Clinical impact of splicing in neurodevelopmental disorders.

Clinical exome sequencing is frequently used to identify gene-disrupting variants in individuals with neurodevelopmental disorders. While splice-disrupting variants are known to contribute to these disorders, clinical interpretation of cryptic splice variants outside of the canonical splice site has been challenging. Here, we discuss papers that improve such detection

Normal mitochondrial structure and genome maintenance in yeast requires the dynamin-like product of the MGM1 gene

The isolation and characterization of MGM1 , and yeast gene with homology to members of the dynamin gene family, is described. The MGM1 gene is located on the right arm of chromosome XV between STE4 and PTP2 . Sequence analysis revealed a single open reading frame of 902 residues capable of encoding a protein with an approximate molecular mass of 101 kDa. Loss of MGM1 resulted in slow growth on rich medium, failure to grow on non-fermentable carbon sources, and loss of mitochondrial DNA. The mitochondria also appeared abnormal when visualized with an antibody to a mitochondrial-matrix marker. MGM1 encodes a dynamin-like protein involved in the propagation of functional mitochondria in yeast.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46976/1/294_2004_Article_BF00324678.pd

Polycyclic aromatic hydrocarbons in citrus fruit irrigated with fresh water under arid conditions: Concentrations, sources, and risk assessment

In Jordan, as well as in all the world countries, consumption of citrus fruits is an essential part of the daily diet, so it is important to assess the potential risk of the persistent organic pollutants such as polyaromatic hydrocarbons (PAHs) in these fruits to the human health and identify their sources in order to eliminate or reduce them. This study reports 16 priority PAHs content in four types of peeled citrus fruits grown in Jordan valley. PAHs were detected in all the studied samples in variable quantities depending on the type of citrus fruits. The results showed that the highest PAH level corresponded to acenaphthene (35.018 µg/kg) in grapefruit. Among the carcinogenic PAHs, benzo[a]anthracene (BaA) and benzo(a)pyrene (BaP) were the most representative and found in all the analyzed fruit, soil, and water samples, whereas anthracene (ANT) was not detected at all. The mean ∑16 PAHs for the different fruits were found to be 62.593 µg kg−1 in grapefruit, 24.840 µg kg−1 in lemon, 22.901 µg kg−1 in mandarin, and 5.082 µg kg−1 in orange. The dominance of naphthalene (NAP) and acenaphthene (ACE) in soil under hot climatic conditions indicates the recent and continuous input of these types in the investigated area. The bioconcentration factor (BCF) for ∑16 PAHs was observed in the order of grapefruit > lemon > mandarin > orange. Based on the results of the principal component analysis (PCA), the primary sources of PAHs in agricultural soils mainly originated from biomass burning and vehicular emissions. The incremental lifetime cancer risk (ILCR) indicated that consumption of these four citrus fruits may expose human health to potential cancer risk. The findings of this study call the policymakers and public administrations to the formulation of stringent policies and actions to control biomass burning and vehicular emissions

Accounting students' IT applicaton skills over a 10-year period

This paper reports on the changing nature of a range of information technology (IT) application skills that students declare on entering an accounting degree over the period from 1996 to 2006. Accounting educators need to be aware of the IT skills students bring with them to university because of the implications this has for learning and teaching within the discipline and the importance of both general and specific IT skills within the practice and craft of accounting. Additionally, IT skills constitute a significant element within the portfolio of employability skills that are increasingly demanded by employers and emphasized within the overall Higher Education (HE) agenda. The analysis of students' reported IT application skills on entry to university, across a range of the most relevant areas of IT use in accounting, suggest that their skills have continued to improve over time. However, there are significant differential patterns of change through the years and within cohorts. The paper addresses the generalizability of these findings and discusses the implications of these factors for accounting educators, including the importance of recognising the differences that are potentially masked by the general increase in skills; the need for further research into the changing nature, and implications, of the gender gap in entrants' IT application skills; and the low levels of entrants' spreadsheet and database skills that are a cause for concern

Single-pot enzymatic synthesis of Dicer-substrate siRNAs

We describe an inexpensive and efficient method for generating functional pools of Dicer-substrate small interfering RNAs (siRNAs) in a single reaction tube. The method exploits a highly active form of the enzyme Dicer from Giardia lamblia, which is capable of accurately processing double-stranded RNA (dsRNA) into 25–27 nt RNA pools during in vitro transcription. The small RNAs produced function as substrates of human Dicer in vitro and induce gene silencing with potency equivalent to traditional siRNAs when introduced into mammalian cells. The overall reaction is simple, can be carried out in any laboratory with access to a PCR machine, and is amenable to high-throughput processes

Accumulation, Source Identification, and Cancer Risk Assessment of Polycyclic Aromatic Hydrocarbons (PAHs) in Different Jordanian Vegetables

The accumulation of polyaromatic hydrocarbons in plants is considered one of the most serious threats faced by mankind because of their persistence in the environment and their carcinogenic and teratogenic effect on human health. The concentrations of sixteen priority polycyclic aromatic hydrocarbons (16 PAHs) were determined in four types of edible vegetables (tomatoes, zucchini, eggplants, and cucumbers), irrigation water, and agriculture soil, where samples were collected from the Jordan Valley, Jordan. The mean total concentration of 16 PAHs (∑16PAHs) ranged from 10.649 to 21.774 µg kg−1 in vegetables, 28.72 µg kg−1 in soil, and 0.218 µg L−1 in the water samples. The tomato samples posed the highest ∑16PAH concentration level in the vegetables, whereas the zucchini samples had the lowest. Generally, the PAHs with a high molecular weight and four or more benzene rings prevailed among the studied samples. The diagnostic ratios and the principal component analysis (PCA) revealed that the PAH contamination sources in soil and vegetables mainly originated from a pyrogenic origin, traffic emission sources, and biomass combustion. The bioconcentration factors (BCF) for ∑16PAHs have been observed in the order of tomatoes > cucumbers and eggplants > zucchini. A potential cancer risk related to lifetime consumption was revealed based on calculating the incremental lifetime cancer risk of PAHs (ILCR). Therefore, sustainable agricultural practices and avoiding biomass combusting would greatly help in minimizing the potential health risk from dietary exposure to PAHs

Targeted knock-down of miR21 primary transcripts using snoMEN vectors induces apoptosis in human cancer cell lines

We have previously reported an antisense technology, 'snoMEN vectors', for targeted knock-down of protein coding mRNAs using human snoRNAs manipulated to contain short regions of sequence complementarity with the mRNA target. Here we characterise the use of snoMEN vectors to target the knock-down of micro RNA primary transcripts. We document the specific knock-down of miR21 in HeLa cells using plasmid vectors expressing miR21-targeted snoMEN RNAs and show this induces apoptosis. Knock-down is dependent on the presence of complementary sequences in the snoMEN vector and the induction of apoptosis can be suppressed by over-expression of miR21. Furthermore, we have also developed lentiviral vectors for delivery of snoMEN RNAs and show this increases the efficiency of vector transduction in many human cell lines that are difficult to transfect with plasmid vectors. Transduction of lentiviral vectors expressing snoMEN targeted to pri-miR21 induces apoptosis in human lung adenocarcinoma cells, which express high levels of miR21, but not in human primary cells. We show that snoMEN-mediated suppression of miRNA expression is prevented by siRNA knock-down of Ago2, but not by knock-down of Ago1 or Upf1. snoMEN RNAs colocalise with Ago2 in cell nuclei and nucleoli and can be co-immunoprecipitated from nuclear extracts by antibodies specific for Ago2

Biological insights from 108 schizophrenia-associated genetic loci

Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia