Deep sequencing of virus-infected cells reveals HIV-encoded small RNAs

Small virus-derived interfering RNAs (viRNAs) play an important role in antiviral defence in plants, insects and nematodes by triggering the RNA interference (RNAi) pathway. The role of RNAi as an antiviral defence mechanism in mammalian cells has been obscure due to the lack of viRNA detection. Although viRNAs from different mammalian viruses have recently been identified, their functions and possible impact on viral replication remain unknown. To identify viRNAs derived from HIV-1, we used the extremely sensitive SOLiDTM 3 Plus System to analyse viRNA accumulation in HIV-1-infected T lymphocytes. We detected numerous small RNAs that correspond to the HIV-1 RNA genome. The majority of these sequences have a positive polarity (98.1%) and could be derived from miRNAs encoded by structured segments of the HIV-1 RNA genome (vmiRNAs). A small portion of the viRNAs is of negative polarity and most of them are encoded within the 3′-UTR, which may represent viral siRNAs (vsiRNAs). The identified vsiRNAs can potently repress HIV-1 production, whereas suppression of the vsiRNAs by antagomirs stimulate virus production. These results suggest that HIV-1 triggers the production of vsiRNAs and vmiRNAs to modulate cellular and/or viral gene expression

Network-based social capital and capacity-building programs: an example from Ethiopia

<p>Abstract</p> <p>Introduction</p> <p>Capacity-building programs are vital for healthcare workforce development in low- and middle-income countries. In addition to increasing human capital, participation in such programs may lead to new professional networks and access to social capital. Although network development and social capital generation were not explicit program goals, we took advantage of a natural experiment and studied the social networks that developed in the first year of an executive-education Master of Hospital and Healthcare Administration (MHA) program in Jimma, Ethiopia.</p> <p>Case description</p> <p>We conducted a sociometric network analysis, which included all program participants and supporters (formally affiliated educators and mentors). We studied two networks: the Trainee Network (all 25 trainees) and the Trainee-Supporter Network (25 trainees and 38 supporters). The independent variable of interest was out-degree, the number of program-related connections reported by each respondent. We assessed social capital exchange in terms of resource exchange, both informational and functional. Contingency table analysis for relational data was used to evaluate the relationship between out-degree and informational and functional exchange.</p> <p>Discussion and evaluation</p> <p>Both networks demonstrated growth and inclusion of most or all network members. In the Trainee Network, those with the highest level of out-degree had the highest reports of informational exchange, χ²(1, <it>N </it>= 23) = 123.61, p < 0.01. We did not find a statistically significant relationship between out-degree and functional exchange in this network, χ²(1, <it>N </it>= 23) = 26.11, p > 0.05. In the Trainee-Supporter Network, trainees with the highest level of out-degree had the highest reports of informational exchange, χ²(1, <it>N </it>= 23) = 74.93, p < 0.05. The same pattern held for functional exchange, χ²(1, <it>N </it>= 23) = 81.31, p < 0.01.</p> <p>Conclusions</p> <p>We found substantial and productive development of social networks in the first year of a healthcare management capacity-building program. Environmental constraints, such as limited access to information and communication technologies, or challenges with transportation and logistics, may limit the ability of some participants to engage in the networks fully. This work suggests that intentional social network development may be an important opportunity for capacity-building programs as healthcare systems improve their ability to manage resources and tackle emerging problems.</p

The AIMSS Project – III. The Stellar Populations of Compact Stellar Systems

In recent years, a growing zoo of compact stellar systems (CSSs) have been found whose physical properties (mass, size, velocity dispersion) place them between classical globular clusters (GCs) and true galaxies, leading to debates about their nature. Here we present results using a so far underutilized discriminant, their stellar population properties. Based on new spectroscopy from 8–10m telescopes, we derive ages, metallicities, and [α/Fe] of 29 CSSs. These range from GCs with sizes of merely a few parsec to compact ellipticals (cEs) larger than M32. Together with a literature compilation, this provides a panoramic view of the stellar population characteristics of early-type systems. We find that the CSSs are predominantly more metal rich than typical galaxies at the same stellar mass. At high mass, the cEs depart from the mass–metallicity relation of massive early-type galaxies, which forms a continuous sequence with dwarf galaxies. At lower mass, the metallicity distribution of ultracompact dwarfs (UCDs) changes at a few times 107 M⊙, which roughly coincides with the mass where luminosity function arguments previously suggested the GC population ends. The highest metallicities in CSSs are paralleled only by those of dwarf galaxy nuclei and the central parts of massive early types. These findings can be interpreted as CSSs previously being more massive and undergoing tidal interactions to obtain their current mass and compact size. Such an interpretation is supported by CSSs with direct evidence for tidal stripping, and by an examination of the CSS internal escape velocities

Turning around an ailing district hospital: a realist evaluation of strategic changes at Ho Municipal Hospital (Ghana)

<p>Abstract</p> <p>Background</p> <p>There is a growing consensus that linear approaches to improving the performance of health workers and health care organisations may only obtain short-term results. An alternative approach premised on the principle of human resource management described as a form of 'High commitment management', builds upon a bundles of balanced practices. This has been shown to contribute to better organisational performance. This paper illustrates an intervention and outcome of high commitment management (HiCom) at an urban hospital in Ghana. Few studies have shown how HiCom management might contribute to better performance of health services and in particular of hospitals in low and middle-income settings.</p> <p>Methods</p> <p>A realist case study design was used to analyse how specific management practices might contribute to improving the performance of an urban district hospital in Ho, Volta Region, in Ghana. Mixed methods were used to collect data, including document review, in-depth interviews, group discussions, observations and a review of routine health information.</p> <p>Results</p> <p>At Ho Municipal Hospital, the management team dealt with the crisis engulfing the ailing urban district hospital by building an alliance between hospital staff to generate a sense of ownership with a focus around participative problem analysis. The creation of an alliance led to improving staff morale and attitude, and contributed also to improvements in the infrastructure and equipment. This in turn had a positive impact on the revenue generating capacity of the hospital. The quick turn around in the state of this hospital showed that change was indeed possible, a factor that greatly motivated the staff.</p> <p>In a second step, the management team initiated the development of a strategic plan for the hospital to maintain the dynamics of change. This was undertaken through participative methods and sustained earlier staff involvement, empowerment and feelings of reciprocity. We found that these factors acted as the core mechanisms underlying the changes taking place at Ho Municipal Hospital.</p> <p>Conclusions</p> <p>This study shows how a hospital management team in Ghana succeeded in resuscitating an ailing hospital. Their high commitment management approach led to the active involvement and empowerment of staff. It also showed how a realist evaluation approach such as this, could be used in the research of the management of health care organisations to explain how management interventions may or may not work.</p

Relocation to get venture capital : a resource dependence perspective

This is the author accepted manuscript. The final version is available from SAGE via the DOI in this record.Using a resource dependence perspective, we theorize and show that non-venture-capital-backed ventures founded in U.S. states with a lower availability of venture capital (VC) are more likely to relocate to California (CA) or Massachusetts (MA)—the two VC richest states—compared to ventures founded in states with a greater availability of VC. Moreover, controlling for self-selection, ventures that relocate to CA or MA subsequently have a greater probability of attracting initial VC compared to ventures that stay in their home state. We discuss the implications for theory, future research, and practice

A century of sea level measurements at Newlyn, SW England

The Newlyn Tidal Observatory is the most important sea level station in the UK. It commenced operations in 1915 as part of the Second Geodetic Levelling of England and Wales, and the mean sea level determined from the tide gauge during the first six years (May 1915-April 1921) defined Ordnance Datum Newlyn (ODN) which became the national height datum for the whole of Great Britain. The 100 years of sea level data now available have contributed significantly to many studies in oceanography, geology and climate change. This paper marks the centenary of this important station by reviewing the sea level (and, more recently, detailed land level) measurements and Newlyn’s contributions to UK cartography, geodesy and sea-level science in general. Recommendations are made on how sea and land level measurements at Newlyn might be enhanced in the future

Host Immune Response to Mosquito-Transmitted Chikungunya Virus Differs from That Elicited by Needle Inoculated Virus

Mosquito-borne diseases are a worldwide public health threat. Mosquitoes transmit viruses or parasites during feeding, along with salivary proteins that modulate host responses to facilitate both blood feeding and pathogen transmission. Understanding these earliest events in mosquito transmission of arboviruses by mosquitoes is essential for development and assessment of rational vaccine and treatment strategies. In this report, we compared host immune responses to chikungunya virus (CHIKV) transmission by (1) mosquito bite, or (2) by needle inoculation.Differential cytokine expression was measured using quantitative real-time RT-PCR, at sites of uninfected mosquito bites, CHIKV-infected mosquito bites, and needle-inoculated CHIKV. Both uninfected and CHIKV infected mosquitoes polarized host cytokine response to a TH2 profile. Compared to uninfected mosquito bites, expression of IL-4 induced by CHIKV-infected mosquitoes were 150 fold and 527.1 fold higher at 3 hours post feeding (hpf) and 6 hpf, respectively. A significant suppression of TH1 cytokines and TLR-3 was also observed. These significant differences may result from variation in the composition of uninfected and CHIKV-infected mosquito saliva. Needle injected CHIKV induced a robust interferon-gamma, no detectable IL-4, and a significant up-regulation of TLR-3.This report describes the first analysis of cutaneous cytokines in mice bitten by CHIKV-infected mosquitoes. Our data demonstrate contrasting immune activation in the response to CHIKV infection by mosquito bite or needle inoculation. The significant role of mosquito saliva in these earliest events of CHIKV transmission and infection are highlighted

Larval Development of Aedes aegypti and Aedes albopictus in Peri-Urban Brackish Water and Its Implications for Transmission of Arboviral Diseases

Aedes aegypti (Linnaeus) and Aedes albopictus Skuse mosquitoes transmit serious human arboviral diseases including yellow fever, dengue and chikungunya in many tropical and sub-tropical countries. Females of the two species have adapted to undergo preimaginal development in natural or artificial collections of freshwater near human habitations and feed on human blood. While there is an effective vaccine against yellow fever, the control of dengue and chikungunya is mainly dependent on reducing freshwater preimaginal development habitats of the two vectors. We show here that Ae. aegypti and Ae. albopictus lay eggs and their larvae survive to emerge as adults in brackish water (water with <0.5 ppt or parts per thousand, 0.5–30 ppt and >30 ppt salt are termed fresh, brackish and saline respectively). Brackish water with salinity of 2 to 15 ppt in discarded plastic and glass containers, abandoned fishing boats and unused wells in coastal peri-urban environment were found to contain Ae. aegypti and Ae. albopictus larvae. Relatively high incidence of dengue in Jaffna city, Sri Lanka was observed in the vicinity of brackish water habitats containing Ae. aegypti larvae. These observations raise the possibility that brackish water-adapted Ae. aegypti and Ae. albopictus may play a hitherto unrecognized role in transmitting dengue, chikungunya and yellow fever in coastal urban areas. National and international health authorities therefore need to take the findings into consideration and extend their vector control efforts, which are presently focused on urban freshwater habitats, to include brackish water larval development habitats