Elevational variation in regional vegetation responses to late‐glacial climate changes in the Carpathians

Aim We used fossil records to explore patterns of change in vegetation composition, turnover and diversity along an elevational gradient during the late‐glacial to early Holocene, and to locate the elevations most sensitive to past climate changes. Location Romania. Methods Changes in the late‐glacial vegetation communities were inferred from seven published pollen records distributed within the main vegetation belts of the Romanian Carpathians, at elevations from 275 to 1840 m. Principal components analysis, detrended canonical correspondence analysis (DCCA) and rarefaction analysis were undertaken on these data. Results DCCA indicates that compositional change is strongest (SD 1.2, c. 70%) at the late‐glacial/Holocene transition (c. 11,500 cal. yr bp ), but significant shifts also occur at c. 14,700, c. 13,800 and c. 12,700 cal. yr bp (SD 0.4–0.8, 25–50%). Palynological turnover is greater for mid‐elevation records (730–1100 m) than at low and high elevations. Intervals of greater palynological richness occur between c. 13,800 and 12,500 cal. yr bp and after 11,500 cal. yr bp , and intervals of lower richness occur before c. 14,000 cal. yr bp and between c. 12,900 and 11,500 cal. yr bp . Main conclusions Variations in species composition during repeated climate changes of the late‐glacial suggest that community composition at a given time was not only a result of the environmental conditions of that period, but also the legacy of previous cumulative recruitment and extirpation events. Turnover estimates suggest that mid‐elevations have been the most sensitive to climate change during the late‐glacial and early Holocene. Palynological richness estimates show a less clear elevational pattern and no evidence for a greater sensitivity of this measure of biodiversity at high elevations to past climate change. However, results may have been affected by taxa with high pollen productivity and distance dispersability. Our finding concurs with other palaeoecological and local‐scale modelling studies in suggesting that small populations have survived in favourable microhabitats embedded within larger unsuitable areas during the late‐glacial, features not captured by broad‐scale model predictions.     

Boundary Layer Flow Past a Stretching Surface in a Porous Medium Saturated by a Nanofluid: Brinkman-Forchheimer Model

In this study, the steady forced convection flow and heat transfer due to an impermeable stretching surface in a porous medium saturated with a nanofluid are investigated numerically. The Brinkman-Forchheimer model is used for the momentum equations (porous medium), whereas, Bongiorno’s model is used for the nanofluid. Uniform temperature and nanofluid volume fraction are assumed at the surface. The boundary layer equations are transformed to ordinary differential equations in terms of the governing parameters including Prandtl and Lewis numbers, viscosity ratio, porous medium, Brownian motion and thermophoresis parameters. Numerical results for the velocity, temperature and concentration profiles, as well as for the reduced Nusselt and Sherwood numbers are obtained and presented graphically.     

Nucleoside diphosphate kinase from human erythrocytes: purification, molecular mass and subunit structure

A new procedure for the purification of nucleoside diphosphate kinase from human erythrocytes is described. The enzyme (105 kDa by gel filtration) is made-up of two different kinds of subunits (19.0 and 20.5 kDa), both displaying enzymatic activity. The probable subunit structure of the enzyme is hexameric. The discrepancies related to earlier work are discussed.     

An intersubunit disulfide bridge stabilizes the tetrameric nucleoside diphosphate kinase of Aquifex aeolicus

The nucleoside diphosphate kinase (Ndk) catalyzes the reversible transfer of the γ-phosphate from nucleoside triphosphate to nucleoside diphosphate. Ndks form hexamers or two types of tetramers made of the same building block, namely, the common dimer. The secondary interfaces of the Type I tetramer found in Myxococcus xanthus Ndk and of the Type II found in Escherichia coli Ndk involve the opposite sides of subunits. Up to now, the few available structures of Ndk from thermophiles were hexameric. Here, we determined the X-ray structures of four crystal forms of the Ndk from the hyperthermophilic bacterium Aquifex aeolicus (Aa-Ndk). Aa-Ndk displays numerous features of thermostable proteins and is made of the common dimer but it is a tetramer of Type I. Indeed, the insertion of three residues in a surface-exposed spiral loop, named the Kpn-loop, leads to the formation of a two-turn α-helix that prevents both hexamer and Type II tetramer assembly. Moreover, the side chain of the cysteine at position 133, which is not present in other Ndk sequences, adopts two alternate conformations. Through the secondary interface, each one forms a disulfide bridge with the equivalent Cys133 from the neighboring subunit. This disulfide bridge was progressively broken during X-ray data collection by radiation damage. Such crosslinks counterbalance the weakness of the common-dimer interface. A 40% decrease of the kinase activity at 60°C after reduction and alkylation of the protein corroborates the structural relevance of the disulfide bridge on the tetramer assembly and enzymatic function.     

Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: a randomized controlled trial

The only currently recommended treatment for nonalcoholic fatty liver disease (NAFLD) is lifestyle modification. Preliminary studies of silybin showed beneficial effects on liver function. Realsil (RA) comprises the silybin phytosome complex (silybin plus phosphatidylcholine) coformulated with vitamin E. We report on a multicenter, phase III, double-blind clinical trial to assess RA in patients with histologically documented NAFLD. Patients were randomized 1:1 to RA or placebo (P) orally twice daily for 12 months. Prespecified primary outcomes were improvement over time in clinical condition, normalization of liver enzyme plasma levels, and improvement of ultrasonographic liver steatosis, homeostatic model assessment (HOMA), and quality of life. Secondary outcomes were improvement in liver histologic score and/or decrease in NAFLD score without worsening of fibrosis and plasma changes in cytokines, ferritin, and liver fibrosis markers. We treated 179 patients with NAFLD; 36 were also HCV positive. Forty-one patients were prematurely withdrawn and 138 patients analyzed per protocol (69 per group). Baseline patient characteristics were generally well balanced between groups, except for steatosis, portal infiltration, and fibrosis. Adverse events (AEs) were generally transient and included diarrhea, dysgeusia, and pruritus; no serious AEs were recorded. Patients receiving RA but not P showed significant improvements in liver enzyme plasma levels, HOMA, and liver histology. Body mass index normalized in 15% of RA patients (2.1% with P). HCV-positive patients in the RA but not the P group showed improvements in fibrogenesis markers. This is the first study to systematically assess silybin in NAFLD patients. Treatment with RA but not P for 12 months was associated with improvement in liver enzymes, insulin resistance, and liver histology, without increases in body weight. These findings warrant further investigation.     

TLR1 polymorphisms in Europeans and spontaneous pregnancy loss

Toll-like receptors (TLRs) are critical components of the pathogen recognition by the host innate immune system. Recently it has been shown that TLR1 is under evolutionary pressure in Europeans. This involves the positive selection of the nonsynonymous TLR1 1805G variant in Europeans, although this is associated with poor TLR1 response and unfavorable prognosis in various infections. In terms of natural selection, differential fertility is another mechanism, independent of infection susceptibility, that may explain the polymorphism pattern observed for TLR1. To test this hypothesis, we assessed the correlation of two TLR1 SNPs (T1805G and G239C) with spontaneous pregnancy loss in a case-control study that included 132 spontaneous pregnancy loss patients and 142 control volunteers. Similar allele frequencies of T1805G were observed between cases and controls, but GG genotype tended to be associated with pregnancy loss (OR 1.91; 95%CI 1.03, 3.53). No differences were observed for the TLR1 G239C SNP. Our findings showed slight differences in the distribution of T1805G variants in women with pregnancy loss, but these were not indicative of a protective effect of the TLR1 1805G allele for this fertility disorder. Although our hypothesis was not proven, potential effects of TLR1 polymorphisms on pregnancy outcome have been suggested, and future studies in larger cohorts are warranted.     

MUFOLD: A new solution for protein 3D structure prediction

There have been steady improvements in protein structure prediction during the past 2 decades. However, current methods are still far from consistently predicting structural models accurately with computing power accessible to common users. Toward achieving more accurate and efficient structure prediction, we developed a number of novel methods and integrated them into a software package, MUFOLD. First, a systematic protocol was developed to identify useful templates and fragments from Protein Data Bank for a given target protein. Then, an efficient process was applied for iterative coarse‐grain model generation and evaluation at the Cα or backbone level. In this process, we construct models using interresidue spatial restraints derived from alignments by multidimensional scaling, evaluate and select models through clustering and static scoring functions, and iteratively improve the selected models by integrating spatial restraints and previous models. Finally, the full‐atom models were evaluated using molecular dynamics simulations based on structural changes under simulated heating. We have continuously improved the performance of MUFOLD by using a benchmark of 200 proteins from the Astral database, where no template with >25% sequence identity to any target protein is included. The average root‐mean‐square deviation of the best models from the native structures is 4.28 Å, which shows significant and systematic improvement over our previous methods. The computing time of MUFOLD is much shorter than many other tools, such as Rosetta. MUFOLD demonstrated some success in the 2008 community‐wide experiment for protein structure prediction CASP8. Proteins 2010. © 2009 Wiley‐Liss, Inc.     

A syndrome of mental retardation, short stature, craniofacial anomalies with palpebral ptosis and pulmonary stenosis in three siblings with normal parents. An example of autosomal recessive inheritance of the Noonan phenotype?

We present a family with four children in which three, a girl and two boys, present a similar MR/MCA syndrome with slight to moderate mental retardation, short stature, peculiar facies with palpebral ptosis, pectus excavatum and pulmonary stenosis. As both parents are mentally and physically normal, autosomal recessive inheritance of this Noonan-like phenotype is most likely. The findings in the present family confirm that the Noonan phenotype may be caused by different etiologies with different types of genetic transmission.