Modulation of the immune response by Middle East respiratory syndrome coronavirus

Coronavirus (CoV) infections are commonly associated with respiratory and enteric disease in humans and animals. In 2012, a new human disease called Middle East respiratory syndrome (MERS) emerged in the Middle East. MERS was caused by a virus that was originally called human coronavirus-Erasmus Medical Center/2012 but was later renamed as Middle East respiratory syndrome coronavirus (MERS-CoV). MERS-CoV causes high fever, cough, acute respiratory tract infection, and multiorgan dysfunction that may eventually lead to the death of the infected individuals. The exact origin of MERS-CoV remains unknown, but the transmission pattern and evidence from virological studies suggest that dromedary camels are the major reservoir host, from which human infections may sporadically occur through the zoonotic transmission. Human to human transmission also occurs in healthcare facilities and communities. Recent studies on Middle Eastern respiratory continue to highlight the need for further understanding the virus-host interactions that govern disease severity and infection outcome. In this review, we have highlighted the major mechanisms of immune evasion strategies of MERS-CoV. We have demonstrated that M, 4a, 4b proteins and Plppro of MERS-CoV inhibit the type I interferon (IFN) and nuclear factor-κB signaling pathways and therefore facilitate innate immune evasion. In addition, nonstructural protein 4a (NSP4a), NSP4b, and NSP15 inhibit double-stranded RNA sensors. Therefore, the mentioned proteins limit early induction of IFN and cause rapid apoptosis of macrophages. MERS-CoV strongly inhibits the activation of T cells with downregulation of antigen presentation. In addition, uncontrolled secretion of interferon ɣ-induced protein 10 and monocyte chemoattractant protein-1 can suppress proliferation of human myeloid progenitor cells.     

Computational study on the structural and optoelectronic properties of a carbazole-benzothiadiazole based conjugated oligomer with various alkyl side-chain lengths

The effect of the alkyl side-chain length on the structural and optoelectronic properties of poly[N-9′-heptadecanyl-27-carbazole-alt-55-(4′,7′-di-2-thienyl-2′,1′,3′-benzothiadiazole)] (PCDTBT) conjugated oligomers have been studied by density functional theory (DFT) and time-dependent density functional theory (TD-DFT). The study was carried out by varying the length of alkyl side-chain attached to the nitrogen atom of the carbazole unit of the PCDTBT oligomers. The structural properties of the optimised oligomers were then studied by determining the bond-length alternation and dihedral angles (Φ) for various side-chain lengths. Total energy calculations for the determination of HOMO energy (E_HOMO), LUMO energy (E_LUMO), and fundamental energy gap (E_Gap) were performed using DFT at the B3LYP/6-31G(d), while the first singlet excitation energies (E_Opt) were calculated by TD-DFT also at the same level of theory. It was observed that there are no significant structural changes occurring as the alkyl chain lengths are varied. For the electronic properties, very small differences (i.e. ~0.01 eV) were observed for E_Gap and E_Opt while the exciton binding energies (E_B) were virtually the same. The results suggest that using shorter alkyl side-chains do not significantly affect the structural and optoelectronic properties of the carbazole-benzothiadiazole based polymer. The observations can aid future computational design studies of analogous systems by reducing large structures thus decreasing computational costs.     

Diversity measures in macroinvertebrate and zooplankton communities related to the trophic status of subtropical reservoirs: Contradictory or complementary responses?

Macroinvertebrate communities have been widely used as a tool for assessing the environmental quality of freshwater ecosystems, whereas zooplankton communities have been to some extent neglected. However, the importance of using different indicators to achieve a more comprehensive framework of assessment regarding water quality has been recognized. This study compared estimates of species richness (number of species) and the Shannon–Wiener index for data on macroinvertebrate and zooplankton communities in tropical reservoirs and related them to their trophic state. The trop+hic classification was obtained by applying the Carlson index (1977) modified by Toledo et al. (1983), and the index of the Brazilian Society of the Environmental Technology Agency. The comparative response of the different indicators was analyzed using a series of bivariate correlations (Draftsman’s plot). The results illustrate that diversity measures, namely species richness, responded differently when related to the trophic classification of reservoirs, depending on the community considered. The species richness of zooplankton was positively related to hypereutrophic conditions, due to the higher number of rotifer species, including tolerant generalist species and at the same time, as a result of the exclusion of species from other groups, whereas for macroinvertebrates, species richness was negatively related to hypereutrophic conditions. Melanoides tuberculatus, which exhibits a high tolerance and competitive ability under such conditions, was the dominant species in macroinvertebrate communities, which excluded endemic species and reduced local richness and diversity. The same indicators applied to the zooplankton and macroinvertebrate communities might therefore provide contradictory responses regarding ecological quality assessment in tropical reservoirs, which suggest that zooplankton should be taken into account among the biological quality elements considered in the ecological quality assessment, management, and restoration of water bodies.     

The potential of generalized additive modelling for the prediction of radial growth of Norway spruce from Central Germany

During the past decades managed forest ecosystems in Central Europe underwent vast changes, induced by extreme climate conditions and occasionally adverse forest management. Tree ring width patterns mirror these changes and thus have been widely examined as environmental archives and reliable empirical data sources in ‘tree growth modelling’. Dendrochronologists often suppose linear co-variation among the covariates, variable independence and homoscedasticity. Conventionally, these assumptions were achieved by eliminating biological age trends (detrending) and removing the autocorrelation from the time series (pre-whitening). Particularly detrending might be biased according to the scientific problem and sometimes inflexible age models. In this study, we tackle these issues and examine the suitability of a flexible Generalized Additive Model (GAM) on recently developed tree ring width time series of 30 Norway spruce stands (Picea abies [L.] H. Karst) from Central Germany.The model was established to simultaneously cope with the mentioned detrending issue, to unravel nonlinear climate-growth relationships and to predict mean ring width time series for spruce stands in the region. Particularly the latter was of primary interest, since recent forest planning relies on static yield tables that often underestimate the actual growth.The model reliably captured the empirical data, indicated by a small Generalized Cross Validation criterion (GCV = 0.045) and a deviance explained of 88.6 %. The flexible additive smoothers accounted for the social status of individual trees, captured low frequency variations of changing growth conditions adequately and displayed a rather flat biological age trend. The radial increment responded positively to summer season precipitation of the current and previous year. Positive temperature responses were found during the early vegetation period, whereas high summer season temperatures negatively affected the radial growth. The seasonal transition from spring to summer in June induced a shift in the climate response of the linear predictor, leading to a distinct negative effect of temperature and a no-role of precipitation on the linear predictor.Most important, utilizing the calibrated GAM for the purely climate-driven prediction of mean ring width time series from five independent spruce sites revealed proper coherencies. Herein, the mean ring width for sites located within the climatic-optimum for spruce growth were more exactly predicted than for sites with adverse spruce growth conditions. In addition, large mean ring widths were systematically underestimated, whereas small mean ring widths were precisely predicted. Overall, we strongly recommend GAMs as a powerful tool for the investigation of nonlinear climate-growth relationships and for the prediction of radial growth in managed forest ecosystems.     

Solution structures of purine base analogues 9-deazaguanine and 9-deazahypoxanthine

Deaza analogues of nucleobases are potential drugs against infectious diseases caused by parasites. A caveat is that apart from binding their target parasite enzymes, they also bind and inhibit enzymes of the host. In order to design derivatives of deaza analogues which specifically bind target enzymes, knowledge of their molecular structure, protonation state, and predominant tautomers at physiological conditions is essential. We have employed resonance Raman spectroscopy at an excitation wavelength of 260 nm, to decipher solution structure of 9-deazaguanine (9DAG) and 9-deazahypoxanthine (9DAH). These are analogues of guanine and hypoxanthine, respectively, and have been exploited to study static complexes of nucleobase binding enzymes. Such enzymes are known to perturb pK_a of their ligands, and thus, we also determined solution structures of these analogues at two, acidic and alkaline, pH. Structure of each possible protonation state and tautomer was computed using density functional theoretical calculations. Species at various pHs were identified based on isotopic shifts in experimental wavenumbers and by comparing these shifts with corresponding computed isotopic shifts. Our results show that at physiological pH, N1 of pyrimidine ring in 9DAG and 9DAH bears a proton. At lower pH, N3 is place of protonation, and at higher pH, deprotonation occurs at N1 position. The proton at N7 of purine ring remains intact even at pH 12.5. We have further compared these results with naturally occurring nucleotides. Our results identify key vibrational modes which can report on hydrogen bonding interactions, protonation and deprotonation in purine rings upon binding to the active site of enzymes.     

Functional classifications of coastal barrier island vegetation

Abstract. Due to the complexity of coastal barrier vegetation, it is useful to apply a functional-type approach to assess the response of barrier island vegetation to climate change. In this paper, a simple clustering analysis is applied to a group of 19 plant associations, based on six plant attributes and six environmental constraints. This analysis results in the suggestion that the main division of the vegetation types at Virginia Coast Reserve is between herbaceous and woody types, which differs from the existing classification which recognizes three groups: xeric-mesic herbaceous, woody and hydric-halophytic herbaceous. Considerations about grouping plant functional types are also addressed in this paper. At a global scale, inclusion of barrier plant functional types may not be so important for the climate-change response of vegetation, but it may be necessary to consider these important systems for spatially explicit modelling of landscape responses.