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Abstract Rift Valley fever virus (RVFV) is a mosquito-borne RNA virus of the Phlebovirus genus in the phenuviridae family. Its genome is trisegmented with small (S), medium (M) and large (L) fragments. In nature, the virus exists as a single serotype that is responsible for outbreaks of Rift Valley fever (RVF), a zoonotic disease that often occurs in Africa and the Middle East. RVFV genomes are thought to undergo both recombination and reassortment and investigations of these events is important for monitoring the emergence of virulent strains and understanding the evolutionary characteristics of this virus. The aim of this study was to characterize the genomes of RVFV isolates from cattle, sheep, and goats collected during an interepidemic period in Kenya between June 2016 and November 2021. A total of 691 serum samples from cattle (n = 144), goats (n = 185) and sheep (n = 362) were analysed at the Central Veterinary Laboratories. The competitive IgM-capture ELISA, was used to screen the samples; 205 samples (29.67%) tested positive for RVFV. Of the 205 positive samples, 42 (20.5%) were from cattle, 57 (27.8%) from goats, and 106 (51.7%) from sheep. All the IgM-positive samples were further analyzed by qPCR, and 24 (11.71%) tested positive with Ct values ranging from 14.788 to 38.286. Two samples, 201808HABDVS from sheep and 201810CML3DVS from cattle, had Ct values of less than 20.0 and yielded whole genome sequences with 96.8 and 96.4 coverage, respectively. There was no statistically significant evidence of recombination in any of the three segments and also phylogenetic analysis showed no evidence of reassortment in the two isolated RVFV segments when compared with other isolates of different lineages from previous outbreaks whose genomes are deposited in the GenBank. No evidence of reassortment leaves room for other factors to be the most probable contributors of change in virulence, pathogenicity and emergence of highly virulent strains of the RVFV.

Low dissolved oxygen (hypoxia) poses significant challenges to aquatic ecosystems, affecting the behavior, reproduction, and survival of aquatic organisms. Some fishes respond to hypoxia by changes in gene expression, which may be regulated by the hypoxia inducible factor (HIF) family of transcription factors. HIF abundance and activity depends upon the post-translational modification of the alpha protein subunit, although several studies indicate that HIFA mRNA abundance increases in tissues of fishes exposed to hypoxia. This study reviewed reports of laboratory exposures of adult ray-finned fishes to hypoxia and used generalized linear mixed effects models to examine the influence of HIFA gene, tissue sampled, and exposure conditions in explaining the diversity of responses seen in HIFA mRNA abundance. The frequency of hypoxia-induced increases in HIFA mRNA was poorly explained by gene, tissue, or the severity of the hypoxic exposure. Rather, the frequency of reported increases was strongly related to the extent to which studies adhered to guidelines for documenting quantitative real-time PCR methods: the frequency of hypoxia-induced increases in HIFA mRNA decreased sharply in studies with more thorough description of experimental design. Future research should (a) adhere to stringent reporting of experimental design, (b) address the relative paucity of data on HIF2A and HIF3A, and (c) determine levels of HIF alpha protein subunits. By following these recommendations, it is hoped that a more complete understanding will be gained of the role of the HIF family of transcription factors in the response of fish to hypoxia.

Abstract As aquatic hypoxia worsens on a global scale, fishes will become increasingly challenged by low oxygen, and understanding the molecular basis of their response to hypoxia may help to better define the capacity of fishes to cope with this challenge. The hypoxia inducible factor (HIF) plays a critical role in the molecular response to hypoxia by activating the transcription of genes that serve to improve oxygen delivery to the tissues or enhance the capacity of tissues to function at low oxygen. The current study examines the molecular evolution of genes encoding the oxygen-dependent HIFα subunit (HIFA) in the ray-finned fishes (Actinopterygii). Genomic analyses demonstrate that several lineages retain four paralogs of HIFA predicted from two rounds of genome duplication at the base of vertebrate evolution, broaden the known distribution of teleost-specific HIFA paralogs, and provide evidence for salmonid-specific HIFA duplicates. Evolution of the HIFA gene family is characterized by widespread episodic positive selection at amino acid sites that potentially mediate protein stability, protein–protein interactions, and transcriptional regulation. HIFA transcript abundance depends upon paralog, tissue, and fish lineage. A phylogenetically-informed gene nomenclature is proposed along with avenues for future research on this critical family of transcription factors.

The COVID-19 pandemic brought the tourism sector to a complete standstill during the hard lockdown because of the global travel ban. This study aims to analyse the effects of COVID-19 on levy administration and revenue collection in Gauteng graded accommodation establishments in South Africa. Gauteng province is a gateway for international tourist arrivals and the most visited province in South Africa. The study used a case study design based on a saturated purposive snowball sampling procedure with data collected through semi-structured interviews from 15 key informants, stakeholders in Tourism marketing, directly working with graded accommodation establishments. The study reports a significant disruption in levy collection due to the COVID19 pandemic. The COVID-19 restrictions led to the loss of business profits due to establishments' permanent and temporary closures. For Gauteng's graded accommodation establishments to survive, technological innovation and reorganisation of operations were critical. The study recommends stakeholder harmonisation in synergy with strategies for levy collection post- COVID-19 era. This study proposes critical interventions to the levy administrators and government to support graded establishments collecting the levy.

Abstract Safety nets in Ethiopia are targeted and delivered in a context in which informal social capital practices also operate. But the role of social relations is largely overlooked in welfare programming. Understanding how social capital is mobilized and under which condition it enhances or constrains social safety net targeting may inform policy to design sustainable and inclusive welfare programs to improve household resilience. Using an ethnographic case study design, we studied the role of social capital in the implementation of a welfare intervention. Data were collected through observations and interviews with 30 households. Besides, data on household social network characteristics were collected using semi-structured interviews. The result suggested that greater access to social capital by a household enhances the efficiency of safety net targeting and delivery. Positioning the social transfer instruments within the broader sets of community social arrangements can optimize the allocation of scarce safety net resources and improves community relationships.

Summary: The cellular origin of sporadic pancreatic neuroendocrine tumors (PNETs) is obscure. Hormone expression suggests that these tumors arise from glucagon-producing alpha cells or insulin-producing β cells, but instability in hormone expression prevents linage determination. We utilize loss of hepatic glucagon receptor (GCGR) signaling to drive alpha cell hyperproliferation and tumor formation to identify a cell of origin and dissect mechanisms that drive progression. Using a combination of genetically engineered Gcgr knockout mice and GCGR-inhibiting antibodies, we show that elevated plasma amino acids drive the appearance of a proliferative population of SLC38A5+ embryonic progenitor-like alpha cells in mice. Further, we characterize tumors from patients with rare bi-allelic germline GCGR loss-of-function variants and find prominent tumor-cell-associated expression of the SLC38A5 paralog SLC7A8 as well as markers of active mTOR signaling. Thus, progenitor cells arise from adult alpha cells in response to metabolic signals and, when inductive signals are chronically present, drive tumor initiation.

Abstract Background This study seeks to compare the performance of HRP2 (First Response) and pLDH/HRP2 (Combo) RDTs for falciparum malaria against microscopy and PCR in acutely ill febrile children at presentation and follow-up. Methods This is an interventional study that recruited children

Abstract Background Malaria is one of the most challenging public health concerns in the developing world. To address its impact in endemic regions, several interventions are implemented by stakeholders. The Affordable Medicine Facility-malaria (AMFm) is an example of such interventions. Its activities include communication interventions to enhance the knowledge of caregivers of children under five years, licensed chemical sellers (LCS) and prescribers on malaria management with artemisinin-based combination therapy (ACT). This study was conducted to evaluate the effectiveness of the AMFm activities on malaria among targeted groups in two rural communities in Ghana. Methods A communication intervention study was conducted in the Asante-Akim North and South Districts of Ghana. Repeated cross-sectional pre and post surveys were deployed. Relevant malaria messages were designed and used to develop the information, education and communication (IEC) tools for the intervention. With the aid of posters and flipcharts developed by our study, community health workers (CHWs), prescribers, and licenced chemical sellers provided proper counselling to clients on malaria management. Trained CHWs and community based volunteers educated caregivers of children under five years on malaria management at their homes and at public gatherings such as churches, mosques, schools. Chi-square tests and logistic regression were run to determine associations and control for demographic differences respectively. Results There was significantly high exposure to malaria/ACT interventions in the intervention district than in the comparison district (OR = 16.02; 95% CI = 7.88–32.55) and same for malaria/ACT-related knowledge (OR = 3.63; 95% CI = 2.52–5.23). The participants in the intervention district were also more knowledgeable about correct administration of dispersible drug for children

In this paper, a mathematical model for vehicle-to-vehicle frontal crash is developed. The experimental data are taken from the National Highway Traffic Safety Administration. To model the crash scenario, the two vehicles are represented by two masses moving in opposite directions. The front structures of the vehicles are modeled by Kelvin elements, consisting of springs and dampers in parallel, and estimated as piecewise linear functions of displacements and velocities, respectively. To estimate and optimize the model parameters, a genetic algorithm approach is proposed. Finally, it is observed that the developed model can accurately reproduce the real kinematic results from the crash test.

The analysis intended to identify the various food consumption of the people of East Nusa Tenggara is carried out by using the data from Susenas in East Nusa Tenggara Province in 1996. There are 500 households included in the analysis those are classified according to income level (low, middle, high) and residence (rural, urban). The estimation of the consumption function is using Maximum Likelihood Method (MLE). Results of the analysis reveals that expenditure allocation for foodstuffs is 63% and 37% for non-foodstuffs. High-income people combine rice and corn to meet their carbohydrate needs while low-income people rely on corn. Protein sources including fish and meat are not affordable by the people of East Nusa Tenggara

Understanding the regulation of islet cell mass has important implications for the discovery of regenerative therapies for diabetes. The liver plays a central role in metabolism and the regulation of endocrine cell number, but liver-derived factors that regulate α-cell and β-cell mass remain unidentified. We propose a nutrient-sensing circuit between liver and pancreas in which glucagon-dependent control of hepatic amino acid metabolism regulates α-cell mass. We found that glucagon receptor inhibition reduced hepatic amino acid catabolism, increased serum amino acids, and induced α-cell proliferation in an mTOR-dependent manner. In addition, mTOR inhibition blocked amino-acid-dependent α-cell replication ex vivo and enabled conversion of α-cells into β-like cells in vivo. Serum amino acids and α-cell proliferation were increased in neonatal mice but fell throughout postnatal development in a glucagon-dependent manner. These data reveal that amino acids act as sensors of glucagon signaling and can function as growth factors that increase α-cell proliferation.

Excessive neutrophil infiltration of the lungs is a common contributor to immune-related pathology in many pulmonary disease states. In response to pathogenic infection, airway epithelial cells produce hepoxilin A3 (HXA3), initiating neutrophil transepithelial migration. Migrated neutrophils amplify this recruitment by producing a secondary gradient of leukotriene B4 (LTB4). We sought to determine whether this two-step eicosanoid chemoattractant mechanism could be exploited by the pathogen Pseudomonas aeruginosa. ExoU, a P. aeruginosa cytotoxin, exhibits phospholipase A2 (PLA2) activity in eukaryotic hosts, an enzyme critical for generation of certain eicosanoids. Using in vitro and in vivo models of neutrophil transepithelial migration, we evaluated the impact of ExoU expression on eicosanoid generation and function. We conclude that ExoU, by virtue of its PLA2 activity, augments and compensates for endogenous host neutrophil cPLA2α function, leading to enhanced transepithelial migration. This suggests that ExoU expression in P. aeruginosa can circumvent immune regulation at key signaling checkpoints in the neutrophil, resulting in exacerbated neutrophil recruitment.

We investigate the radiation patterns of sharp conical gold tapers, which were designed as adiabatic nanofocusing probes for scanning near-field optical microscopy (SNOM). Field calculations show that only the lowest order eigenmode of such a taper can reach the very apex and thus induce the generation of strongly enhanced near-field signals. Higher-order modes are coupled into the far field at finite distances from the apex. Here, we demonstrate experimentally how to distinguish and separate between the lowest and higher-order eigenmodes of such a metallic taper by filtering in the spatial frequency domain. Our approach has the potential to considerably improve the signal-to-background ratio in spectroscopic experiments at the nanoscale.

Estimating the vehicle crashworthiness experimentally is expensive and time-consuming. For these reasons, different modelling approaches are utilised to predict the vehicle behaviour and reduce the need for full-scale crash testing. The earlier numerical methods used for vehicle crashworthiness analysis were based on the use of lumped parameters models (LPM), a combination of masses and nonlinear springs interconnected in various configurations. Nowadays, the explicit nonlinear finite element analysis (FEA) is probably the most widely recognised modelling technique. Although informative, finite element models (FEM) of vehicle crash are expensive both in terms of man-hours put into assembling the model and related computational costs. A simpler analytical tool for preliminary analysis of vehicle crashworthiness could greatly assist the modelling and save time. In this paper, the authors investigate whether a simple piecewise LPM can serve as such a tool. The model is first calibrated at an impact velocity of 56 km/h. After the calibration, the LPM is applied to a range of velocities (40, 48, 64 and 72 km/h) and the crashworthiness parameters such as the acceleration severity index (ASI) and the maximum dynamic crush are calculated. The predictions for crashworthiness parameters from the LPM are then compared with the same predictions from the FEA.

ABSTRACT Atherosclerosis, a disease condition resulting from the buildup of fatty plaque deposits within arterial walls, is the major underlying cause of ischemia (restriction of the blood), leading to obstruction of peripheral arteries, congestive heart failure, heart attack, and stroke in humans. Emerging research indicates that factors including inflammation and infection may play a key role in the progression of atherosclerosis. In the current work, atherosclerotic carotid artery explants from 15 patients were all shown to test positive for the presence of eubacterial 16S rRNA genes. Density gradient gel electrophoresis of 5 of these samples revealed that each contained 10 or more distinct 16S rRNA gene sequences. Direct microscopic observation of transverse sections from 5 diseased carotid arteries analyzed with a eubacterium-specific peptide nucleic acid probe revealed these to have formed biofilm deposits, with from 1 to 6 deposits per thin section of plaque analyzed. A majority, 93%, of deposits was located proximal to the internal elastic lamina and associated with fibrous tissue. In 6 of the 15 plaques analyzed, 16S rRNA genes from Pseudomonas spp. were detected. Pseudomonas aeruginosa biofilms have been shown in our lab to undergo a dispersion response when challenged with free iron in vitro. Iron is known to be released into the blood by transferrin following interaction with catecholamine hormones, such as norepinephrine. Experiments performed in vitro showed that addition of physiologically relevant levels of norepinephrine induced dispersion of P. aeruginosa biofilms when grown under low iron conditions in the presence but not in the absence of physiological levels of transferrin. IMPORTANCE The association of bacteria with atherosclerosis has been only superficially studied, with little attention focused on the potential of bacteria to form biofilms within arterial plaques. In the current work, we show that bacteria form biofilm deposits within carotid arterial plaques, and we demonstrate that one species we have identified in plaques can be stimulated in vitro to undergo a biofilm dispersion response when challenged with physiologically relevant levels of norepinephrine in the presence of transferrin. Biofilm dispersion is characterized by the release of bacterial enzymes into the surroundings of biofilm microcolonies, allowing bacteria to escape the biofilm matrix. We believe these enzymes may have the potential to damage surrounding tissues and facilitate plaque rupture if norepinephrine is able to stimulate biofilm dispersion in vivo. This research, therefore, suggests a potential mechanistic link between hormonal state and the potential for heart attack and stroke.

The epithelial-to-mesenchymal transition (EMT) is a highly conserved physiological program involved in development and tissue repair; however, its aberrant activation has been implicated in accelerating the progression of a variety of cancers. In breast cancer, the microRNAs (miRNAs) miR-221 and miR-222 (miR-221/222) are differentially expressed in the clinically more aggressive basal-like subtype compared to luminal subtype of breast cancer and upregulation of miR-221/222 induces the EMT by targeting the 3' untranslated region (3'UTR) of the GATA family transcriptional repressor TRPS1 (tricho-rhino-phalangeal syndrome type 1). The complete mechanism through which miR-221/222 promotes the EMT, however, is not fully understood. We identified adiponectin receptor 1 (ADIPOR1), a receptor for the adipocytokine adiponectin, as a direct target of miR-221/222. ADIPOR1 is expressed at higher levels in the luminal compared to the basal-like subtype of breast cancer cell lines, which can be reduced by miR-221/222 targeting of its 3'UTR. In addition, miR-221/222 were negatively correlated with ADIPOR1 expression across breast cancer cell lines and tumors. ADIPOR1 depletion by siRNA in MCF10A cells induced the EMT and increased cell invasion. Depletion of ADIPOR1 by siRNA induced activation of the canonical nuclear factor-kappaB (NF-κB) and subsequent phosphorylation of signal transducer and activator of transcription 3 (STAT3) in an interleukin 6 (IL6)-dependent manner. Finally, overexpression of ADIPOR1 in the basal-like cell line, MDA-MB-231, attenuated cell invasion and promoted the mesenchymal-to-epithelial transition (MET). We conclude that ADIPOR1 negatively regulates EMT in breast cancer and provides an additional node by which miR-221/222 induces the EMT. These results suggest that ADIPOR1 may play an important role in breast cancer progression and metastasis, and could potentially offer an alternative therapeutic strategy for basal-like breast cancer patients.

Low dissolved oxygen (hypoxia) poses significant challenges to aquatic ecosystems, affecting the behavior, reproduction, and survival of aquatic organisms. Some fishes respond to hypoxia by changes in gene expression, which may be regulated by the hypoxia inducible factor (HIF) family of transcription factors. HIF abundance and activity depends upon the post-translational modification of the alpha protein subunit, although several studies indicate that HIFA mRNA abundance increases in tissues of fishes exposed to hypoxia. This study reviewed reports of laboratory exposures of adult ray-finned fishes to hypoxia and used generalized linear mixed effects models to examine the influence of HIFA gene, tissue sampled, and exposure conditions in explaining the diversity of responses seen in HIFA mRNA abundance. The frequency of hypoxia-induced increases in HIFA mRNA was poorly explained by gene, tissue, or the severity of the hypoxic exposure. Rather, the frequency of reported increases was strongly related to the extent to which studies adhered to guidelines for documenting quantitative real-time PCR methods: the frequency of hypoxia-induced increases in HIFA mRNA decreased sharply in studies with more thorough description of experimental design. Future research should (a) adhere to stringent reporting of experimental design, (b) address the relative paucity of data on HIF2A and HIF3A , and (c) determine levels of HIF alpha protein subunits. By following these recommendations, it is hoped that a more complete understanding will be gained of the role of the HIF family of transcription factors in the response of fish to hypoxia. [ABSTRACT FROM AUTHOR]

Bull. Chem. Soc. Ethiop., 3(2), 103-106 (1989).

Academic inquiry into theoretical positions on sustainable development in Africa have risen to prominence in recent times. This paper questions the traditional paradigms of thought on Africa's underdevelopment. It advances novel perspectives in rethinking resource governance by suggesting that an Induced Cumulative Causative Theory is key to understanding the proverbial 'box' in which Africans have to think out of to re-invent resource governance. The paper makes the connect between historical colonial antecedents of foreign resource control with the present proxy control of the same resources as a key structure that needs reinventing in the face of the 'New scramble for Africa'. The paper suggests that depreciating global resources has put Africa in the crosshairs global imperial forces making the control of Africa's resources by Africans a nearimpossible task. Policymakers will face the task of reinventing Africa's engagement with International corporations who are at the forefront the 'New Scramble'. The paper recommends that the control of African resources should be placed at the centre of the discourse on confronting the 'new scramble'. [ABSTRACT FROM AUTHOR]

Low dissolved oxygen (hypoxia) is recognized as a major threat to aquatic ecosystems worldwide. Because oxygen is paramount for the energy metabolism of animals, understanding the functional and genetic drivers of whole-animal hypoxia tolerance is critical to predicting the impacts of aquatic hypoxia. In this study, we investigate the molecular evolution of key genes involved in the detection of and response to hypoxia in ray-finned fishes: the prolyl hydroxylase domain (PHD)–hypoxia-inducible factor (HIF) oxygen-sensing system, also known as the EGLN (egg-laying nine)– HIF oxygen-sensing system. We searched fish genomes for HIFA and EGLN genes, discovered new paralogs from both gene families, and analyzed protein-coding sites under positive selection. The physicochemical properties of these positively selected amino acid sites were summarized using linear discriminants for each gene. We employed phylogenetic generalized least squares to assess the relationship between these linear discriminants for each HIFA and EGLN and hypoxia tolerance as reflected by the critical oxygen tension (P crit) of the corresponding species. Our results demonstrate that P crit in ray-finned fishes correlates with the physicochemical variation of positively selected sites in specific HIFA and EGLN genes. For HIF2A , two linear discriminants captured more than 90% of the physicochemical variation of these sites and explained between 20% and 39% of the variation in P crit. Thus, variation in HIF2A among fishes may contribute to their capacity to cope with aquatic hypoxia, similar to its proposed role in conferring tolerance to high-altitude hypoxia in certain lineages of terrestrial vertebrates. [ABSTRACT FROM AUTHOR]

SLURP1, a member of the lymphocyte antigen 6 protein family, is secreted by suprabasal keratinocytes. Mutations in SLURP1 cause a palmoplantar keratoderma (PPK) known as mal de Meleda. SLURP2, another secreted lymphocyte antigen 6 protein, is encoded by a gene located ?20 kb downstream from SLURP1. SLURP2 is produced by suprabasal keratinocytes. To investigate the importance of SLURP2, we first examined Slurp2 knockout mice in which exon 2-3 sequences had been replaced with lacZ and neo cassettes. Slurp2(-/-) mice exhibited hyperkeratosis on the volar surface of the paws (i.e., palmoplantar keratoderma), increased keratinocyte proliferation, and an accumulation of lipid droplets in the stratum corneum. They also exhibited reduced body weight and hind limb clasping. These phenotypes are similar to those of Slurp1(-/-) mice. To solidify a link between Slurp2 deficiency and palmoplantar keratoderma and to be confident that the disease phenotypes in Slurp2(-/-) mice were not secondary to the effects of the lacZ and neo cassettes on Slurp1 expression, we created a new line of Slurp2 knockout mice (Slurp2X(-/-)) in which Slurp2 was inactivated with a simple nonsense mutation. Slurp2X(-/-) mice exhibited the same disease phenotypes. Thus, Slurp2 deficiency and Slurp1 deficiencies cause the same disease phenotypes.