The dual role of MamB in magnetosome membrane assembly and magnetite biomineralization

Magnetospirillum gryphiswaldense MSR‐1 synthesizes membrane‐enclosed magnetite (Fe₃O₄) nanoparticles, magnetosomes, for magnetotaxis. Formation of these organelles involves a complex process comprising key steps which are governed by specific magnetosome‐associated proteins. MamB, a cation diffusion facilitator (CDF) family member has been implicated in magnetosome‐directed iron transport. However, deletion mutagenesis studies revealed that MamB is essential for the formation of magnetosome membrane vesicles, but its precise role remains elusive. In this study, we employed a multi‐disciplinary approach to define the role of MamB during magnetosome formation. Using site‐directed mutagenesis complemented by structural analyses, fluorescence microscopy and cryo‐electron tomography, we show that MamB is most likely an active magnetosome‐directed transporter serving two distinct, yet essential functions. First, MamB initiates magnetosome vesicle formation in a transport‐independent process, probably by serving as a landmark protein. Second, MamB transport activity is required for magnetite nucleation. Furthermore, by determining the crystal structure of the MamB cytosolic C‐terminal domain, we also provide mechanistic insight into transport regulation. Additionally, we present evidence that magnetosome vesicle growth and chain formation are independent of magnetite nucleation and magnetic interactions respectively. Together, our data provide novel insight into the role of the key bifunctional magnetosome protein MamB, and the early steps of magnetosome formation.     

The effect of change in skin temperature due to evaporative cooling on sweating response during exercise

 The purpose of this study was to investigate whether there are any effects of skin temperature changes on sweating response in the first few minutes of mild exercise. Six healthy males performed a bicycle exercise at 100 W (50 rpm) for 30 min under an ambient temperature of 23° C (40% RH). Esophageal temperature (T _es), mean skin temperature (T– _sk), local skin temperature at the lower left scapula (T _sl), local sweating rate (M. _sw), and cutaneous blood flow by laser-Doppler flowmetry (LDF) were measured continuously. Although T _sl decreased markedly just after the onset of sweating, T– _sk did not change. M. _sw did not increase constantly in the early stages of exercise, and there was a temporary interruption in the increase of M. _sw. This interruption in sweating was affected by the rate of change in T _sl rather than by the absolute value of T _sl, since there was a positive and significant correlation between the time of the interruption in the increase of M. _sw and the rate of decrease in T _sl (y=6.47x+0.04; r=0.86, P<0.05). The results suggest that sweating response in the early stages of exercise may be influenced by changes in local skin temperature due to evaporative cooling. Received: 31 August 1995 / Revised: 26 February 1996 / Accepted: 26 July 1996,     

Prevalence of blood type A and risk of vascular complications following transcatheter aortic valve implantation

Objectives

To assess the prevalence of blood type A among patients referred for transcatheter aortic valve implantation (TAVI) and whether it is related to vascular complications.

Backgrounds

Vascular complications following TAVI are associated with adverse outcomes. Various blood types, particularly type A, have been shown to be more prevalent in cardiovascular diseases and to be related to prognosis.

Methods

The prevalence of various blood types in a cohort of 491 consecutive patients who underwent TAVI was compared with a control group of 6500 consecutive hospitalised patients. The prevalence and predictors of vascular complications and bleeding events were evaluated in the blood type A group and were compared with non-type A patients.

Results

The mean age of TAVI patients was 83?±?6 years, and 40?% were males. Patients were divided into two groups: blood type A (n?=?220) and non-type A (n?=?271). Type A was significantly more prevalent in the TAVI group than in the control group (45 vs. 38?%, p?=?0.023). Compared with the non-type A group, patients with blood type A had more major and fatal bleeding (14.5 vs. 8.1?%, p?=?0.027) and more vascular complications (any vascular complication: 24.5 vs. 15.9?% p?=?0.016; major vascular complications: 12.3 vs. 7?% p?=?0.047). In a multivariable analysis, blood type A emerged as a significant and independent predictor for vascular complications and bleeding events.

Conclusions

Blood type A is significantly more prevalent in TAVI patients than in the general population and is related to higher rates of vascular and bleeding complications.

     

Effects of salinity and varying boron concentrations on boron uptake and growth of wheat

Summary Two sandculture experiments were conducted with wheat (Triticum aestivum) to determine the effects of (1) osmotic potential (Ψ_π) and (2) fluctuating boron (B) concentrations on B availability (toxicity), shoot growth and leaf concentrations of B of wheat. The first experiment consisted of growing wheat to the spike emergence stage in sandcultures irrigated with a complete nutrient solution containing 1.0, 7.5, and 15.0 mg Bl⁻¹ and having Ψ_π values of −0.02, −0.07, −0.12, and −0.17 MPa produced by CaCl₂−NaCl additions. Statistically, shoot weight was independently influenced by the B and Ψ_π treatments but not by their interaction. Only the B treatment had a significant effect on leaf boron concentrations; the B x Ψ_π interaction was nonsignificant with respect to leaf B concentrations. The second experiment was designed to determine if growth and B uptake of wheat responds to the time integrated mean (TIM) concentration of B. This experiment consisted of four fixed-B concentrations and four fluctuating-B concentrations designed to produce two TIM concentrations (3.9 and 7.4 mg Bl⁻¹) approached low to high and vice versa. With respect to shoot weight, there was no statistical difference among treatments having the same TIM concentration during the 10 week experiment. However, shoot B concentrations differed greatly; they were higher when the B concentration was progressively increased over the 10 week period. Leaf B concentrations (Y leaf at flowering), while not as high as the shoot B concentrations, were also higher under the treatment of increasing B concentration, indicating B uptake rates are higher for mature plants than for seedlings.     

Towards clarification of the biological role of microcystins, a family of cyanobacterial toxins

Microcystins constitute a serious threat to the quality of drinking water worldwide. These protein phosphatase inhibitors are formed by various cyanobacterial species, including Microcystis sp. Microcystins are produced by a complex microcystin synthetase, composed of peptide synthetases and polyketide synthases, encoded by the mcyA-J gene cluster. Recent phylogenetic analysis suggested that the microcystin synthetase predated the metazoan lineage, thus dismissing the possibility that microcystins emerged as a means of defence against grazing, and their original biological role is not clear. We show that lysis of Microcystis cells, either mechanically or because of various stress conditions, induced massive accumulation of McyB and enhanced the production of microcystins in the remaining Microcystis cells. A rise in McyB content was also observed following exposure to microcystin or the protease inhibitors micropeptin and microginin, also produced by Microcystis. The extent of the stimulation by cell extract was strongly affected by the age of the treated Microcystis culture. Older cultures, or those recently diluted from stock cultures, hardly responded to the components in the cell extract. We propose that lysis of a fraction of the Microcystis population is sensed by the rest of the cells because of the release of non-ribosomal peptides. The remaining cells respond by raising their ability to produce microcystins thereby enhancing their fitness in their ecological niche, because of their toxicity.     

Modeling cancer metabolism on a genome scale

Cancer cells have fundamentally altered cellular metabolism that is associated with their tumorigenicity and malignancy. In addition to the widely studied Warburg effect, several new key metabolic alterations in cancer have been established over the last decade, leading to the recognition that altered tumor metabolism is one of the hallmarks of cancer. Deciphering the full scope and functional implications of the dysregulated metabolism in cancer requires both the advancement of a variety of omics measurements and the advancement of computational approaches for the analysis and contextualization of the accumulated data. Encouragingly, while the metabolic network is highly interconnected and complex, it is at the same time probably the best characterized cellular network. Following, this review discusses the challenges that genome‐scale modeling of cancer metabolism has been facing. We survey several recent studies demonstrating the first strides that have been done, testifying to the value of this approach in portraying a network‐level view of the cancer metabolism and in identifying novel drug targets and biomarkers. Finally, we outline a few new steps that may further advance this field.     

nMAT1, a nuclear-encoded maturase involved in the trans-splicing of nad1 intron 1, is essential for mitochondrial complex I assembly and function

Mitochondrial genomes (mtDNAs) in angiosperms contain numerous group II-type introns that reside mainly within protein-coding genes that are required for organellar genome expression and respiration. While splicing of group II introns in non-plant systems is facilitated by proteins encoded within the introns themselves (maturases), the mitochondrial introns in plants have diverged and have lost the vast majority of their intron-encoded ORFs. Only a single maturase gene (matR) is retained in plant mtDNAs, but its role(s) in the splicing of mitochondrial introns is currently unknown. In addition to matR, plants also harbor four nuclear maturase genes (nMat 1 to 4) encoding mitochondrial proteins that are expected to act in the splicing of group II introns. Recently, we established the role of one of these proteins, nMAT2, in the splicing of several mitochondrial introns in Arabidopsis. Here, we show that nMAT1 is required for trans-splicing of nad1 intron 1 and also functions in cis-splicing of nad2 intron 1 and nad4 intron 2. Homozygous nMat1 plants show retarded growth and developmental phenotypes, modified respiration activities and altered stress responses that are tightly correlated with mitochondrial complex I defects.