Viscoelastic properties of differentiating blood cells are fate- and function-dependent.

Although cellular mechanical properties are known to alter during stem cell differentiation, understanding of the functional relevance of such alterations is incomplete. Here, we show that during the course of differentiation of human myeloid precursor cells into three different lineages, the cells alter their viscoelastic properties, measured using an optical stretcher, to suit their ultimate fate and function. Myeloid cells circulating in blood have to be advected through constrictions in blood vessels, engendering the need for compliance at short time-scales (minutes), compared to undifferentiated cells. These findings suggest that reduction in steady-state viscosity is a physiological adaptation for enhanced migration through tissues. Our results indicate that the material properties of cells define their function, can be used as a cell differentiation marker and could serve as target for novel therapies

Actin polymerization as a key innate immune effector mechanism to control Salmonella infection.

Salmonellosis is one of the leading causes of food poisoning worldwide. Controlling bacterial burden is essential to surviving infection. Nucleotide-binding oligomerization domain-like receptors (NLRs), such as NLRC4, induce inflammasome effector functions and play a crucial role in controlling Salmonella infection. Inflammasome-dependent production of IL-1β recruits additional immune cells to the site of infection, whereas inflammasome-mediated pyroptosis of macrophages releases bacteria for uptake by neutrophils. Neither of these functions is known to directly kill intracellular salmonellae within macrophages. The mechanism, therefore, governing how inflammasomes mediate intracellular bacterial-killing and clearance in host macrophages remains unknown. Here, we show that actin polymerization is required for NLRC4-dependent regulation of intracellular bacterial burden, inflammasome assembly, pyroptosis, and IL-1β production. NLRC4-induced changes in actin polymerization are physically manifested as increased cellular stiffness, and leads to reduced bacterial uptake, production of antimicrobial molecules, and arrested cellular migration. These processes act in concert to limit bacterial replication in the cell and dissemination in tissues. We show, therefore, a functional link between innate immunity and actin turnover in macrophages that underpins a key host defense mechanism for the control of salmonellosis.Financial support for this work was provided by a Cambridge International Scholarship (to S.M.M.), European Research Council Starting Investigator Grant “LightTouch” 282060 (to J.R.G.), Biotechnology and Biological Sciences Research Council (BBSRC) Grants BB/H003916/1 and BB/K006436/1 and BBSRC Research Development Fellowship BB/ H021930/1 (to C.E.B.)This is the accepted manuscript. The final version is available from PNAS at http://www.pnas.org/content/111/49/17588.abstract

Harnessing the potential of African youth for transforming health research in Africa

Africa faces a significant burden of infectious diseases, including Malaria and HIV/AIDS, along with an increasing prevalence of non-infectious diseases such as diabetes and cancer. This dual health challenge is amplified by socioeconomic difficulties, restricted access to healthcare, and lifestyle changes, thus present unique scientific needs. Effectively addressing these issues requires a skilled scientific workforce adept in comprehensive healthcare strategies. This analysis explores the critical landscape of health research in Africa, emphasizing the unique opportunity presented by the continent’s youthful population, projected to reach almost 1 billion by 2050. The youth’s innovative potential and fresh perspectives offer a chance to overcome development barriers in health research. Nevertheless, challenges such as under-resourced education, limited research training, inadequate mentorship, and funding difficulties persist. This paper urgently calls upon African leaders, international partners, and stakeholders to prioritize health research, mobilize funding, forge strategic partnerships, and empower the youth as essential steps to capitalize on the continent’s dynamic youth for breakthrough health outcomes. Such investments are vital not just for health but for the overall economic, social, and strategic growth of the continent. Through shared responsibility and a united effort, the potential of African youth can be harnessed, leading to transformative research, improved health outcomes, and a prosperous future. This perspective represents the collective voice of passionate young researchers and advocates across Africa, calling for a new era of health research on the continent

PrimeStore MTM and OMNIgene sputum for the preservation of sputum for Xpert MTB/RIF testing in Nigeria

This research was funded by the European and Developing Countries Clinical Trial Partnership (EDCTP), grant number DRIA2014-309, and its co-funders were the Medical Research Council (MRC), UK, Instituto de Salud Carlos III (ISCIII Spain) and Global Affairs Canada, through the TB REACH Initiative of the Stop TB Partnership, Wave 5, project number STBP/TBREACH//GSA/W5-07.Background: Xpert MTB/RIF (GX) for tuberculosis (TB) diagnosis is often located in reference laboratories, and sputum needs to be transported using a cold chain. Transport media to preserve sputum are available, but performance data under programmatic conditions are limited. Methods: Sputum samples were collected from patients with presumptive TB in Nigeria. One sputum was transported in a cold chain, tested immediately with GX and cultured. One sputum was swabbed and stored in PrimeStore-Molecular-Transport-Medium (Primestore), and the remainder was stored in OMNIGene-sputum (Omnigene), kept for seven days and tested with GX. Results: Of 248 patients, 63 were fresh-sputum culture-positive and 56 GX-positive (sensitivity 88.9%, 95% CI: 78.4–95.4%). Four of 185 culture-negative patients were GX-positive (specificity 97.8%, 94.6–99.4%). Omnigene GX and Primestore GX were positive in 56/62 (90.3%, 80.1–96.4%) and 49/62 (79.0%, 66.8–88.3%) culture-positive, respectively, and 1/185 (99.5%, 97.0–100.0%) and 3/185 (98.4%, 95.3–99.7%) were culture-negative patients. 14 Human Immunodeficiency Virus (HIV)-infected and 44 HIV-uninfected patients were culture-positive. Omnigene and Primestore detected 12/14 (85.7%, 57.2–98.2%) and 5/14 (35.7%, 12.8–64.9%) HIV-infected and 41/44 (93.2%, 81.3–98.6%) HIV-uninfected culture-positive patients. Interpretation : Omnigene stored and fresh sputum samples had similar GX results. The GX results of Primestore-stored samples were similar to those found in the fresh sputum of non-HIV infected patients, but GX-positivity was lower in HIV-infected patients. This was likely due to the lower amount of bacilli collected by the swab and transferred to PrimeStore.Publisher PDFPeer reviewe

The influence of learning styles on knowledge acquisition in public sector management

This research note outlines a project designed to investigate the role of training institutions in providing effective training and development programmes for managers. The investigation is being carried out in the light of recent criticisms levelled against the nature of formal learning environments prevalent in most institutional settings. The traditional role of trainers and developers as the providers of knowledge and skills for the development of competent managers runs contrary to recent findings, which suggest that managers learn more effectively in informal settings, rather than the formal settings evident in many development programmes. The idea that explicitly extracted competencies are the target every manager should aim for to improve their effectiveness is also challenged because competencies alone are no longer regarded as a sufficient criterion for success. Recent research has attached greater importance to the need for helping managers to see knowledge as a social phenomenon, and one factor that might distinguish successful managers from others is tacit knowledge (Wagner & Sternberg, 1987; Argyris, 1999). A major focus of this study is to explore the possibility that the level and content of tacit knowledge acquired by managers may be influenced by their individual learning styles, and the degree to which their dominant styles are matched with the context of their work environment

Experiential learning and the acquisition of managerial tacit knowledge

Tacit knowledge is believed to be one factor that distinguishes successful managers from others. We sought to determine whether levels of accumulated managerial tacit knowledge (LAMTK) were associated with managers' dominant learning styles. Instruments used in the study, involving 356 Malaysian public sector employees, included Sternberg et al.'s (2000) Tacit Knowledge Inventory for Managers and a normative version of Kolb's (1999a) Learning Styles Inventory (LSI-Ill). Findings suggest that LAMTK is independent of the length of subjects' general work experience, but positively related to the amount of time spent working in a management context. Learning styles also had a significant relationship. Subjects who spent most of their time performing management functions and whose dominant learning styles were accommodating had significantly higher LAMTK than those with different learning styles. We also found support for the belief that learners with a strong preference for all four different abilities defined in Kolb's learning theory may be critical for effective experiential learning

Use of GIS and Remote Sensing Techniques for Environmental Monitoring and Evaluation of the Lower Qua Iboe River Estuary.

In: Cartography, GIS and Agricultural Development (Robert E. Ekpenyong and Nnabugwu Uluocha, Eds). P 26 - 4

Prevalence and risk factors for diabetes and diabetic retinopathy: results from the Nigeria national blindness and visual impairment survey.

BACKGROUND: In Nigeria, urbanisation and increasing life expectancy are likely to increase the incidence of non-communicable diseases. As the epidemic of diabetes matures, visual loss from diabetic retinopathy (DR) will increase unless mechanisms for early detection and treatment improve, and health systems respond to the growing burden of non-communicable diseases. METHODS: A nationally-representative population-based sample of 13,591 participants aged ≥40 years selected by multistage-stratified-cluster-random-sampling with probability-proportional-to-size procedures were examined in 305 clusters in Nigeria between January 2005 to June 2007. All were asked about history of diabetes and underwent basic eye examination. Visual acuity (VA) was measured using logMAR E-chart. Participants with VA11.1mmol/l or had DR. Data in the subsample were used to estimate the prevalence and to analyse risk factors for diabetes and DR using multivariable logistic regression. Additional information on the types of DR was obtained from participants not in the subsample. RESULTS: In the subsample, 164 participants were excluded due to missing data; and 1,595 analysed. 52/1,595 had diabetes, a prevalence of 3.3% (95%CI 2.5-4.3%); and 25/52(48%) did not know. Media opacity in 8/52 precluded retinal examination. 9/44(20.5%) had DR. Higher prevalence of diabetes was associated with urban residence (Odds ratio [OR]1.87) and overweight/obesity (OR3.02/4.43 respectively). Although not statistically significant, DR was associated with hypertension (OR3.49) and RBG>15.0mmol/L (OR8.10). Persons with diabetes had 3 times greater odds of blindness. Of 11,832 other participants in the study sample, 175(1.5%) had history of diabetes; 28 had DR. Types of DR (total=37) included 10.8% proliferative, 51.4% macular oedema. CONCLUSION: The age-adjusted prevalence of diabetes in Nigeria was 3.25% (95%CI 2.50-4.30) and over 10% of people with diabetes aged ≥40 years had sight-threatening-DR. These data will enable the development of better public health strategies for the control of diabetes and planning services for DR to prevent vision loss