Conductance studies on the interaction of lactose with alkali-metal halides in water and in formamide

The interaction of lactose with alkali-metal halides in solution in water and in formamide has been studied by employing conductance measurements. Conductance data of sodium and potassium halides in water and in formamide saturated with lactose at 50.0 ±0.05° are reported at several temperatures within a range of 25 to 70°. Plots of —log- K against 1/T showed a break at the saturation temperature, where two straight lines intersect one another. Divergence of the pairs of straight lines in these ternary, homogeneous systems has been found to be highly influenced by the structural properties of the solutes. The transitional behavior in the conductance values is explained for the system in terms of solute-solvent interactions involved in the electrolyte-solvent-nonelectrolyte systems.     

Conformational changes in pennisetin using intrinsic fluorescence spectroscopy

Fluorescence spectra of native pennisetin resulted in a single emission peak at 335 nm at excitation wavelength of 274 and 295 nm with quantum yield values for tyrosine and tryptophan as 0.086 and 0.097, respectively. These results indicate the presence of tryptophan residues in a polar environment and quenching of tyrosine residues in the native state of pennisetin. In the presence of an increasing concentration of guanidine hydrochloride (Gdn · HCl), changes such as red shift in emission peak from 335 to 344 nm, decrease in relative fluorescence intensity and increase in quantum yield value were observed, suggesting unfolding of the pennisetin molecule during denaturation. The quenching of tryptophanyl fluorescence by acrylamide and iodide further showed the presence of a single kind of tryptophanyl residue and its polar environment in pennisetin molecule.     

Extracellular invertase from Aspergillus athecius: Isolation and immobilization

Summary A fungal strain isolated from soil and identified asAspergillus athecius, when grown on moistened wheat bran produced large amounts of extracellular invertase. Most of the invertase from the moldy bran was easily extracted by low ionic strength buffer (0.005 M, pH 5.7). The crude invertase immobilized on DEAE cellulose showed not only increased activity (45%) but also greater thermal and storage stability than the free enzyme. The free and the bound enzymes showed a temperature optimum of 50–55°C and a pH optimum of 5.7 and 4.8 respectively. The K_m app. of the bound enzyme was lower than that of the free enzyme.     

Warming and drought reduce temperature sensitivity of nitrogen transformations

Shifts in nitrogen (N) mineralization and nitrification rates due to global changes can influence nutrient availability, which can affect terrestrial productivity and climate change feedbacks. While many single‐factor studies have examined the effects of environmental changes on N mineralization and nitrification, few have examined these effects in a multifactor context or recorded how these effects vary seasonally. In an old‐field ecosystem in Massachusetts, USA, we investigated the combined effects of four levels of warming (up to 4 °C) and three levels of precipitation (drought, ambient, and wet) on net N mineralization, net nitrification, and potential nitrification. We also examined the treatment effects on the temperature sensitivity of net N mineralization and net nitrification and on the ratio of C mineralization to net N mineralization. During winter, freeze–thaw events, snow depth, and soil freezing depth explained little of the variation in net nitrification and N mineralization rates among treatments. During two years of treatments, warming and altered precipitation rarely influenced the rates of N cycling, and there was no evidence of a seasonal pattern in the responses. In contrast, warming and drought dramatically decreased the apparent Q₁₀ of net N mineralization and net nitrification, and the warming‐induced decrease in apparent Q₁₀ was more pronounced in ambient and wet treatments than the drought treatment. The ratio of C mineralization to net N mineralization varied over time and was sensitive to the interactive effects of warming and altered precipitation. Although many studies have found that warming tends to accelerate N cycling, our results suggest that warming can have little to no effect on N cycling in some ecosystems. Thus, ecosystem models that assume that warming will consistently increase N mineralization rates and inputs of plant‐available N may overestimate the increase in terrestrial productivity and the magnitude of an important negative feedback to climate change.     

Genetic structure, relatedness and helping behaviour in the yellow mongoose in a farmland and a natural habitat

The yellow mongoose Cynictis penicillata is a facultatively social species and provides an opportunity to study the evolution of social behaviour. We examined genetic structure, relatedness and helping behaviour in the yellow mongoose in natural habitat in the Kalahari Desert, where the species lives in small family groups of up to four individuals and shows no cooperative breeding; and in farmland in the Western Cape Province of South Africa, where they live in larger groups of up to 13 individuals, engage in numerous social interactions and show cooperative breeding. The farmland population showed significant inbreeding, and lower genetic variability than the desert population, but there was no evidence of a recent population bottleneck. The genetic relatedness between individuals within social groups and that between future potential helpers and pups were higher in the farmland population than in the desert population. However, based on a limited sample, helping effort (in the farmland population) was not preferentially directed towards kin. Thus, the origin of helping in the farmland population is consistent with kin selection, but in the absence of kin discrimination, future research should investigate whether long-term breeding opportunities or group augmentation contribute to maintaining cooperative breeding in this population.     

Epidemiological profile of India: Historical and contemporary perspectives

Knowledge and understanding of the epidemiological profile is an essential pre-requisite to assess and address public health needs in the country and to enable efficient programme planning and management. The need for adequate and accurate health information and data to undertake such an exercise cannot be over-emphasized. The present effort is a modest attempt to critically analyse the epidemiological profile of India from the historical and contemporary perspective. In order to assess the successes achieved as well caution against the daunting challenges awaiting the country, parameters such as disease burden and health status indicators, are increasingly being used. Changes in the population age structure, improvements in the nation’s economic status, altered life-styles of people and duality of disease burden testify to the demographic, development and health transition occurring in the country. Population stabilization, poverty alleviation, life-style modification, surveillance and control of communicable and non-communicable diseases constitute the major challenges demanding urgent attention in the future.     

Complement activation product C5a is a selective suppressor of TLR4-induced, but not TLR3-induced, production of IL-27(p28) from macrophages

There is accumulating evidence that the complement activation product, C5a, can orchestrate cellular immune functions. IL-27(p28/EBI3) is an emerging key player essential for regulating inflammatory responses and T cells. In this article, we report that C5a robustly suppressed IL-27(p28) gene expression and release in peritoneal macrophages. These cells from C57BL/6J mice abundantly produced IL-27(p28) after engagement of either the TLR3 (polyinosinic-polycytidylic acid) or TLR4 (LPS) receptor. Genetic deficiency of either TLR4 or LBP completely incapacitated the ability of macrophages to secrete IL-27(p28) in response to LPS. IL-27(p28)-producing macrophages also expressed the C5aR receptor, thus displaying an IL-27(p28)(+)F4/80(+)C5aR(+) phenotype. C5a suppressed IL-27(p28) in LPS-stimulated macrophages via interactions with the C5aR receptor rather than the C5L2 receptor. After endotoxemia, C5aR(-/-) mice displayed higher plasma levels of IL-27(p28) compared with C57BL/6J mice. C5a did not affect the release of IL-27(p28) or the frequency of IL-27(p28)(+)F4/80(+) macrophages after engagement of TLR3. Mechanistically, LPS activated both the NF-κB and the PI3K/Akt pathways, whereas C5a activated only the PI3K/Akt pathway. Engagement of PI3K/Akt was inhibitory for IL-27(p28) production, because PI3K/Akt pharmacologic blockade resulted in increased amounts of IL-27(p28) and reversed the suppressive effects of C5a. Blockade of PI3K/Akt in endotoxemic C57BL/6J mice resulted in higher generation of IL-27(p28). In contrast, the PI3K/Akt pathway was not involved in TLR3-mediated release of IL-27(p28). These data provide new evidence about how complement activation may selectively interfere with production of T cell regulatory cytokines by APCs in the varying contexts of either bacterial (TLR4 pathway) or viral (TLR3 pathway) infection.     

Evidence for anti-inflammatory effects of C5a on the innate IL-17A/IL-23 axis

There is growing evidence that the complement activation product C5a positively or negatively regulates inflammatory functions. The studies presented here report that C5a exerts anti-inflammatory effects by altering production of the cytokines IL-17A and IL-23 during endotoxic shock in young adult male C57BL/6J mice and has similar effects on macrophages from the same mice. IL-17A and IL-23 both appeared in plasma during endotoxemia, and their neutralization improved survival. The relevant sources of IL-17A during endotoxemia were not CD4(+) cells, γδ T cells, or NK cells but CD11b(+)F4/80(+) macrophages. The addition in vitro of C5a to lipopolysaccharide-activated peritoneal macrophages dose dependently antagonized the production of IL-17A (IC(50), 50-100 nM C5a) and IL-23 (IC(50), 10 nM C5a). This suppression required the receptor C5aR, but was independent of the second C5a receptor, C5L2. Genetic absence of C5aR was associated with much higher levels of IL-17A and IL-23 during endotoxic shock. Mechanistically, C5a mediated its effects on the IL-17A/IL-23 axis in a 2-step process. C5a caused activation of the PI3K-Akt and MEK1/2-ERK1/2 pathways, resulting in induction of IL-10, which powerfully inhibited production of IL-17A and IL-23. These data identify previously unknown mechanisms by which the anaphylatoxin C5a limits acute inflammation and antagonizes the IL-17A/IL-23 axis.     

TGF-β1 re-programs TLR4 signaling in L. donovani infection: enhancement of SHP-1 and ubiquitin-editing enzyme A20

Visceral leishmaniasis (VL), caused by Leishmania donovani, is a major health concern in India. It represents T-helper type 2 (Th2) bias of cytokines in active state and Th1 bias at cure. However, the role of the parasite in regulating Toll-like receptor (TLR)-mediated macrophage activation in VL patients remains elusive. In this report, we demonstrated that later stages of L. donovani infection rendered tolerance to macrophages, leading to incapability for the production of inflammatory cytokines like tumor necrosis factor (TNF)-α and interleukin (IL)-1β in response to TLR stimulation. Overexpression of transforming growth factor (TGF)-β(1), but not IL-10, resulted in suppressed lipopolysaccharide (LPS)-induced production of TNF-α and downregulation of TLR4 expression in L. donovani-infected macrophages. Recombinant human (rh)TGF-β(1) markedly enhanced tyrosine phosphatase (Src homology region 2 domain-containing phosphatase-1) activity, but inhibited IL-1 receptor-activated kinase (IRAK)-1 activation. Addition of neutralizing TGF-β(1) antibody reversed these effects, and thus suggesting the pivotal role of TGF-β(1) in promoting refractoriness for LPS in macrophages. Surprisingly, the use of a tyrosine phosphatase inhibitor (sodium orthovanadate, Na(3)VO(4)) promoted IRAK-1 activation, confirming the negative inhibitory role of tyrosine phosphatase in macrophage activation. Furthermore, rhTGF-β(1) induced tolerance in infected macrophages by reducing inhibitory protein (IκBα) degradation in a time-dependent manner. In addition, short interfering RNA studies proved that overexpression of A20 ubiquitin-editing protein complex induced inhibitory activity of TGF-β(1) on LPS-mediated nuclear factor-κB activation. Thus, these findings suggest that TGF-β(1) promotes overexpression of A20 through tyrosine phosphatase activity that ensures transient activation of inflammatory signaling pathways in macrophages in active L. donovani infection.