ZAP's stress granule localization is correlated with its antiviral activity and induced by virus replication.

Cellular antiviral programs encode molecules capable of targeting multiple steps in the virus lifecycle. Zinc-finger antiviral protein (ZAP) is a central and general regulator of antiviral activity that targets pathogen mRNA stability and translation. ZAP is diffusely cytoplasmic, but upon infection ZAP is targeted to particular cytoplasmic structures, termed stress granules (SGs). However, it remains unclear if ZAP's antiviral activity correlates with SG localization, and what molecular cues are required to induce this localization event. Here, we use Sindbis virus (SINV) as a model infection and find that ZAP's localization to SGs can be transient. Sometimes no apparent viral infection follows ZAP SG localization but ZAP SG localization always precedes accumulation of SINV non-structural protein, suggesting virus replication processes trigger SG formation and ZAP recruitment. Data from single-molecule RNA FISH corroborates this finding as the majority of cells with ZAP localization in SGs contain low levels of viral RNA. Furthermore, ZAP recruitment to SGs occurred in ZAP-expressing cells when co-cultured with cells replicating full-length SINV, but not when co-cultured with cells replicating a SINV replicon. ZAP recruitment to SGs is functionally important as a panel of alanine ZAP mutants indicate that the anti-SINV activity is correlated with ZAP's ability to localize to SGs. As ZAP is a central component of the cellular antiviral programs, these data provide further evidence that SGs are an important cytoplasmic antiviral hub. These findings provide insight into how antiviral components are regulated upon virus infection to inhibit virus spread

Comparison of three topologies for VRM fast transient application

This paper compares three topologies for voltage regulator module VRM for fast transient application. The topologies are the most popular multi-phase converter, a synchronous rectifier buck converter topology and a recently introduced new stepping inductor converter. Analysis and simulation show that the stepping inductor topology gives the fastest response with minimal amount of output filter capacitance.published_or_final_versio

Loss analysis of a single phase fast transient VRM converter

This paper analyzes the losses of a stepping inductor converter in the presence of load transients. Stepping inductor converter is a buck VRM topology which only employs a single phase. Stepping inductor converter is very effective in dealing with fast transient and at the same time it can give better steady state efficiency. Occurrences of transient load current changes are measured in a PC and data are used for the comparison to evaluate the real world performance of the stepping inductor converter and the multiphase interleaved buck converter.published_or_final_versio

Prevalence of workplace violence against nurses in Hong Kong

Objectives. To determine the prevalence and nature of workplace violence against nurses, and how nurses deal with such aggression; and to identify the risk factors related to violence in the hospital environment. Design. Cross-sectional questionnaire study. Setting. University teaching hospital, Hong Kong. Participants. All nursing staff in the hospital, except nurses who were unable to read Chinese or who did not have patient contact (eg those worked in administrative positions), were invited to complete a questionnaire. Main outcome measures. Demographic data of the respondents, incidence of and risk factors contributing to workplace violence. Results. A total of 420 nurses returned the completed questionnaire (response rate, 25%). Three hundred and twenty (76%; 95% confidence interval, 72-80%) nurses reported abuse of any kind - verbal abuse, 73%; bullying, 45%; physical abuse, 18%; and sexual harassment, 12%. Most (82%) nurses who experienced verbal abuse tended to confide in friends, family members, or colleagues. Some (42%) ignored the incident. Risk factors for workplace violence included: working in male wards and in certain specialties such as the Accident and Emergency Department, Community Nursing Service, and the Orthopaedics and Traumatology Department. Conclusion. Workplace violence against nurses is a significant problem in Hong Kong. Further large-scale studies should be conducted to more closely examine the problem.published_or_final_versio

Genetic Relationship Between Endometriosis and Melanoma

Epidemiological studies have observed that risk of endometriosis is associated with history of cutaneous melanoma and vice versa. Evidence for shared biological mechanisms between the two traits is limited. The aim of this study was to investigate the genetic correlation and causal relationship between endometriosis and melanoma. Summary statistics from genome-wide association meta-analyses (GWAS) for endometriosis and melanoma were used to estimate the genetic correlation between the traits and Mendelian randomization was used to test for a causal association. When using summary statistics from separate female and male melanoma cohorts we identified a significant positive genetic correlation between melanoma in females and endometriosis (rg = 0.144, se = 0.065, p = 0.025). However, we find no evidence of a correlation between endometriosis and melanoma in males or a combined melanoma dataset. Endometriosis was not genetically correlated with skin color, red hair, childhood sunburn occasions, ease of skin tanning, or nevus count suggesting that the correlation between endometriosis and melanoma in females is unlikely to be influenced by pigmentary traits. Mendelian Randomization analyses also provided evidence for a relationship between the genetic risk of melanoma in females and endometriosis. Colocalization analysis identified 27 genomic loci jointly associated with the two diseases regions that contain different causal variants influencing each trait independently. This study provides evidence of a small genetic correlation and relationship between the genetic risk of melanoma in females and endometriosis. Genetic risk does not equate to disease occurrence and differences in the pathogenesis and age of onset of both diseases means it is unlikely that occurrence of melanoma causes endometriosis. This study instead provides evidence that having an increased genetic risk for melanoma in females is related to increased risk of endometriosis. Larger GWAS studies with increased power will be required to further investigate these associations

Phenotypic and molecular assessment of seven patients with 6p25 deletion syndrome: Relevance to ocular dysgenesis and hearing impairment

BACKGROUND: Thirty-nine patients have been described with deletions involving chromosome 6p25. However, relatively few of these deletions have had molecular characterization. Common phenotypes of 6p25 deletion syndrome patients include hydrocephalus, hearing loss, and ocular, craniofacial, skeletal, cardiac, and renal malformations. Molecular characterization of deletions can identify genes that are responsible for these phenotypes. METHODS: We report the clinical phenotype of seven patients with terminal deletions of chromosome 6p25 and compare them to previously reported patients. Molecular characterization of the deletions was performed using polymorphic marker analysis to determine the extents of the deletions in these seven 6p25 deletion syndrome patients. RESULTS: Our results, and previous data, show that ocular dysgenesis and hearing impairment are the two most highly penetrant phenotypes of the 6p25 deletion syndrome. While deletion of the forkhead box C1 gene (FOXC1) probably underlies the ocular dysgenesis, no gene in this region is known to be involved in hearing impairment. CONCLUSIONS: Ocular dysgenesis and hearing impairment are the two most common phenotypes of 6p25 deletion syndrome. We conclude that a locus for dominant hearing loss is present at 6p25 and that this locus is restricted to a region distal to D6S1617. Molecular characterization of more 6p25 deletion patients will aid in refinement of this locus and the identification of a gene involved in dominant hearing loss

A common intronic variant of PARP1 confers melanoma risk and mediates melanocyte growth via regulation of MITF

Previous genome-wide association studies have identified a melanoma-associated locus at 1q42.1 that encompasses a ~100-kb region spanning the PARP1 gene. Expression quantitative trait locus (eQTL) analysis in multiple cell types of the melanocytic lineage consistently demonstrated that the 1q42.1 melanoma risk allele (rs3219090[G]) is correlated with higher PARP1 levels. In silico fine-mapping and functional validation identified a common intronic indel, rs144361550 (−/GGGCCC; r2 = 0.947 with rs3219090), as displaying allele-specific transcriptional activity. A proteomic screen identified RECQL as binding to rs144361550 in an allele-preferential manner. In human primary melanocytes, PARP1 promoted cell proliferation and rescued BRAFV600E-induced senescence phenotypes in a PARylation-independent manner. PARP1 also transformed TERT-immortalized melanocytes expressing BRAFV600E. PARP1-mediated senescence rescue was accompanied by transcriptional activation of the melanocyte-lineage survival oncogene MITF, highlighting a new role for PARP1 in melanomagenesis

Multichannel electrocardiogram diagnostics for the diagnosis of arrhythmogenic right ventricular dysplasia

Aims: The identification of arrhythmogenic right ventricular dysplasia (ARVD) from 12-channel standard electrocardiogram (ECG) is challenging. High density ECG data may identify lead locations and criteria with a higher sensitivity. Methods and results: Eighty-channel ECG recording from patients diagnosed with ARVD and controls were quantified by magnitude and integral measures of QRS and T waves and by a measure (the average silhouette width) of differences in the shapes of the normalized ECG cycles. The channels with the best separability between ARVD patients and controls were near the right ventricular wall, at the third intercostal space. These channels showed pronounced differences in P waves compared to controls as well as the expected differences in QRS and T waves. Conclusion: Multichannel recordings, as in body surface mapping, add little to the reliability of diagnosing ARVD from ECGs. However, repositioning ECG electrodes to a high anterior position can improve the identification of ECG variations in ARVD. Additionally, increased P wave amplitude appears to be associated with ARVD

Physical and Electrical Performance of Vapor–Solid Grown ZnO Straight Nanowires

Physical and electrical properties of wurtzitic ZnO straight nanowires grown via a vapor–solid mechanism were investigated. Raman spectrum shows four first-order phonon frequencies and a second-order Raman frequency of the ZnO nanowires. Electrical and photoconductive performance of individual ZnO straight nanowire devices was studied. The results indicate that the nanowires reported here are n-type semi-conductors and UV light sensitive, and a desirable candidate for fabricating UV light nanosensors and other applications

3D Printed Bioscaffolds for Developing Tissue-Engineered Constructs

Tissue engineering techniques enable the fabrication of tissue substitutes integrating cells, biomaterials, and bioactive compounds to replace or repair damaged or diseased tissues. Despite the early success, current technology is unable to fabricate reproducible tissue-engineered constructs with the structural and functional similarity of the native tissue. The recent development of 3D printing technology empowers the opportunities of developing biofunctional complex tissue substitutes via layer-by-layer fabrication of cell(s), biomaterial(s), and bioactive compound(s) in precision. In this chapter, the current development of fabricating tissue-engineered constructs using 3D bioprinting technology for potential biomedical applications such as tissue replacement therapy, personalized therapy, and in vitro 3D modeling for drug discovery will be discussed. The current challenges, limitations, and role of stakeholders to grasp the future success also will be highlighted