Analysis of Gγ-158(C→T) polymorphism in hemoglobin E/β-thalassemia major in Southern China

<p>Abstract</p> <p>Background</p> <p>The ^Gγ-158(C→T) polymorphism plays important function in the clinical variability of HbE/β-thalassemia. There is little known about ^Gγ-158(C→T) polymorphism in HbE/β-thalassemia major in Southern China. This study aimed to explore the association between HbE/β-thalassemia major and this polymorphism in Southern China.</p> <p>Methods and Results</p> <p>The frequency of the ^Gγ-158(C→T) polymorphism has been evaluated in 32 patients with HbE/β-thalassemia major from Southern China. Further analysis of the ^Gγ-158(C→T) polymorphism revealed the prominent frequency of this polymorphic pattern among HbE/β-thalassemia major patients (65.63%). The presence of this polymorphism was strongly correlated with the increase of HbF synthesis.</p> <p>Conclusions</p> <p>The frequency of the ^Gγ-158(C→T) polymorphism was relatively high in Southern Chinese patients with HbE/β-thalassemia major, often accompanying with high production of HbF. This feature appears to be different with reports in other races and regions.</p

Poly[aqua­(μ11-4,6-dihy­droxy­benzene-1,3-disulfonato)­dipotassium]

In the title salt, [K2(C6H4O8S2)(H2O)]n, both K+ ions exhibit a seven-coordination with K—O bond lengths in the range 2.6600 (14) to 3.0522 (16) Å. One K+ ion is coordinated by seven O atoms from the sulfonate and phenolic hy­droxy groups of six 4,6-dihy­droxy­benzene-1,3-disulfonate (L 2−) anions while the other K+ ion is coordinated by six O atoms from the sulfonate and phenolic hy­droxy groups of five L 2− anions and one water O atom. The L 2− anion exhibits chelating–bridging multidentate coordination to potassium, resulting in the formation of a cross-linked three-dimensional network

How early can myocardial iron overload occur in Beta thalassemia major?

BACKGROUND: Myocardial siderosis is the most common cause of death in patients with beta thalassemia major(TM). This study aimed at investigating the occurrence, prevalence and severity of cardiac iron overload in a young Chinese population with beta TM. METHODS AND RESULTS: We analyzed T2* cardiac magnetic resonance (CMR), left ventricular ejection fraction (LVEF) and serum ferritin (SF) in 201 beta TM patients. The median age was 9 years old. Patients received an average of 13 units of blood per year. The median SF level was 4536 ng/ml and 165 patients (82.1%) had SF>2500 ng/ml. Myocardial iron overload was detected in 68 patients (33.8%) and severe myocardial iron overload was detected in 26 patients (12.6%). Twenty-two patients ≤10 years old had myocardial iron overload, three of whom were only 6 years old. No myocardial iron overload was detected under the age of 6 years. Median LVEF was 64% (measured by CMR in 175 patients). Five of 6 patients with a LVEF<56% and 8 of 10 patients with cardiac disease had myocardial iron overload. CONCLUSIONS: The TM patients under follow-up at this regional centre in China patients are younger than other reported cohorts, more poorly-chelated, and have a high burden of iron overload. Myocardial siderosis occurred in patients younger than previously reported, and was strongly associated with impaired LVEF and cardiac disease. For such poorly-chelated TM patients, our data shows that the first assessment of cardiac T2* should be performed as early as 6 years old

A Chronic Oral Toxicity Study of Marine Collagen Peptides Preparation from Chum Salmon (Oncorhynchus keta) Skin Using Sprague-Dawley Rat

Due to the increased consumption of marine collagen peptides preparation (MCP) as ingredients in functional foods and pharmaceuticals, it was necessary to carry out safety requirements in the form of an oral chronic toxicity assessment. In order to define the oral chronic toxicity of MCP, a 24-month feeding study of MCP was carried out. Sprague-Dawley (S-D) rats at the age of four-week of both sexes were treated with MCP at the diet concentrations of 0%, 2.25%, 4.5%, 9% and 18% (wt/wt). The actual food intake and bodyweight of the individual animals were recorded periodically until sacrifice. Blood and urine samples were collected for serum chemistry evaluations and urinalysis. Throughout the experimental period, there was no toxicologically significant difference between the vehicle and MCP-treated animals with respect to the survival rate, body weight, food consumption, urinalysis, clinical biochemistry parameter and relative organ weight in either sex. Moreover, incidences of non-neoplastic lesions in MCP-treated groups did not significantly increase compared with the control group. Under the present experimental conditions, no higher risk of chronic toxic effects was observed in MCP-treated rats at the diet concentrations of 2.25%, 4.5%, 9% and 18% (wt/wt) than in the rats fed with basal rodent diet

The Toxoplasma monocarboxylate transporters are involved in the metabolism within the apicoplast and are linked to parasite survival

The apicoplast is a four-membrane plastid found in the apicomplexans, which harbors biosynthesis and organelle housekeeping activities in the matrix. However, the mechanism driving the flux of metabolites, in and out, remains unknown. Here we used TurboID and genome engineering to identify apicoplast transporters in Toxoplasma gondii. Among the many novel transporters, we show that one pair of apicomplexan monocarboxylate transporters (AMTs) appears to be evolved from the putative host cell that engulfed a red alga. Protein depletion showed that AMT1 and AMT2 are critical for parasite growth. Metabolite analyses supported the notion that AMT1 and AMT2 are associated with biosynthesis of isoprenoids and fatty acids. However, stronger phenotypic defects were observed for AMT2, including in the inability to establish T. gondii parasite virulence in mice. This study clarifies, significantly, the mystery of apicoplast transporter composition and reveals the importance of the pair of AMTs in maintaining the apicoplast activity in apicomplexan

Functional screening reveals Toxoplasma prenylated proteins required for endocytic trafficking and rhoptry protein sorting

In the apicomplexans, endocytosed cargos (e.g., hemoglobin) are trafficked to a specialized organelle for digestion. This follows a unique endocytotic process at the micropore/cytostome in these parasites. However, the mechanism underlying endocytic trafficking remains elusive, due to the repurposing of classical endocytic proteins for the biogenesis of apical organelles. To resolve this issue, we have exploited the genetic tractability of the model apicomplexan Toxoplasma gondii, which ingests host cytosolic materials (e.g., green fluorescent protein[GFP]). We determined an association between protein prenylation and endocytic trafficking, and using an alkyne-labeled click chemistry approach, the prenylated proteome was characterized. Genome editing, using clustered regularly interspaced short palindromic repaet/CRISPR-associated nuclease 9 (CRISPR/Cas9), was efficiently utilized to generate genetically modified lines for the functional screening of 23 prenylated candidates. This identified four of these proteins that regulate the trafficking of endocytosed GFP vesicles. Among these proteins, Rab1B and YKT6.1 are highly conserved but are non-classical endocytic proteins in eukaryotes. Confocal imaging analysis showed that Rab1B and Ras are substantially localized to both the trans-Golgi network and the endosome-like compartments in the parasite. Conditional knockdown of Rab1B caused a rapid defect in secretory trafficking to the rhoptry bulb, suggesting a trafficking intersection role for the key regulator Rab1B. Further experiments confirmed a critical role for protein prenylation in regulating the stability/activity of these proteins (i.e., Rab1B and YKT6.1) in the parasite. Our findings define the molecular basis of endocytic trafficking and reveal a potential intersection function of Rab1B on membrane trafficking in T. gondii. This might extend to other related protists, including the malarial parasites

Statistical Optimization of Process Variables for Antibiotic Activity of Xenorhabdus bovienii

The production of secondary metabolites with antibiotic properties is a common characteristic to entomopathogenic bacteria Xenorhabdus spp. These metabolites not only have diverse chemical structures but also have a wide range of bioactivities of medicinal and agricultural interests. Culture variables are critical to the production of secondary metabolites of microorganisms. Manipulating culture process variables can promote secondary metabolite biosynthesis and thus facilitate the discovery of novel natural products. This work was conducted to evaluate the effects of five process variables (initial pH, medium volume, rotary speed, temperature, and inoculation volume) on the antibiotic production of Xenorhabdus bovienii YL002 using response surface methodology. A 25–1 factorial central composite design was chosen to determine the combined effects of the five variables, and to design a minimum number of experiments. The experimental and predicted antibiotic activity of X. bovienii YL002 was in close agreement. Statistical analysis of the results showed that initial pH, medium volume, rotary speed and temperature had a significant effect (P<0.05) on the antibiotic production of X. bovienii YL002 at their individual level; medium volume and rotary speed showed a significant effect at a combined level and was most significant at an individual level. The maximum antibiotic activity (287.5 U/mL) was achieved at the initial pH of 8.24, medium volume of 54 mL in 250 mL flask, rotary speed of 208 rpm, temperature of 32.0°C and inoculation volume of 13.8%. After optimization, the antibiotic activity was improved by 23.02% as compared with that of unoptimized conditions

The genome sequence of the orchid Phalaenopsis equestris

Orchidaceae, renowned for its spectacular flowers and other reproductive and ecological adaptations, is one of the most diverse plant families. Here we present the genome sequence of the tropical epiphytic orchid Phalaenopsis equestris, a frequently used parent species for orchid breeding. P. equestris is the first plant with crassulacean acid metabolism (CAM) for which the genome has been sequenced. Our assembled genome contains 29,431 predicted protein-coding genes. We find that contigs likely to be underassembled, owing to heterozygosity, are enriched for genes that might be involved in self-incompatibility pathways. We find evidence for an orchid-specific paleopolyploidy event that preceded the radiation of most orchid clades, and our results suggest that gene duplication might have contributed to the evolution of CAM photosynthesis in P. equestris. Finally, we find expanded and diversified families of MADS-box C/D-class, B-class AP3 and AGL6-class genes, which might contribute to the highly specialized morphology of orchid flowers. (Résumé d'auteur

Precision measurement of the branching fractions of J/psi -> pi+pi-pi0 and psi' -> pi+pi-pi0

We study the decays of the J/psi and psi' mesons to pi+pi-pi0 using data samples at both resonances collected with the BES III detector in 2009. We measure the corresponding branching fractions with unprecedented precision and provide mass spectra and Dalitz plots. The branching fraction for J/psi -> pi+pi-pi0 is determined to be (2.137 +- 0.004 (stat.) +0.058-0.056 (syst.) +0.027-0.026 (norm.))*10-2, and the branching fraction for psi' -> pi+pi-pi0 is measured as (2.14 +- 0.03 (stat.) +0.08-0.07 (syst.) +0.09-0.08 (norm.))*10-4. The J/psi decay is found to be dominated by an intermediate rho(770) state, whereas the psi' decay is dominated by di-pion masses around 2.2 GeV/c2, leading to strikingly different Dalitz distributions.Comment: 15 pages, 2 figure

Higher-order multipole amplitude measurement in ψ(2S)→γχc2\psi(2S)\to\gamma\chi_{c2}

Using $106\times10^6$ $\psi(2S)$ events collected with the BESIII detector at the BEPCII storage ring, the higher-order multipole amplitudes in the radiative transition $\psi(2S)\to\gamma\chi_{c2}\to\gamma\pi\pi/\gamma KK$ are measured. A fit to the $\chi_{c2}$ production and decay angular distributions yields $M2=0.046\pm0.010\pm0.013$ and $E3=0.015\pm0.008\pm0.018$, where the first errors are statistical and the second systematic. Here $M2$ denotes the normalized magnetic quadrupole amplitude and $E3$ the normalized electric octupole amplitude. This measurement shows evidence for the existence of the $M2$ signal with $4.4\sigma$ statistical significance and is consistent with the charm quark having no anomalous magnetic moment.Comment: 14 pages, 4 figure