Gastric dilatation and intestinal obstruction mimicking acute coronary syndrome with dynamic electrocardiographic changes

Background

Hyperuricemia may be associated with an increased risk of coronary heart disease (CHD) mortality; however, the results from prospective studies are conflicting. The objective of this study was to assess the association between hyperuricemia and risk of CHD mortality by performing a meta-analysis.

Methods

Pubmed and Embase were searched for relevant prospective cohort studies published until July 2015. Studies were included only if they reported data on CHD mortality related to hyperuricemia in a general population. The pooled adjusted relative risk (RR) was calculated using a random-effects model.

Results

A total of 14 studies involving 341 389 adults were identified. Hyperuricemia was associated with an increased risk of CHD mortality (RR: 1.14; 95 % CI: 1.06–1.23) and all-cause mortality (RR: 1.20; 95 % CI: 1.13–1.28). For each increase of 1 mg/dl of serum uric acid (SUA), the overall risks of CHD and all-cause mortality increased by 20 and 9 %, respectively. According to the gender subgroup analyses, hyperuricemia increased the risk of CHD mortality in women (RR: 1.47; 95 % CI: 1.21–1.73) compared to men (RR: 1.10; 95 % CI: 1.00–1.19). The risk of all-cause mortality was greater in women.

Conclusions

Hyperuricemia may modestly increase the risk of CHD and all-cause mortality. Future research is needed to determine whether urate–lowering therapy has beneficial effects for reducing CHD mortality.

     

Plasma membrane calcium ATPase is concentrated in the head of sea urchin spermatozoa

Plasma membrane Ca2+ATPases (PMCAs) export Ca2+ from cells in a highly regulated manner, providing fine-tuning to the maintenance of intracellular Ca2+ concentrations. There are few studies of PMCAs in spermatozoa, which is surprising considering the importance of this enzyme in all cell types. Here we describe the primary structure and localization of the PMCA of sea urchin spermatozoa (suPMCA). The suPMCA is 1,154 amino acids and has 56% identity and 76% similarity to all 4 human PMCA isoforms. The suPMCA shares the features of a typical PMCA, including domains for calmodulin binding, ATP binding, ATPase phosphorylation, and 10 putative transmembrane segments with two large cytoplasmic loops. Southern blots show that suPMCA is a single copy gene. Treatment of live sea urchin sperm with the PMCA inhibitor, 5-(-6)-carboxyeosin, results in elevations of intracellular Ca2+ and loss of flagellar motility. Immunoblotting and immunoflorescence show that suPMCA is concentrated in the sperm head plasma membrane. In previous work, we showed that a plasma membrane K+ dependent Na+/Ca2+ exchanger (suNCKX), which also keeps Ca2+ low in these cells, is concentrated in the sperm flagellum. Thus, the sperm head and flagellum localize different gene products, both functioning to keep intracellular Ca2+ low, while the sperm swims in seawater containing 10 mM Ca2+.     

A functional genomic and proteomic perspective of sea urchin calcium signaling and egg activation

The sea urchin egg has a rich history of contributions to our understanding of fundamental questions of egg activation at fertilization. Within seconds of sperm-egg interaction, calcium is released from the egg endoplasmic reticulum, launching the zygote into the mitotic cell cycle and the developmental program. The sequence of the Strongylocentrotus purpuratus genome offers unique opportunities to apply functional genomic and proteomic approaches to investigate the repertoire and regulation of Ca(2+) signaling and homeostasis modules present in the egg and zygote. The sea urchin "calcium toolkit" as predicted by the genome is described. Emphasis is on the Ca(2+) signaling modules operating during egg activation, but the Ca(2+) signaling repertoire has ramifications for later developmental events and adult physiology as well. Presented here are the mechanisms that control the initial release of Ca(2+) at fertilization and additional signaling components predicted by the genome and found to be expressed and operating in eggs at fertilization. The initial release of Ca(2+) serves to coordinate egg activation, which is largely a phenomenon of post-translational modifications, especially dynamic protein phosphorylation. Functional proteomics can now be used to identify the phosphoproteome in general and specific kinase targets in particular. This approach is described along with findings to date. Key outstanding questions regarding the activation of the developmental program are framed in the context of what has been learned from the genome and how this knowledge can be applied to functional studies.     

Cloning of a sea urchin sarco/endoplasmic reticulum Ca2+ ATPase

Sarco/endoplasmic reticulum Ca2+ ATPase (SERCA), a vesicular integral membrane protein, is the best-characterized member of the P-type ion translocating ATPase superfamily. Here we describe the cloning and structural analysis of a sea urchin SERCA (suSERCA) cloned from testis cDNA. The approximately 112 kDa suSERCA is 1022 amino acids with approximately 70% identity and 80% similarity to all known mammalian SERCA isoforms. suSERCA shares all the structural features of mammalian SERCAs, including domains: A, actuator; N, nucleotide-binding; and P, phosphorylation, and also 10 transmembrane helices. Like human SERCA2, the suSERCA has a possible 11th transmembrane segment in its extreme C-terminus. The alignment of three sequences (suSERCA, human SERCA2, and rabbit SERCA1a) shows that the Ca2+ binding residues and kinks (required to form the ion-binding pocket) are 100% conserved. The annotated suSERCA gene consists of 24 exons separated by 23 introns and is approximately 30 kb. Western blots show that suSERCA is present in sea urchin eggs and testis, but not in mature spermatozoa. Treatment of live sperm with SERCA inhibitors has no effect on intracellular calcium, suggesting the absence of SERCA in sea urchin spermatozoa.     

Isolation,enzyme-bound structure and antibacterial activity of platencin A1 from Streptomyces platensis

Natural products continue to serve as one of the best sources for discovery of antibacterial agents as exemplified by the recent discoveries of platensimycin and platencin. Chemical modifications as well as discovery of congeners are the main sources for gaining knowledge of structure–activity relationship of natural products. Screening for congeners in the extracts of the fermentation broths of Streptomyces platensis led to the isolation of platencin A₁, a hydroxy congener of platencin. The hydroxylation of the tricyclic enone moiety negatively affected the antibacterial activity and appears to be consistent with the hydrophobic binding pocket of the FabF. Isolation, structure, enzyme-bound structure and activity of platencin A₁ and two other congeners have been described.     

Rapid Identification of Genes Encoding DNA Polymerases by Function-Based Screening of Metagenomic Libraries Derived from Glacial Ice

Small-insert and large-insert metagenomic libraries were constructed from glacial ice of the Northern Schneeferner, which is located on the Zugspitzplatt in Germany. Subsequently, these libraries were screened for the presence of DNA polymerase-encoding genes by complementation of an Escherichia coli polA mutant. Nine novel genes encoding complete DNA polymerase I proteins or domains typical of these proteins were recovered.DNA polymerases are essential for DNA replication and DNA repair. Based on sequence similarities and phylogenetic relationships, DNA polymerases are grouped into six different families (A, B, C, D, X, and Y) (17). In this study, we used a DNA polymerase I (polA) mutant of Escherichia coli as a host for the screening of metagenomic libraries. PolA belongs to family A and contains three different domains: a 5′-3′ exonuclease domain at the N terminus, a central proofreading 3′-5′ exonuclease domain, and a polymerase domain at the C terminus of the enzyme (11). These polymerases are employed as tools in molecular biology, including probe labeling, DNA sequencing, and mutagenic PCR (13). To improve their suitability for such applications, various family A DNA polymerases have been modified; e.g., the Klenow fragment of E. coli DNA polymerase I has been redesigned by the removal of the 5′-3′ exonuclease domain (12). Nevertheless, expanding the known DNA polymerase sequence space and discovery of polymerases with novel properties are required for the development of novel or improved molecular methods and tools (13, 20).Metagenomics based on direct isolation of DNA from environmental samples, generation of metagenomic libraries from the isolated DNA, and function-based screening of the constructed libraries has led to identification and characterization of a variety of novel biocatalysts, such as lipases, amylases, amidases, nitrilases, and oxidoreductases (for reviews, see references 6, 7, and 10). In particular, the use of host strains or mutants of host strains that require heterologous complementation for growth under selective conditions has proven to be an efficient strategy to screen complex metagenomic libraries. This approach has been applied to, e.g., the isolation of genes encoding Na⁺/H⁺ antiporters (14), antibiotic resistance (18), or enzymes involved in poly-3-hydroxybutyrate metabolism (21).In this study, we employed the last-named strategy to recover functional genes encoding DNA polymerases. To our knowledge, this is the first report of identification of polymerases or other DNA-modifying enzymes by function-driven screening of metagenomes. For this purpose, we constructed small-insert and large-insert metagenomic libraries from DNA isolated from glacial ice. The employment of glacial ice samples for metagenomic library construction has not been reported by other researchers. The screening for the targeted genes was based on complementation of a cold-sensitive lethal mutation in the polA gene of E. coli (16).     

Persistence of resprouting species after fire in natural and post‐mine restored shrublands in southwestern Australia

Questions: Is post‐fire persistence of resprouting species lower in restored sites, and is survival related to lignotuber size? Location: Southwestern Australia, Eneabba, 300 km north of Perth. Methods: Post‐fire persistence of 10 lignotuberous shrub species was compared between three sites restored 8–24 years ago after mineral‐sand mining and three surrounding natural shrubland sites (8–24 years since previous fire). Results: Overall persistence of species was 11–93% in restored sites (mean 52%) and 79–100% in natural sites (mean 96%). Persistence increased with time since rehabilitation for five species with <25% of individuals in three species surviving in the youngest stand. For equivalent crown size, average lignotuber circumferences were 50% smaller at restored sites and this probably accounted for their higher post‐fire mortality. Apart from differences in the age of plants, restored sites had lower soil penetrability than natural sites, which may have restricted rootstock development. A tradeoff favoring a higher crown volume to lignotuber size ratio was apparent in nine of the ten species with greater crown volumes (by 37%) and smaller lignotubers (by 36%) in restored sites. Two resprouting species for which crown seed store was quantified had much higher fecundity in restored sites. Conclusions: Fires reduced resprouter persistence in restored sites owing to poor development/insufficient size of lignotubers. Further management after fires is required, including application of resprouter seeds/seedlings on restored topsoil, transplanting adult resprouters (where viable) from natural areas ahead of the mining front. Low intensity/patchy fires are recommended on long unburnt sites. Resprouter survival would have likely been much greater in the first place if a deeper sandy soil profile was rehabilitated, thereby providing a more suitable medium for lignotuber development.     

Patterns of infection,origins, and transmission of ranaviruses among the ectothermic vertebrates of Asia

Ranaviral infections, a malady of ectothermic vertebrates, are becoming frequent, severe, and widespread, causing mortality among both wild and cultured species, raising odds of species extinctions and economic losses. This increase in infection is possibly due to the broad host range of ranaviruses and the transmission of these pathogens through regional and international trade in Asia, where outbreaks have been increasingly reported over the past decade. Here, we focus attention on the origins, means of transmission, and patterns of spread of this infection within the region. Infections have been recorded in both cultured and wild populations in at least nine countries/administrative regions, together with mass die‐offs in some regions. Despite the imminent seriousness of the disease in Asia, surveillance efforts are still incipient. Some of the viral strains within Asia may transmit across host–taxon barriers, posing a significant risk to native species. Factors such as rising temperatures due to global climate change seem to exacerbate ranaviral activity, as most known outbreaks have been recorded during summer; however, data are still inadequate to verify this pattern for Asia. Import risk analysis, using protocols such as Pandora+, pre‐border pathogen screening, and effective biosecurity measures, can be used to mitigate introduction of ranaviruses to uninfected areas and curb transmission within Asia. Comprehensive surveillance using molecular diagnostic tools for ranavirus species and variants will help in understanding the prevalence and disease burden in the region. This is an important step toward conserving native biodiversity and safeguarding the aquaculture industry.     

Determination of selectivity and efficacy of fatty acid synthesis inhibitors

Type II fatty acid synthesis (FASII) is essential to bacterial cell viability and is a promising target for the development of novel antibiotics. In the past decade, a few inhibitors have been identified for this pathway, but none of them lend themselves to drug development. To find better inhibitors that are potential drug candidates, we developed a high throughput assay that identifies inhibitors simultaneously against multiple targets within the FASII pathway of most bacterial pathogens. We demonstrated that the inverse t(1/2) value of the FASII enzyme-catalyzed reaction gives a measure of FASII activity. The Km values of octanoyl-CoA and lauroyl-CoA were determined to be 1.1 +/- 0.3 and 10 +/- 2.7 microM in Staphylococcus aureus and Bacillus subtilis, respectively. The effects of free metals and reducing agents on enzyme activity showed an inhibition hierarchy of Zn2+ > Ca2+ > Mn2+ > Mg2+; no inhibition was found with beta-mercaptoethanol or dithiothreitol. We used this assay to screen the natural product libraries and isolated an inhibitor, bischloroanthrabenzoxocinone (BABX) with a new structure. BABX showed IC50 values of 11.4 and 35.3 microg/ml in the S. aureus and Escherichia coli FASII assays, respectively, and good antibacterial activities against S. aureus and permeable E. coli strains with minimum inhibitory concentrations ranging from 0.2 to 0.4 microg/ml. Furthermore, the effectiveness, selectivity, and the in vitro and in vivo correlations of BABX as well as other fatty acid inhibitors were elucidated, which will aid in future drug discovery.     

Effect of growth temperature on carbon isotopic ratios in barley, pea and rape

Barley, pea and rape were grown in controlled environments atday/night temperatures ranging from 13/4 to 35/27?C. Shoot tissuewas analyzed for changes in the natural abundance ratio of ^l3C/¹²C.More¹³C was incorporated during growth at low temperatures thanat higher temperatures, but the change in isotopic ratio wasnot linear over the temperature range employed. ³Present address: Faculty of Agriculture, University of Ceylon,Peradeniya, Ceylon. (Received September 13, 1972; )