Deciphering the mode of action of a mutant Allium sativum Leaf Agglutinin (mASAL), a potent antifungal protein on Rhizoctonia solani

LC MS/MS analysis of identified interactors of mASAL from R.solani Matched peptides highlighted in yellow. Green colour indicated probable sites of mutation and modification. (DOCX 2225 kb

Probing liquid surface waves, liquid properties and liquid films with light diffraction

Surface waves on liquids act as a dynamical phase grating for incident light. In this article, we revisit the classical method of probing such waves (wavelengths of the order of mm) as well as inherent properties of liquids and liquid films on liquids, using optical diffraction. A combination of simulation and experiment is proposed to trace out the surface wave profiles in various situations (\emph{eg.} for one or more vertical, slightly immersed, electrically driven exciters). Subsequently, the surface tension and the spatial damping coefficient (related to viscosity) of a variety of liquids are measured carefully in order to gauge the efficiency of measuring liquid properties using this optical probe. The final set of results deal with liquid films where dispersion relations, surface and interface modes, interfacial tension and related issues are investigated in some detail, both theoretically and experimentally. On the whole, our observations and analyses seem to support the claim that this simple, low--cost apparatus is capable of providing a wealth of information on liquids and liquid surface waves in a non--destructive way.Comment: 25 pages, 12 figures, to appear in Measurement Science and Technology (IOP

Chronic pancreatitis in dogs: A retrospective study of clinical, clinicopathological, and histopathological findings in 61 cases

The objective of the present study was to characterize the clinical, clinicopathologic, and histopathologic findings of dogs with chronic pancreatitis. The necropsy database at Texas A&M University was searched for reports of dogs with histologic evidence of chronic pancreatitis defined as irreversible histologic changes of the pancreas, i.e. fibrosis and atrophy. Medical records and necropsy reports were retrieved and reviewed. A reference necropsy population of 100 randomly selected dogs was used for signalment and concurrent disease comparisons. Cases were categorized as clinical or incidental chronic pancreatitis based on the presence of vomiting, decreased appetite, or both versus neither of these signs. All archived pancreata samples were evaluated histologically and scored using a published pancreatic scoring system. A total of 61 dogs with chronic pancreatitis were included in the study. The most frequent clinical signs were lethargy, decreased appetite, vomiting, and diarrhea. Compared to the reference necropsy population, chronic pancreatitis cases were more likely to be older, neutered, and of the non-sporting/toy breed group and to have concurrent endocrine, hepatobiliary, or neurologic diseases. Clinical chronic pancreatitis cases had significantly higher histological scores for pancreatic necrosis and peripancreatic fat necrosis. Clinical chronic pancreatitis cases were significantly more likely to have hepatobiliary or endocrine disease as well as increased liver enzyme activities, and cholesterol and bilirubin concentrations. In conclusion, clinical disease resulting from chronic pancreatitis might be related to the presence of pancreatic necrosis and pancreatic fat necrosis. The signalment, presentation, and concurrent diseases of dogs with chronic pancreatitis are similar to those previously reported for dogs with acute pancreatitis.http://www.elsevier.com/locate/tvjlam2013ab201

The complexity of mesoporous silica nanomaterials unravelled by single molecule microscopy

Mesoporous silica nanomaterials are a novel class of materials that offer a highly complex porous network with nanometre-sized channels into which a wide amount of differently sized guests can be incorporated. This makes them an ideal host for various applications for example in catalysis, chromatography and nanomedicine. For these applications, analyzing the host properties and understanding the complicated host–guest interactions is of pivotal importance. In this perspective we review some of our recent work that demonstrates that single molecule microscopy techniques can be utilized to characterize the porous silica host with unprecedented detail. Furthermore, the single molecule studies reveal sample heterogeneities and are a highly efficient tool to gain direct mechanistic insights into the host–guest interactions. Single molecule microscopy thus contributes to a thorough understanding of these nanomaterials enabling the development of novel tailor-made materials and hence optimizing their applicability significantly

Conformational effects on the Circular Dichroism of Human Carbonic Anhydrase II: a multilevel computational study

Circular Dichroism (CD) spectroscopy is a powerful method for investigating conformational changes in proteins and therefore has numerous applications in structural and molecular biology. Here a computational investigation of the CD spectrum of the Human Carbonic Anhydrase II (HCAII), with main focus on the near-UV CD spectra of the wild-type enzyme and it seven tryptophan mutant forms, is presented and compared to experimental studies. Multilevel computational methods (Molecular Dynamics, Semiempirical Quantum Mechanics, Time-Dependent Density Functional Theory) were applied in order to gain insight into the mechanisms of interaction between the aromatic chromophores within the protein environment and understand how the conformational flexibility of the protein influences these mechanisms. The analysis suggests that combining CD semi empirical calculations, crystal structures and molecular dynamics (MD) could help in achieving a better agreement between the computed and experimental protein spectra and provide some unique insight into the dynamic nature of the mechanisms of chromophore interactions

Loan growth and riskiness of banks

We investigate whether loan growth affects the riskiness of individual banks in 16 major countries. Using Bankscope data from more than 16,000 individual banks during 1997-2007, we test three hypotheses on the relation between abnormal loan growth and asset risk, bank profitability, and bank solvency. We find that loan growth leads to an increase in loan loss provisions during the subsequent three years, to a decrease in relative interest income, and to lower capital ratios. Further analyses show that loan growth also has a negative impact on the risk-adjusted interest income. These results suggest that loan growth represents an important driver of the riskiness of banks

Balloon measurements of the vertical ionization profile over southern Israel and comparison to mid-latitude observations

Airborne measurements using meteorological balloons were conducted for the first time from southern Israel (geographic 30°35’N, 34°45’E geomagnetic 27°6’N 112°23’E) for measuring the vertical ionization profile during solar cycle 24. The results show the differences (increase of ~30%) in count rates as we proceed from solar maximum toward solar minimum. The observed altitude of maximum ionization (the Regener-Pfotzer maximum) was between 17–20 km, and it agrees well with results from other simultaneous measurements conducted at different latitudes (Reading, UK and Zaragoza-Barcelona, Spain). When compared with predictions of an analytical model, we find a highly significant correlation (R2=0.97) between our observations and the computed ionization profiles. The difference in count rates can be attributed to the height of the tropopause due to the model using a US standard atmosphere that differs from the measured atmospheric parameters above Israel

JNK signalling in cancer: In need of new, smarter therapeutic targets

Copyright © 2013 The British Pharmacological Society. This is the accepted version of the following article: Bubici, C. and Papa, S. (2014), JNK signalling in cancer: in need of new, smarter therapeutic targets. British Journal of Pharmacology, 171: 24–37, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/bph.12432/abstract.The JNKs are master protein kinases that regulate many physiological processes, including inflammatory responses, morphogenesis, cell proliferation, differentiation, survival and death. It is increasingly apparent that persistent activation of JNKs is involved in cancer development and progression. Therefore, JNKs represent attractive targets for therapeutic intervention with small molecule kinase inhibitors. However, evidence supportive of a tumour suppressor role for the JNK proteins has also been documented. Recent studies showed that the two major JNK proteins, JNK1 and JNK2, have distinct or even opposing functions in different types of cancer. As such, close consideration of which JNK proteins are beneficial targets and, more importantly, what effect small molecule inhibitors of JNKs have on physiological processes, are essential. A number of ATP-competitive and ATP-non-competitive JNK inhibitors have been developed, but have several limitations such as a lack of specificity and cellular toxicity. In this review, we summarize the accumulating evidence supporting a role for the JNK proteins in the pathogenesis of different solid and haematological malignancies, and discuss many challenges and scientific opportunities in the targeting of JNKs in cancer.Kay Kendall Leukemia Fund, Italian Association for Cancer Research and Foundation for Liver Research

Cholesterol Corrects Altered Conformation of MHC-II Protein in Leishmania donovani Infected Macrophages: Implication in Therapy

Previously we reported that Kala-azar patients show progressive decrease in serum cholesterol as a function of splenic parasite burden. Splenic macrophages (MΦ) of Leishmania donovani (LD) infected mice show decrease in membrane cholesterol, while LD infected macrophages (I-MΦ) show defective T cell stimulating ability that could be corrected by liposomal delivery of cholesterol. T helper cells recognize peptide antigen in the context of class II MHC molecule. It is known that the conformation of a large number of membrane proteins is dependent on membrane cholesterol. In this investigation we tried to understand the influence of decreased membrane cholesterol in I-MΦ on the conformation of MHC-II protein and peptide-MHC-II stability, and its bearing on the antigen specific T-cell activatio