Homozygous mutation in the prokineticin-receptor2 gene (Val274Asp) presenting as reversible Kallmann syndrome and persistent oligozoospermia: case report.

Prokineticin 2 (Prok2) or prokineticin-receptor2 (Prok-R2) gene mutations are associated with Kallmann syndrome (KS). We describe a new homozygous mutation of Prok-R2 gene in a man displaying KS with an apparent reversal of hypogonadism. The proband, offspring of consanguineous parents, presented at age 19 years with absent puberty, no sense of smell, low testosterone and gonadotrophin levels. Magnetic resonance imaging showed olfactory bulb absence. The patient achieved virilization and spermatogenesis with gonadotrophin administration. Two years after discontinuing hormonal therapy, he maintained moderate oligozoospermia and normal testosterone levels. Prok2 and Prok- R2 gene sequence analyses were performed. The proband had a homozygous mutation in Prok-R2 exon 2 that harbours the c.T820>A base substitution, causing the introduction of an aspartic acid in place of valine at position 274 (Val274Asp). His mother had the same mutation in heterozygous state. This report describes a novel homozygous mutation of Prok-R2 gene in a man with variant KS, underlying the role of Prok-R2 gene in the olfactory and reproductive system development in humans. Present findings indicate that markedly delayed activation of gonadotrophin secretion may occur in some KS cases with definite gene defects, and that oligozoospermia might result from a variant form of reversible hypogonadotrophic hypogonadism

Reaction Time of a Group of Physics Students

The reaction time of a group of students majoring in Physics is reported here. Strong co-relation between fatigue, reaction time and performance have been seen and may be useful for academicians and administrators responsible of working out time-tables, course structures, students counsellings etc.Comment: 10 pages, 4 figure

Bioluminescence Imaging for Assessment and Normalization in Transfected Cell Arrays

Transfected cell arrays (TCAs) represent a high-throughput technique to correlate gene expression with functional cell responses. Despite advances in TCAs, improvements are needed for the widespread application of this technology. We have developed a TCA that combines a two-plasmid system and dual-bioluminescence imaging to quantitatively normalize for variability in transfection and increase sensitivity. The two-plasmids consist of: (i) normalization plasmid present within each spot, and (ii) functional plasmid that varies between spots, responsible for the functional endpoint of the array. Bioluminescence imaging of dual-luciferase reporters (renilla, firefly luciferase) provides sensitive and quantitative detection of cellular response, with minimal post-transfection processing. The array was applied to quantify estrogen receptor α (ERα) activity in MCF-7 breast cancer cells. A plasmid containing an ERα-regulated promoter directing firefly luciferase expression was mixed with a normalization plasmid, complexed with cationic lipids and deposited into an array. ER induction mimicked results obtained through traditional assays methods, with estrogen inducing luciferase expression 10-fold over the antiestrogen fulvestrant or vehicle. Furthermore, the array captured a dose response to estrogen, demonstrating the sensitivity of bioluminescence quantification. This system provides a tool for basic science research, with potential application for the development of patient specific therapies

Bioluminescence Imaging for Assessment and Normalization in Transfected Cell Arrays

Transfected cell arrays (TCAs) represent a high-throughput technique to correlate gene expression with functional cell responses. Despite advances in TCAs, improvements are needed for the widespread application of this technology. We have developed a TCA that combines a two-plasmid system and dual-bioluminescence imaging to quantitatively normalize for variability in transfection and increase sensitivity. The two-plasmids consist of: (i) normalization plasmid present within each spot, and (ii) functional plasmid that varies between spots, responsible for the functional endpoint of the array. Bioluminescence imaging of dual-luciferase reporters (renilla, firefly luciferase) provides sensitive and quantitative detection of cellular response, with minimal post-transfection processing. The array was applied to quantify estrogen receptor α (ERα) activity in MCF-7 breast cancer cells. A plasmid containing an ERα-regulated promoter directing firefly luciferase expression was mixed with a normalization plasmid, complexed with cationic lipids and deposited into an array. ER induction mimicked results obtained through traditional assays methods, with estrogen inducing luciferase expression 10-fold over the antiestrogen fulvestrant or vehicle. Furthermore, the array captured a dose response to estrogen, demonstrating the sensitivity of bioluminescence quantification. This system provides a tool for basic science research, with potential application for the development of patient specific therapies

Adverse childhood experiences during childhood and academic attainment at age 7 and 11 years: an electronic birth cohort study

Objectives Adverse childhood experiences (ACEs) have a negative impact on childhood health, but their impact on education outcomes is less well known. We investigated whether or not ACEs were associated with reduced educational attainment at age 7 and 11 years. Study design The study design used in the study is a population-based electronic cohort study. Methods We analysed data from a total population electronic child cohort in Wales, UK. ACEs (exposures) were living with an adult household member with any of (i) serious mental illness, (ii) common mental disorder (CMD), (iii) an alcohol problem; (iv) child victimisation, (v) death of a household member and (vi) low family income. We used multilevel logistic regression to model exposure to these ACEs and not attaining the expected level at statutory education assessments, Key Stage (KS) 1 and KS2 separately, adjusted for known confounders including perinatal, socio-economic and school factors. Results There were 107,479 and 43,648 children included in the analysis, with follow-up to 6–7 years (KS1) and 10–11 years (KS2), respectively. An increased risk of not attaining the expected level at KS1 was associated with living with adult household members with CMD (adjusted odds ratio [aOR]: 1.13 [95% confidence interval [CI]: 1.09–1.17]) or an alcohol problem (adjusted odds ratio [aOR]: 1.16 [95% confidence interval [CI]: 1.10–1.22]), childhood victimisation (adjusted odds ratio [aOR]: 1.58 [95% confidence interval [CI]: 1.37–1.82]), death of a household member (adjusted odds ratio [aOR]: 1.14 [95% confidence interval [CI]: 1.04–1.25]) and low family income (adjusted odds ratio [aOR]: 1.92 [95% confidence interval [CI]: 1.84–2.01]). Similar results were observed for KS2. Children with multiple adversities had substantially increased odds of not attaining the expected level at each educational assessment. Conclusion The educational potential of many children may not be achieved due to exposure to adversity in childhood. Affected children who come in to contact with services should have relevant information shared between health and care services, and schools to initiate and facilitate a coordinated approach towards providing additional support and help for them to fulfil their educational potential, and subsequent economic and social participation

The monitoring program of grapevine phytoplasmas in Tuscany (Italy): Results of a four year survey

Quantitative PCR protocols for phytoplasma detection were used to monitor grapevine yellows (GY) in 373 vineyards located in nine Tuscan districts. Among more than 70,000 plants visually monitored, 1.867 plants were sampled and “flavescence dorée” phytoplasmas (FD) were detected in 122 plants and mainly identified as trains belonging to 16SrV-C subgroup. The “bois noir” (BN) phytoplasma was found in 734 samples, with prevalence of tufB type-b strains. The 2013–2015 monitoring program was strongly influenced by the first survey (2012) in which FD was found consistently in the North West (15 samples), whereas only a few cases were observed in the East territory (2 samples). Both areas were thoroughly monitored in the following years: few foci were found in the East (2 in 2014, 1 in 2015), while several infected areas were found in the North West (6, 10 and 22 foci in 2013, 2014 and 2015, respectively). Definitely, the novel FD foci detected in the survey (17, 6, 12 and 23 in each year of survey) and the widespread of BN, suggest a dangerous distribution of GY in Tuscan

A novel human aquaporin-4 splice variant exhibits a dominant-negative activity: a new mechanism to regulate water permeability.

Two major isoforms of aquaporin-4 (AQP4) have been described in human tissue. Here we report the identification and functional analysis of an alternatively spliced transcript of human AQP4, AQP4-Δ4, that lacks exon 4. In transfected cells AQP4-Δ4 is mainly retained in the endoplasmic reticulum and shows no water transport properties. When AQP4-Δ4 is transfected into cells stably expressing functional AQP4, the surface expression of the full-length protein is reduced. Furthermore, the water transport activity of the cotransfectants is diminished in comparison to transfectants expressing only AQP4. The observed down-regulation of both the expression and water channel activity of AQP4 is likely to originate from a dominant-negative effect caused by heterodimerization between AQP4 and AQP4-Δ4, which was detected in coimmunoprecipitation studies. In skeletal muscles, AQP4-Δ4 mRNA expression inversely correlates with the level of AQP4 protein and is physiologically associated with different types of skeletal muscles. The expression of AQP4-Δ4 may represent a new regulatory mechanism through which the cell-surface expression and therefore the activity of AQP4 can be physiologically modulated