Herpes Simplex Virus 1 (HSV-1) Infected Cell Protein 0 (ICP0) Targets of Ubiquitination during Productive Infection of Primary Adult Sensory Neurons

Herpes simplex virus 1 (HSV-1) enters sensory neurons with the potential for productive or latent infection. For either outcome, HSV-1 must curtail the intrinsic immune response, regulate viral gene expression, and remove host proteins that could restrict viral processes. Infected cell protein 0 (ICP0), a virus-encoded E3 ubiquitin ligase, supports these processes by mediating the transfer of ubiquitin to target proteins to change their location, alter their function, or induce their degradation. To identify ubiquitination targets of ICP0 during productive infection in sensory neurons, we immunoprecipitated ubiquitinated proteins from primary adult sensory neurons infected with HSV-1 KOS (wild-type), HSV-1 n212 (expressing truncated, defective ICP0), and uninfected controls using anti-ubiquitin antibody FK2 (recognizing K29, K48, K63 and monoubiquitinated proteins), followed by LC-MS/MS and comparative analyses. We identified 40 unique proteins ubiquitinated by ICP0 and 17 ubiquitinated by both ICP0 and host mechanisms, of which High Mobility Group Protein I/Y (HMG I/Y) and TAR DNA Binding Protein 43 (TDP43) were selected for further analysis. We show that ICP0 ubiquitinates HMG I/Y and TDP43, altering protein expression at specific time points during productive HSV-1 infection, demonstrating that ICP0 manipulates the sensory neuronal environment in a time-dependent manner to regulate infection outcome in neurons

Neurotrophic Factors NGF, GDNF and NTN Selectively Modulate HSV1 and HSV2 Lytic Infection and Reactivation in Primary Adult Sensory and Autonomic Neurons

Herpes simplex viruses (HSV1 and HSV2) establish latency in peripheral ganglia after ocular or genital infection, and can reactivate to produce different patterns and frequencies of recurrent disease. Previous studies showed that nerve growth factor (NGF) maintains HSV1 latency in embryonic sympathetic and sensory neurons. However, adult sensory neurons are no longer dependent on NGF for survival, some populations cease expression of NGF receptors postnatally, and the viruses preferentially establish latency in different populations of sensory neurons responsive to other neurotrophic factors (NTFs). Thus, NGF may not maintain latency in adult sensory neurons. To identify NTFs important for maintaining HSV1 and HSV2 latency in adult neurons, we investigated acute and latently-infected primary adult sensory trigeminal (TG) and sympathetic superior cervical ganglia (SCG) after NTF removal. NGF and glial cell line-derived neurotrophic factor (GDNF) deprivation induced HSV1 reactivation in adult sympathetic neurons. In adult sensory neurons, however, neurturin (NTN) and GDNF deprivation induced HSV1 and HSV2 reactivation, respectively, while NGF deprivation had no effects. Furthermore, HSV1 and HSV2 preferentially reactivated from neurons expressing GFRα2 and GFRα1, the high affinity receptors for NTN and GDNF, respectively. Thus, NTN and GDNF play a critical role in selective maintenance of HSV1 and HSV2 latency in primary adult sensory neurons

A survey of quality of life indicators in the Romanian Roma population following the ‘Decade of Roma Inclusion’ [version 3; referees: 2 approved, 1 approved with reservations]

Background: This study explores how the Roma in Romania, the EU’s most concentrated population, are faring in terms of a number of quality of life indicators, including poverty levels, healthcare, education, water, sanitation, and hygiene. It further explores the role of synthetic populations and modelling in identifying at-risk populations and delivering targeted aid. Methods: 135 surveys were conducted across five geographically diverse Romanian communities. Household participants were selected through a comprehensive random walk method. Analyses were conducted on all data using Pandas for Python. Combining land scan data, time-use survey analyses, interview data, and ArcGIS, the resulting synthetic population was analysed via classification and regression tree (CART) analysis to identify hot-spots of need, both ethnically and geographically. Results: These data indicate that the Roma in Romania face significant disparities in education, with Roma students less likely to progress beyond 8 th grade. In addition, the Roma population remains significantly disadvantaged with regard to safe and secure housing, poverty, and healthcare status, particularly in connection to diarrheal disease. In contrast, however, both Roma and non-Roma in rural areas face difficulties regarding full-time employment, sanitation, and water, sanitation, and hygiene infrastructure. In addition, the use of a synthetic population can generate information about ‘hot spots’ of need, based on geography, ethnicity, and type of aid required. Conclusions: These data demonstrate the challenges that remain to the Roma population in Romania, and also point to the myriad of ways in which all rural Romanians, regardless of ethnicity, are encountering hardship. This study highlights an approach that combines traditional survey data with more wide-reaching geographically based data and CART analysis to determine ‘hot spot’ areas of need in a given population. With the appropriate inputs, this tool can be extrapolated to any population in any country

Vorzeitige Vertragslösungen und Ausbildungsabbrüche in der dualen Berufsausbildung. Eine Studie aus der Perspektive von Lehrkräften an berufsbildenden Schulen.

Im Rahmen dieser Forschungsarbeit wird das Thema »Vorzeitige Vertragslösungen und Ausbildungsabbrüche in der dualen Berufsausbildung aus der Perspektive der Lehrkräfte an berufsbildenden Schulen« bearbeitet. Die vorzeitigen Vertragslösungen und Ausbildungsabbrüche stellen ein wesentliches Merkmal für die bildungspolitische Diskussion dar. In diesem Zusammenhang werden die Berufsschullehrkräfte bisher nur in geringem Maße beachtet. Aufgrund dessen wird in dieser Arbeit die Perspektive der Lehrkräfte gesondert untersucht. Die Lehrkräfte nehmen durch den Bildungsauftrag und die Nähe zu den Auszubildenden sowie durch den Lernort berufsbildende Schule eine relevante Position im Kontext von vorzeitigen Vertragslösungen und Ausbildungsabbrüchen ein. Die Perspektive der Lehrkräfte zu vorzeitigen Vertragslösungen und Ausbildungsabbrüchen wird qualitativ untersucht, indem mit 16 Lehrkräften von berufsbildenden Schulen Experteninterviews geführt wurden. Die zentralen Ergebnisse dieser Untersuchung lauten, dass die betrieblichen und die auf die Auszubildenden bezogenen Beweggründe die Hauptursachen von vorzeitigen Vertragslösungen und Ausbildungsabbrüchen aus der Perspektive der Lehrkräfte bilden. Besonders betont wird unter den betrieblichen Gründen beispielsweise die Ausbildungsqualität. Des Weiteren stellte sich bei der Studie heraus, dass insbesondere durch die Lehrkräfte die Präventionsaspekte als kennzeichnend für das Themengebiet herausgestellt werden. Die Lehrkräfte an berufsbildenden Schulen fungieren als ein wichtiges Element in Form einer beratenden Instanz bei vorzeitigen Vertragslösungen und Ausbildungsabbrüchen

Herpes simplex virus 1 and 2 educational assessment of young adults in rural southwest Virginia

<div><p>Purpose</p><p>Herpes simplex virus 2 (HSV-2) causes genital herpes, one of the most common sexually transmitted infections (STIs) in the U.S. HSV-1, commonly associated with cold sores, is increasing as a cause of genital herpes. Abstinence-only sexual health classes, commonly taught in Virginia, generate young adults who are under-educated in sexual health, increasing STI risks. College students in southwest Virginia were surveyed to assess comprehensiveness of high school health education regarding HSV-1 and HSV-2 and to identify students’ preferred methods for STI education.</p><p>Methods</p><p>To obtain data on knowledge of HSV, comprehensiveness of sexual health education in high school, and preferred learning methods, 237 college students participated in an online questionnaire and 28 students were interviewed using structured interviews.</p><p>Results</p><p>Questionnaire and interview data indicated that Family Life Education classes need to include more comprehensive information on prevention, viral transmission, and differences between HSV-1 and HSV-2. The majority of total respondents (both the questionnaire and interview) (65%) reported non-comprehensive high school sexual health education. The majority of interview (79%) and questionnaire (55%) respondents wished they had learned more about herpes and other STIs in high school. Education preferences of both interviewed and surveyed respondents included interactive internet programs or games, more realistic lectures, and learning about STIs later in high school when students reported greater sexual activity.</p><p>Conclusion</p><p>Our results indicate that more comprehensive sexual health education is needed and wanted by students in southwest Virginia. More relevant educational programs should be implemented for VA high school students utilizing technology and interactive methods to improve student engagement in sexual health education.</p><p>Implications and contribution</p><p>These studies provide information on knowledge of herpes simplex viruses among college students, comprehensiveness of sexual health education received in high schools, and preferred methods to learn about HSV and other STIs. These studies inform the facilitation of improved health education practices and programs for high school and college students.</p></div

Preferred methods for questionnaire respondents to learn about STIs and sexual health.

<p>The majority of respondents indicated a preference to learn either from a doctor or nurse, an interactive internet program, or from a lecture in class about STD/STIs. (n = 237).</p

Self reported infection of HSV-1 and HSV-2.

<p>The majority of respondents self-reported that they did not have either HSV1 or HSV2. (n = 236).</p

Interview respondents’ ideas for how to change the way sexual health education is taught in schools.

<p>Interview participants indicated a preference to learn from a younger instructor, have realistic lectures with real life stories, have workshops and guest speakers during sex education class, and to have sexual health education taught in the later years of high school (junior or senior year) because that was when they were more sexually active. (n = 26).</p