaced by the bicA genotype at elevated CO2. Similarly, in a eutrophic lake, bicA + sbtA strains were dominant when Ci concentrations were depleted during a dense cyanobacterial bloom, but were replaced by strains with only the high-flux bicA gene when Ci concentrations increased later in the season. Hence, our results provide both laboratory and field evidence that increasing carbon concentrations induce rapid adaptive changes in the genotype composition of harmful cyanobacterial blooms.
Modeling of Soldering Quality by Using Artificial Neural Networks

Multilayer perceptrons (MLPs ) are well-known artificial neural networks (ANNs) that are used in many different applications. In this paper, MLP neural networks were used to predict product quality in a wave soldering research case. The aims were to construct process models and to determine whether the formation of soldering defects could be predicted reliably by using the method. In addition, the scope of the research included demonstrating the prediction performance of the created models. A MLP-based variable selection procedure with a back-propagation algorithm was used to create defect formation models and to find the most important factors affecting the number of detected defects. The process parameters were used as inputs for the MLP network and each defect type in turn as a model output. In conclusion, the results were promising, and the method used showed potential considering the wider use of the data processing procedure in the electronics or any other industry.
Population structure and intraspecific aggression in the invasive ant species Anoplolepis gracilipes in Malaysian Borneo

Invasive species are one of the main sources of the ongoing global loss of biodiversity. Invasive ants are known as particularly damaging invaders and their introductions are often accompanied by population‐level behavioural and genetic changes that may contribute to their success. Anoplolepis gracilipes is an invasive ant that has just recently received increased attention due to its negative impact on native ecosystems. We examined the behaviour and population structure of A. gracilipes in Sabah, Malaysia. A total of 475 individuals from 24 colonies were genotyped with eight microsatellite markers. Intracolonial relatedness was high, ranging from 0.37 to 1 (mean ± SD: 0.82 ± 0.04), while intercolonial relatedness was low (0.0 ± 0.02, range −0.5–0.76). We compared five distinct sampling regions in Sabah and Brunei. A three‐level hierarchical F‐analysis revealed high genetic differentiation among colonies within the same region, but low genetic differentiation within colonies or across regions. Overall levels of heterozygosity were unusually high (mean HO = 0.95, mean HE = 0.71) with two loci being entirely heterozygous, indicating an unusual reproductive system in this species. Bioassays revealed a negative correlation between relatedness and aggression, suggesting kinship as one factor facilitating supercolony formation in this species. Furthermore, we genotyped one individual per nest from Sabah (22 nests), Sarawak (one nest), Brunei (three nests) and the Philippines (two nests) using two mitochondrial DNA markers. We found six haplotypes, two of which included 82.1% of all sequences. Our study shows that the sampled area in Sabah consists of a mosaic of differently interrelated nests in different stages of colony establishment. While some of the sampled colonies may belong to large supercolonies, others are more likely to represent recently introduced or dispersed propagules that are just beginning to expand.
Selective Cleavage of the Heregulin Receptor ErbB-4 by Protein Kinase C Activation*

The 180-kDa transmembrane tyrosine kinase ErbB-4 is a receptor for the growth factor heregulin. 125I-Heregulin binding to NIH 3T3 cells overexpressing the ErbB-4 receptor is rapidly decreased by 12-O-tetradecanoylphorbol-13-acetate (TPA) pretreatment. Immunologic analysis demonstrates that TPA treatment of cells induces the proteolytic cleavage of ErbB-4, producing an 80-kDa cytoplasmic domain fragment, which contains a low level of phosphotyrosine, and a 120-kDa ectodomain fragment, which is released into the extracellular medium. Cleavage of ErbB-4 was also enhanced by other protein kinase C activators, i.e. platelet-derived growth factor, ionomycin, and synthetic diacylglycerol, while protein kinase C inhibition or down-regulation suppressed the TPA stimulation of ErbB-4 degradation. TPA did not induce the degradation of related receptors (ErbB-1, ErbB-2, and ErbB-3) in the EGF receptor family. The phorbol ester-induced cleavage of ErbB-4 occurs within or close to the ectodomain, as the 80-kDa cytoplasmic domain fragment is recognized by antibody to the ErbB-4 carboxyl terminus and is membrane-associated. Coprecipitation experiments show that, while the 80-kDa ErbB-4 fragment is associated with the SH2-containing molecules PLC-γ1 and Shc, TPA did not induce the phosphorylation of these substrates in intact cells. In addition, kinase assays in vitro indicate that the 80-kDa fragment is not an active tyrosine kinase. These results show that protein kinase C negatively regulates heregulin signaling through the ErbB-4 receptor by the activation of a selective proteolytic mechanism.
p53 Immunohistochemistry in malignant fibrous histiocytomas and other mesenchymal tumours

In this study we analysed by immunohistochemistry the expression of p53 protein in 14 malignant fibrous histiocytomas (MFHs), 22 other types of sarcoma (eight leiomyosarcomas, four rhabdomyosarcomas, four liposarcomas, two fibrosarcomas, two chondrosarcomas, one malignant schwannoma, and one dermatofibrosarcoma protuberans), and 25 non‐malignant mesenchymal lesions (eight dermatofibromas, four cases of nodular fasciitis, three leiomyomas, three fibromatoses, two epithelioid leiomyomas, two neurofibromas, one schwannoma, one myositis ossificans, and one giant cell tumour of tendon sheath). Four MFHs and nine other types of sarcoma (four leiomyosarcomas, two chondrosarcomas, one liposarcoma, one fibrosarcoma, and one dermatofibrosarcoma protuberans) showed nuclear positivity for p53. Of the benign soft tissue lesions, p53 positivity was observed in two fibromatoses, one nodular fasciitis, and one dermatofibroma. The number of p53‐positive cells in these benign lesions was considerably smaller than that in most of the p53‐positive sarcomas.
Modifying therapy in patients with advanced Hodgkin's lymphoma by integrating early metabolic response by interim PET-CT.

Hodgkin’s lymphoma shows an annual incidence of around 2-3 per 100,000 habitants in the Western hemisphere with a larger peak in younger adults between 20 and 30 years and a smaller peak in adults above 65 years. Although Hodgkin’s lymphoma is rare within the general population (accounting for less than 1% of all de novo neoplasms occurring every year worldwide) (1), it belongs to the most frequent malignancies in young adults and represents the most frequent hematological malignancy in this age group (2). Outcomes of patients with Hodgkin’s lymphoma in general are favorable, with the vast majority of patients achieving permanent cure by standard therapies. Survivors, however, may face the problems caused by late toxicities such as secondary tumors or cardiovascular complications.
Origin and management of primary and acquired drug-resistant tuberculosis in The Netherlands: the truth behind the rates.

SETTING The Netherlands, May 1994 to May 1996. OBJECTIVE 1) To estimate to what extent drug-resistant tuberculosis was acquired or recently transmitted in The Netherlands, 2) to assess the relevance of drug resistance data as routinely collected, and 3) to describe case management. DESIGN Prospective descriptive study. Patients diagnosed with drug-resistant tuberculosis were interviewed. Information on patient management and contact tracing was collected. IS6110 restriction fragment length polymorphism (RFLP) patterns of all strains were compared with those of the National RFLP library and clusters were analyzed. RESULTS In total 193 cases were included in the study. Acquired drug resistance (ADR) was rare. Dutch ADR patients reported receiving treatment a long time previously (mean age 58, mean treatment interval 23 years). Most foreign ADR patients had been treated recently in their country of origin. Of 151 primary drug-resistant (PDR) cases, 129 (85%) were foreign-born, of whom few (8%-19%) had been infected in The Netherlands. Few Dutch PDR cases had been infected recently (mean age 49 years). Rifampicin resistance was more frequently observed in foreign ADR cases than in foreign PDR cases (28% vs 5%; P < 0.001). One third of cases had not been treated according to treatment guidelines. CONCLUSION Only a small proportion of drug-resistant cases resulted from recent infection or treatment in The Netherlands. General rates of ADR and PDR do not reflect current Dutch programme performance. For programme monitoring, ADR/PDR rates and their trends must be reported and evaluated in Dutch and foreign patients separately.
Chemotyping of yeast mutants using robotics

By now, the EUROFAN programme for the functional analysis of genes from the yeast genome has attained its cruising speed. Indeed, several hundreds of yeast mutants with no phenotype as tested by growth on standard media and no significant sequence similarity to proteins of known function are available through the efforts of various laboratories. Based on the methodology initiated during the pilot project on yeast chromosome III (Yeast 13, 1547–1562, 1997) we adapted it to High Throughput Screening (HTS), using robotics. The first 100 different gene deletions from EUROSCARF, constructed in an FY1679 strain background, were run against a collection of about 300 inhibitors. Many of these inhibitors have not been reported until now to interfere in vivo with growth of Saccharomyces cerevisiae. In the present paper we provide a list of novel growth conditions and a compilation of 49 yeast deletants (from chromosomes II, IV, VII, X, XIV, XV) corresponding to 58% of the analysed genes, with at least one clear and stringent phenotype. The majority of these deletants are sensitive to one or two compounds (monotropic phenotype) while a distinct subclass of deletants displays a hyper‐pleiotropic phenotype with sensitivities to a dozen or more compounds. Therefore, chemotyping of unknown genes with a large spectrum of drugs opens new vistas for a more in‐depth functional analysis and a more precise definition of molecular targets. Copyright © 1999 John Wiley & Sons, Ltd.
Reconciling Differences in Effective Solute Removal Between Intermittent and Continuous Therapies

Solute removal by various forms of renal replacement therapy (RRT) differs from that occurring in the native kidney in several ways. Among the dialytic therapies, the relationship between clearance and mass removal rate may differ substantially. The purpose of this article is to review the various approaches that have been proposed to account for this differing relationship among the various types of RRT. Specific quantitative approaches along with clinical applications are provided.
Postconcussion Syndrome: A Review of Pathophysiology and Potential Nonpharmacological Approaches to Treatment

Abstract The incidence of all-cause concussions in the United States is estimated to range from 1.6 to 3.8 million annually, with the reported number of sport- or recreation-related concussions increasing dramatically, especially in youth sports.1,2 Additionally, the use of roadside bombs in Iraq and Afghanistan has propelled the incidence of concussion and other traumatic brain injuries to the highest levels ever encountered by the US military. As a result, there has also been a marked increase in postconcussion syndrome (PCS) and the associated cognitive, emotional, and memory disabilities associated with the condition. Unfortunately, however, there have been no significant advancements in the understanding or treatment of PCS for decades. The current management of PCS mainly consists of rest, reduction of sensory inputs, and treating symptoms as needed. Recently, researchers investigating the underlying mechanisms of PCS have proposed that activation of the immune inflammatory response may be an underlying pathophysiology that occurs in those who experience prolonged symptoms after a concussion. This article reviews the literature and summarizes the immune inflammatory response known as immunoexcitotoxicity. This article also discusses the use of nonpharmacological agents for the management of PCS that directly address this underlying mechanism.
Ant Colony Optimization-Based Approach to Optimal Reactive Power Dispatch: A Comparison of Various Ant Systems

The optimal reactive power dispatch (ORPD) problem is formulated as a combinatorial optimization problem involving nonlinear objective function with multiple local minima. In this paper, as a new approach, different ant colony optimization (ACO) algorithms are applied to the reactive power dispatch problem. Ant system (AS), the firstly introduced ant colony optimization algorithm, and its direct successors, elitist ant system (EAS), rank-based ant system (ASrank) and max-min ant system (MMAS), are employed to solve the reactive power dispatch problem. To analyze the efficiency and effectiveness of these modern search algorithms, the proposed methods are applied to the IEEE 30-bus system and the results are compared to those of conventional mathematical methods, genetic algorithm, evolutionary programming, and particle swarm optimization.
Principles of flexible protein–protein docking

Treating flexibility in molecular docking is a major challenge in cell biology research. Here we describe the background and the principles of existing flexible protein–protein docking methods, focusing on the algorithms and their rational. We describe how protein flexibility is treated in different stages of the docking process: in the preprocessing stage, rigid and flexible parts are identified and their possible conformations are modeled. This preprocessing provides information for the subsequent docking and refinement stages. In the docking stage, an ensemble of pre‐generated conformations or the identified rigid domains may be docked separately. In the refinement stage, small‐scale movements of the backbone and side‐chains are modeled and the binding orientation is improved by rigid‐body adjustments. For clarity of presentation, we divide the different methods into categories. This should allow the reader to focus on the most suitable method for a particular docking problem. Proteins 2008. Published Wiley‐Liss, Inc.