Transgelin is a TGFβ-inducible gene that regulates osteoblastic and adipogenic differentiation of human skeletal stem cells through actin cytoskeleston organization

Regenerative medicine is a novel approach for treating conditions in which enhanced bone regeneration is required. We identified transgelin (TAGLN), a transforming growth factor beta (TGFβ)-inducible gene, as an upregulated gene during in vitro osteoblastic and adipocytic differentiation of human bone marrow-derived stromal (skeletal) stem cells (hMSC). siRNA-mediated gene silencing of TAGLN impaired lineage differentiation into osteoblasts and adipocytes but enhanced cell proliferation. Additional functional studies revealed that TAGLN deficiency impaired hMSC cell motility and in vitro transwell cell migration. On the other hand, TAGLN overexpression reduced hMSC cell proliferation, but enhanced cell migration, osteoblastic and adipocytic differentiation, and in vivo bone formation. In addition, deficiency or overexpression of TAGLN in hMSC was associated with significant changes in cellular and nuclear morphology and cytoplasmic organelle composition as demonstrated by high content imaging and transmission electron microscopy that revealed pronounced alterations in the distribution of the actin filament and changes in cytoskeletal organization. Molecular signature of TAGLN-deficient hMSC showed that several genes and genetic pathways associated with cell differentiation, including regulation of actin cytoskeleton and focal adhesion pathways, were downregulated. Our data demonstrate that TAGLN has a role in generating committed progenitor cells from undifferentiated hMSC by regulating cytoskeleton organization. Targeting TAGLN is a plausible approach to enrich for committed hMSC cells needed for regenerative medicine application

Genetic Diversity among Nigeria Maiwa Type of Pearl Millet Germplasm

Characterization of pearl millet germplasm is imperative for categorization of germplasm and identification of the desirable genotypes for introgression into breeding programs. The available pearl millet genetic resources from Nigeria, and especially photoperiodsensitive materials or stay-green traits, have so far been exploited only to a limited extent. The present study was undertaken for initial morphological and phonological characterization of unexploited ‘maiwa’ or stay-green pearl millet accession in geographical gaps of Nigeria, to ensure high precision in future genotyping and phenotyping. The germplasm displayed considerable variability for Downy mildew severity,,days to 50 % flowering, plant height, panicle length and grain weight. There was no significant differences to striga infestation since there was no experience of striga emergence, suggesting resistance

Towards identifying novel sources of resistance to striga in pearl millet under natural field infestation

Pearl millet is an important major staple food for millions of people in Africa and Asia especially in the northern regions of Nigeria where it is consumed on daily basis in different forms. Its productivity has been severely hindered by various biotic and abiotic factors, such as Striga. Striga alone can result in yield losses of between 20 to 100% in severe cases. Breeding for resistance to this parasitic weed has been constrained due to limited source of resistance, therefore searching new sources of resistance from pearl millet germplasm is essential to facilitate progress in developing new varieties with farmers preferred traits. The present work was carried out to identify novel sources of resistance from adapted landraces and exotic germplasm for further use in breeding. Results have shown existence of pearl millet genotypes with good performance in terms of low to no Striga emergence and high yield which are important features associated with Striga resistance in Striga prone areas. This work lays the foundation for development of Striga resistant pearl millet varieties for northern savannah areas of Nigeria

Farmers’ Production Constraints, Knowledge of Striga and Preferred Traits of Pearl Millet in Jigawa State, Nigeria

A participatory rural appraisal was performed in order to identify farmers’ pearl millet production constraints, preferred varietal traits and their knowledge about Striga hermonthica. This was conducted in Dutse (Madobi and Kudai), Birninkudu (Kantoga and Kafingana) and Kiyawa (Karfawa and Shuwarin) local governments of Jigawa state Nigeria. Questionnaires and focus group discussion were used to gather information from 143 respondents. Results shows that the five most important traits selected were resistance to Striga infestation, resistance to downy mildew, tolerance to shattering, good quality local beverage, and tolerance to lodging. The major constraints to production across all the districts were low soil fertility, Striga, downy mildew, and high labour costs. Farmers had a good knowledge about Striga and their control methods across the locations were hand-pulling and or hoe weeding

Discrete microfluidics for the isolation of circulating tumor cell subpopulations targeting fibroblast activation protein alpha and epithelial cell adhesion molecule

Circulating tumor cells consist of phenotypically distinct subpopulations that originate from the tumor microenvironment. We report a circulating tumor cell dual selection assay that uses discrete microfluidics to select circulating tumor cell subpopulations from a single blood sample; circulating tumor cells expressing the established marker epithelial cell adhesion molecule and a new marker, fibroblast activation protein alpha, were evaluated. Both circulating tumor cell subpopulations were detected in metastatic ovarian, colorectal, prostate, breast, and pancreatic cancer patients and 90% of the isolated circulating tumor cells did not co-express both antigens. Clinical sensitivities of 100% showed substantial improvement compared to epithelial cell adhesion molecule selection alone. Owing to high purity (>80%) of the selected circulating tumor cells, molecular analysis of both circulating tumor cell subpopulations was carried out in bulk, including next generation sequencing, mutation analysis, and gene expression. Results suggested fibroblast activation protein alpha and epithelial cell adhesion molecule circulating tumor cells are distinct subpopulations and the use of these in concert can provide information needed to navigate through cancer disease management challenges

Influenza Activity and Composition of the 2022-23 Influenza Vaccine - United States, 2021-22 Season

Before the emergence of SARS-CoV-2, the virus that causes COVID-19, influenza activity in the United States typically began to increase in the fall and peaked in February. During the 2021-22 season, influenza activity began to increase in November and remained elevated until mid-June, featuring two distinct waves, with A(H3N2) viruses predominating for the entire season. This report summarizes influenza activity during October 3, 2021-June 11, 2022, in the United States and describes the composition of the Northern Hemisphere 2022-23 influenza vaccine. Although influenza activity is decreasing and circulation during summer is typically low, remaining vigilant for influenza infections, performing testing for seasonal influenza viruses, and monitoring for novel influenza A virus infections are important. An outbreak of highly pathogenic avian influenza A(H5N1) is ongoing; health care providers and persons with exposure to sick or infected birds should remain vigilant for onset of symptoms consistent with influenza. Receiving a seasonal influenza vaccine each year remains the best way to protect against seasonal influenza and its potentially severe consequences

Human Embryonic Stem Cells and Embryonal Carcinoma Cells Have Overlapping and Distinct Metabolic Signatures

While human embryonic stem cells (hESCs) and human embryonal carcinoma cells (hECCs) have been studied extensively at the levels of the genome, transcriptome, proteome and epigenome our knowledge of their corresponding metabolomes is limited. Here, we present the metabolic signatures of hESCs and hESCs obtained by untargeted gas chromatography coupled to mass spectrometry (GC-MS). Whilst some metabolites are common to both cell types, representing the self-renewal and house-keeping signatures, others were either higher (e.g., octadecenoic acid, glycerol-3-phosphate, 4-hydroxyproline) or lower (e.g., glutamic acid, mannitol, malic acid, GABA) in hESCs (H9) compared to hECCs (NTERA2), these represent cell type specific signatures. Further, our combined results of GC-MS and microarray based gene expression profiling of undifferentiated and OCT4-depleted hESCs are consistent with the Warburg effect which is increased glycolysis in embryonic cells and tumor cells in the presence of O2 while oxidative phosphorylation (OXPHOS) is impaired or even shut down. RNAi-based OCT4 knock down mediated differentiation resulted in the activation of the poised OXPHOS machinery by expressing missing key proteins such as NDUFC1, UQCRB and COX, increase in TCA cycle activity and decreased lactate metabolism. These results shed light on the metabolite layer of pluripotent stem cells and could potentially establish novel metabolic markers of self renewal and pluripotency

Twelve-month observational study of children with cancer in 41 countries during the COVID-19 pandemic

Introduction Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality. Methods Prospective cohort study in 109 institutions in 41 countries. Inclusion criteria: children <18 years who were newly diagnosed with or undergoing active treatment for acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, retinoblastoma, Wilms tumour, glioma, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, medulloblastoma and neuroblastoma. Of 2327 cases, 2118 patients were included in the study. The primary outcome measure was all-cause mortality at 30 days, 90 days and 12 months. Results All-cause mortality was 3.4% (n=71/2084) at 30-day follow-up, 5.7% (n=113/1969) at 90-day follow-up and 13.0% (n=206/1581) at 12-month follow-up. The median time from diagnosis to multidisciplinary team (MDT) plan was longest in low-income countries (7 days, IQR 3-11). Multivariable analysis revealed several factors associated with 12-month mortality, including low-income (OR 6.99 (95% CI 2.49 to 19.68); p<0.001), lower middle income (OR 3.32 (95% CI 1.96 to 5.61); p<0.001) and upper middle income (OR 3.49 (95% CI 2.02 to 6.03); p<0.001) country status and chemotherapy (OR 0.55 (95% CI 0.36 to 0.86); p=0.008) and immunotherapy (OR 0.27 (95% CI 0.08 to 0.91); p=0.035) within 30 days from MDT plan. Multivariable analysis revealed laboratory-confirmed SARS-CoV-2 infection (OR 5.33 (95% CI 1.19 to 23.84); p=0.029) was associated with 30-day mortality. Conclusions Children with cancer are more likely to die within 30 days if infected with SARS-CoV-2. However, timely treatment reduced odds of death. This report provides crucial information to balance the benefits of providing anticancer therapy against the risks of SARS-CoV-2 infection in children with cancer

Effect of Vitamins C & E on Aspirin Induced Gastric Mucosal Damage and Oxidative Stress

Abstract: The effects of Vitamins C & E on Aspirin -induced gastric mucosal damage on gastric ulcer parameters and stomach oxidative stress markers were determined in acute and sub-acute studies in Wistar rats. Aspirin produced a significant (p<0.05) increase in gastric ulcer score in both studies. Vitamins C & E conferred protection in acute and sub-acute studies with preventive indices of 54 and 60% respectively. Histologically the gastric mucosa of animals in the sub-acute study showed a severe necrosis of the epithelial cells than observed in the acute study. Acute aspirin administration did not increase the stomach tissue Malondialdehyde (MDA) but sub-acute administration significantly (p<0.05) increased MDA, while vitamins C & E caused a significant (p<0.05) decrease below the level seen in normal controls. Aspirin in both studies significantly decreased Catalase activity. While acute aspirin exposure had no effect on Superoxide Dismutase (SOD) activity, sub-acute exposure raised it significantly (p<0.05). Administration of Vitamins C and E significantly increased SOD activity only in the acute study. Aspirin significantly decreased reduced Glutathione (GSH) in both studies and was reversed by Vitamin C and E. The level of GSH reductase (GSHRD) in the acute study was significantly decreased by aspirin but subacutely and prior treatment with vitamins C and E had no significant effect. Combine administration of vitamins C & E prior to intake of aspirin significantly prevented aspirin-induced gastric ulceration with decrease in some oxidative stress markers