Nosocomial Plasmodium falciparum infections confirmed by molecular typing in Medellín, Colombia

Background

Malaria is a serious, sometimes fatal, disease caused by Plasmodium infection of human red blood cells. The host-parasite co-evolutionary processes are well understood by the association of coding variations such as G6PD, Duffy blood group receptor, HLA, and beta-globin gene variants with malaria resistance. The profound genetic diversity in host is attributed to polymorphic microsatellites loci. The microsatellite alleles in bacterial species are known to have aided their survival in fatal environmental conditions. The fascinating question is whether microsatellites are genomic cushion in the human genome to combat disease stress and has cause-effect relationships with infections.

Presentation of the hypothesis

It is hypothesized that repeat units or alleles of microsatellites TH01 and D5S818, located in close proximity to beta-globin gene and immune regulatory region in human play a role in malaria predisposition. Association of alleles at aforesaid microsatellites with malaria infection was analysed. To overrule the false association in unrecognized population stratification, structure analysis and AMOVA were performed among the sampled groups.

Testing of hypothesis

Associations of microsatellite alleles with malaria infection were verified using recombination rate, Chi-square, and powerful likelihood tests. Further investigation of population genetic structure, and AMOVA was done to rule out the confounding effects of population stratification in interpretation of association studies.

Implication of the hypothesis

Lower recombination rate (θ) between microsatellites and genes implicated in host fitness; positive association between alleles -13 (D5S818), 9 (TH01) and strong susceptibility to Plasmodium falciparum; and alleles-12 (D5S818) and 6 (TH01) rendering resistance to human host were evident. The interesting fact emerging from the study was that while predisposition to malaria was a prehistoric attribute, among TH01 alleles; evolution of resistant allele-6 was a recent phenomenon, which could conceivably be driven by infection related selective forces. The host's microsatellite allelic associations with malaria infection were valid in the light of low genetic variance between sampled groups and no population stratification.     

A small molecule ubiquitination inhibitor blocks NF-kappa B-dependent cytokine expression in cells and rats

A small molecule inhibitor of NF-kappaB-dependent cytokine expression was discovered that blocked tumor necrosis factor (TNF) alpha-induced IkappaB(alpha) degradation in MM6 cells but not the degradation of beta-catenin in Jurkat cells. Ro106-9920 blocked lipopolysaccharide (LPS)-dependent expression of TNFalpha, interleukin-1beta, and interleukin-6 in fresh human peripheral blood mononuclear cells with IC(50) values below 1 microm. Ro106-9920 also blocked TNFalpha production in a dose-dependent manner following oral administration in two acute models of inflammation (air pouch and LPS challenge). Ro106-9920 was observed to inhibit an ubiquitination activity that does not require betaTRCP but associates with IkappaB(alpha) and will ubiquitinate IkappaB(alpha) S32E,S36E (IkappaB(alpha)(ee)) specifically at lysine 21 or 22. Ro106-9920 was identified in a cell-free system as a time-dependent inhibitor of IkappaB(alpha)(ee) ubiquitination with an IC(50) value of 2.3 +/- 0.09 microm. The ubiquitin E3 ligase activity is inhibited by cysteine-alkylating reagents, supported by E2UBCH7, and requires cIAP2 or a cIAP2-associated protein for activity. These activities are inconsistent with what has been reported for SCF(betaTRCP), the putative E3 for IkappaB(alpha) ubiquitination. Ro106-9920 was observed to be selective for IkappaB(alpha)(ee) ubiquitination over the ubiquitin-activating enzyme (E1), E2UBCH7, nonspecific ubiquitination of cellular proteins, and 97 other molecular targets. We propose that Ro106-9920 selectively inhibits an uncharacterized but essential ubiquitination activity associated with LPS- and TNFalpha-induced IkappaB(alpha) degradation and NF-kappaB activation.     

The glutamine residue of the conserved GGQ motif in Saccharomyces cerevisiae release factor eRF1 is methylated by the product of the YDR140w gene

Polypeptide release factors from eubacteria and eukaryotes, although similar in function, belong to different protein families. They share one sequence motif, a GGQ tripeptide that is vital to release factor (RF) activity in both kingdoms. In bacteria, the Gln residue of the motif in RF1 and RF2 is modified to N(5)-methyl-Gln by the S-adenosyl l-methionine-dependent methyltransferase PrmC and the absence of Gln methylation decreases the release activity of Escherichia coli RF2 in vitro severalfold. We show here that the same modification is made to the GGQ motif of Saccharomyces cerevisiae release factor eRF1, the first time that N(5)-methyl-Gln has been found outside the bacterial kingdom. The product of the YDR140w gene is required for the methylation of eRF1 in vivo and for optimal yeast cell growth. YDR140w protein has significant homology to PrmC but lacks the N-terminal domain thought to be involved in the recognition of the bacterial release factors. Overproduced in S. cerevisiae, YDR140w can methylate eRF1 from yeast or man in vitro using S-adenosyl l-methionine as methyl donor provided that eRF3 and GTP are also present, suggesting that the natural substrate of the methyltransferase YDR140w is the ternary complex eRF1.eRF3.GTP.     

Egg morphology of seven noctuid species (Lepidoptera: Noctuidae) from Chilean and updated key to their identification

Eggs from seven Noctuid moth species, Eriopyga perfusca (Hampson), Magnagrotis oorti (Koehler), Pseudoleucania brosii (Koehler), Scania simillima (Koehler). Scriptania americana (Blanchard), Scriptania leucofasciata Rodriguez, were collected at La Mina, 925 msnm, (35 degrees 21' S; 71 degrees 41' W) and Paso Internacional Pchucnche (35 degrees 57' S: 70 degrees 23' W), 2560 msnm, Chile. The Scanning Electron Microscope showed that egg morphology allows identification to species level. This is particularly useful in agricultural pest control, and morphological differences are used in this report to present an updated taxonomic key to the Chilean Noctuidae.     

Import of the transfer RNase colicin D requires site-specific interaction with the energy-transducing protein TonB

The transfer RNase colicin D and ionophoric colicin B appropriate the outer membrane iron siderophore receptor FepA and share a common translocation requirement for the TonB pathway to cross the outer membrane. Despite the almost identical sequences of the N-terminal domains required for the translocation of colicins D and B, two spontaneous tonB mutations (Arg158Ser and Pro161Leu) completely abolished colicin D toxicity but did not affect either the sensitivity to other colicins or the FepA-dependent siderophore uptake capacity. The sensitivity to colicin D of both tonB mutants was fully restored by specific suppressor mutations in the TonB box of colicin D, at Ser18(Thr) and Met19(Ile), respectively. This demonstrates that the interaction of colicin D with TonB is critically dependent on certain residues close to position 160 in TonB and on the side chains of certain residues in the TonB box of colicin D. The effect of introducing the TonB boxes from other TonB-dependent receptors and colicins into colicins D and B was studied. The results of these and other changes in the two TonB boxes show that the role of residues at positions 18 and 19 in colicin D is strongly modulated by other nearby and/or distant residues and that the overall function of colicin D is much more dependent on the interaction with TonB involving the TonB box than is the function of colicin B.     

Comparative Study on the Changes in Photosynthetic Activity of the Homoiochlorophyllous Desiccation-Tolerant Haberlea Rhodopensis and Desiccation-Sensitive Spinach Leaves During Desiccation and Rehydration

The functional peculiarities and responses of the photosynthetic system in the flowering homoiochlorophyllous desiccation-tolerant (HDT) Haberlea rhodopensis and the non-desiccation-tolerant spinach were compared during desiccation and rehydration. Increasing rate of water loss clearly modifies the kinetic parameters of fluorescence induction, thermoluminescence emission, far-red induced P700 oxidation and oxygen evolution in the leaves of both species. The values of these parameters returned nearly to the control level after 24 h rehydration only of the leaves of HDT plant. PS II was converted in a non-functional state in desiccated spinach in accordance with the changes in membrane permeability, malondialdehyde, proline and H₂O₂ contents. Moreover, our data showed a strong reduction of the total number of PS II centers in Haberlea without any changes in the energetics of the charge recombination. We consider this observation, together with the previously reported unusually high temperature of B-band (S₂Q_B-) emission of Haberlea to reflect some specific adaptive characteristics of the photosynthetic system. As far as we know this is the first time when such adaptive characteristics and mechanism of the photosynthetic system of a flowering HDT higher plant is described. These features of Haberlea can explain the fast recovery of its photosynthesis after desiccation, which enable this HDT plant to rapidly take advantage of frequent changes in water availability.     

Polymorphism of VDR gene--the most effective molecular marker of osteoporotic bone fractures risk within postmenopausal women from Wielkopolska region of Poland

The major public health problem which will arise is a frequency of osteoporosis. The first manifestations of this disease are often bone fractures. Identification and evaluation of individual bone fracture risk will be the most effective way of solving the problem. Genetic determination of osteoporosis is unquestionable. The aim of this study is to detect which variants of genotypes lead to illness. We investigated 187 patients with osteoporosis (161 women, 26 men) and 19 healthy subjects. Polymorphisms of the following genes were investigated: OPG, VDR, ESR1, TGFB1 COL1A1, and BMP2. The statistically significant relationship between BMD value and T allele of Taq I VDR gene were found. Genotypes: aa, bb, TT of VDR gene occur more frequently in polish osteoporotic population in Wielkopolska region within patients with higher risk of bone fractures.     

The relationship between violent video games,acculturation, and aggression among Latino adolescents

Multiple factors are involved in the occurrence of aggressive behavior. The purpose of this study was to evaluate the hypotheses that Latino middle school children exposed to higher levels of video game playing will exhibit a higher level of aggression and fighting compared to children exposed to lower levels and that the more acculturated middle school Latino children will play more video games and will prefer more violent video games compared to less acculturated middle school Latino children. This study involved 5,831 students attending eight public schools in Texas. A linear relationship was observed between the time spent playing video games and aggression scores. Higher aggression scores were significantly associated with heavier video playing for boys and girls (p < 0.0001). The more students played video games, the more they fought at school (p < 0.0001). As Latino middle school students were more acculturated, their preference for violent video game playing increased, as well as the amount of time they played video games. Students who reported speaking more Spanish at home and with their friends were less likely to spend large amounts of time playing video games and less likely to prefer violent video games (p < 0.05).