Bcl-2 but not clusterin/apolipoprotein J protected human diploid fibroblasts and immortalized keratinocytes from ceramide-induced apoptosis: role of p53 in the ceramide response

The role of clusterin/apolipoprotein J (Clu/ApoJ) and Bcl-2 on C(2)-ceramide-induced apoptosis of embryonic human diploid fibroblasts, MRC-5 and immortalized adult skin keratinocytes, HaCaT was investigated. C(2)-ceramide-induced apoptosis of HaCaT in a time- and dose-dependent manner, while in MRC-5 only at higher concentrations. There was a dose-dependent accumulation of Clu/ApoJ and downregulation of Bcl-2 which correlated with C(2)-ceramide-induced apoptosis of MRC-5. While overexpression of Bcl-2 suppressed C(2)-ceramide-mediated apoptosis in both cell types, Clu/ApoJ failed to do so, accessed by morphological changes, DNA fragmentation and PARP cleavage. There was no change in the expression of endogenous p53 or p21(Waf1/Cip1) upon C(2)-ceramide treatment of MRC-5. However, mutant p53(143ala) increased the sensitivity of MRC-5 to C(2)-ceramide-induced apoptosis by markedly downregulating Bcl-2, pointing to a role for p53. These results suggested that whereas downregulation of Bcl-2 may be a crucial factor involved in C(2)-ceramide-induced apoptosis, accumulation of Clu/ApoJ may be a signal of stress response. Moreover, the ceramide-activated apoptotic pathway may be regulated by p53.     

Cytochrome P450 1A1 (CYP1A1) gene polymorphisms and ovarian cancer risk: a meta-analysis

This meta-analysis aims to examine whether the genotype status of MspI, Ile462Val, and Thr461Asn polymorphisms in Cytochrome P450 1A1 (CYP1A1) is associated with ovarian cancer risk. Eligible case-control studies were identified through search in MEDLINE (end of search: October 2010). Pooled odds ratios (ORs) were appropriately derived from fixed effects or random effects models. Concerning MspI polymorphism, seven studies were eligible (1,051 cases and 1,613 controls); 11 studies were eligible (1,680 cases and 3,345 controls) for Ile462Val and three studies were eligible (349 cases and 785 controls) for Thr461Asn. Ile462Val polymorphism seemed to confer elevated ovarian cancer risk concerning homozygous carriers (pooled OR?=?2.65, 95?% CI: 1.40-5.03, p?=?0.003, fixed effects), as well as at the recessive model (pooled OR?=?2.10, 95?% CI: 1.13-3.92, p?=?0.020, fixed effects); these findings were replicated upon Caucasian subjects. MspI polymorphism was not associated with ovarian cancer risk (for heterozygous TC vs TT carriers pooled OR?=?1.10, 95?% CI: 0.91-1.34, p?=?0.329, fixed effects; for homozygous CC vs. TT carriers pooled OR?=?1.11, 95?% CI: 0.65-1.90, p?=?0.693, fixed effects). With respect to Thr461Asn polymorphism a finding of borderline statistical significance emerged, pointing to marginally elevated ovarian cancer risk in heterozygous Thr/Asn carriers (pooled OR?=?1.62, 95?% CI: 0.97-2.70, p?=?0.066, fixed effects), but not in homozygous Asn/Asn carriers (pooled OR?=?1.40, 95?% CI: 0.18-10.89, p?=?0.749, fixed effects). Ile462Val status seems to represent a meaningful risk factor for ovarian cancer in Caucasians. Additional case-control studies of high methodological quality are needed in order to further substantiate and enrich the present findings. Special attention should be paid upon the design of future studies; Asian and African populations should represent points of focus.     

Endogenous growth hormone and insulin after interposition of a reversed jejunal segment in short bowel syndrome. An experimental study on pigs

ABSTRACT: BACKGROUND: Interposition of a reversed jejunal loop in short bowel sydrome has previously been investigated in human along with animal models and seemed able to facilitate intestinal adaptation. However, it is unclear if growth hormone and insulin, well known for their implication in short bowel pathophysiology, intervene on this effect. FINDINGS: Porcine models were randomly allocated to two cohorts: (1) short bowel (SB) group (n = 8) and (2) short bowel reverse jejunal segment (SB-RS) group (n = 8). Amongst other parameters serum growth hormone and insulin were measured at baseline, as well as on postoperative day 30 and 60. CONCLUSION: Both endogenous hormones failed to demonstrate significant difference in respect to potential direct effect to mechanisms of enhanced intestinal adaptation in reversed group.     

Lactate threshold and performance adaptations to 4 weeks of training in untrained swimmers: volume vs. intensity

The purpose of this study was to investigate the impact of 4 weeks of high-intensity vs. high-volume swim training on lactate threshold (LT) characteristics and performance. Thirteen untrained swimmers with a mean age of 19.0 ± 0.5 undertook an incremental swimming test before and after 4 weeks of training for the determination of LT. Performance was evaluated by a 50-m maximum freestyle test. The swimmers were assigned to 1 of each of 2 training groups. The high-intensity group (n = 6) focused on sprint training (SP) and swam a total of 1,808 ± 210 m. The high-volume group (n = 7) followed the same program as the SP group but swam an additional 1,100 m (38% more) of endurance swimming (SP + End). A training effect was evident in both groups as seen by the similar improvements in sprint performance of the 50-m maximum time (p < 0.01), peak velocity increases and the lower value of lactate at the individual LTs (p < 0.01). Lactate threshold velocity improved only in the SP + End group from 1.20 ± 0.12 m·s(-1) pretraining to 1.32 ± 0.12 m·s(-1) posttraining (p = 0.77, effect size = 1, p < 0.01), expressed by the rightward shifts of the individual lactate-velocity curves, indicating an improvement in the aerobic capacity. Peak lactate and lactate concentrations at LT did not significantly change. In conclusion, this study was able to demonstrate that 4 weeks of either high-intensity or high-volume training was able to demonstrate similar improvements in swimming performance. In the case of lack of significant changes in lactate profiling in response to high-intensity training, we could suggest a dissociation between the 2.     

Differential expression of two small Hsps during diapause in the corn stalk borer Sesamia nonagrioides (Lef.)

We isolated and characterized two members of the α-crystallin/sHsp family, SnoHsp19.5 and SnoHsp20.8 from Sesamia nonagrioides (Lepidoptera: Noctuidae). The cDNAs encoded proteins of 174 and 185 amino acids, with calculated molecular weights of 19.5 and 20.8 kDa, respectively. The deduced amino acid sequences of SnoHsp19.5 and SnoHsp20.8 showed highest homology to Hsp19.7 of Mamestra brassicae and to Bombyx mori Hsp20.4, respectively. Expression patterns of SnoHsp19.5 and SnoHsp20.8 in non-diapausing individuals under different environmental conditions (heat or cold) showed different accumulation profiles for the two genes after heat and cold treatment. SnoHsp19.5 was consistently expressed, while SnoHsp20.8 gene was down-regulated in deep diapause and was up-regulated at the termination of diapause. Our results suggest that these two genes play distinctive roles in the regulation of diapause.     

N-alkyl-4-piperidinyl-2,3-diarylpyrrole derivatives with heterocyclic substitutions as potent and broad spectrum anticoccidial agents

Diaryl-(4-piperidinyl)-pyrrole derivatives bearing cyclic amine substituents have been synthesized and evaluated as anticoccidial agents. Improvements in potency of Et-PKG inhibition, such as azetidine derivative 3a, and broad spectrum anticoccidial activities in feed, such as morpholine derivative 8c, have been achieved.     

Estimating lagoonal biodiversity in Greece: comparison of rapid assessment techniques

An attempt is made to compare the results of different rapid biodiversity assessment techniques at the pan-Mediterranean, sectorial and local levels. A uniform multivariate pattern exists at the pan-Mediterranean and national (sectorial) levels: lagoons can be different when they host only a few species, but as species numbers increase, lagoons become homogenous in composition. Multivariate techniques cannot distinguish anthropogenically-impacted lagoons from those, which are naturally disturbed. In the pan-Mediterranean context it is the higher taxonomic levels, but in the national and local context it is the most abundant macrobenthic groups (polychaetes, molluscs and crustaceans) and meiobenthos which provide patterns closest to that derived from the species level. Taxonomic distinctness indices applied to polychaete and mollusc inventories provide meaningful results at most levels and scales of observation. These indices seem to be robust enough to discriminate anthropogenically impacted from naturally disturbed lagoons.     

Methionine sulfoxides on PrPSc: a prion-specific covalent signature

Prion diseases are fatal neurodegenerative disorders believed to be transmitted by PrP (Sc), an aberrant form of the membrane protein PrP (C). In the absence of an established form-specific covalent difference, the infectious properties of PrP (Sc) were uniquely ascribed to the self-perpetuation properties of its aberrant fold. Previous sequencing of the PrP chain isolated from PrP(27-30) showed the oxidation of some methionine residues; however, at that time, these findings were ascribed to experimental limitations. Using the unique recognition properties of alphaPrP mAb IPC2, protein chemistry, and state of the art mass spectrometry, we now show that while a large fraction of the methionine residues in brain PrP (Sc) are present as methionine sulfoxides this modification could not be found on brain PrP (C) as well as on its recombinant models. In particular, the pattern of oxidation of M213 with respect to the glycosylation at N181 of PrP (Sc) differs both within and between species, adding another diversity factor to the structure of PrP (Sc) molecules. Our results pave the way for the production of prion-specific reagents in the form of antibodies against oxidized PrP chains which can serve in the development of both diagnostic and therapeutic strategies. In addition, we hypothesize that the accumulation of PrP (Sc) and thereafter the pathogenesis of prion disease may result from the poor degradation of oxidized aberrantly folded PrP.