94 research outputs found
Interaction and Modulation of Two Antagonistic Cell Wall Enzymes of Mycobacteria
Bacterial cell growth and division require coordinated cell wall hydrolysis and synthesis, allowing for the removal and expansion of cell wall material. Without proper coordination, unchecked hydrolysis can result in cell lysis. How these opposing activities are simultaneously regulated is poorly understood. In Mycobacterium tuberculosis, the resuscitation-promoting factor B (RpfB), a lytic transglycosylase, interacts and synergizes with Rpf-interacting protein A (RipA), an endopeptidase, to hydrolyze peptidoglycan. However, it remains unclear what governs this synergy and how it is coordinated with cell wall synthesis. Here we identify the bifunctional peptidoglycan-synthesizing enzyme, penicillin binding protein 1 (PBP1), as a RipA-interacting protein. PBP1, like RipA, localizes both at the poles and septa of dividing cells. Depletion of the ponA1 gene, encoding PBP1 in M. smegmatis, results in a severe growth defect and abnormally shaped cells, indicating that PBP1 is necessary for viability and cell wall stability. Finally, PBP1 inhibits the synergistic hydrolysis of peptidoglycan by the RipA-RpfB complex in vitro. These data reveal a post-translational mechanism for regulating cell wall hydrolysis and synthesis through protein–protein interactions between enzymes with antagonistic functions
Effective Rheology of Bubbles Moving in a Capillary Tube
We calculate the average volumetric flux versus pressure drop of bubbles
moving in a single capillary tube with varying diameter, finding a square-root
relation from mapping the flow equations onto that of a driven overdamped
pendulum. The calculation is based on a derivation of the equation of motion of
a bubble train from considering the capillary forces and the entropy production
associated with the viscous flow. We also calculate the configurational
probability of the positions of the bubbles.Comment: 4 pages, 1 figur
The contributions of muscarinic receptors and changes in plasma aldosterone levels to the anti-hypertensive effect of Tulbaghia violacea
Background: Tulbaghia violacea Harv. (Alliaceae) is used to treat various ailments, including hypertension (HTN) in
South Africa. This study aims to evaluate the contributions of muscarinic receptors and changes in plasma
aldosterone levels to its anti-hypertensive effect.
Methods: In the acute experiments, methanol leaf extracts (MLE) of T. violacea (30–120 mg/kg), muscarine (0.16
-10 μg/kg), and atropine (0.02 - 20.48 mg/kg), and/or the vehicle (dimethylsulfoxide (DMSO) and normal saline (NS))
were respectively and randomly administered intravenously in a group of spontaneously hypertensive (SHR)
weighing 300 to 350 g and aged less than 5 months. Subsequently, T. violacea (60 mg/kg) or muscarine (2.5 μg/kg)
was infused into eight SHRs, 20 min after atropine (5.12 mg/kg) pre-treatment. In the chronic (21 days) experiments,
the SHRs were randomly divided into three groups, and given the vehicle (0.2 ml/day of DMSO and NS), T. violacea
(60 mg/kg/day) and captopril (10 mg/kg/day) respectively into the peritoneum, to investigate their effects on blood
pressure (BP), heart rate (HR), and plasma aldosterone levels. Systolic BP and HR were measured using tail-cuff
plethysmography during the intervention. BP and HR were measured via a pressure transducer connecting the
femoral artery and the Powerlab at the end of each intervention in the acute experiment; and on day 22 in the
chronic experiment.
Results: In the acute experiments, T. violacea, muscarine, and atropine significantly (p < 0.05) reduced BP
dose-dependently. T. violacea and muscarine produced dose-dependent decreases in HR, while the effect of
atropine on HR varied. After atropine pre-treatment, dose-dependent increases in BP and HR were observed with
T. violacea; while the BP and HR effects of muscarine were nullified. In the chronic experiments, the T. violaceatreated
and captropril-treated groups had signicantly lower levels of aldosterone in plasma when compared to
vehicle-treated group. Compared to the vehicle-treated group, significant reduction in BP was only seen in the
captopril-treated group; while no difference in HR was observed among the groups.
Conclusion: The results obtained in this study suggest that stimulation of the muscarinic receptors and a reduction
in plasma aldosterone levels contribute to the anti-hypertesive effect of T. violacea.IS
Prevention and treatment of cardiovascular disease in Ethiopia: a cost-effectiveness analysis
Preliminary study on hazards and critical control points of kokoro, a Nigerian indigenous fermented maize snack
A systematic quality assessment of Environmental Impact Statements in the oil and gas industry
Neuromuscular disease genetics in under-represented populations: increasing data diversity
\ua9 The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. Neuromuscular diseases (NMDs) affect ∼15 million people globally. In high income settings DNA-based diagnosis has transformed care pathways and led to gene-specific therapies. However, most affected families are in low-to-middle income countries (LMICs) with limited access to DNA-based diagnosis. Most (86%) published genetic data is derived from European ancestry. This marked genetic data inequality hampers understanding of genetic diversity and hinders accurate genetic diagnosis in all income settings. We developed a cloud-based transcontinental partnership to build diverse, deeply-phenotyped and genetically characterized cohorts to improve genetic architecture knowledge, and potentially advance diagnosis and clinical management. We connected 18 centres in Brazil, India, South Africa, Turkey, Zambia, Netherlands and the UK. We co-developed a cloud-based data solution and trained 17 international neurology fellows in clinical genomic data interpretation. Single gene and whole exome data were analysed via a bespoke bioinformatics pipeline and reviewed alongside clinical and phenotypic data in global webinars to inform genetic outcome decisions. We recruited 6001 participants in the first 43 months. Initial genetic analyses \u27solved\u27 or \u27possibly solved\u27 ∼56% probands overall. In-depth genetic data review of the four commonest clinical categories (limb girdle muscular dystrophy, inherited peripheral neuropathies, congenital myopathy/muscular dystrophies and Duchenne/Becker muscular dystrophy) delivered a ∼59% \u27solved\u27 and ∼13% \u27possibly solved\u27 outcome. Almost 29% of disease causing variants were novel, increasing diverse pathogenic variant knowledge. Unsolved participants represent a new discovery cohort. The dataset provides a large resource from under-represented populations for genetic and translational research. In conclusion, we established a remote transcontinental partnership to assess genetic architecture of NMDs across diverse populations. It supported DNA-based diagnosis, potentially enabling genetic counselling, care pathways and eligibility for gene-specific trials. Similar virtual partnerships could be adopted by other areas of global genomic neurological practice to reduce genetic data inequality and benefit patients globally
Comparison of fixed and mobile-bearing total knee arthroplasty in terms of patellofemoral pain and function: a prospective, randomised, controlled trial
Estimating the burden of selected non-communicable diseases in Africa: a systematic review of the evidence
Background
The burden of non-communicable diseases (NCDs) is rapidly increasing globally, and
particularly in Africa, where the health focus, until recently, has been on infectious diseases. The
response to this growing burden of NCDs in Africa has been affected owing to a poor
understanding of the burden of NCDs, and the relative lack of data and low level of research on
NCDs in the continent. Recent estimates on the burden of NCDs in Africa have been mostly
derived from modelling based on data from other countries imputed into African countries, and
not usually based on data originating from Africa itself. In instances where few data were
available, estimates have been characterized by extrapolation and over-modelling of the scarce
data. It is therefore believed that underestimation of NCDs burden in many parts of Africa cannot
be unexpected. With a gradual increase in average life expectancy across Africa, the region now
experiencing the fastest rate of urbanization globally, and an increase adoption of unhealthy
lifestyles, the burden of NCDs is expected to rise. This thesis will, therefore, be focussing on
understanding the prevalence, and/or where there are available data, the incidence, of four major
NCDs in Africa, which have contributed highly to the burden of NCDs, not only in Africa, but
also globally.
Methods
I conducted a systematic search of the literature on three main databases (Medline, EMBASE and
Global Health) for epidemiological studies on NCDs conducted in Africa. I retained and
extracted data from original population-based (cohort or cross sectional), and/or health service
records (hospital or registry-based studies) on prevalence and/or incidence rates of four major
NCDs in Africa. These include: cardiovascular diseases (hypertension and stroke), diabetes,
major cancer types (cervical, breast, prostate, ovary, oesophagus, bladder, Kaposi, liver, stomach,
colorectal, lung and non-Hodgkin lymphoma), and chronic respiratory diseases (chronic
obstructive pulmonary disease (COPD) and asthma). From extracted crude prevalence and
incidence rates, a random effect meta-analysis was conducted and reported for each NCD. An
epidemiological model was applied on all extracted data points. The fitted curve explaining the
largest proportion of variance (best fit) from the model was further applied. The equation
generated from the fitted curve was used to determine the prevalence and cases of the specific
NCD in Africa at midpoints of the United Nations (UN) population 5-year age-group population
estimates for Africa.
Results
From the literature search, studies on hypertension had the highest publication output at 7680, 92
of which were selected, spreading across 31 African countries. Cancer had 9762 publications and
39 were selected across 20 countries; diabetes had 3701 publications and 48 were selected across
28 countries; stroke had 1227 publications and 19 were selected across 10 countries; asthma had
790 publications and 45 were selected across 24 countries; and COPD had the lowest output with
243 publications and 13 were selected across 8 countries. From studies reporting prevalence
rates, hypertension, with a total sample size of 197734, accounted for 130.2 million cases and a
prevalence of 25.9% (23.5, 34.0) in Africa in 2010. This is followed by asthma, with a sample
size of 187904, accounting for 58.2 million cases and a prevalence of 6.6% (2.4, 7.9); COPD,
with a sample size of 24747, accounting for 26.3 million cases and a prevalence of 13.4% (9.4,
22.1); diabetes, with a sample size of 102517, accounting for 24.5 million cases and a prevalence
of 4.0% (2.7, 6.4); and stroke, with a sample size of about 6.3 million, accounting for 1.94
million cases and a prevalence of 317.3 per 100000 population (314.0, 748.2). From studies
reporting incidence rates, stroke accounted for 496 thousand new cases in Africa in 2010, with a
prevalence of 81.3 per 100000 person years (13.2, 94.9). For the 12 cancer types reviewed, a total
of 775 thousand new cases were estimated in Africa in 2010 from registry-based data covering a
total population of about 33 million. Among women, cervical cancer and breast cancer had 129
thousand and 81 thousand new cases, with incidence rates of 28.2 (22.1, 34.3) and 17.7 (13.0,
22.4) per 100000 person years, respectively. Among men, prostate cancer and Kaposi sarcoma
closely follows with 75 thousand and 74 thousand new cases, with incidence rates of 14.5 (10.9,
18.0) and 14.3 (11.9, 16.7) per 100000 person years, respectively.
Conclusion
This study suggests the prevalence rates of the four major NCDs reviewed (cardiovascular
diseases (hypertension and stroke), diabetes, major cancer types, and chronic respiratory diseases
(COPD and asthma) in Africa are high relative to global estimates. Due to the lack of data on
many NCDs across the continent, there are still doubts on the true prevalence of these diseases
relative to the current African population. There is need for improvement in health information
system and overall data management, especially at country level in Africa. Governments of
African nations, international organizations, experts and other stakeholders need to invest more
on NCDs research, particularly mortality, risk factors, and health determinants to have
evidenced-based facts on the drivers of this epidemic in the continent, and prompt better,
effective and overall public health response to NCDs in Africa
Weight-loss strategies of South African female university students and comparison of weight management-related characteristics between dieters and non-dieters
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