Association of polymorphisms in the Chr18q11.2 locus with tuberculosis in Chinese population

A GWAS study has reported that two single nucleotide polymorphisms (SNPs) were associated with predisposition to tuberculosis (TB) in African populations. These two loci represented the long-waited GWAS hits for TB susceptibility. To determine whether these two SNPs are associated with TB in Chinese population, we attempted an replication in a cohort of over one thousand Chinese TB patients and 1,280 healthy controls using melting temperature shift allele-specific genotyping analysis. We found that only SNP rs4331426 was significantly associated with TB in Chinese population (p = 0.011). However, the effect was opposite. The G allele of the SNP in Chinese population is a protective allele (OR = 0.62, 95 % CI 0.44–0.87), while it was the risk allele for African population (OR = 1.19, 95 % CI 1.12–1.26). No significance was found for SNP rs2335704. The results provided an independent support for a role in susceptibility to TB for SNP rs4331426. However, it also indicated that direct predisposition element to TB and the association effects may vary across ethnic groups.     

Modulation of bone marrow mesenchymal stem cell secretome by ECM-like hydrogels

It has been demonstrated that bone marrow mesenchymal stem cell (BM-MSCs) transplantation has beneficial effects on several central nervous system (CNS) debilitating conditions. Growing evidence indicate that trophic factors secreted by these cells are the key mechanism by which they are acting. These cells are frequently used in combination with 3D artificial matrices, for instance hydrogels, in tissue engineering-based approaches. However, so far, no study has been reported on the influence of such matrices, namely the presence or absence of extracellular matrix motifs, on BM-MSCs secretome and its effects in neuronal cell populations. In this sense, we herein studied the impact of a hydrogel, gellan gum, on the behavior and secretome of BM-MSCs, both in its commercial available form (commonly used in tissue engineering) and in a fibronectin peptide-modified form. The results showed that in the presence of a peptide in the gellan gum hydrogel, BM-MSCs presented higher proliferation and metabolic activity than in the regular hydrogel. Moreover, the typical spindle shape morphology of BM-MSCs was only observed in the modified hydrogel. The effects of the secretome of BM-MSCs were also affected by the chemical nature of the extracellular matrix. BM-MSCs cultured in the modified hydrogel were able to secrete factors that induced higher metabolic viabilities and neuronal cell densities, when compared to those of the unmodified hydrogel. Thus adding a peptide sequence to the gellan gum had a significant effect on the morphology, activity, proliferation and secretome of BM-MSCs. These results highlight the importance of mimicking the extracellular matrix when BM-MSCs are cultured in hydrogels for CNS applications.     

Life in Its Uniqueness Remains Difficult to Define in Scientific Terms

Abstract

The crystal structure of the dehydro octapeptide Boc-Val-ΔPhe-Phe-Ala-Leu-Ala-ΔPhe-Leu-OH has been determined to atomic resolution by X-ray crystallographic methods. The crystals grown by slow evaporation of peptide solution in methanol/water are orthorhombic, space group P2₁2₁2₁. The unit cell parameters are a= 8.404 (3), b= 25.598(2) and c = 27.946(3) Å, Z=4. The agreement factor is R= 7.58% for 3636 reflections having (IF₀I) ≥ 3σ (IF₀I). The peptide molecule is characterised by a 3₁₀-helix at the N-terminus and a π-turn at the C-terminus. This conformation is exactly similar to the helix termination features observed in proteins. The π-turn conformation observed in the octapeptide is in good agreement with the conformational features of π-turns seen in some proteins. The α_L-position in the π-turn of the octapeptide is occupied by ΔPhe⁷, which shows that even bulky residues can be accommodated in this position of the π-turns. In proteins, it is generally seen that aL- position is occupied by glycine residue. No intermolecular head-to-tail hydrogen bonds are observed in solid state structure of the octapeptide. A water molecule located in the unit cell of the peptide molecule is mainly used to hold the peptide molecule together in the crystal. The conformation observed for the octapeptide might be useful to understand the helix termination and chain reversal in proteins and to construct helix terminators for denovo protein design.     

B,Z Conformations and Mechanism of the Z-B-Coil Transitions of the Self-Complementary Deoxy-hexanucleotide d(C-G-m5C-G-C-G) by 1H-NMR and CD Spectroscopy

Abstract

The helical structures of d(C-G-m⁵C-G-C-G) were studied in aqueous solution at various salt concentrations and temperatures by CD and ¹H-NMR spectroscopy. At room temperature only the B form is observed in 0.1 M NaCl whereas the B and Z forms are simultaneously present in 1.8 M NaCl. At high salt concentration (4 M NaCl) the Z form is largely predominant (> 95%). The Z form proton resonances were assigned by using the polarisation transfer method (between B and Z at 1.8 M NaCl) and by proton-proton decoupling (at high salt concentration).

The Z-B-Coil transitions were studied as a function of temperature with the 1.8 M NaCl solution. At high temperature (95°C) only the coil form (S) is present. Below 55°C the coil proportion is negligible, and the B-Z exchange is slow. The disappearance of the coil gives rise at first to the B form and on lowering the temperature the Z proportion increases to the detriment of the B form. Proton linewidth, relaxation and polarisation transfer studies confirm the conclusion in the previous report on d(m⁵C-G-C-G-m⁵C-G) (Tran-Dinh et al Biochemistry 1984 in the press) that Z exchanges only with B whereas the latter also exchanges with S,Z ? B ? S. The present data show that even at high salt concentration where only the Z form of d(C-G-m⁵C-G-C-G) is observed the Z-S transition also passes through the B form as an intermediate stage. The B-Z transition takes place when the Watson-Crick hydrogen bonds are firmly maintained and is greatly favoured when there are three hydrogen bonds between the base-pairs.     

Potassium deficiency triggers the development of dormant cells (akinetes) in Aphanizomenon ovalisporum (Nostocales,Cyanoprokaryota)1

Akinetes are spore‐like nonmotile cells that differentiate from vegetative cells of filamentous cyanobacteria from the order Nostocales. They play a key role in the survival and distribution of these species and contribute to their perennial blooms. Various environmental factors were reported to trigger the differentiation of akinetes including light intensity and quality, temperature, and nutrient deficiency. Here, we report that deprivation of potassium ion (K⁺) triggers akinete development in the cyanobacterium Aphanizomenon ovalisporum. Akinetes formation is initiated 3 d–7 d after an induction by K⁺ depletion, followed by 2–3 weeks of a maturation process. Akinete formation occurs within a restricted matrix of environmental conditions such as temperature, light intensity or photon flux. Phosphate is essential for akinete maturation and P‐limitation restricts the number of mature akinetes. DNA replication is essential for akinete maturation and akinete development is limited in the presence of Nalidixic acid. While our results unequivocally demonstrated the effect of K⁺ deficiency on akinete formation in laboratory cultures of A. ovalisporum, this trigger did not cause Cylindrospermopsis raciborskii to produce akinetes. Anabaena crassa however, produced akinetes upon potassium deficiency, but the highest akinete concentration was achieved at conditions that supported vegetative growth. It is speculated that an unknown internal signal is associated with the cellular response to K⁺ deficiency to induce the differentiation of a certain vegetative cell in a trichome into an akinete. A universal stress protein that functions as mediator in K⁺ deficiency signal transduction cascade, may communicate between the lack of K⁺ and akinete induction.     

Laboratory and microcosm experiments testing the toxicity of chlorinated hydrocarbons on a cyanobacterium strain (Synechococcus PCC 6301) and on natural phytoplankton assemblages

In the last few years, halogenated hydrocarbons have been detected in the soil, in the aquatic environment, in organisms, and even in drinking water. The toxic effects of three chlorinated aliphatic hydrocarbons (trichloroethylene, tetrachloroethylene and tetrachloroethane) were studied in laboratory experiments (using the cyanobacterium Synecococcus elongatus PCC 6301 as test organism) and in field-like circumstances (natural phytoplankton assemblages enclosed in microcosms). The results of the laboratory experiments showed that all of the tested compounds significantly inhibited the growth of the cultures within the first 4 h. Enzymatic changes of the treated cultures suggested that oxidative stress occured—all of the three compounds caused an increase in the activity of peroxidases and superoxide dismutase, and also increased the levels of lipid peroxidation. Observed changes in microcosms were comparable with the results of the laboratory experiments: the number of individuals and chlorophyll contents decreased in the treated assemblages. The elevated levels of peroxidation on the second day in the assemblages treated with tetrachloroethane and tetrachloroetylene suggest that oxidative stress could occur in field conditions. One of the most important findings is the decrease in species number. Our results showed that cryptomonads, some green algae species and the cyanobacterium Limnothrix gradually disappeared from the treated beakers during the experiment.