Zebrafish hoxd4a Acts Upstream of meis1.1 to Direct Vasculogenesis, Angiogenesis and Hematopoiesis

10.1371/journal.pone.0058857PLoS ONE83

COVID-19 Preventive Practices, Psychological Distress, and Reported Barriers to Healthcare Access during the Pandemic among Adult Community Members in Sub-Saharan Africa: A Phone Survey

The COVID-19 pandemic has had serious negative health and economic impacts in sub-Saharan Africa. Continuous monitoring of these impacts is crucial to formulate interventions to minimize the consequences of COVID-19. This study surveyed 2,829 adults in urban and rural sites among five sub-Saharan African countries: Burkina Faso, Ethiopia, Nigeria, Tanzania, and Ghana. Participants completed a mobile phone survey that assessed self-reported sociodemographics, COVID-19 preventive practices, psychological distress, and barriers to healthcare access. A modified Poisson regression model was used to estimate adjusted prevalence ratios (aPRs) and 95% CIs to investigate potential factors related to psychological distress and barriers to reduced healthcare access. At least 15.6% of adults reported experiencing any psychological distress in the previous 2 weeks, and 10.5% reported that at least one essential healthcare service was difficult to access 2 years into the pandemic. The majority of participants reported using several COVID-19 preventive methods, with varying proportions across the sites. Participants in the urban site of Ouagadougou, Burkina Faso (aPR: 2.29; 95% CI: 1.74–3.03) and in the rural site of Kintampo, Ghana (aPR: 1.68; 95% CI: 1.21–2.34) had a higher likelihood of experiencing any psychological distress compared with those in the rural area of Nouna, Burkina Faso. Loss of employment due to COVID-19 (aPR: 1.77; 95% CI: 1.47–2.11) was also associated with an increased prevalence of psychological distress. The number of children under 5 years in the household (aPR: 1.23; 95% CI: 1.14–1.33) and participant self-reported psychological distress (aPR: 1.83; 95% CI: 1.48–2.27) were associated with an increased prevalence of reporting barriers to accessing health services, whereas wage employment (aPR: 0.67; 95% CI: 0.49–0.90) was associated with decreased prevalence of reporting barriers to accessing health services. Overall, we found a high prevalence of psychological distress and interruptions in access to healthcare services 2 years into the pandemic across five sub-Saharan African countries. Increased effort and attention should be given to addressing the negative impacts of COVID-19 on psychological distress. An equitable and collaborative approach to new and existing preventive measures for COVID-19 is crucial to limit the consequences of COVID-19 on the health of adults in sub-Saharan Africa

COVID-19 vaccine hesitancy and its determinants among sub-Saharan African adolescents.

COVID-19 vaccine hesitancy among adolescents poses a challenge to the global effort to control the pandemic. This multi-country survey aimed to assess the prevalence and determinants of COVID-19 vaccine hesitancy among adolescents in sub-Saharan Africa between July and December 2021. The survey was conducted using computer-assisted telephone interviewing among adolescents in five sub-Saharan African countries, Burkina Faso, Ethiopia, Ghana, Nigeria, and Tanzania. A rural area and an urban area were included in each country (except Ghana, which only had a rural area), with approximately 300 adolescents in each area and 2662 in total. Sociodemographic characteristics and perceptions and attitudes on COVID-19 vaccines were measured. Vaccine hesitancy was defined as definitely not getting vaccinated or being undecided on whether to get vaccinated if a COVID-19 vaccine were available. Log-binomial models were used to calculate the adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs) for associations between potential determinants and COVID-19 vaccine hesitancy. The percentage of COVID-19 vaccine hesitancy was 14% in rural Kersa, 23% in rural Ibadan, 31% in rural Nouna, 32% in urban Ouagadougou, 37% in urban Addis Ababa, 48% in rural Kintampo, 65% in urban Lagos, 76% in urban Dar es Salaam, and 88% in rural Dodoma. Perceived low necessity, concerns about vaccine safety, and concerns about vaccine effectiveness were the leading reasons for hesitancy. Healthcare workers, parents or family members, and schoolteachers had the greatest impacts on vaccine willingness. Perceived lack of safety (aPR: 3.52; 95% CI: 3.00, 4.13) and lack of effectiveness (aPR: 3.46; 95% CI: 2.97, 4.03) were associated with greater vaccine hesitancy. The prevalence of COVID-19 vaccine hesitancy among adolescents is alarmingly high across the five sub-Saharan African countries, especially in Tanzania. COVID-19 vaccination campaigns among sub-Saharan African adolescents should address their concerns and misconceptions about vaccine safety and effectiveness

Initial Public Offerings and the Firm Location

The firm geographic location matters in IPOs because investors have a strong preference for newly issued local stocks and provide abnormal demand in local offerings. Using equity holdings data for more than 53,000 households, we show the probability to participate to the stock market and the proportion of the equity wealth is abnormally increasing with the volume of the IPOs inside the investor region. Upon nearly the universe of the 167,515 going public and private domestic manufacturing firms, we provide consistent evidence that the isolated private firms have higher probability to go public, larger IPO underpricing cross-sectional average and volatility, and less pronounced long-run under-performance. Similar but opposite evidence holds for the local concentration of the investor wealth. These effects are economically relevant and robust to local delistings, IPO market timing, agglomeration economies, firm location endogeneity, self-selection bias, and information asymmetries, among others. Findings suggest IPO waves have a strong geographic component, highlight that underwriters significantly under-estimate the local demand component thus leaving unexpected money on the table, and support state-contingent but constant investor propensity for risk

Breaches of contract in construction industry

The doctrine of freedom to contract, as the cornerstone of contract law in the common law countries (Malaysia inclusive) has consequently generated an extensive array of contracts of various characteristics and varieties. In Malaysia, there are two basic components in the contract documents used for the contracting of most construction work that is the Contract Conditions and technical specifications and drawings. As a general principle, once a party enters into a contract, he must perform his obligations strictly according to the terms of the contract. However, in the construction industry, breaches of contract are commonplace to the point of routine. Moreover, under the complicated provisions of many construction contracts the possible breaches of contract either by contractor or employer are numerous, and in each case the general principles must be applied in order to determine what, if any, damage is recoverable for the breach. This research therefore set out to illustrate the types of breaches of contract that are currently fashionable in Malaysian construction industry. The research is also to address the legal issues in relation to damages. The approach adopted in this research is documentary analysis of case laws. A total number of 53 cases were studied, where only 11 of them were associated with the breaches of contract. Findings show that there are 7 types of breaches existed in construction industry for the past thirty years. Most of the cases were breached due to the reason of “abandonment of work”. On the other hand, 3 legal issues closely related to damages were addressed in this research. In summary, findings of this research may assist the relevant parties in addressing and overcoming the problems associated to breaches of contract and creates a win-win situation for all parties in the Malaysian construction industry

Characterization of Creb-regulated transcription coactivator 1 (Crtc1) during embryogenesis of Zebrafish (Danio rerio)

The function of homeobox (HOX) proteins depends on formation of higher order complexes with members of the three-amino-acid-loop-extension (TALE) family of cofactors such as Myeloid Ecotropic Insertion Site (MEIS) and Pre-B-Cell Leukemia Homeobox (PBX). The importance of such complexes is to impart selectivity and specificity to HOX proteins in homing in to their target genes and to confer repressor or activator activity depending on cellular and environmental cues. Furthermore, the function of HOX complexes is regulated by PKA signalling in a manner dependent on interaction with the cAMP responsive element binding (CREB) transcription factor and its co-activators CREB Regulated Transcription Coactivator (CRTC) and CREB Binding Protein (CBP). The biological significance of such interactions has been demonstrated in the context of leukemogenesis; however, much remains to be elucidated in term of embryonic development. Zebrafish is a vertebrate model system which has been extensively used by developmental biologists due to its embryological and genetic tractability. The availability of knockdown technology mediated by antisense morpholino oligonucleotides has been instrumental in the study of gene function during zebrafish embryonic development. Our lab is interested in the study of the cooperative action of HOX-MEIS-PBX complexes with CREB-CRTC during embryonic development. We aim to achieve this by elucidating the genetic interactions of the complex members, particularly MEIS1 and CRTC1. The N-terminal region of CRTC1 has been shown to interact with C-terminal transactivation domain of MEIS1, thus bridging HOX and CREB biological functions. Several labs have characterized the role of meis1 during zebrafish development. However, crtc1 function has not been explored in zebrafish. The aim of this thesis is to characterize the biological role of crtc1 during zebrafish development by a reverse genetics approach using morpholino technology. I have characterized the spatial and temporal expression of crtc1 and crtc1b during zebrafish development, and identified unique splicing of maternal and zygotic specific crtc1b transcripts. Also, I have demonstrated the co-activator function of zebrafish Crtc1 and Crtc1b by using CRE luciferase reporter assay in cell culture. Morpholino knockdown of crtc1 or crtc1b suggested partial functional redundancy of the crtc1 members. Knockdown of crtc1 function provoked a phenotype that overlaps with that of meis1 or creb morphants, such as reduction of the eye and brain. In addition, crtc1 morphants exhibited smaller body size and abnormal body shape (e.g. “curly-tail-down” phenotype). ISH results demonstrated reduction in cells expressing neural and retinal progenitor/differentiation markers in morphants. Other biological processes were shown to be affected by crtc1 knockdown, namely perturbed notochord maturation (as assessed by persistent expression of shha and ihhb), early dorsal-ventral patterning (as indicated by ventral expansion of gsc expression), and convergence movement (as demonstrated by reduced myod-expressing cell migration toward the dorsal midline). These results provide a platform for future work to elucidate the collaborative role of meis1 and creb-crtc1 during zebrafish embryonic development.DOCTOR OF PHILOSOPHY (SBS

The Musical Styles Of The Berawan People Within The Upper Reaches Of Sungai Bunut, Sarawak, East Malaysia

This paper accompanies the production of a 20-minute observational documentary titled "Voices of Loagan Bunut". This document presents a series of cultural and personal portraits of Iban, Berawan and Penan musicians, singers and dancers living in the periphery of Loagan Bunut National Park (LBNP), Sarawak It also demonstrates the social finctions of traditional music in the context of this contemporary era of rapid modemisation. The documentary portrays two objectives. Firstly, the music traditions of the communities, which include the role of music in the culture and society, musical instruments and various forms of songs and dances. Secondly, it aims to highlight the current predicament faced by the musicians and their music. The digital recording media deployed ensures that historical data on the Iban, Berawan and Penan music and culture are more broadly disseminated and hence, appreciated

Loss of <i>hoxd4a</i> function impairs development of the vasculature.

<p>(A–D) Fluorescent images of the trunk and tail regions of Tg(<i>fli1</i>:EGFP) embryos at 48 hpf. The panels present merged bright field and fluorescent images (A,C) or fluorescent images only (B,D) The normal pattern of the vasculature (A,B) is severely disrupted in <i>hoxd4a</i> morphants (C,D) Dorsal extremities of ISV sprouts that fail to contact the DLAV are marked by white dots (D). The caudal vein plexus of control embryos (E, arrowheads) is replaced by a disorganized mass of endothelial tissue in <i>hoxd4a</i> morphants (F, arrowheads). (G–I) Alkaline phosphatase staining at 72 hpf revealing the vasculature in (G) control-injected larvae, (H) <i>hoxd4a</i> morphants, and (I) rescued larvae co-injected with capped mRNA for <i>hoxd4a</i>. Dorsal aorta (DA), posterior cardinal vein (PCV), inter-segmental vessels (ISV), caudal artery (CA), dorsal longitudinal anastomotic vessel (DLAV), caudal vein (CV) and vertebral artery (VTA). All images show lateral views, with anterior to the left and dorsal on top. Scale bars equal 100 µm.</p

<i>hoxd4a</i> is required for hemangioblast formation.

<p>(A,B) Normal expression at 13 hpf of posterior hemangioblast markers <i>scl1</i> (A) and <i>lmo2</i> (B) in the PLM. (C,D) Expression of these markers is greatly reduced in <i>hoxd4a</i> morphants, but is rescued by co-injection of capped mRNA for <i>hoxd4a</i> (E,F). Ratios indicate the fraction of embryos showing the presented phenotype. Anterior is to the left. A, C and E are dorsal views of flat-mounted specimens while B, D and F are lateral views. Scale bars equal 100 µm. A is at a lower magnification than C and E.</p

<i>meis1.1</i> is down regulated in <i>hoxd4a</i> morphants and <i>meis1.1</i> mRNA rescues hematopoietic and vasculogenic gene expression in <i>hoxd4a</i> morphants.

<p>Expression of <i>meis1.1</i> in control (A), morphant (B) and <i>hoxd4a</i>-rescuant (C) embryos at 26–28 hpf. (D–I) At 13 hpf, normal expression of <i>gata1</i>, <i>scl1</i> and <i>fli1</i> (D–F) is reduced in <i>hoxd4a</i> morphants (G–I), but rescued upon co-injection with capped mRNA for <i>meis1.1</i> (J–L). (M,N) Rescue of vascular patterning in <i>hoxd4a</i> morphants by co-injection with capped mRNA for <i>meis1.1</i> as visualized in Tg(fli1:EGFP) transgenics at 48 hpf (M) and by alkaline phosphatase staining at 72 hpf (N). Scale bars equal 100 µm.</p