Impact of template backbone heterogeneity on RNA polymerase II transcription.

Variations in the sugar component (ribose or deoxyribose) and the nature of the phosphodiester linkage (3'-5' or 2'-5' orientation) have been a challenge for genetic information transfer from the very beginning of evolution. RNA polymerase II (pol II) governs the transcription of DNA into precursor mRNA in all eukaryotic cells. How pol II recognizes DNA template backbone (phosphodiester linkage and sugar) and whether it tolerates the backbone heterogeneity remain elusive. Such knowledge is not only important for elucidating the chemical basis of transcriptional fidelity but also provides new insights into molecular evolution. In this study, we systematically and quantitatively investigated pol II transcriptional behaviors through different template backbone variants. We revealed that pol II can well tolerate and bypass sugar heterogeneity sites at the template but stalls at phosphodiester linkage heterogeneity sites. The distinct impacts of these two backbone components on pol II transcription reveal the molecular basis of template recognition during pol II transcription and provide the evolutionary insight from the RNA world to the contemporary 'imperfect' DNA world. In addition, our results also reveal the transcriptional consequences from ribose-containing genomic DNA

BindingDB in 2015: A public database for medicinal chemistry, computational chemistry and systems pharmacology.

BindingDB, www.bindingdb.org, is a publicly accessible database of experimental protein-small molecule interaction data. Its collection of over a million data entries derives primarily from scientific articles and, increasingly, US patents. BindingDB provides many ways to browse and search for data of interest, including an advanced search tool, which can cross searches of multiple query types, including text, chemical structure, protein sequence and numerical affinities. The PDB and PubMed provide links to data in BindingDB, and vice versa; and BindingDB provides links to pathway information, the ZINC catalog of available compounds, and other resources. The BindingDB website offers specialized tools that take advantage of its large data collection, including ones to generate hypotheses for the protein targets bound by a bioactive compound, and for the compounds bound by a new protein of known sequence; and virtual compound screening by maximal chemical similarity, binary kernel discrimination, and support vector machine methods. Specialized data sets are also available, such as binding data for hundreds of congeneric series of ligands, drawn from BindingDB and organized for use in validating drug design methods. BindingDB offers several forms of programmatic access, and comes with extensive background material and documentation. Here, we provide the first update of BindingDB since 2007, focusing on new and unique features and highlighting directions of importance to the field as a whole

Pedagogía del corazón y desempeño docente percibido por los estudiantes de un centro de educación técnico productivo de Villa El Salvador

El objetivo de la presente investigación fue determinar la relación entre la Pedagogía del corazón y el desempeño docente desde la percepción de los estudiantes. La investigación se ciñe a un diseño No Experimental, correlacional no causal. La muestra estuvo conformada por 186 estudiantes, cuyas edades oscilan entre los 18 y 60 años, todos provenientes de un Centro de Educación Técnico Productivo (CETPRO) de Villa El Salvador. Para los fines del estudio se diseñaron dos cuestionarios a los cuales se les realizaron los respectivos análisis psicométricos para determinar sus evidencias de validez y fiabilidad. El primer instrumento utilizado fue el Cuestionario de Pedagogía del corazón y el segundo instrumento fue el Cuestionario de desempeño docente, los cuales alcanzaron adecuadas medidas de validez y fiabilidad para la muestra de estudio. Entre los principales resultados se halló que la pedagogía del corazón tiene una relación directa y estadísticamente significativa con el desempeño docente y con un tamaño de efecto medio.The objective of the present investigation was to determine the relationship between the Pedagogy of the heart and the teaching performance from the perception of the students. The research adheres to a non-experimental, non-causal correlational design. The sample consisted of 186 students, whose ages range between 18 and 60, all from a Center for Productive Technical Education (CETPRO) of Villa El Salvador. For the purposes of the study, two questionnaires were designed to which the respective psychometric analyzes were performed to determine their evidence of validity and reliability. The first instrument used was the Heart Pedagogy Questionnaire and the second instrument was the Teacher Performance Questionnaire, which achieved adequate validity and reliability measures for the study sample. Among the main results, it was found that the pedagogy of the heart has a direct and statistically significant relationship with teaching performance and with an average effect size

Social and family characteristics of Hispanics with epilepsy

AbstractThe purpose of this study is to determine how acculturation, social support, family emotional involvement, perceived family criticism and stigma are associated with epilepsy self-efficacy and depression. A principal components analysis (PCA) was used to describe the salience of these characteristics within a sample of Hispanics with epilepsy.A total of 50 Hispanic adults of Mexican descent identified in our Epilepsy Clinic participated in this study. The PCA identified four distinct types, two were relatively culture-free, and two were distinctly culturally oriented. The first non-culture affiliated type described a well-adjusted group of individuals that tended to be males with moderate self-efficacy, who received social support, and who were unlikely to have depression or feel stigmatized. The second non-culture affiliated type described a dimension in which family emotional involvement tended to co-occur with perceived criticism. The Anglo-oriented group had a family environment that did not appear to criticize the individual with epilepsy and had good self-efficacy. The Mexican-oriented group had high self-efficacy and was unlikely to have depression. Results suggest that acculturation variables must be taken into consideration among ethnic groups because social, psychological and acculturation variables interact in complex ways. Additionally, it is clear that a diagnosis of epilepsy does not automatically lead to poor quality of life, stigma, or depression

Functional interplay between NTP leaving group and base pair recognition during RNA polymerase II nucleotide incorporation revealed by methylene substitution.

RNA polymerase II (pol II) utilizes a complex interaction network to select and incorporate correct nucleoside triphosphate (NTP) substrates with high efficiency and fidelity. Our previous 'synthetic nucleic acid substitution' strategy has been successfully applied in dissecting the function of nucleic acid moieties in pol II transcription. However, how the triphosphate moiety of substrate influences the rate of P-O bond cleavage and formation during nucleotide incorporation is still unclear. Here, by employing β,γ-bridging atom-'substituted' NTPs, we elucidate how the methylene substitution in the pyrophosphate leaving group affects cognate and non-cognate nucleotide incorporation. Intriguingly, the effect of the β,γ-methylene substitution on the non-cognate UTP/dT scaffold (∼3-fold decrease in kpol) is significantly different from that of the cognate ATP/dT scaffold (∼130-fold decrease in kpol). Removal of the wobble hydrogen bonds in U:dT recovers a strong response to methylene substitution of UTP. Our kinetic and modeling studies are consistent with a unique altered transition state for bond formation and cleavage for UTP/dT incorporation compared with ATP/dT incorporation. Collectively, our data reveals the functional interplay between NTP triphosphate moiety and base pair hydrogen bonding recognition during nucleotide incorporation

Recruiting Volunteers for New Horizons\u27 Apprenticeship Program for Homeless Young Adults

Introduction New Horizons is a Seattle-based organization focused on meeting the basic needs of homeless young adults ages 18-25 through food, shelter, clothing, health clinics, and social work appointments. To help their clients achieve a sustainable lifestyle, New Horizons addresses the most challenging obstacles including job and house hunting through an innovative apprenticeship program through their café, Street Bean Coffee Roasters. Clients can learn skills transferable to other careers, including barista basics, work experience, and networking. Our project is to help New Horizons find volunteers or employees for their apprenticeship program. In finding volunteers or employees for the café, we are providing professional training and networking opportunities for the apprentices so when the apprenticeship program is completed, the participants have job experience for their resume and connections to assist in their job search. In addition to recruiting staff for the café, we are also building a connection between New Horizons and Seattle Pacific University’s (SPU) volunteer groups in hopes of providing more volunteer opportunities and creating a quarterly volunteer event. Background Homelessness is a local and national crisis, disproportionately affecting Black, Native American, Hispanic, and LGBTQ populations (Huffman et al., 2021). According to the National Conference of State Legislators (NSCL, 2022), an estimated 4.2 million youth and young adults experience homelessness each year. Of these, about 700,000 are unaccompanied minors, meaning they are not part of a family or accompanied by a parent or guardian. In Seattle, the homeless population has risen exponentially. According to New Horizons (2018), “The number of unstably housed persons in King County has steadily risen by roughly 20% each year for the past three years”; over 1,500 youth in King County are affected by homelessness. The barriers the homeless youth encounter can be divided into four groups: domestic, health, bureaucratic, and social support (Huffman et al., 2021). Issues identified within these categories include maintaining personal hygiene, inability to find and receive proper medical treatment, education and employment gaps, criminal records, and limited support from potential employers. These issues are multifactorial, overlapping and intersecting on multiple planes, “mutually reinforcing the structures undergirding work and home” (Huffman et al., 2021), creating the ‘scaffolded city’ phenomenon the homeless population lives within. A survey conducted to analyze the needs insecurity among Florida college students identified extensive support programs as essential to the inclusion of students traditionally excluded by higher education via remediation, transfer, vocational training, and contract education (Nix et al., 2021). New Horizons confronts most of these challenges by providing an abundance of holistic resources for the homeless youths of Seattle. Although there is a lot known about the social inequities that the homeless youth population face, there is not much information regarding sustainable resources to transition off the streets and become included in the socioeconomic world. A quasi-experimental longitudinal study aimed to assess the feasibility of improving socioeconomic inclusion outcomes by supporting identity capital in youths who struggled to shake the identity of homelessness (Thulien et al., 2021). Identity capital includes fostering hope, focusing on personal strengths, and improving self-esteem. Most notably, many participants expressed gratitude for the normalization of strategies and skills they learned, framing them as something one needs (Thulien et al., 2021). These findings suggest that targeting identity capital is feasible and may be a promising approach to incorporate into a more complex intervention that includes housing, education, and employment resources to help youth transition out of homelessness. New Horizons offers an apprenticeship program through Street Bean Coffee that gives a chance to gain work experience and skills, but also provides networking opportunities and higher chances of long-term employment. Activities with Rationale To support the community of New Horizons our group has developed flyers with QR codes and other deliverables to help find adequate staffing, volunteers, and providing supplies. The QR codes itself has direct links to their amazon wish list, donation needs, volunteer page, street bean coffee roaster barista position. With these codes people can access their website to not just look for a job position but it provides awareness to a community in need of support. We also were able to connect New Horizons with SPU’s volunteer programs Latreia an Urban Involvement. Our group provided resources and points of contact to the coordinator of these SPU volunteer programs in hopes the relationship between New Horizons and SPU would strengthen. This connection allows for there to be volunteer events to better assist and help serve the community. Outcomes We had short term goals of providing for the population of New Horizons through creation of resources so that they can utilize them to cater to their needs and New Horizons will receive student volunteers from Latreia before March 9th 2022. Our long-term goals were to have the homeless youth population located around New Horizons gain more knowledge regarding resources that are available to them, such as job opportunities via Street Bean Coffee Roasters within 3 months and have New Horizons obtain a consistent flow of volunteers and resources via collaboration with SPU\u27s Urban Involvement, quarterly. These short term goals were both met while the long term goals are still in progress. Evaluation The utilization of mixed methods, both qualitative and quantitative data, proves to help evaluate the success of our interventions more efficiently (Abilgaard et al., 2016). The qualitative data analyzed was whether the barista position was filled and whether SPU’s volunteer programs formed a connection with New Horizons. After the initiation of our interventions, there was the removal of the job application on New Horizons website, the barista position filled, and Latreia partnering with New Horizons where a group of SPU volunteers painting their garage to be used as a blank canvas for young adults to do graffiti artwork. These outcomes display evidence of an effective relationship between SPU’s volunteering programs and New Horizons and our goals being met. The quantitative data analyzed was the number of people that attended the Latreia event and how many people scanned the flyer QR codes. Ten volunteers attended the event compared to their average range of 10-15 people that regularly attend their events. Data collected from the QR code tracking website suggested that 34 people scanned the QR code for the barista position, 28 people scanned the QR code for New Horizon’s Amazon wish list, and 27 people scanned the QR code for the volunteering page. These evaluations proved that the SPU community interacted with the flyers and were successful in bringing attention to New Horizons’ needs. Conclusion To help New Horizons and the community they serve we were able to help them form long term relationships that will continue on when we leave. By creating this relationship with SPU volunteer programs and access to a new barista, New Horizons can better serve the population of homeless youth through job training and acts of service. With the aid of our interventions bringing awareness to New Horizons by various means, we were able to engage with their culture to help change their world. Limitations of Research There are limitations to our project and research. Due to the COVID-19 pandemic, there is a limited amount of recent national and local research and statistics available to analyze and collect around homelessness (NSCL, 2022). Due to social distancing and isolation precautions, surveys and data collection cannot be completed or are very limited (NSCL, 2022). The small sample size or cross-sectional instead of longitudinal methods can limit a study. Diversity in age groups and selected sample size may not represent the total population (Thulien et al., 2021). Different geographic locations or urban vs rural areas may affect the availability of resources, programs, or tactics utilized based on the prevalence of the homeless population. In Nix et al. (2021), the inadequacy of faculty and staff training was evident in varied faculty and staff awareness of basic need opportunities. For future interview-based studies such as Huffman et al. (2021), training young adults who have experience being homeless to conduct the interviews may mediate socioeconomic differences between interviewers and interviewees, allowing for more fully open reflection, trust, and nuanced interpretation. Shared experiences between the interviewers and interviewees may also demonstrate effectiveness of apprenticeship programs for homeless youths while providing a supportive role model who has transitioned from their homeless identity into a successfully employed individual with professional networking connections. References Abildgaard, J., Saksvik, P., & Nielsen, K. (2016). How to measure the intervention process: An assessment of qualitative and quantitative approaches to data collection in the process evaluation of organizational interventions. Frontiers in Psychology, 7, Article 1380. https://doi.org/10.3389/fpsyg.2016.01380 Huffman, T., Leier, C., Generous. M., Hinrichs, M., & Brenneman, L. (2021). Climbing the ‘scaffolded city’: Tactics used by homeless young adults to navigate employment barriers. Journal of Applied Communication Research, 49(2), 148-167. https://doi.org/10.1080/00909882.2020.1839119 National Conference of State Legislatures. (2022). Youth homelessness overview. National Conference of State Legislatures. https://www.ncsl.org/research/human-services/homeless-and-runaway-youth.aspx New Horizons. (2018). About: Youth homelessness. New Horizons. https://nhmin.org/youth-homelessness-seattle/ Nix, A., Bertrand Jones, T., Daniels, H., Hu, P., & Hu, S. (2021). “There’s so much that we’re doing”: How Florida college system institutions address basic needs insecurity among students. Community College Review, 1, 1-20. https://doi.org/10.1177/00915521211047674 Thulien, N., Wang, A., Mathewson, C., Wang, R., & Hwang, S. (2021). Tackling exclusion: A pilot mixed method quasi-experimental identity capital intervention for young people exiting homelessness. PLoS ONE, 16(8), 1-19. https://doi.org/10.1371/journal.pone.025628

Markers of cardiac dysfunction in cognitive impairment and dementia

Markers of cardiac dysfunction such as amino terminal pro-brain natriuretic peptide (NTpro-BNP) and high sensitivity cardiac troponin T (hs-cTnT) may be associated with dementia. However, limited data exist on their association with either pre-dementia stages, that is, cognitive impairment no dementia (CIND), or the burden of cerebrovascular diseases (CeVD). We therefore, examined the association of these biomarkers of cardiac dysfunction with CeVD in both CIND and dementia. A case–control study, with cases recruited from memory clinics and controls from memory clinics and community. All subjects underwent collection of blood samples, neuropsychological assessment, and neuroimaging. Subjects were classified as CIND and dementia based on clinical criteria whilst significant CeVD was defined as the presence of cortical infarcts and/or more than 2 lacunes and/or confluent white matter lesions in two regions of brain on Age-Related White Matter Changes Scale. We included a total of 35 controls (mean age: 65.9 years), 78 CIND (mean age: 70.2 years) and 80 cases with dementia (mean age: 75.6 years). Plasma concentrations of hs-cTnT were associated significantly with CeVD in both CIND (odds ratios [OR]: 9.05; 95% confidence interval [CI]: 1.64–49.79) and dementia (OR: 16.89; 95%CI: 2.02–142.67). In addition, NTpro-BNP was associated with dementia with CeVD (OR: 7.74; 95%CI: 1.23–48.58). These associations were independent of other vascular risk factors. In this study, we showed that plasma NTproBNP and hs-cTnT are associated with dementia and CIND, only when accompanied by presence of CeVD

Humic acid and indigenous microbe treatments for better yield of pak choy grown in dairy farm effluent compost

The consumption of Pak Choy in Malaysia is higher than the local production. This vegetable has to be imported to meet the demand. The present study was carried out to investigate the effect of humic acid (HA) and indigenous microbe formulation (IMF) on the growth and yield of Curly Dwarf Pak Choy (CDP) grown in 100 % dairy farm effluent compost (DFEC). DFEC was sterilized and added or not added with HA, IMF or NPK 15: 15: 15. The vegetable was planted in 18 L pots. The treatments were applied following a completely randomized design of three replicates with three CDP per replicate. Data were collected for growth (plant height, leaf number, leaf area, and root length) and yield (fresh and dry matter weights). Addition of HA or IMF alone or in combination did not increase the growth and yield significantly. Yield was better only when HA + IMF was added with NPK where the CDP achieved 63.98 g fresh weight/plant (52.40 g/pot). HA+IMF appears to increase nutrient uptake. HA+IMF is recommended for farmers to use together with NPK to improve Pak Choy production