beta-Endorphin: characteristics of binding sites in the rat brain.

Stereospecific binding of human β-endorphin to rat membrane preparations is described for the first time using $\text{[}{}^3\text{H-Tyr}{}^{27}\text{]-β}{}_{\mathrm{h}}\text{-endorphin}$ as the ligand. The binding is time dependent and saturable with respect to β_h-endorphin with an apparent dissociation constant of 0.3 nM. Sodium ion (100 mM) elevates this value to 2.5 nM but has no effect on the total number of binding sites present in the membrane preparation. The ability of certain β-endorphin analogs, opiate agonists as well as antagonists to inhibit the binding of β_h-endorphin, is presented.     

NMR studies of prebiotic polypeptides

Several polypeptides prepared by means of pyrocondensation have been the subject of structural investigations. Attention has been focused on the constitutional characterization of homo-and co-polymers containing Asp and Glu residues, whose role is essential for the formation of the so-called proteinoids. Contrary to the literature data based on chemical degradation, nmr studies show conclusively that in thermal poly-aspartic acid only β-peptide linkages are present. This result casts serious doubt on the role thermal condensation might have played in prebiotic polypeptide syntheses.     

Microfluidic‐Assisted Blade Coating of Compositional Libraries for Combinatorial Applications: The Case of Organic Photovoltaics

Microfluidic technologies are highly adept at generating controllable compositional gradients in fluids, a feature that has accelerated the understanding of the importance of chemical gradients in biological processes. That said, the development of versatile methods to generate controllable compositional gradients in the solid‐state has been far more elusive. The ability to produce such gradients would provide access to extensive compositional libraries, thus enabling the high‐throughput exploration of the parametric landscape of functional solids and devices in a resource‐, time‐, and cost‐efficient manner. Herein, the synergic integration of microfluidic technologies is reported with blade coating to enable the controlled formation of compositional lateral gradients in solution. Subsequently, the transformation of liquid‐based compositional gradients into solid‐state thin films using this method is demonstrated. To demonstrate efficacy of the approach, microfluidic‐assisted blade coating is used to optimize blending ratios in organic solar cells. Importantly, this novel technology can be easily extended to other solution processable systems that require the formation of solid‐state compositional lateral gradients.     

Diagnosis,Burden and Mortality of Pneumocystis jirovecii Pneumonia in Venezuela

Current Fungal Infection Reports - The aim of this work is to contribute to the knowledge of diagnosis, burden, and mortality of pneumocystosis or Pneumocystis jirovecii pneumonia (PCP) in...     

A New Synthesis of the Potent and Selective Anti-Herpesvirus Agent (S)-1-[3-Hydroxy-2-(Phosphonylmethoxy)Propyl]Cytosine

Abstract

A new synthetic approach to (S)-1-[3-hydroxy-2-(phosphonyl-methoxy)propyl]cytosine (3, (S)-HPMPC) is based on coupling of the heterocyclic moiety with a glycerol-derived side chain, followed by introduction of the phosphonylmethyl ether group.     

Legacies of Prehistoric Agricultural Practices Within Plant and Soil Properties Across an Arid Ecosystem

Closely integrated research between archaeologists and ecologists provides a long-term view of human land use that is rare in the ecological literature, allowing for investigation of activities that lead to enduring environmental outcomes. This extended temporal perspective is particularly important in aridlands where succession occurs slowly and ecosystem processes are mediated by abiotic, geomorphic factors. Numerous studies show that impacts from ancient human actions can persist, but few have explored the types of practices or mechanisms that lead to either transient or long-term environmental change. We compared plant and soil properties and processes from a range of landscape patch types in the Sonoran Desert of the US Southwest that supported different, well-documented prehistoric farming practices from AD 750–1300. Our results show that the types of ancient human activities that leave long-term ecological legacies in aridlands are those that fundamentally alter “slow variables” such as soil properties that regulate the timing and supply of water. Prehistoric Hohokam floodwater-irrigation practices, but not dryland farming techniques, substantially altered soil texture, which was strongly associated with desert plant community and functional composition. However, prehistoric agriculture did not consistently alter long-term nutrient availability and thus had no impact on “fast variables” such as production of seasonal annual plants that are restricted to periods of ample rainfall. In this arid ecosystem, the inverse texture model explained patterns in plant functional composition at large scales, but is less predictive of production of short-lived desert annuals that experience a more mesic precipitation regime.     

The exocyst subunit Exo70B1 is involved in the immune response of Arabidopsis thaliana to different pathogens and cell death

Components of the vesicle trafficking machinery are central to the immune response in plants. The role of vesicle trafficking during pre-invasive penetration resistance has been well documented. However, emerging evidence also implicates vesicle trafficking in early immune signaling. Here we report that Exo70B1, a subunit of the exocyst complex which mediates early tethering during exocytosis is involved in resistance. We show that exo70B1 mutants display pathogen-specific immuno-compromised phenotypes. We also show that exo70B1 mutants display lesion-mimic cell death, which in combination with the reduced responsiveness to pathogen-associated molecular patterns (PAMPs) results in complex immunity-related phenotypes.     

Glucose Phosphorylation Is Required for Mycobacterium tuberculosis Persistence in Mice

Mycobacterium tuberculosis (Mtb) is thought to preferentially rely on fatty acid metabolism to both establish and maintain chronic infections. Its metabolic network, however, allows efficient co-catabolism of multiple carbon substrates. To gain insight into the importance of carbohydrate substrates for Mtb pathogenesis we evaluated the role of glucose phosphorylation, the first reaction in glycolysis. We discovered that Mtb expresses two functional glucokinases. Mtb required the polyphosphate glucokinase PPGK for normal growth on glucose, while its second glucokinase GLKA was dispensable. ¹³C-based metabolomic profiling revealed that both enzymes are capable of incorporating glucose into Mtb''s central carbon metabolism, with PPGK serving as dominant glucokinase in wild type (wt) Mtb. When both glucokinase genes, ppgK and glkA, were deleted from its genome, Mtb was unable to use external glucose as substrate for growth or metabolism. Characterization of the glucokinase mutants in mouse infections demonstrated that glucose phosphorylation is dispensable for establishing infection in mice. Surprisingly, however, the glucokinase double mutant failed to persist normally in lungs, which suggests that Mtb has access to glucose in vivo and relies on glucose phosphorylation to survive during chronic mouse infections.     

Huntington's Disease Induced Cardiac Amyloidosis Is Reversed by Modulating Protein Folding and Oxidative Stress Pathways in the Drosophila Heart

Amyloid-like inclusions have been associated with Huntington''s disease (HD), which is caused by expanded polyglutamine repeats in the Huntingtin protein. HD patients exhibit a high incidence of cardiovascular events, presumably as a result of accumulation of toxic amyloid-like inclusions. We have generated a Drosophila model of cardiac amyloidosis that exhibits accumulation of PolyQ aggregates and oxidative stress in myocardial cells, upon heart-specific expression of Huntingtin protein fragments (Htt-PolyQ) with disease-causing poly-glutamine repeats (PolyQ-46, PolyQ-72, and PolyQ-102). Cardiac expression of GFP-tagged Htt-PolyQs resulted in PolyQ length-dependent functional defects that included increased incidence of arrhythmias and extreme cardiac dilation, accompanied by a significant decrease in contractility. Structural and ultrastructural analysis of the myocardial cells revealed reduced myofibrillar content, myofibrillar disorganization, mitochondrial defects and the presence of PolyQ-GFP positive aggregates. Cardiac-specific expression of disease causing Poly-Q also shortens lifespan of flies dramatically. To further confirm the involvement of oxidative stress or protein unfolding and to understand the mechanism of PolyQ induced cardiomyopathy, we co-expressed expanded PolyQ-72 with the antioxidant superoxide dismutase (SOD) or the myosin chaperone UNC-45. Co-expression of SOD suppressed PolyQ-72 induced mitochondrial defects and partially suppressed aggregation as well as myofibrillar disorganization. However, co-expression of UNC-45 dramatically suppressed PolyQ-72 induced aggregation and partially suppressed myofibrillar disorganization. Moreover, co-expression of both UNC-45 and SOD more efficiently suppressed GFP-positive aggregates, myofibrillar disorganization and physiological cardiac defects induced by PolyQ-72 than did either treatment alone. Our results demonstrate that mutant-PolyQ induces aggregates, disrupts the sarcomeric organization of contractile proteins, leads to mitochondrial dysfunction and increases oxidative stress in cardiomyocytes leading to abnormal cardiac function. We conclude that modulation of both protein unfolding and oxidative stress pathways in the Drosophila heart model can ameliorate the detrimental PolyQ effects, thus providing unique insights into the genetic mechanisms underlying amyloid-induced cardiac failure in HD patients.