Lamin B receptor regulates the growth and maturation of myeloid progenitors via its sterol reductase domain: implications for cholesterol biosynthesis in regulating myelopoiesis

Lamin B receptor (LBR) is a bifunctional nuclear membrane protein with N-terminal lamin B and chromatin-binding domains plus a C-terminal sterol Δ(14) reductase domain. LBR expression increases during neutrophil differentiation, and deficient expression disrupts neutrophil nuclear lobulation characteristic of Pelger-Hu?t anomaly. Thus, LBR plays a critical role in regulating myeloid differentiation, but how the two functional domains of LBR support this role is currently unclear. We previously identified abnormal proliferation and deficient functional maturation of promyelocytes (erythroid, myeloid, and lymphoid [EML]-derived promyelocytes) derived from EML-ic/ic cells, a myeloid model of ichthyosis (ic) bone marrow that lacks Lbr expression. In this study, we provide new evidence that cholesterol biosynthesis is important to myeloid cell growth and is supported by the sterol reductase domain of Lbr. Cholesterol biosynthesis inhibitors caused growth inhibition of EML cells that increased in EML-derived promyelocytes, whereas cells lacking Lbr exhibited complete growth arrest at both stages. Lipid production increased during wild-type neutrophil maturation, but ic/ic cells exhibited deficient levels of lipid and cholesterol production. Ectopic expression of a full-length Lbr in EML-ic/ic cells rescued both nuclear lobulation and growth arrest in cholesterol starvation conditions. Lipid production also was rescued, and a deficient respiratory burst was corrected. Expression of just the C-terminal sterol reductase domain of Lbr in ic/ic cells also improved each of these phenotypes. Our data support the conclusion that the sterol Δ(14) reductase domain of LBR plays a critical role in cholesterol biosynthesis and that this process is essential to both myeloid cell growth and functional maturation.     

Biological Control of <Emphasis Type="Italic">Fusarium</Emphasis> sp. NBRI-PMSF12 Pathogenic to Cultivated Betelvine by <Emphasis Type="Italic">Bacillus</Emphasis> sp. NBRI-W9, a Potential Biological Control Agent

Betelvine is prone to several fungal diseases including leaf spots, foot and root rot caused by Fusarium spp. due to humid conditions prevailing in fields. In the present study, a potent antagonistic bacterial endophyte and a virulent fungal pathogen were selected after rigorous screening of isolates from different betelvine varieties to provide an efficient biocontrol strategy in cultivation of betelvine. Wild varieties of crops are a rich source of untapped endophytes. Of the four betelvine varieties used for isolations and screening, the wild variety was richest in endophytic populations. Using 16S rRNA sequencing, the selected antagonist was identified as Bacillus sp. (NBRI-W9). The pathogen, virulent against cultivated varieties, was identified as Fusarium sp. (NBRI-PMSF12) using ITS 1 and 2 region sequencing. Under in vitro and field conditions, NBRI-W9 was able to induce early rooting, provide plant growth promotion, increase leaf size and yield (leaf number) and provide biocontrol against the Fusarium sp. infection. NBRI-W9 treatments showed bacterial colonization on the leaf surface preferably in the vicinity of pearl glands and the collenchyma region in scanning electron microscope (SEM) studies. NBRI-W9 was observed to directly enter the leaf by degrading cell walls and colonize the subcellular layers. SEM analysis showed direct confrontation of NBRI-W9 with Fusarium on the leaf surface and in the collenchyma region as one of the probable modes of biocontrol.     

Non-dipping blood pressure in the metabolic syndrome among Arabs of the Oman family study

Objective: The objective was to examine the circadian changes in blood pressure and their relation to the metabolic syndrome and its components in Omani Arabs. Research Methods and Procedures: Ambulatory blood pressure (ABPM) was recorded in 1124 subjects from 5 large, extended, consanguineous, and young Arab pedigrees. According to the International Diabetes Federation's definition, 264 subjects had the metabolic syndrome, a prevalence of 23%. Subjects were defined as non‐dippers when their nocturnal systolic blood pressure (SBP) fell by <10% from daytime SBP. Results: Non‐dippers with the metabolic syndrome were 131 of 264 (50%), compared with 265 of 860 (31%) without the metabolic syndrome. Of the non‐dippers, 99 of 131 (76%) were females and 32 of 131 (24%) were males. Daytime and nighttime SBP and DBP and nighttime pulse pressure were significantly higher in non‐dipper subjects with the metabolic syndrome. The important determinants of a non‐dipping BP in this cohort were high BMI and high serum triglycerides. Discussion: We hypothesize that obesity and nocturnal volume‐dependent hypertension may be involved in the pathophysiology of non‐dipping in the metabolic syndrome. This study showed that non‐dipping BP was common in subjects with the metabolic syndrome. Higher 24‐hour blood pressure load may add to the indices of the overall cardiovascular burden already associated with the metabolic syndrome.     

Geochemical assessment of fluoride enriched groundwater and health implications from a part of Yavtmal District,India

Abstract

A comprehensive study was conducted from a semi-arid part of Yavtmal District, Maharashtra, India through combination approaches of geochemical modeling and its health consequences. The groundwater quality assessment shows that 55% of groundwater samples have the concentration of fluoride above the desirable limit. The high Na⁺/Ca⁺ ratio (>1.0) suggest the occurrence of cation exchange, which is further supported by Scholler’ chloro-alkaline indices. The geochemical modeling reveals that the existence of CaCO₃ precipitation and CaF₂ in groundwater. Simulation analysis indicates the dissolution of calcite, gypsum, and albite and precipitation of dolomite, fluorite, halite, and K-feldspar along with cation exchange as the main water–rock interactions influencing the groundwater chemistry. This is further significantly supported by pollution index of groundwater (PIG). PIG indicates about 18% of total samples fall in very high pollution zone, 3% in high pollution zone, 8% in moderate pollution zone, 24% in low pollution zone, and remaining (47%) express insignificant pollution. The 28% of subject studied have skeletal fluorosis varying from mild to severe type. In different pollution zones, the affected persons by dental fluorosis are varying from 15% to 41%. A proper monitoring and treatment are required for high fluoride water before its use for drinking and cooking.