The Wnt-Driven Mll1 Epigenome Regulates Salivary Gland and Head and Neck Cancer

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The biotechnological use and potential of plant pathogenic smut fungi

Plant pathogens of the family Ustilaginaceae parasitise mainly on grasses and cause smut disease. Among the best characterised members of this family are the covered smut fungus Ustilago hordei colonising barley and oat as well as the head smut Sporisorium reilianum and the corn smut Ustilago maydis, both infecting maize. Over the past years, U. maydis in particular has matured into a model system for diverse topics like plant–pathogen interaction, cellular transport processes or DNA repair. Consequently, a broad set of genetic, molecular and system biological methods has been established. This set currently serves as a strong foundation to improve existing and establish novel biotechnological applications. Here, we review four promising aspects covering different fields of applied science: (1) synthesis of secondary metabolites produced at fermenter level. (2) Lipases and other hydrolytic enzymes with potential roles in biocatalytic processes. (3) Degradation of ligno-cellulosic plant materials for biomass conversion. (4) Protein expression based on unconventional secretion, a novel approach inspired by basic research on mRNA transport. Thus, plant pathogenic Ustilaginaceae offer a great potential for future biotechnological applications by combining basic research and applied science.     

Differential Expression of the Middle East Respiratory Syndrome Coronavirus Receptor in the Upper Respiratory Tracts of Humans and Dromedary Camels

Middle East respiratory syndrome coronavirus (MERS-CoV) is not efficiently transmitted between humans, but it is highly prevalent in dromedary camels. Here we report that the MERS-CoV receptor—dipeptidyl peptidase 4 (DPP4)—is expressed in the upper respiratory tract epithelium of camels but not in that of humans. Lack of DPP4 expression may be the primary cause of limited MERS-CoV replication in the human upper respiratory tract and hence restrict transmission.     

Prevalence and Clinical Course in Invasive Infections with Meningococcal Endotoxin Variants

Background

Meningococci produce a penta-acylated instead of hexa-acylated lipid A when their lpxL1 gene is inactivated. Meningococcal strains with such lipid A endotoxin variants have been found previously in adult meningitis patients, where they caused less blood coagulopathy because of decreased TLR4 activation.

Methods

A cohort of 448 isolates from patients with invasive meningococcal disease in the Netherlands were screened for the ability to induce IL-6 in monocytic cell Mono Mac 6 cells. The lpxL1 gene was sequenced of isolates, which show poor capacity to induce IL-6.. Clinical characteristics of patients were retrieved from hospital records.

Results

Of 448 patients, 29 (6.5%) were infected with meningococci expressing a lipid A variant strain. Lipid A variation was not associated with a specific serogroup or genotype. Infections with lipid A variants were associated with older age (19.3 vs. 5.9 (median) years, p = 0.007) and higher prevalence of underlying comorbidities (39% vs. 17%; p = 0.004) compared to wild-type strains. Patients infected with lipid A variant strains had less severe infections like meningitis or shock (OR 0.23; 95%CI 0.09–0.58) and were less often admitted to intensive care (OR 0.21; 95%CI 0.07–0.60) compared to wild-type strains, independent of age, underlying comorbidities or strain characteristics.

Conclusions

In adults with meningococcal disease lipid A variation is rather common. Infection with penta-acylated lipid A variant meningococci is associated with a less severe disease course.     

Macromolecular rate theory (MMRT) provides a thermodynamics rationale to underpin the convergent temperature response in plant leaf respiration

Temperature is a crucial factor in determining the rates of ecosystem processes, for example, leaf respiration (R) – the flux of plant respired CO₂ from leaves to the atmosphere. Generally, R increases exponentially with temperature and formulations such as the Arrhenius equation are widely used in earth system models. However, experimental observations have shown a consequential and consistent departure from an exponential increase in R. What are the principles that underlie these observed patterns? Here, we demonstrate that macromolecular rate theory (MMRT), based on transition state theory (TST) for enzyme‐catalyzed kinetics, provides a thermodynamic explanation for the observed departure and the convergent temperature response of R using a global database. Three meaningful parameters emerge from MMRT analysis: the temperature at which the rate of respiration would theoretically reach a maximum (the optimum temperature, T_opt), the temperature at which the respiration rate is most sensitive to changes in temperature (the inflection temperature, T_inf) and the overall curvature of the log(rate) versus temperature plot (the change in heat capacity for the system, ). On average, the highest potential enzyme‐catalyzed rates of respiratory enzymes for R are predicted to occur at 67.0 ± 1.2°C and the maximum temperature sensitivity at 41.4 ± 0.7°C from MMRT. The average curvature (average negative ) was ?1.2 ± 0.1 kJ mol^?1 K^?1. Interestingly, T_opt, T_inf and appear insignificantly different across biomes and plant functional types, suggesting that thermal response of respiratory enzymes in leaves could be conserved. The derived parameters from MMRT can serve as thermal traits for plant leaves that represent the collective temperature response of metabolic respiratory enzymes and could be useful to understand regulations of R under a warmer climate. MMRT extends the classic TST to enzyme‐catalyzed reactions and provides an accurate and mechanistic model for the short‐term temperature response of R around the globe.     

Increased T-type Ca2+ channel activity as a determinant of cellular toxicity in neuronal cell lines expressing polyglutamine-expanded human androgen receptors

We have analyzed Ca²⁺ currents in two neuroblastoma-motor neuron hybrid cell lines that expressed normal or glutamine-expanded human androgen receptors (polyGln-expanded AR) either transiently or stably. The cell lines express a unique, low-threshold, transient type of Ca²⁺ current that is not affected by L-type Ca²⁺ channel blocker (PN 200-110), N-type Ca²⁺ channel blocker (-conotoxin GVIA) or P-type Ca²⁺ channel blocker (Agatoxin IVA) but is blocked by either Cd²⁺ or Ni²⁺. This pharmacological profile most closely resembles that of T-type Ca²⁺ channels [1-3]. Exposure to androgen had no effect on control cell lines or cells transfected with normal AR but significantly changed the steady-state activation in cells transfected with expanded AR. The observed negative shift in steady-state activation results in a large increase in the T-type Ca²⁺ channel window current. We suggest that Ca²⁺ overload due to abnormal voltage-dependence of transient Ca²⁺ channel activation may contribute to motor neuron toxicity in spinobulbar muscular atrophy (SBMA). This hypothesis is supported by the additional finding that, at concentrations that selectively block T-type Ca²⁺ channel currents, Ni²⁺ significantly reduced cell death in cell lines transfected with polyGln-expanded AR.     

Localization and kinetics of pyruvate-metabolizing enzymes in relation to aerobic alcoholic fermentation in Saccharomyces cerevisiae CBS 8066 and Candida utilis CBS 621

The role of pyruvate metabolism in the triggering of aerobic, alcoholic fermentation in Saccharomyces cerevisiae has been studied. Since Candida utilis does not exhibit a Crabtree effect. this yeast was used as a reference organism. The localization, activity and kinetic properties of pyruvate carboxylase (EC 6.4.1.1), the pyruvate dehydrogenase complex and pyruvate decarboxylase (EC 4.1.1.1) in cells of glucose-limited chemostat cultures of the two yeasts were compared. In contrast to the general situation in fungi, plants and animals, pyruvate carboxylase was found to be a cytosolic enzyme in both yeasts. This implies that for anabolic processes, transport of C4-dicarboxylic acids into the mitochondria is required. Isolated mitochondria from both yeasts exhibited the same kinetics with respect to oxidation of malate. Also, the affinity of isolated mitochondria for pyruvate oxidation and the in situ activity of the pyruvate dehydrogenase complex was similar in both types of mitochondria. The activity of the cytosolic enzyme pyruvate decarboxylase in S. cerevisiae from glucose-limited chemostat cultures was 8-fold that in C. utilis. The enzyme was purified from both organisms, and its kinetic properties were determined. Pyruvate decarboxylase of both yeasts was competitively inhibited by inorganic phosphate. The enzyme of S. cerevisiae was more sensitive to this inhibitor than the enzyme of C. utilis. The in vivo role of phosphate inhibition of pyruvate decarboxylase upon transition of cells from glucose limitation to glucose excess and the associated triggering of alcoholic fermentation was investigated with 31P-NMR. In both yeasts this transition resulted in a rapid drop of the cytosolic inorganic phosphate concentration. It is concluded that the relief from phosphate inhibition does stimulate alcoholic fermentation, but it is not a prerequisite for pyruvate decarboxylase to become active in vivo. Rather, a high glycolytic flux and a high level of this enzyme are decisive for the occurrence of alcoholic fermentation after transfer of cells from glucose limitation to glucose excess.     

On the importance of trait interrelationships for understanding environmental responses of stream macroinvertebrates

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