Miracle-dz/UniFAR-FTUs huggingface dataset:
Juxtaposition of heterozygous and homozygous regions causes reciprocal crossover remodelling via interference during Arabidopsis meiosis

During meiosis homologous chromosomes undergo crossover recombination. Sequence differences between homologs can locally inhibit crossovers. Despite this, nucleotide diversity and population-scaled recombination are positively correlated in eukaryote genomes. To investigate interactions between heterozygosity and recombination we crossed Arabidopsis lines carrying fluorescent crossover reporters to 32 diverse accessions and observed hybrids with significantly higher and lower crossovers than homozygotes. Using recombinant populations derived from these crosses we observed that heterozygous regions increase crossovers when juxtaposed with homozygous regions, which reciprocally decrease. Total crossovers measured by chiasmata were unchanged when heterozygosity was varied, consistent with homeostatic control. We tested the effects of heterozygosity in mutants where the balance of interfering and non-interfering crossover repair is altered. Crossover remodeling at homozygosity-heterozygosity junctions requires interference, and non-interfering repair is inefficient in heterozygous regions. As a consequence, heterozygous regions show stronger crossover interference. Our findings reveal how varying homolog polymorphism patterns can shape meiotic recombination. DOI: http://dx.doi. org/10.7554/eLife.03708. 001
Design and Application of Water Environment SCADA for Tuojiang River

To protect the water environment of Tuojiang River, a supervisory control and data acquisition (SCADA) system was designed as three-tier structure: monitoring station, central station, and control & management center. In monitoring station, data from survey instrument were transmitted to computer system through RS-232. Because of geographical and economic conditions, there were several different plans for data transmission between monitoring station and central station. A classic one was based on MOTOROLA SCADA (MOSCAD), mainly including MOSCAD-M RTU, MOSCAD FIU, and MDLC. Usually Internet connects central station and control & management center. To draw concise and accurate conclusions of water pollution, factor analysis method was used to process the original data by statistical program for social sciences (SPSS). According to the results, the accumulative contribution rate of 6 common factors accounts for 94.053%, including most information of 14 original indexes. It proves that at present total inorganic nitrogen, total phosphorus, and organic pollutants mainly pollute the water of Tuojiang River. So the work of protection should focus on industrial pollution, agricultural irrigation, and domestic sewage. The system has been applied for 2 years and it has been proved that the reliability, accuracy and real-time performance can be used as needed.
A Meta-Analytic Review of the Association Between Pubertal Timing and Psychopathology in Adolescence: Are There Sex Differences in Risk?

Research examining pubertal timing effects on psychopathology has emphasized that a subset of adolescents, particularly females, who experience early pubertal maturation relative to their peers appear to be at increased risk for psychopathology. The aims of the current meta-analysis were (a) to quantify the magnitude of early pubertal timing effects on psychopathology, (b) to examine potential moderators of pubertal timing effects (sex, psychopathology domain, sample composition, measurement method, and mean sample age), and (c) to examine findings in relation to hypotheses in the extant literature explicating differential pubertal timing effects for early versus late youth and males versus females. A systematic literature search was conducted in PubMed and PsycInfo databases and 101 articles met criteria for inclusion. Included studies reported a quantitative association between pubertal timing and higher-order broadband dimensions of psychopathology (i.e., internalizing, externalizing), and/or lower-order subdomains (i.e., distress, fear, antisocial behavior, substance abuse, eating pathology). Using meta-analytic methods, we estimated global effect sizes (Cohen’s ds) for the association between pubertal timing and psychopathology. Adolescent sex did not moderate early pubertal timing effects on emotional and behavior problems. However, robust early pubertal timing effects emerged for both males and females across all domains of psychopathology that were small in magnitude (ds∼.20). Measurement method of pubertal timing, but not sample composition or mean sample age, significantly contributed to the heterogeneity of effect sizes across studies. Findings have implications for refinement of theoretical models of pubertal timing effects on psychopathology and highlight the importance of empirical work that can identify pathways which may link offset pubertal timing to psychopathology during adolescence.
Underestimation of risk associations due to regression dilution in long-term follow-up of prospective studies.

In prospective studies, disease rates during follow-up are typically analyzed with respect to the values of factors measured during an initial baseline survey. However, because of "regression dilution," this generally tends to underestimate the real associations of disease rates with the "usual" levels of such risk factors during some particular exposure period. The "regression dilution ratio" describes the ratio of the steepness of the uncorrected association to that of the real association. To assess the relevance of the usual value of a risk factor during particular exposure periods (e.g., first, second, and third decades) to disease risks, regression dilution ratios can be derived by relating baseline measurements of the risk factor to replicate measurements from a reasonably representative sample of study participants after an interval equivalent to about the midpoint of each exposure period (e.g., at 5, 15, and 25 years, respectively). This report illustrates the impact of this time interval on the magnitude of the regression dilution ratios for blood pressure and blood cholesterol. The analyses were based on biennial remeasurements over 30 years for participants in the Framingham Study (Framingham, Massachusetts) and a 26-year resurvey for a sample of men in the Whitehall Study (London, England). They show that uncorrected associations of disease risk with baseline measurements underestimate the strength of the real associations with usual levels of these risk factors during the first decade of exposure by about one-third, the second decade by about one-half, and the third decade by about two-thirds. Hence, to correct appropriately for regression dilution, replicate measurements of such risk factors may be required at varying intervals after baseline for at least a sample of participants.
Characterization of amplicons in neuroblastoma: High‐resolution mapping using DNA microarrays, relationship with outcome, and identification of overexpressed genes

Somatically acquired chromosomal imbalances are a key feature of neuroblastoma, a heterogeneous pediatric solid tumor. Among these alterations, genomic amplification targeting the MYCN oncogene and observed in about 25–30% of the cases, strongly correlates with advanced stage and poor outcome. In this work, we have used BAC and SNP arrays as well as gene expression arrays to characterize amplifications in neuroblastoma. Eighty‐eight distinct BACs defining high‐level amplification events were identified in 65 samples, including 43 tumors and 22 cell lines. Although the highest recurrence was observed on chromosome 2, clones on chromosomes 8, 12, 16, and 17 also revealed genomic amplification in several samples. A detailed analysis of the 2p22‐2p25 MYCN containing region indicated highly complex patterns in a number of cases. Coamplifications involving MYCN and other regions were explored by FISH in three cell lines. High‐resolution arrays then allowed us to further refine the mapping of 25 amplicons in 19 samples, either reducing the size of a single continuous amplicon or increasing the complexity by highlighting multiple noncontiguous regions of amplification. Combined analysis of gene expression profiling and array‐CGH data indicated that 12 to 25% of the genes that are targeted by genomic amplification are actually over‐expressed in tumor cells, several of them having already been implicated in cancer. Finally, our results suggest that the presence of amplicons localized outside of chromosome 2, in addition to MYCN amplification, may be linked to a particularly severe outcome in neuroblastoma patients. © 2008 Wiley‐Liss, Inc.
Butter as an indicator of regional persistent organic pollutant contamination: further development of the approach using polychlorinated dioxins and furans (PCDD/Fs), and dioxin-like polychlorinated biphenyls (PCBs)

The potential for use of butter as a widely available, relatively uniform lipid-rich matrix for the determination of spatial distributions of persistent organic pollutants has already been demonstrated. The present study determines the contributions to toxicity equivalence (TEQ) from polychlorinated dioxins and furans (PCDD/Fs) and polychlorinated biphenyls (PCBs) using butter samples from 24 countries world wide. Concentrations of PCDD/Fs and dioxin-like PCBs ranged from 0.07 to 5.69 pg ΣWHO-TEQ g-1 lipid. For most samples, PCDD/F TEQ fell within ranges reported for European dairy products over the last decade (0.3–2 pg g-1 lipid I-TEQ), though a single sample from Spain was a notable exception. Other than this sample, the highest values were recorded for samples from the Netherlands and Italy, with those from India, China and Tunisia also being relatively high. The contribution from non- ortho -PCBs was particularly significant in samples from Germany, Austria, Italy, the Czech Republic, Tunisia, India and Argentina. Although overall TEQs were generally highest in European and Mediterranean butters, elevated levels were also apparent in industrializing regions of Asia (India, China) and Latin America (Argentina). More detailed regional studies would be necessary to identify likely dioxin and PCB sources in each case. Nevertheless, this study supports the utility of butter as a monitoring matrix that may be especially applicable in regions for which monitoring programmes are currently lacking.
MAPK pathway control of stem cell proliferation and differentiation in the embryonic pituitary provides insights into the pathogenesis of papillary craniopharyngioma

Despite the importance of the RAS-RAF-MAPK pathway in normal physiology and disease of numerous organs, its role during pituitary development and tumourigenesis remains largely unknown. Here, we show that the over-activation of the MAPK pathway, through conditional expression of the gain-of-function alleles BrafV600E and KrasG12D in the developing mouse pituitary, results in severe hyperplasia and abnormal morphogenesis of the gland by the end of gestation. Cell-lineage commitment and terminal differentiation are disrupted, leading to a significant reduction in numbers of most of the hormone-producing cells before birth, with the exception of corticotrophs. Of note, Sox2+ stem cells and clonogenic potential are drastically increased in the mutant pituitaries. Finally, we reveal that papillary craniopharyngioma (PCP), a benign human pituitary tumour harbouring BRAF p.V600E also contains Sox2+ cells with sustained proliferative capacity and disrupted pituitary differentiation. Together, our data demonstrate a crucial function of the MAPK pathway in controlling the balance between proliferation and differentiation of Sox2+ cells and suggest that persistent proliferative capacity of Sox2+ cells may underlie the pathogenesis of PCP. Highlighted Article: Constitutive activation of the MAPK/ERK pathway causes pituitary hyperplasia, abnormal morphogenesis, and abnormal endocrine cell specification due to the sustained proliferation of the Sox2+ stem cell compartment.
Cooperative guidance and control for rendezvous with uncooperative target based on Augment Proportional Navigation

This paper presents a guidance and control scheme based on three dimensional Augment Proportion Navigation (APN) for rendezvous with uncooperative target based on rotating line of sight coordinates. Application of classic proportion navigation is expanded to rendezvous with introduction of sliding mode control along line-of-sight. The algorithm can deal with the maneuvering target by measuring only elevation and azimuth angles between each chaser and target. Cooperative scheme provides the distance measurement by estimation which improves the observability of angle only navigation. Simulation scenarios with various maneuverability and control parameter settings are conducted to demonstrate the efficiency of proposed guidance and control system.
Hypomorphic MKS1 mutation in a Pakistani family with mild Joubert syndrome and atypical features: Expanding the phenotypic spectrum of MKS1‐related ciliopathies

Postaxial polydactyly (PAP) is one of the most common congenital malformations observed in the general population. However, it can also occur as part of a syndrome. Unbiased genetic screening techniques such as exome sequencing are highly appropriate methods to provide a molecular diagnosis in patients with polydactyly due to the large number of mutated genes associated with it. The present study describes a consanguineous family of Pakistani origin with PAP, speech impairment, hearing impairment of variable degree, and proportionate short stature with no prominent intellectual disability or ophthalmological abnormalities. One affected individual of the family was subjected to exome sequencing which resulted in the identification of four homozygous variants including an in‐frame deletion (c.1115_1117delCCT; p.(Ser372del) in MKS1, which was later shown to be the only variant segregating with the phenotype. In silico predictions supported the potential pathogenicity of the identified mutation. Additional clinical tests and MRI features of a patient in the family showed a molar tooth sign, which is a hallmark of Joubert syndrome. In conclusion, we have described a pathogenic variant in the MKS1 resulting in a mild Joubert syndrome phenotype, which broadens the spectrum of mutations in the MKS1. © 2016 Wiley Periodicals, Inc.
Dynamic interaction of HMGA1a proteins with chromatin

High-mobility-group proteins A1 (HMGA1; previously named HMGI/Y) function as architectural chromatin-binding proteins and are involved in the transcriptional regulation of several genes. We have used cells expressing proteins fused to green fluorescent protein (GFP) and fluorescence recovery after photobleaching (FRAP) to analyze the distribution and dynamics of HMGA1a in vivo. HMGA1-GFP proteins localize preferentially to heterochromatin and remain bound to chromosomes during mitosis. FRAP experiments showed that they are highly mobile components of euchromatin, heterochromatin and of mitotic chromosomes, although with different resident times. For a more-detailed investigation on the interaction of HMGA1a with chromatin, the contribution of the AT-hook DNA-binding motifs was analyzed using point-mutated HMGA1a-GFP proteins. Furthermore, by inhibiting kinase or histone deacetylase activities, and with the help of fusion proteins lacking specific phosphorylation sites, we analyzed the effect of reversible modifications of HMGA1a on chromatin binding. Collectively our data show that the kinetic properties of HMGA1a proteins are governed by the number of functional AT-hooks and are regulated by specific phosphorylation patterns. The higher residence time in heterochromatin and chromosomes, compared with euchromatic regions, correlates with an increased phosphorylation level of HMGA1a. The regulated dynamic properties of HMGA1a fusion proteins indicate that HMGA1 proteins are mechanistically involved in local and global changes in chromatin structure.
Genetic utility of broadly defined bipolar schizoaffective disorder as a diagnostic concept

Background Psychiatric phenotypes are currently defined according to sets of descriptive criteria. Although many of these phenotypes are heritable, it would be useful to know whether any of the various diagnostic categories in current use identify cases that are particularly helpful for biological–genetic research. Aims To use genome-wide genetic association data to explore the relative genetic utility of seven different descriptive operational diagnostic categories relevant to bipolar illness within a large UK case–control bipolar disorder sample. Method We analysed our previously published Wellcome Trust Case Control Consortium (WTCCC) bipolar disorder genome-wide association data-set, comprising 1868 individuals with bipolar disorder and 2938 controls genotyped for 276 122 single nucleotide polymorphisms (SNPs) that met stringent criteria for genotype quality. For each SNP we performed a test of association (bipolar disorder group v. control group) and used the number of associated independent SNPs statistically significant at P<0.00001 as a metric for the overall genetic signal in the sample. We next compared this metric with that obtained using each of seven diagnostic subsets of the group with bipolar disorder: Research Diagnostic Criteria (RDC): bipolar I disorder; manic disorder; bipolar II disorder; schizoaffective disorder, bipolar type; DSM–IV: bipolar I disorder; bipolar II disorder; schizoaffective disorder, bipolar type. Results The RDC schizoaffective disorder, bipolar type (v. controls) stood out from the other diagnostic subsets as having a significant excess of independent association signals (P<0.003) compared with that expected in samples of the same size selected randomly from the total bipolar disorder group data-set. The strongest association in this subset of participants with bipolar disorder was at rs4818065 (P = 2.42 × 10–7). Biological systems implicated included gamma amniobutyric acid (GABA)A receptors. Genes having at least one associated polymorphism at P<10–4 included B3GALTS, A2BP1, GABRB1, AUTS2, BSN, PTPRG, GIRK2 and CDH12. Conclusions Our findings show that individuals with broadly defined bipolar schizoaffective features have either a particularly strong genetic contribution or that, as a group, are genetically more homogeneous than the other phenotypes tested. The results point to the importance of using diagnostic approaches that recognise this group of individuals. Our approach can be applied to similar data-sets for other psychiatric and non-psychiatric phenotypes.
Applying the Triangle Taste Test to Assess Differences between Low Sodium Salts and Common Salt: Evidence from Peru

Background In resourced-constrained settings, daily cooking practices are still the norm. Replacing sodium in regular salt to produce potassium-enriched salts are potential alternative routes to reduce sodium intake, paired with the benefit associated with potassium intake. This change would likely have effects on palatability and taste of prepared foods, yet a threshold to discriminate sensorial changes can be determined. The main goal of this study was to assess if the use of potassium-enriched salt substitutes lead to perceived differences in taste utilizing a sensory discrimination test. Methods and Results A triangle taste test was conducted and participants were offered samples of cooked rice prepared with different salts. The only ingredient that differed in the preparation was the salt used: 100%NaCl (regular salt) and salts where sodium was replaced by 50%, 33% or 25% KCl (potassium-enriched salt). Comparisons were carried out according to the minimum number of correct judgments. A total of 156 subjects, 49% males, mean age 41.0 years (SD±15.5) years, participated in the study. Samples using 25% potassium-enrichment were indistinguishable in terms of taste from regular salt, whereas samples with 33% and 50% potassium-enrichment were distinguishable. Results were consistent when stratified by sex and age. Less than 10% of participants attributed the differences to bitterness or metallic flavor. Conclusions The 25% potassium-enriched salt is indistinguishable from regular salt. These findings suggest a potential to achieve sodium intake reduction strategies in cooking practices by substituting regular salt with potassium-enriched salt without affecting palatability.
Is Suicide Training Sufficient for Psychology Trainees to Respond Appropriately to Suicidal Clients

This study reports the frequency of suicide training for current psychology trainees. Additionally, the research uses the Suicide Intervention Response Inventory – Second Edition (SIRI-2) to assess psychology trainees’ ability to respond appropriately to suicidal clients. This study compares scores on the SIRI-2 between participants who are in pre-internship years of training and those currently in internship or having completed internship training. Finally, this study compares SIRI-2 scores between high training, low training, and no-training groups, as well as the scores of no-training versus training groups. Findings indicate no statistically significant difference in SIRI-2 scores between participants early in their programs and those who received training later in their programs. Also, the study shows no statistically significant difference between scores of high, low, and no-training groups. However, research found a statistically significant difference between no-training and training groups, indicating that any amount of training provided to students could increase their ability to respond appropriately to suicidal clients.
Computational approaches for prediction of pathogen-host protein-protein interactions

Infectious diseases are still among the major and prevalent health problems, mostly because of the drug resistance of novel variants of pathogens. Molecular interactions between pathogens and their hosts are the key parts of the infection mechanisms. Novel antimicrobial therapeutics to fight drug resistance is only possible in case of a thorough understanding of pathogen-host interaction (PHI) systems. Existing databases, which contain experimentally verified PHI data, suffer from scarcity of reported interactions due to the technically challenging and time consuming process of experiments. These have motivated many researchers to address the problem by proposing computational approaches for analysis and prediction of PHIs. The computational methods primarily utilize sequence information, protein structure and known interactions. Classic machine learning techniques are used when there are sufficient known interactions to be used as training data. On the opposite case, transfer and multitask learning methods are preferred. Here, we present an overview of these computational approaches for predicting PHI systems, discussing their weakness and abilities, with future directions.