Intracellular and tissue levels of vitamin B12 in hepatocytes are modulated by CD320 receptor and TCN2 transporter

The liver mass constitutes hepatocytes expressing receptors for vitamin B12 (B12)-bound transporters in circulation. However, intrahepatic and circulating B12 interrelationship levels remain unclear. We assessed the intracellular B12 levels at various circulating B12 concentrations in human HepG2 cell-line and liver tissue levels of B12 in the C57BL/6 mouse model. In HepG2 cells treated with a range of B12 concentrations, the intracellular and circulatory B12 levels, transcript and protein levels of B12 receptor (CD320) and transporter (TCN2) were determined using immu-noassays, qRT-PCR and Western blot, respectively. Similar assessments were done in plasma and liver tissue of C57BL/6 mice, previously fed a diet of either a high or low B12 (30.82 μg B12/kg and 7.49 μg B12/kg, respectively) for 8-10 weeks. The physiological B12 status (0.15-1 nM) resulted in increased levels of intracellular B12 in HepG2 cells compared to supraphysiological levels of B12 (>1 nM). Gene and protein expression of CD320 and TCN2 were also higher at physiological levels of B12. Progressively increasing extracellular B12 to supraphysiological levels led to relative decreased levels of intracellular B12, lower expression of gene and protein levels of CD320 and TCN2. Similar results were observed in liver tissue from mice fed on a low B12 diet verses high B12 diet. These findings suggest that unlike supraphysiological B12, physiological levels of B12 in the extra-cellular media or circulation accelerates active transport of B12, and expression of CD320 and TCN2, resulting in higher relative uptake of B12 in hepatocytes

Vitamin B12 deficiency and altered one-carbon metabolites in early pregnancy is associated with maternal obesity and dyslipidaemia

Vitamin B12 (B12) is a micronutrient essential for one-carbon (1C) metabolism. B12 deficiency disturbs the 1C cycle and alters DNA methylation which is vital for most metabolic processes. Studies show that B12 deficiency may be associated with obesity, insulin resistance and gestational diabetes; and with obesity in child-bearing women. We therefore hypothesised that the associations between B12 deficiency, BMI and the metabolic risk could be mediated through altered 1C metabolites in early pregnancy. We explored these associations in two different early pregnancy cohorts in the UK (cohort 1; n = 244 and cohort 2; n = 60) with anthropometric data at 10–12 weeks and plasma/serum sampling at 16–18 weeks. B12, folate, total homocysteine (tHcy), methionine, MMA, metabolites of 1C metabolism (SAM, SAH) and anthropometry were measured. B12 deficiency (< 150 pmol/l) in early pregnancy was 23% in cohort 1 and 18% in cohort 2. Regression analysis after adjusting for likely confounders showed that B12 was independently and negatively associated with BMI (Cohort 1: β = − 0.260, 95% CI (− 0.440, − 0.079), p = 0.005, Cohort 2: (β = − 0.220, 95% CI (− 0.424, − 0.016), p = 0.036) and positively with HDL cholesterol (HDL-C) (β = 0.442, 95% CI (0.011,0.873), p = 0.045). We found that methionine (β = − 0.656, 95% CI (− 0.900, − 0.412), p < 0.0001) and SAH (β = 0.371, 95% CI (0.071, 0.672), p = 0.017) were independently associated with triglycerides. Low B12 status and alteration in metabolites in 1C metabolism are common in UK women in early pregnancy and are independently associated with maternal obesity and dyslipidaemia. Therefore, we suggest B12 monitoring in women during peri-conceptional period and future studies on the pathophysiological relationship between changes in 1C metabolites and its association with maternal and fetal outcomes on larger cohorts. This in turn may offer potential to reduce the metabolic risk in pregnant women and their offspring

Bi-allelic variants in HOPS complex subunit VPS41 cause cerebellar ataxia and abnormal membrane trafficking.

Membrane trafficking is a complex, essential process in eukaryotic cells responsible for protein transport and processing. Deficiencies in vacuolar protein sorting (VPS) proteins, key regulators of trafficking, cause abnormal intracellular segregation of macromolecules and organelles and are linked to human disease. VPS proteins function as part of complexes such as the homotypic fusion and vacuole protein sorting (HOPS) tethering complex, composed of VPS11, VPS16, VPS18, VPS33A, VPS39 and VPS41. The HOPS-specific subunit VPS41 has been reported to promote viability of dopaminergic neurons in Parkinson's disease but to date has not been linked to human disease. Here, we describe five unrelated families with nine affected individuals, all carrying homozygous variants in VPS41 that we show impact protein function. All affected individuals presented with a progressive neurodevelopmental disorder consisting of cognitive impairment, cerebellar atrophy/hypoplasia, motor dysfunction with ataxia and dystonia, and nystagmus. Zebrafish disease modelling supports the involvement of VPS41 dysfunction in the disorder, indicating lysosomal dysregulation throughout the brain and providing support for cerebellar and microglial abnormalities when vps41 was mutated. This provides the first example of human disease linked to the HOPS-specific subunit VPS41 and suggests the importance of HOPS complex activity for cerebellar function

Współczynnik LCI jako podstawowe kryterium oceny zdrowotnej emisji lotnych związków organicznych z wyrobów budowlanych

W niniejszym artykule została przedstawiona koncepcja stosowania wartości LCI (ang. Lowest Concentration of Interest) do oceny wpływu na zdrowie emitowanych z wyrobów budowlanych lotnych związków organicznych (LZO). Wartości LCI zostały pierwotnie opracowane przez grupę wiodących europejskich naukowców i opublikowane w 1997 r. w Raporcie nr 18 European Collaborative Action. Obecnie współczynnik ten jest coraz częściej wykorzystywany w przepisach krajów wspólnoty europejskiej do oceny emisji LZO z wyrobów budowlanych. Został również użyty w projekcie klasyfikacji emisji lotnych związków organicznych Komisji Europejskiej

Ocena jakości powietrza wewnętrznego jako element wielokryterialnej oceny budynków metodą BREEAM

W pracy omówiono wymagania dotyczące jakości powietrza wewnętrznego (IAQ) przyjęte w systemie certyfikacji budynków BREEAM. Ustalone w tym zakresie kryteria skupiają się na minimalizacji źródeł zanieczyszczenia powietrza i wykorzystaniu potencjału naturalnej wentylacji. Wymagania dotyczące emisji z podstawowych grup materiałów wykończeniowych, zapewniają stosowanie wyrobów o niskiej emisji zanieczyszczeń lotnych, a prawidłowa wentylacja zapewnia rozcieńczanie i usuwanie zanieczyszczeń. Jakość powietrza ma szczególne znaczenie dla zdrowia i samopoczucia użytkowników obiektów. Przedstawiono wyniki badań stężenia formaldehydu i lotnych związków organicznych w certyfikowanych nowych obiektach biurowych

New methodology for breaking steganographic techniques for JPEGs

In this paper, we present general methodology for developing attacks on steganographic systems for the JPEG image format. The detection first starts by decompressing the JPEG stego image, geometrically distorting it (e.g., by cropping), and recompressing. Because the geometrical distortion breaks the quantized structure of DCT coefficients during recompression, the distorted/recompressed image will have many macroscopic statistics approximately equal to those of the cover image. We choose such macroscopic statistic S that also predictably changes with the embedded message length. By doing so, we estimate the unknown message length by comparing the values of S for the stego image and the cropped/recompressed stego image. The details of this detection methodology are explained on the F5 algorithm and OutGuess. The accuracy of the message length estimate is demonstrated on test images for both algorithms. Finally, we identify two limitations of the proposed approach and show how they can be overcome to obtain accurate detection in every case. The paper is closed with outlining a condition that must be satisfied by all secure high-capacity steganographic algorithms for JPEGs

Steganalysis Based on JPEG Compatibility

In this paper, we introduce a new forensic tool that can reliably detect modifications in digital images, such as distortion due to steganography and watermarking, in images that were originally stored in the JPEG format. The JPEG compression leaves unique fingerprints and serves as a “fragile watermark ” enabling us to detect changes as small as modifying the LSB of one randomly chosen pixel. The detection of changes is based on investigating the compatibility of 8×8 blocks of pixels with JPEG compression with a given quantization matrix. The proposed steganalytic method is applicable to virtually all steganographic and watermarking algorithms with the exception of those that embed message bits into the quantized JPEG DCT coefficients. The method can also be used to estimate the size of the secret message and identify the pixels that carry message bits. As a consequence of our steganalysis, we strongly recommend avoiding using images that have been originally stored in the JPEG format as cover-images for spatial-domain steganography