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.

     

The intranuclear bodies of Entamoeba

Intranuclear bodies which are spherical in shape are clearly seen by ‘Anoptral’ (negative) phase microscopy in the nucleus of Entamoeba. These bodies vary in size and numbers from cell to cell. With interference microscopy the intranuclear bodies appear as spherical granules in the nucleus of the cell. Their distribution and numbers are again very variable. With electron microscopy the bodies can be clearly seen inside the nucleus. They are always spherical in shape but vary in size from 0·1 to 1·5 μm. They may be empty or contain granular or membranous material. They display the capacity to move out of the nucleus.     

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.     

Discovery of 1,3-diphenyl-1H-pyrazole derivatives containing rhodanine-3-alkanoic acid groups as potential PTP1B inhibitors

Two series of 1,3-diphenyl-1H-pyrazole derivatives containing rhodanine-3-alkanoic acid groups were identified as competitive protein tyrosine phosphatase 1B (PTP1B) inhibitors. Among the compounds studied, IIIv was found to have the best in vitro inhibition activity against PTP1B (IC₅₀?=?0.67?±?0.09?µM) and the best selectivity (9-fold) between PTP1B and T-cell protein tyrosine phosphatase (TCPTP). Molecular docking studies demonstrated that compounds IIIm, IIIv and IVg could occupy simultaneously at both the catalytic site and the adjacent pTyr binding site. These results provide novel lead compounds for the design of inhibitors of PTP1B as well as other PTPs.     

Synthesis of quinoline derivatives as diabetic II inhibitors and molecular docking studies

In searchof the potenttherapeutic agent as an α-glucosidase inhibitor, we have synthesized twenty-five analogs (1–25) of quinoline-based Schiff bases as an inhibitoragainst α-glucosidase enzyme under positive control acarbose (IC₅₀ = 38.45 ± 0.80 µM). From the activity profile it was foundthat analogs 1, 2, 3, 4, 11, 12 and 20with IC₅₀values 12.40 ± 0.40, 9.40 ± 0.30, 14.10 ± 0.40, 6.20 ± 0.30, 14.40 ± 0.40, 7.40 ± 0.20 and 13.20 ± 0.40 µMrespectively showed most potent inhibition among the series even than standard drug acarbose (IC₅₀ = 38.45 ± 0.80 µM). Here in the present study analog 4 (IC₅₀ = 6.20 ± 0.30 µM) was found with many folds better α-glucosidase inhibitory activity than the reference drug. Eight analogs like 5, 7, 8, 16, 17, 22, 24 and 25 among the whole series displayed less than 50% inhibition. The substituents effects on phenyl ring thereby superficially established through SAR study. Binding interactions of analogs and the active site of ligands proteins were confirmed through molecular docking study. Spectroscopic techniques like ¹H NMR, ¹³C NMR and ESIMS were used for characterization.     

Efficacy and safety of canakinumab in adolescents and adults with colchicine-resistant familial Mediterranean fever

IntroductionThis open-label pilot study aimed to investigate the efficacy of canakinumab in colchicine-resistant familial Mediterranean fever (FMF) patients.MethodPatients with one or more attacks in a month in the preceding 3 months despite colchicine were eligible to enter a 30-day run-in period. Patients who had an attack during the first run-in period advanced to a second 30-day period. At the first attack, patients started to receive three canakinumab 150 mg subcutaneous injections at 4-week intervals, and were then followed for an additional 2 months. Primary efficacy outcome measure was the proportion of patients with 50 % or more reduction in attack frequency. Secondary outcome measures included time to next attack following last canakinumab dose and changes in quality of life assessed by SF-36.ResultsThirteen patients were enrolled in the run-in period and 9 advanced to the treatment period. All 9 patients achieved a 50 % or more reduction in attack frequency, and only one patient had an attack during the treatment period. C-reactive protein and serum amyloid A protein levels remained low throughout the treatment period. Significant improvement was observed in both physical and mental component scores of the Short Form-36 at Day 8. Five patients had an attack during the 2-month follow-up, occurring median 71 (range, 31 to 78) days after the last dose. Adverse events were similar to those observed in the previous canakinumab trials.ConclusionCanakinumab was effective at controlling the attack recurrence in patients with FMF resistant to colchicine. Further investigations are warranted to explore canakinumab’s potential in the treatment of patients with colchicine resistant FMF.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01088880","term_id":"NCT01088880"}}NCT01088880. Registered 16 March 2010.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0765-4) contains supplementary material, which is available to authorized users.     

Rapid Quantification of 3D Collagen Fiber Alignment and Fiber Intersection Correlations with High Sensitivity

Metastatic cancers aggressively reorganize collagen in their microenvironment. For example, radially orientated collagen fibers have been observed surrounding tumor cell clusters in vivo. The degree of fiber alignment, as a consequence of this remodeling, has often been difficult to quantify. In this paper, we present an easy to implement algorithm for accurate detection of collagen fiber orientation in a rapid pixel-wise manner. This algorithm quantifies the alignment of both computer generated and actual collagen fiber networks of varying degrees of alignment within 5°°. We also present an alternative easy method to calculate the alignment index directly from the standard deviation of fiber orientation. Using this quantitative method for determining collagen alignment, we demonstrate that the number of collagen fiber intersections has a negative correlation with the degree of fiber alignment. This decrease in intersections of aligned fibers could explain why cells move more rapidly along aligned fibers than unaligned fibers, as previously reported. Overall, our paper provides an easier, more quantitative and quicker way to quantify fiber orientation and alignment, and presents a platform in studying effects of matrix and cellular properties on fiber alignment in complex 3D environments.     

Novel Penicillin Analogues as Potential Antimicrobial Agents; Design,Synthesis and Docking Studies

A number of penicillin derivatives (4a-h) were synthesized by the condensation of 6-amino penicillinic acid (6-APA) with non-steroidal anti-inflammatory drugs as antimicrobial agents. In silico docking study of these analogues was performed against Penicillin Binding Protein (PDBID 1CEF) using AutoDock Tools 1.5.6 in order to investigate the antimicrobial data on structural basis. Penicillin binding proteins function as either transpeptidases or carboxypeptidases and in few cases demonstrate transglycosylase activity in bacteria. The excellent antibacterial potential was depicted by compounds 4c and 4e against Escherichia coli, Staphylococcus epidermidus and Staphylococcus aureus compared to the standard amoxicillin. The most potent penicillin derivative 4e exhibited same activity as standard amoxicillin against S. aureus. In the enzyme inhibitory assay the compound 4e inhibited E. coli MurC with an IC₅₀ value of 12.5 μM. The docking scores of these compounds 4c and 4e also verified their greater antibacterial potential. The results verified the importance of side chain functionalities along with the presence of central penam nucleus. The binding affinities calculated from docking results expressed in the form of binding energies ranges from -7.8 to -9.2kcal/mol. The carboxylic group of penam nucleus in all these compounds is responsible for strong binding with receptor protein with the bond length ranges from 3.4 to 4.4 Ǻ. The results of present work ratify that derivatives 4c and 4e may serve as a structural template for the design and development of potent antimicrobial agents.