Transpiration difference under high evaporative demand in chickpea (Cicer arietinum L.) may be explained by differences in the water transport pathway in the root cylinder

• Terminal drought substantially reduces chickpea yield. Reducing water use at vegetative stage by reducing transpiration under high vapor pressure deficit (VPD), i.e. under dry/hot conditions, contributes to drought adaptation. We hypothesized that this trait could relate to differences in a genotype's dependence on root water transport pathways and hydraulics.
• Transpiration rate responses in conservative and profligate chickpea genotypes were evaluated under increasing VPD in the presence/absence of apoplastic and cell‐to‐cell transport inhibitors.
• Conservative genotypes ICC 4958 and ICC 8058 restricted transpiration under high VPD compared to the profligate genotypes ICC 14799 and ICC 867. Profligate genotypes were more affected by aquaporin inhibition of the cell‐to‐cell pathway than conservative genotypes, as measured by the root hydraulic conductance and transpiration under high VPD. Aquaporin inhibitor treatment also led to a larger reduction in root hydraulic conductivity in profligate than in conservative genotypes. In contrast, blockage of the apoplastic pathway in roots decreased transpiration more in conservative than in profligate genotypes. Interestingly, conservative genotypes had high early vigour, whereas profligate genotypes had low early vigour.
• In conclusion, profligate genotypes depend more on the cell‐to‐cell pathway, which might explain their higher root hydraulic conductivity, whereas water‐saving by restricting transpiration led to higher dependence on the apoplastic pathway. This opens the possibility to screen for conservative or profligate chickpea phenotypes using inhibitors, itself opening to the search of the genetic basis of these differences.

     

Molecular Mapping of a Gene for Fertility Restoration of Wild Abortive (WA) Cytoplasmic Male Sterility using a Basmati Rice Restorer Line

The inheritance and molecular mapping of a fertility restorer gene in basmati quality restorer line PRR-78 was carried out using an F₂ mapping population from the cross IR58025A X PRR-78 employing microsatellite markers. Dominant monogenic control of fertility restoration was observed in the F₂, and further confirmed by test cross data. Out of 44 sequence tagged microsatellite (STMS) markers used in the bulked segregant analysis (BSA), four differentiated the fertile bulk from the sterile bulk as well as the two parental lines from each other. One of these markers, RM258 located on chromosome 10, was found linked to the restorer gene at a distance of9.5 cM. Considering the RM258 location, additional STMS (RM171 and RM294A) and sequence tagged site (STS) primers derived from restriction fragment length polymorphic (RFLP) clones (G2155 and C1361) linked to fertility restorer gene(s) in other populations, were also used to find out a marker more tightly linked to the restorer gene. However, of these, RM171, RM294A and G2155 based primers amplified monomorphic fragments between parental lines and no amplification was observed with C1361. Cleaved amplified polymorphic sequence (CAPS) analysis of non-polymorphic STMS and STS markers and random amplified polymorphic DNA (RAPD) analysis using five random primers reportedly linked to restorer gene in other populations, also failed to differentiate the two parents. While, the marker RM258 is being used in the restorer breeding to identify putative restorer lines, search for additional tightly linked markers is underway.     

A theoretical entropy score as a single value to express inhibitor selectivity

Background  

Designing maximally selective ligands that act on individual targets is the dominant paradigm in drug discovery. Poor selectivity can underlie toxicity and side effects in the clinic, and for this reason compound selectivity is increasingly monitored from very early on in the drug discovery process. To make sense of large amounts of profiling data, and to determine when a compound is sufficiently selective, there is a need for a proper quantitative measure of selectivity.     

Serum Levels of Soluble CD26/Dipeptidyl Peptidase-IV in Type 2 Diabetes Mellitus and Its Association with Metabolic Syndrome and Therapy with Antidiabetic Agents in Malaysian Subjects

BackgroundA soluble form of CD26/dipeptidyl peptidase-IV (sCD26/DPP-IV) induces DPP-IV enzymatic activity that degrades incretin. We investigated fasting serum levels of sCD26/DPP-IV and active glucagon-like peptide-1 (GLP-1) in Malaysian patients with type 2 diabetes mellitus (T2DM) with and without metabolic syndrome (MetS), as well as the associations between sCD26/DPP-IV levels, MetS, and antidiabetic therapy.MethodsWe assessed sCD26/DPP-IV levels, active GLP-1 levels, body mass index (BMI), glucose, insulin, A1c, glucose homeostasis indices, and lipid profiles in 549 Malaysian subjects (including 257 T2DM patients with MetS, 57 T2DM patients without MetS, 71 non-diabetics with MetS, and 164 control subjects without diabetes or metabolic syndrome).ResultsFasting serum levels of sCD26/DPP-IV were significantly higher in T2DM patients with and without MetS than in normal subjects. Likewise, sCD26/DPP-IV levels were significantly higher in patients with T2DM and MetS than in non-diabetic patients with MetS. However, active GLP-1 levels were significantly lower in T2DM patients both with and without MetS than in normal subjects. In T2DM subjects, sCD26/DPP-IV levels were associated with significantly higher A1c levels, but were significantly lower in patients using monotherapy with metformin. In addition, no significant differences in sCD26/DPP-IV levels were found between diabetic subjects with and without MetS. Furthermore, sCD26/DPP-IV levels were negatively correlated with active GLP-1 levels in T2DM patients both with and without MetS. In normal subjects, sCD26/DPP-IV levels were associated with increased BMI, cholesterol, and LDL-cholesterol (LDL-c) levels.ConclusionSerum sCD26/DPP-IV levels increased in T2DM subjects with and without MetS. Active GLP-1 levels decreased in T2DM patients both with and without MetS. In addition, sCD26/DPP-IV levels were associated with Alc levels and negatively correlated with active GLP-1 levels. Moreover, metformin monotherapy was associated with reduced sCD26/DPP-IV levels. In normal subjects, sCD26/DPP-IV levels were associated with increased BMI, cholesterol, and LDL-c.     

Poultry Slaughtering Practices in Rural Communities of Bangladesh and Risk of Avian Influenza Transmission: A Qualitative Study

Slaughtering sick poultry is a risk factor for human infection with highly pathogenic avian influenza and is a common practice in Bangladesh. This paper describes human exposures to poultry during slaughtering process and the customs and rituals influencing these practices in two Bangladeshi rural communities. In 2009, we conducted 30 observations to observe slaughtering practices and 110 in-depth and short interviews and 36 group discussions to explore reasons behind those practices. The villagers reported slaughtering 103 poultry, including 20 sick poultry during 2 months. During different stages of slaughtering, humans, the environment, healthy poultry, and other animals were exposed to poultry blood and body parts. Women performed most of the slaughtering tasks, including evisceration. Defeathering required the most time and involved several persons. During festivals, ceremonies, and rituals, many people gathered and participated in the slaughtering of poultry. Exposure to poultry slaughtering created numerous opportunities for potential avian influenza transmission. Strategies that can be further tested to determine if they reduce the risk of transmission include skinning the carcasses of sick poultry, using hot water for defeathering and cleaning, using a bucket to contain slaughtering blood and carcass, burying the offal and encouraging handwashing.     

Sarcocystis nesbitti Causes Acute,Relapsing Febrile Myositis with a High Attack Rate: Description of a Large Outbreak of Muscular Sarcocystosis in Pangkor Island,Malaysia, 2012

Background

From the 17^th to 19^th January 2012, a group of 92 college students and teachers attended a retreat in a hotel located on Pangkor Island, off the west coast of Peninsular Malaysia. Following the onset of symptoms in many participants who presented to our institute, an investigation was undertaken which ultimately identified Sarcocystis nesbitti as the cause of this outbreak.

Methodology/Principal Findings

All retreat participants were identified, and clinical and epidemiological information was obtained via clinical review and self-reported answers to a structured questionnaire. Laboratory, imaging and muscle biopsy results were evaluated and possible sources of exposure, in particular water supply, were investigated. At an average of 9–11 days upon return from the retreat, 89 (97%) of the participants became ill. A vast majority of 94% had fever with 57% of these persons experiencing relapsing fever. Myalgia was present in 91% of patients. Facial swelling from myositis of jaw muscles occurred in 9 (10%) patients. The median duration of symptoms was 17 days (IQR 7 to 30 days; range 3 to 112). Out of 4 muscle biopsies, sarcocysts were identified in 3. S. nesbitti was identified by PCR in 3 of the 4 biopsies including one biopsy without observed sarcocyst. Non-Malaysians had a median duration of symptoms longer than that of Malaysians (27.5 days vs. 14 days, p = 0.001) and were more likely to experience moderate or severe myalgia compared to mild myalgia (83.3% vs. 40.0%, p = 0.002).

Conclusions/Significance

The similarity of the symptoms and clustered time of onset suggests that all affected persons had muscular sarcocystosis. This is the largest human outbreak of sarcocystosis ever reported, with the specific Sarcocystis species identified. The largely non-specific clinical features of this illness suggest that S. nesbitti may be an under diagnosed infection in the tropics.     

A Multisclae Probabilisitc Framework to Model Early Steps in Tumor Metastasis

Tumor metastasis is the leading cause of nearly all cancer related deaths. While several experimental and computational studies have addressed individual stages of the complex metastasis process, a comprehensive systems-biology model that links various stages of metastasis has not been put forth as of yet. In this paper we discuss the formulation and application of such a model that utilizes basic principles of cell biology, physics and mechanics to study the migratory patterns of tumor cells as they move from the parent tumor site to the connective tissue via the basement membrane. The model is first of its kind in capturing the essential early features of metastasis in a single simulation and shows good agreement with recent experimental studies.     

Heparin promotes fibrillation of most phenol-soluble modulin virulence peptides from Staphylococcus aureus

Phenol-soluble modulins (PSMs), such as α-PSMs, β-PSMs, and δ-toxin, are virulence peptides secreted by different Staphylococcus aureus strains. PSMs are able to form amyloid fibrils, which may strengthen the biofilm matrix that promotes bacterial colonization of and extended growth on surfaces (e.g., cell tissue) and increases antibiotic resistance. Many components contribute to biofilm formation, including the human-produced highly sulfated glycosaminoglycan heparin. Although heparin promotes S. aureus infection, the molecular basis for this is unclear. Given that heparin is known to induce fibrillation of a wide range of proteins, we hypothesized that heparin aids bacterial colonization by promoting PSM fibrillation. Here, we address this hypothesis using a combination of thioflavin T-fluorescence kinetic studies, CD, FTIR, electron microscopy, and peptide microarrays to investigate the mechanism of aggregation, the structure of the fibrils, and identify possible binding regions. We found that heparin accelerates fibrillation of all α-PSMs (except PSMα2) and δ-toxin but inhibits β-PSM fibrillation by blocking nucleation or reducing fibrillation levels. Given that S. aureus secretes higher levels of α-PSM than β-PSM peptides, heparin is therefore likely to promote fibrillation overall. Heparin binding is driven by multiple positively charged lysine residues in α-PSMs and δ-toxins, the removal of which strongly reduced binding affinity. Binding of heparin did not affect the structure of the resulting fibrils, that is, the outcome of the aggregation process. Rather, heparin provided a scaffold to catalyze or inhibit fibrillation. Based on our findings, we speculate that heparin may strengthen the bacterial biofilm and therefore enhance colonization via increased PSM fibrillation.     

β-Arrestin-biased signaling of PTH analogs of the type 1 parathyroid hormone receptor

Parathyroid hormone (PTH) is an anabolic agent that mediates bone formation through activation of the Gα_s-, Gα_q- and β-arrestin-coupled parathyroid hormone receptor type 1 (PTH1R). Pharmacological evidence based on the effect of PTH(7–34), a PTH derivative that is said to preferentially activate β-arrestin signaling through PTH1R, suggests that PTH1R-activated β-arrestin signaling mediates anabolic effects on bone. Here, we performed a thorough evaluation of PTH(7–34) signaling behaviour using quantitative assays for β-arrestin recruitment, Gα_s- and Gα_q-signaling. We found that PTH(7–34) inhibited PTH-induced cAMP accumulation, but was unable to induce β-arrestin recruitment, PTH1R internalization and ERK1/2 phosphorylation in HEK293, CHO and U2OS cells. Thus, the β-arrestin bias of PTH(7–34) is not apparent in every cell type examined, suggesting that correlating in vivo effects of PTH(7–34) to in vitro pharmacology should be done with caution.