Centromere and telomere sequence alterations reflect the rapid genome evolution within the carnivorous plant genus Genlisea

Linear chromosomes of eukaryotic organisms invariably possess centromeres and telomeres to ensure proper chromosome segregation during nuclear divisions and to protect the chromosome ends from deterioration and fusion, respectively. While centromeric sequences may differ between species, with arrays of tandemly repeated sequences and retrotransposons being the most abundant sequence types in plant centromeres, telomeric sequences are usually highly conserved among plants and other organisms. The genome size of the carnivorous genus Genlisea (Lentibulariaceae) is highly variable. Here we study evolutionary sequence plasticity of these chromosomal domains at an intrageneric level. We show that Genlisea nigrocaulis (1C = 86 Mbp; 2n = 40) and G. hispidula (1C = 1550 Mbp; 2n = 40) differ as to their DNA composition at centromeres and telomeres. G. nigrocaulis and its close relative G. pygmaea revealed mainly 161 bp tandem repeats, while G. hispidula and its close relative G. subglabra displayed a combination of four retroelements at centromeric positions. G. nigrocaulis and G. pygmaea chromosome ends are characterized by the Arabidopsis‐type telomeric repeats (TTTAGGG); G. hispidula and G. subglabra instead revealed two intermingled sequence variants (TTCAGG and TTTCAGG). These differences in centromeric and, surprisingly, also in telomeric DNA sequences, uncovered between groups with on average a > 9‐fold genome size difference, emphasize the fast genome evolution within this genus. Such intrageneric evolutionary alteration of telomeric repeats with cytosine in the guanine‐rich strand, not yet known for plants, might impact the epigenetic telomere chromatin modification.     

Production of an Attenuated Phenol-Soluble Modulin Variant Unique to the MRSA Clonal Complex 30 Increases Severity of Bloodstream Infection

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of morbidity and death. Phenol-soluble modulins (PSMs) are recently-discovered toxins with a key impact on the development of Staphylococcus aureus infections. Allelic variants of PSMs and their potential impact on pathogen success during infection have not yet been described. Here we show that the clonal complex (CC) 30 lineage, a major cause of hospital-associated sepsis and hematogenous complications, expresses an allelic variant of the PSMα3 peptide. We found that this variant, PSMα3N22Y, is characteristic of CC30 strains and has significantly reduced cytolytic and pro-inflammatory potential. Notably, CC30 strains showed reduced cytolytic and chemotactic potential toward human neutrophils, and increased hematogenous seeding in a bacteremia model, compared to strains in which the genome was altered to express non-CC30 PSMα3. Our findings describe a molecular mechanism contributing to attenuated pro-inflammatory potential in a main MRSA lineage. They suggest that reduced pathogen recognition via PSMs allows the bacteria to evade elimination by innate host defenses during bloodstream infections. Furthermore, they underscore the role of point mutations in key S. aureus toxin genes in that adaptation and the pivotal importance PSMs have in defining key S. aureus immune evasion and virulence mechanisms.     

It doesn’t always pay to be fit: success landscapes

Journal of Biological Physics - Landscapes play an important role in many areas of biology, in which biological lives are deeply entangled. Here we discuss a form of landscape in evolutionary...     

Plasma exchange therapy for thrombotic microangiopathies

Thrombotic microangiopathies (TMAs) are syndromes associated with thrombocytopenia and multiple organ failure. Plasma exchange is a proven therapy for primary TMA such as thrombotic thrombocytopenic purpura (TTP). There is growing evidence that plasma exchange therapy might also facilitate resolution of organ dysfunction and improve outcomes for secondary TMAs such as disseminated intravascular coagulation (DIC) and systemic inflammation-induced TTP. In this review, we survey the current available evidence and practice of plasma exchange therapy for TMAs.     

Improved NYVAC-based vaccine vectors

While as yet there is no vaccine against HIV/AIDS, the results of the phase III Thai trial (RV144) have been encouraging and suggest that further improvements of the prime/boost vaccine combination of a poxvirus and protein are needed. With this aim, in this investigation we have generated derivatives of the candidate vaccinia virus vaccine vector NYVAC with potentially improved functions. This has been achieved by the re-incorporation into the virus genome of two host range genes, K1L and C7L, in conjunction with the removal of the immunomodulatory viral molecule B19, an antagonist of type I interferon action. These novel virus vectors, referred to as NYVAC-C-KC and NYVAC-C-KC-ΔB19R, have acquired relevant biological characteristics, giving higher levels of antigen expression in infected cells, replication-competency in human keratinocytes and dermal fibroblasts, activation of selective host cell signal transduction pathways, and limited virus spread in tissues. Importantly, these replication-competent viruses have been demonstrated to maintain a highly attenuated phenotype.     

Interior decoration: Tropomyosin in actin dynamics and cell migration

Cell migration and invasion requires the precise temporal and spatial orchestration of a variety of biological processes. Filaments of polymerized actin are critical players in these diverse processes, including the regulation of cell anchorage points (both cell-cell and cell-extracellular matrix), the uptake and delivery of molecules via endocytic pathways and the generation of force for both membrane protrusion and retraction. How the actin filaments are specialized for each of these discrete functions is yet to be comprehensively elucidated. The cytoskeletal tropomyosins are a family of actin associating proteins that form head-to-tail polymers which lay in the major groove of polymerized actin filaments. In the present review we summarize the emerging isoform-specific functions of tropomyosins in cell migration and invasion and discuss their potential roles in the specialization of actin filaments for the diverse cellular processes that together regulate cell migration and invasion.Key words: tropomyosin, actin, migration, invasion, cytoskeleton, actin dynamics, adhesionActin is the most abundant protein in eukaryotic cells and is critical for maintaining structural integrity. The polymerization of globular (G)-actin monomers forms actin filaments (F-actin),¹ which play a role in diverse and complex cellular functions including intercellular transport of organelles and vesicles,^2,3 cytokinesis,⁴ apoptosis⁵ and cell motility.⁶ Intricate details describing the molecular scale interactions between regulatory proteins and actin have been extensively investigated but the mechanistic control of diverse actin filament functions remain largely unclear. Recent improvements in analysis techniques⁷ and the use of physiologically relevant models of 3D cell culturing⁸ have now begun to reveal mechanisms of actin cytoskeleton regulation. Accruing evidence suggests that the actin decorating protein tropomyosin is a key regulator of actin filament specialization. Of particular interest is the impact that tropomyosin regulation has on actin filament activity during cell migration and invasion that underpins immunological cell homing, development, wound healing and metastasis.     

Dextran fractional clearance studies in acute dengue infection

Background

Although increased capillary permeability is the major clinical feature associated with severe dengue infections the mechanisms underlying this phenomenon remain unclear. Dextran clearance methodology has been used to investigate the molecular sieving properties of the microvasculature in clinical situations associated with altered permeability, including during pregnancy and in various renal disorders. In order to better understand the characteristics of the vascular leak associated with dengue we undertook formal dextran clearance studies in Vietnamese dengue patients and healthy volunteers.

Methodology/Principal Findings

We carried out serial clearance studies in 15 young adult males with acute dengue and evidence of vascular leakage a) during the phase of maximal leakage and b) one and three months later, as well as in 16 healthy control subjects. Interestingly we found no difference in the clearance profiles of neutral dextran solutions among the dengue patients at any time-point or in comparison to the healthy volunteers.

Conclusions/Significance

The surface glycocalyx layer, a fibre-matrix of proteoglycans, glycosaminoglycans, and plasma proteins, forms a complex with the underlying endothelial cells to regulate plasma volume within circumscribed limits. It is likely that during dengue infections loss of plasma proteins from this layer alters the permeability characteristics of the complex; physical and/or electrostatic interactions between the dextran molecules and the glycocalyx structure may temporarily restore normal function, rendering the technique unsuitable for assessing permeability in these patients. The implications for resuscitation of patients with dengue shock syndrome (DSS) are potentially important. It is possible that continuous low-dose infusions of dextran may help to stabilize the permeability barrier in patients with profound or refractory shock, reducing the need for repeated boluses, limiting the total colloid volume required. Formal clinical studies should help to assess this strategy as an alternative to conventional fluid resuscitation for severe DSS.     

Endothelial cell behavior inside myoblast sheets with different thickness

Using a cell sheet stacking method, we developed an in vitro culture system in which green fluorescent protein expressing human umbilical vein endothelial cells (GFP-HUVECs) were cultured under human skeletal muscle myoblast (HSMM) sheets with different layer numbers. Our aim in developing this system was to examine the different endothelial behaviors in the cell sheet. During 96 h of incubation, in monolayer HSMM sheet, HUVECs quickly reached the top of the cell sheet and detached. In three-layered HSMM sheet, HUVECs also migrated to the top layer and formed island-shaped aggregates. In five-layered HSMM sheet, HUVECs migrated into the middle of the cell sheet and formed net-shaped aggregates. In seven-layered HSMM sheet, HUVECs migrated in the basal of the cell sheet and formed sparse net-shaped aggregates. The thickness of the HSMM sheet, which can be controlled by the layer number of the cell sheet, is therefore an important parameter that affects the migration time, encounters, localization, and morphology of HUVECs inside the HSMM sheet.     

Enhanced Intestinal Motility during Oral Glucose Tolerance Test after Laparoscopic Sleeve Gastrectomy: Preliminary Results Using Cine Magnetic Resonance Imaging

Background

Enhanced secretion of glucagon-like peptide-1 (GLP-1) has been suggested as a possible mechanism underlying the improvement in type 2 diabetes mellitus (T2DM) after laparoscopic sleeve gastrectomy (LSG). However, the reason for enhanced GLP-1 secretion during glucose challenge after LSG remains unclear because LSG does not include intestinal bypass. In this study, we focused on the effects of LSG on GLP-1 secretion and intestinal motility during the oral glucose tolerance test (OGTT) using cine magnetic resonance imaging (MRI) before and 3 months after LSG.

Methods

LSG was performed in 12 obese patients with a body mass index >35 kg/m². Six patients had T2DM. OGTT was performed before and 3 months after the surgery. Body weight, hemoglobin A1c (HbA1c), and GLP-1 levels during OGTT were examined, and intestinal motility during OGTT was assessed using cine MRI.

Results

Body weight was significantly decreased after surgery in all the cases. HbA1c was markedly decreased in all the diabetic subjects. In all cases, GLP-1 secretion during OGTT was enhanced and cine MRI showed markedly increased intestinal motility at 15 and 30 min during OGTT after LSG.

Conclusions

LSG leads to accelerated intestinal motility and reduced intestinal transit time, which may be involved in the mechanism underlying enhanced GLP-1 secretion during OGTT after LSG.     

Sunlight irradiation‐assisted green synthesis,characteristics and antibacterial activity of silver nanoparticles using the leaf extract of Jasminum subtriplinerve Blume

Journal of Plant Biochemistry and Biotechnology - Silver nanoparticles (AgNPs) were biosynthesized at room temperature under sunlight irradiation, using the extract of Jasminum subtriplinerve Blume...