Synthesis of 2,3:4,6-di-O-isopropylidene-D-allopyranose from D-glucose

2,3:4,6-Di-O-isopropylidene-d-allopyranose can be conveniently prepared from d-glucose via a synthetic sequence, which includes Mitsunobu inversion at O-3, di-O-isopropylidenation of phenyl-1-thio-d-alloside and anomeric deprotection on treatment with NBS/CaCO3.     

Why do fleshy-fruit plants of the mediterranean scrub intercept fall-but not spring-passage of seed-dispersing migratory birds?

Summary Production of fleshy fruits by 8 tree and shrub species, and patterns of their utilization by 6 resident and 6 transient bird species, were assessed in an Israeli Mediterranean scrub. Whereas more than half the ripe crop of plants that fruit in one relatively short burst is not removed by birds, the greater part of the crop of species that fruit throughout a long period, is removed. Of two plant species that fruit simultaneously, the one with an inconspicuous fruit is utilized by a single, year-round resident frugivorous bird, whereas the species with bright fruits is utilized by several non-resident and omnivorous bird species. A further two simultaneously fruiting species differ in fat content and the color of their conspicuous ripe fruits; the low-fat fruit being taken by a resident species and the high-fat fruit by a transient congener, just prior to the desert-crossing portion of its Fall-passage.Though more migrants pass through in Spring than in Fall, none of the fleshy-fruit plants fruit in Spring, and most fruit during the Fall. Two non-exclusive explanations for this phenomenon are (a) Fall dispersal ensures immediate germination, with least exposure to desiccation and predation; (b) Spring transients approaching their breeding territories may either be reluctant to spend much time on feeding, or mostly require proteins, amply supplied by the Spring flush of insects, typical of the Mediterranean region. Fall transients approaching the desert require mostly fats and carbohydrates, supplied by fruits. Fruits attract birds easily in the Fall, when insects are scarce.     

Calcium-dependent oxidation of thioredoxin during cellular growth initiation.

The fraction of cell thiol proteins in the oxidized disulfide form were quantified during mitogen-induced HaCaT keratinocyte growth initiation. Oxidized thioredoxin increased from 11 +/- 1.2% in resting cells to 80 and 61% 2 min after addition of bradykinin or EGF. Thioredoxin oxidation was transient returning toward normal values by 20 min. The disulfide forms of other cellular proteins rose in parallel with thioredoxin oxidation. The oxidation of thioredoxin depended on a rise in cytosolic calcium. It was prevented by preloading cells with BAPTA, a Ca(2+) chelator and induced by addition of Ca(2+)-ionophore A23187 or of thapsigargin. In cell extracts, thioredoxin reductase was inhibited by micromolar calcium. The rise in cytosolic Ca(2+) led to a concomitant burst of H(2)O(2) formation. The oxidizing intracellular milieu suggests that redox regulation actively participates in the growth initiation cascade. The role of peroxiredoxins and ASK 1 cascade activation are discussed in this context.     

Alpha-fetoprotein receptors in a human breast cancer cell line

Evidence is presented for the existence of specific receptors for alpha-fetoprotein on the surface of MCF-7 human breast cancer cells. At 4 degrees C, the binding of alpha-fetoprotein to these cells displayed a biphasic saturation curve. Scatchard analysis revealed the presence of at least two binding sites with dissociation constants of 4.5 X 10(-9) M (2,000 sites/cell) and 1.3 X 10(-8) M (135,000 sites/cell), respectively. Binding was inhibited by 85% in the presence of a 5,000-fold excess of unlabeled alpha-fetoprotein and by 50% with the same excess of serum albumin. Competition by other serum proteins was not significant. At 37 degrees C, alpha-fetoprotein was endocytosed and the uptake curve reached a plateau after 3-4 hours of incubation.     

Rat alpha-fetoprotein: isolation, characterization and estrogen-binding properties

Rat α-fetoprotein (α-FP) was isolated from amniotic fluid by an immuno-chemical procedure using high capacity immunoadsorbents. The yield was about 75 p. cent of the initial content in α-FP. The isolated α-FP was found pure by electrophoretic and immunochemical criteria. A molecular weight of 72.000 daltons and a sedimentation coefficient of 4.5 S were estimated by SDS-acrylamide-agarose electrophoresis and sucrose gradient centrifugation, respectively. The latter procedure was also used to study the binding activity of α-FP toward several steroids. All the estrogens tested, estrone, estradiol, estriol and diethylstylbestrol, were bound. By equilibrium dialysis, the intrinsic association constant of pure α-FP was 1 × 10⁸M⁻¹ for estrone and 6 × 10⁷M⁻¹ for estradiol. One molecule of estrone and estradiol was bound per molecule of protein. No significant binding was observed with testosterone and progesterone. The specificity of the estrophilic activity of α-FP appears as a characteristic property of this protein.After electrophoresis of pure α-FP in acrylamide-agarose gels of low porosity (11 p. cent of acrylamide monomer), two closely migrating but distinct bands could be demonstrated. Both forms possess estrogen-binding activity and common antigenic properties. The same molecular heterogeneity of α-FP was observed in whole amniotic fluid.     

Epidemic and Endemic Malaria Transmission Related to Fish Farming Ponds in the Amazon Frontier

Fish farming in the Amazon has been stimulated as a solution to increase economic development. However, poorly managed fish ponds have been sometimes associated with the presence of Anopheles spp. and consequently, with malaria transmission. In this study, we analyzed the spatial and temporal dynamics of malaria in the state of Acre (and more closely within a single county) to investigate the potential links between aquaculture and malaria transmission in this region. At the state level, we classified the 22 counties into three malaria endemicity patterns, based on the correlation between notification time series. Furthermore, the study period (2003–2013) was divided into two phases (epidemic and post-epidemic). Higher fish pond construction coincided both spatially and temporally with increased rate of malaria notification. Within one malaria endemic county, we investigated the relationship between the geolocation of malaria cases (2011–2012) and their distance to fish ponds. Entomological surveys carried out in these ponds provided measurements of anopheline abundance that were significantly associated with the abundance of malaria cases within 100 m of the ponds (P < 0.005; r = 0.39). These results taken together suggest that fish farming contributes to the maintenance of high transmission levels of malaria in this region.     

High Rates of O’Nyong Nyong and Chikungunya Virus Transmission in Coastal Kenya

BackgroundChikungunya virus (CHIKV) and o’nyong nyong virus (ONNV) are mosquito-borne alphaviruses endemic in East Africa that cause acute febrile illness and arthritis. The objectives of this study were to measure the seroprevalence of CHIKV and ONNV in coastal Kenya and link it to demographics and other risk factors.MethodologyDemographic and exposure questionnaires were administered to 1,848 participants recruited from two village clusters (Milalani-Nganja and Vuga) in 2009. Sera were tested for alphavirus exposure using standardized CHIKV IgG ELISA protocols and confirmed with plaque reduction neutralization tests (PRNT). Logistic regression models were used to determine the variables associated with seropositivity. Weighted K test for global clustering of houses with alphavirus positive participants was performed for distance ranges of 50–1,000 meters, and G* statistic and kernel density mapping were used to identify locations of higher seroprevalence.Conclusions/SignificanceAlphavirus exposure, particularly ONNV exposure, is common in coastal Kenya with ongoing interepidemic transmission of both ONNV and CHIKV. Women and adults were more likely to be seropositive. Household location may be a defining factor for the ecology of alphaviral transmission in this region.     

Correlation of Hypertension and Proteinuria with Outcome in Elderly Bevacizumab-Treated Patients with Metastatic Colorectal Cancer

Background

Studies suggest a relationship between hypertension and outcome in bevacizumab-treated patients with metastatic colorectal cancer (mCRC). We performed a retrospective analysis of two phase II studies (BECA and BECOX) to determine if hypertension and proteinuria predict outcome in elderly patients with mCRC treated with bevacizumab.

Patients and Methods

Patients ≥70 years of age received either capecitabine 1250 mg/m² bid days 1–14 + bevacizumab 7.5 mg/kg day 1 every 21 days (BECA study) or capecitabine 1000 mg/m² bid days 1–14 with bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m² day 1 (BECOX study). The primary objective was to correlate hypertension and proteinuria with overall response rate (ORR), time to progression (TTP) and overall survival (OS). Secondary objectives included identification of risk factors associated with the development of hypertension and proteinuria and determining whether development of hypertension or proteinuria in the first 2 cycles was related to ORR, disease-control rate (DCR), TTP or OS.

Results

In total, 127 patients (median age 75.5 years) were included in the study. Hypertension correlated with DCR and OS; proteinuria correlated with ORR and DCR. Proteinuria or hypertension in the first 2 cycles did not correlate with efficacy. Risk factors for hypertension were female gender (odds ratio [OR] 0.241; P = 0.011) and more bevacizumab cycles (OR 1.112; P = 0.002); risk factors for proteinuria were diabetes (OR 3.869; P = 0.006) and more bevacizumab cycles (OR 1.181; P<0.0001). Multivariate analysis identified as having prognostic value: baseline lactate dehydrogenase, haemoglobin, number of metastatic lesions and DCR.

Conclusion

This analysis of two phase II studies suggests that hypertension is significantly correlated with OS but not with ORR and TTP, whereas proteinuria is correlated with ORR but not with OS and TTP. Both hypertension and proteinuria are associated with the duration of bevacizumab treatment and do not represent an independent prognostic factor.