Boro-norleucine as a P1 residue for the design of selective and potent DPP7 inhibitors

Dipeptide-based inhibitors with C-substituted (alkyl or aminoalkyl) alpha-amino acids in the P2 position and boro-norleucine (boro-Nle) in the P1 position were synthesized. Relative to boro-proline, boro-Nle as a P1 residue was shown able to significantly dial out DPP4, FAP, DPP8, and DPP9 activity. Dab-boro-Nle (4g) proved to be the most selective and potent DPP7 inhibitor with a DPP7 IC50 value of 480 pM.     

Detection and identification of microorganisms in wine: a review of molecular techniques

The microbial ecology of wine is complex. Microbes can play both positive and negative roles in the quality of the final product. Due to this impact, the microbial ecology of wine has been well studied. Traditional indirect methods, such as plating, have largely been replaced by a number of molecular methods. These methods are typically either indirect methods used for identification of cultured organisms, or direct methods used to profile whole populations or identify specific microbes in a mixed population. These molecular methods offer a number of advantages over traditional methods including speed and precision. This review will examine both direct and indirect molecular methods, provide examples of their impact on the study of the microbial ecology of wine, and also discuss their strengths and limitations.     

Short-term effects of a summer wildfire on a desert grassland arthropod community in New Mexico

Surface-active arthropods were sampled after a lightning-caused wildfire in desert grassland habitat on the Sevilleta National Wildlife Refuge, Socorro County, NM. Pitfall traps (n = 32 per treatment) were used to evaluate species-specific "activity-density" indices after the June wildfire in both burned and unburned areas. In total, 5,302 individuals were collected from 69 taxa. Herbivore activity-densities generally decreased, whereas predators often increased in the burned area; pitfall trap bias likely contributed to this latter observation. Fire caused the virtual extirpation of scaly crickets (Mogoplistidae), field crickets (Gryllidae), and camel crickets (Raphidophoridae), but recolonization began during the first postfire growing season. Several grasshoppers (Acrididae) also exhibited significant postfire declines [Ageneotettix deorum (Scudder), Eritettix simplex (Scudder), Melanoplus bowditchi Scudder, and Amphitornus coloradus (Thomas)]. Some beetles showed lower activity-density, including Pasimachus obsoletus LeConte (Carabidae) and Eleodes extricatus (Say) (Tenebrionidae). Taxa exhibiting significant postfire increases in activity-density included acridid grasshoppers (Aulocara femoratum (Scudder), Hesperotettix viridis (Thomas), Trimerotropis pallidipennis (Burmeis.), and Xanthippus corallipes Haldeman); carabid beetles (Amblycheila picolominii Reiche, Cicindela punctulata Olivier), tenebrionid beetles (Eleodes longicollis LeConte, Edrotes rotundus (Say), Glyptasida sordida (LeConte), Stenomorpha consors (Casey); the centipedes Taiyubius harrietae Chamberlin (Lithobiidae) and Scolopendra polymorpha Wood (Scolopendridae); scorpions (Vaejovis spp.; Vaejovidae); and sun spiders (Eremobates spp.; Eremobatidae). Native sand roaches (Arenivaga erratica Rehn, Eremoblata subdiaphana (Scudder); Polyphagidae) displayed no significant fire response. Overall, arthropod responses to fire in this desert grassland (with comparatively low and patchy fuel loads) were comparable to those in mesic grasslands with much higher and more continuous fuel loads.     

Evidence Against the Involvement of Ionically Bound Cell Wall Proteins in Pea Epicotyl Growth

Ionically bound cell wall proteins were extracted from 7 day old etiolated pea (Pisum sativum L. cv Alaska) epicotyls with 3 molar LiCl. Polyclonal antiserum was raised in rabbits against the cell wall proteins. Growth assays showed that treatment of growing region segments (5-7 millimeters) of peas with either dialyzed serum, serum globulin fraction, affinity purified immunoglobulin, or papain-cleaved antibody fragments had no effect on growth. Immunofluorescence microscopy confirmed antibody binding to cell walls and penetration of the antibodies into the tissues. Western blot analysis, immunoassay results, and affinity chromatography utilizing Sepharose-bound antibodies confirmed recognition of the protein preparation by the antibodies. Experiments employing in vitro extension as a screening measure indicated no effect upon extension by antibodies, by 50 millimolar LiCl perfusion of the apoplast or by 3 molar LiCl extraction. Addition of cell wall protein to protease pretreated segments did not restore extension nor did addition of cell wall protein to untreated segments increase extension. It is concluded that, although evidence suggests that protein is responsible for the process of extension, the class(es) of proteins which are extracted from pea cell walls with 3 molar LiCl are probably not involved in this process.     

Enzymatic Synthesis of 2′,5′-Dideoxv Purine Nucleosides and Related Compounds

Abstract

A wide range of 2′,5′-dideoxy-nucleosides, including 6- substituted purine, pyrazolo[3,4-d]pyrimidine and 1-deazapurine derivatives, has been enzymatically prepared using purine nucleoside phosphorylase. Specificity towards cleavage by bacterial versus mammalian purine nucleoside phosphorylase was evaluated.     

Short-term responses of ecosystem carbon fluxes to experimental soil warming at the Swiss alpine treeline

Climatic warming will probably have particularly large impacts on carbon fluxes in high altitude and latitude ecosystems due to their great stocks of labile soil C and high temperature sensitivity. At the alpine treeline, we experimentally warmed undisturbed soils by 4 K for one growing season with heating cables at the soil surface and measured the response of net C uptake by plants, of soil respiration, and of leaching of dissolved organic carbon (DOC). Soil warming increased soil CO₂ effluxes instantaneously and throughout the whole vegetation period (+45%; +120 g C m y^?1). In contrast, DOC leaching showed a negligible response of a 5% increase (NS). Annual C uptake of new shoots was not significantly affected by elevated soil temperatures, with a 17, 12, and 14% increase for larch, pine, and dwarf shrubs, respectively, resulting in an overall increase in net C uptake by plants of 20–40 g C m^?2y^?1. The Q ₁₀ of 3.0 measured for soil respiration did not change compared to a 3-year period before the warming treatment started, suggesting little impact of warming-induced lower soil moisture (?15% relative decrease) or increased soil C losses. The fraction of recent plant-derived C in soil respired CO₂ from warmed soils was smaller than that from control soils (25 vs. 40% of total C respired), which implies that the warming-induced increase in soil CO₂ efflux resulted mainly from mineralization of older SOM rather than from stimulated root respiration. In summary, one season of 4 K soil warming, representative of hot years, led to C losses from the studied alpine treeline ecosystem by increasing SOM decomposition more than C gains through plant growth.     

Cytomegaloviral hypophysitis in a simian immunodeficiency virus‐infected rhesus macaque (Macacca mulatta)

Rhesus macaques experimentally infected with Simian Immunodeficiency Virus (SIV) experience immunosuppression and often opportunistic infection. Among the most common opportunistic infections are rhesus cytomegalovirus (RhCMV), a ubiquitous betaherpesvirus that undergoes continuous low‐level replication in immunocompetent monkeys. Upon SIV‐mediated immunodeficiency, RhCMV reactivates and results in lesions in numerous organ systems including the nervous and reproductive systems. We report the first case of cytomegaloviral hypophysitis in a SIV‐immunocompromised rhesus macaque.     

Identification of neuronal RNA targets of TDP-43-containing ribonucleoprotein complexes

TAR DNA-binding protein 43 (TDP-43) is associated with a spectrum of neurodegenerative diseases. Although TDP-43 resembles heterogeneous nuclear ribonucleoproteins, its RNA targets and physiological protein partners remain unknown. Here we identify RNA targets of TDP-43 from cortical neurons by RNA immunoprecipitation followed by deep sequencing (RIP-seq). The canonical TDP-43 binding site (TG)(n) is 55.1-fold enriched, and moreover, a variant with adenine in the middle, (TG)(n)TA(TG)(m), is highly abundant among reads in our TDP-43 RIP-seq library. TDP-43 RNA targets can be divided into three different groups: those primarily binding in introns, in exons, and across both introns and exons. TDP-43 RNA targets are particularly enriched for Gene Ontology terms related to synaptic function, RNA metabolism, and neuronal development. Furthermore, TDP-43 binds to a number of RNAs encoding for proteins implicated in neurodegeneration, including TDP-43 itself, FUS/TLS, progranulin, Tau, and ataxin 1 and -2. We also identify 25 proteins that co-purify with TDP-43 from rodent brain nuclear extracts. Prominent among them are nuclear proteins involved in pre-mRNA splicing and RNA stability and transport. Also notable are two neuron-enriched proteins, methyl CpG-binding protein 2 and polypyrimidine tract-binding protein 2 (PTBP2). A PTBP2 consensus RNA binding motif is enriched in the TDP-43 RIP-seq library, suggesting that PTBP2 may co-regulate TDP-43 RNA targets. This work thus reveals the protein and RNA components of the TDP-43-containing ribonucleoprotein complexes and provides a framework for understanding how dysregulation of TDP-43 in RNA metabolism contributes to neurodegeneration.     

Characterization of Carriage Isolates of Neisseria meningitidis in the Adolescents and Young Adults Population of Bogota (Colombia)

Background

Meningococcal carriage studies are important to improve our understanding of the epidemiology of meningococcal disease. The aim of this study was to determine the prevalence of meningococcal carriage and the phenotypic and genotypic characteristics of isolates collected from a sample of students in the city of Bogotá, Colombia.

Materials and Methods

A total of 1459 oropharyngeal samples were collected from students aged 15–21 years attending secondary schools and universities. Swabs were plated on a Thayer Martin agar and N. meningitidis was identified by standard microbiology methods and PCR.

Results

The overall carriage prevalence was 6.85%. Carriage was associated with cohabitation with smokers, and oral sex practices. Non-groupable and serogroup Y isolates were the most common capsule types found. Isolates presented a high genetic diversity, and circulation of the hypervirulent clonal complexes ST-23, ST-32 and ST-41/44 were detected.

Conclusion

The meningococcal carriage rate was lower than those reported in Europe and Africa, but higher than in other Latin American countries. Our data also revealed antigenic and genetic diversity of the isolates and the circulation of strains belonging to clonal complexes commonly associated with meningococcal disease.