蛇场病死蛇与感染腐败谢瓦纳拉菌的探讨

目的探讨蛇场蛇死亡与细菌感染的关系。方法从８５条死蛇中随机抽样２０条,取其心脏积血进行微生物检验。结果从其中的１４条死蛇中分离出腐败谢瓦纳拉菌,分离阳性率为７０％。结论认为该菌可能是蛇病死的原因之一。     

330例2型糖尿病患者死因分析

目的:通过对80年代、90年代及近6年(2000-2006)我院2型糖尿病患者死因的比较,探讨分析糖尿病患者的死亡原因及其变迁,为提高糖尿病防治水平,减少糖尿病死亡率提供科学依据。方法:采用回顾性调查方法对我院1983-2006年住院2型糖尿病患者死因进行分析,并分三阶段进行比较。共调查2型糖尿病死亡病例330例。结果:不同年代心脑血管疾病均是导致2型糖尿病患者死亡的主要原因,位居死因第一,占总死亡人数的38.2%。肿瘤作为2型糖尿病患者的死因所占比例明显增加,占总死亡人数的19.4%。以感染为直接死因逐渐下降,但仍为重要死因,占14.2%。而糖尿病酮症酸中毒、高渗昏迷和低血糖昏迷等急性并发症所占比例显著减少,占8.8%。结论:糖尿病慢性并发症尤其是心脑血管病变是2型糖尿病的主要死因,近年来肿瘤已经成为2型糖尿病患者的重要死因,以感染为直接死因逐渐下降,但仍为重要死因,而糖尿病酮症酸中毒、高渗昏迷和低血糖昏迷等急性并发症所占比例显著减少。     

Serotypes of Escherichia coli in Sudden Infant Death Syndrome

Aim: To examine the diversity of Escherichia coli serotypes found in the intestinal contents of infants who died of Sudden Infant Death Syndrome (SIDS) compared with that in comparison infants. Methods and Results: Over the 3‐year period, 1989–1991, in South Australia and Victoria (Australia), a total of 687 E. coli isolates from 231 patients with SIDS (348 isolates), 98 infants who had died from other causes (144 isolates) and 160 healthy infants (195 isolates) were studied. The isolates from patients with SIDS were found to represent 119 different serotypes; the isolates from ‘other cause’ infants represent 97 different serotypes; and the isolates from healthy infants represent 117 different serotypes. The seven common serotypes isolated most frequently from infants with SIDS belonged to those associated with extra‐intestinal infections in humans. Compared to healthy infants (6%), these were found in significantly higher proportions among infants who died of other causes (13%, P < 0·05) or infants with SIDS (18·7%, P = 0·0002). Conclusions: Despite these sources yielding a wide variety of serotypes of E. coli, a pattern of certain potential pathotypes of E. coli being associated with SIDS is apparent. Significance and Impact of the Study: While SIDS remains one of the most important diagnoses of postneonatal death, its causes are still unexplained. If E. coli has a role in the pathogenesis of SIDS (as suggested by the pathotypes identified on the basis of serotype), further studies may reveal novel virulence factors that may clarify the role of this bacterium in SIDS.     

Celastrol, a Triterpene, Enhances TRAIL-induced Apoptosis through the Down-regulation of Cell Survival Proteins and Up-regulation of Death Receptors

Whether celastrol, a triterpene from traditional Chinese medicine, can modulate the anticancer effects of TRAIL, the cytokine that is currently in clinical trial, was investigated. As indicated by assays that measure plasma membrane integrity, phosphatidylserine exposure, mitochondrial activity, and activation of caspase-8, caspase-9, and caspase-3, celastrol potentiated the TRAIL-induced apoptosis in human breast cancer cells, and converted TRAIL-resistant cells to TRAIL-sensitive cells. When examined for its mechanism, we found that the triterpene down-regulated the expression of cell survival proteins including cFLIP, IAP-1, Bcl-2, Bcl-xL, survivin, and XIAP and up-regulated Bax expression. In addition, we found that celastrol induced the cell surface expression of both the TRAIL receptors DR4 and DR5. This increase in receptors was noted in a wide variety of cancer cells including breast, lung, colorectal, prostate, esophageal, and pancreatic cancer cells, and myeloid and leukemia cells. Gene silencing of the death receptor abolished the effect of celastrol on TRAIL-induced apoptosis. Induction of the death receptor by the triterpenoid was found to be p53-independent but required the induction of CAAT/enhancer-binding protein homologous protein (CHOP), inasmuch as gene silencing of CHOP abolished the induction of DR5 expression by celastrol and associated enhancement of TRAIL-induced apoptosis. We found that celastrol also induced reactive oxygen species (ROS) generation, and ROS sequestration inhibited celastrol-induced expression of CHOP and DR5, and consequent sensitization to TRAIL. Overall, our results demonstrate that celastrol can potentiate the apoptotic effects of TRAIL through down-regulation of cell survival proteins and up-regulation of death receptors via the ROS-mediated up-regulation of CHOP pathway.     

Betanodavirus B2 Causes ATP Depletion-induced Cell Death via Mitochondrial Targeting and Complex II Inhibition in Vitro and in Vivo

The betanodavirus non-structural protein B2 is a newly discovered necrotic death factor with a still unknown role in regulation of mitochondrial function. In the present study, we examined protein B2-mediated inhibition of mitochondrial complex II activity, which results in ATP depletion and thereby in a bioenergetic crisis in vitro and in vivo. Expression of protein B2 was detected early at 24 h postinfection with red-spotted grouper nervous necrosis virus in the cytoplasm. Later B2 was found in mitochondria using enhanced yellow fluorescent protein (EYFP) and immuno-EM analysis. Furthermore, the B2 mitochondrial targeting signal peptide was analyzed by serial deletion and specific point mutation. The sequence of the B2 targeting signal peptide (⁴¹RTFVISAHAA⁵⁰) was identified and its presence correlated with loss of mitochondrial membrane potential in fish cells. Protein B2 also was found to dramatically inhibit complex II (succinate dehydrogenase) activity, which impairs ATP synthesis in fish GF-1 cells as well as human embryonic kidney 293T cells. Furthermore, when B2 was injected into zebrafish embryos at the one-cell stage to determine its cytotoxicity and ability to inhibit ATP synthesis, we found that B2 caused massive embryonic cell death and depleted ATP resulting in further embryonic death at 10 and 24 h post-fertilization. Taken together, our results indicate that betanodavirus protein B2-induced cell death is due to direct targeting of the mitochondrial matrix by a specific signal peptide that targets mitochondria and inhibits mitochondrial complex II activity thereby reducing ATP synthesis.     

A Novel Intracellular Peptide Derived from G1/S Cyclin D2 Induces Cell Death

Intracellular peptides are constantly produced by the ubiquitin-proteasome system, and many are probably functional. Here, the peptide WELVVLGKL (pep5) from G₁/S-specific cyclin D2 showed a 2-fold increase during the S phase of HeLa cell cycle. pep5 (25–100 μm) induced cell death in several tumor cells only when it was fused to a cell-penetrating peptide (pep5-cpp), suggesting its intracellular function. In vivo, pep5-cpp reduced the volume of the rat C6 glioblastoma by almost 50%. The tryptophan at the N terminus of pep5 is essential for its cell death activity, and N terminus acetylation reduced the potency of pep5-cpp. WELVVL is the minimal active sequence of pep5, whereas Leu-Ala substitutions totally abolished pep5 cell death activity. Findings from the initial characterization of the cell death/signaling mechanism of pep5 include caspase 3/7 and 9 activation, inhibition of Akt2 phosphorylation, activation of p38α and -γ, and inhibition of proteasome activity. Further pharmacological analyses suggest that pep5 can trigger cell death by distinctive pathways, which can be blocked by IM-54 or a combination of necrostatin-1 and q-VD-OPh. These data further support the biological and pharmacological potential of intracellular peptides.     

Distinct Regulation of Cytoplasmic Calcium Signals and Cell Death Pathways by Different Plasma Membrane Calcium ATPase Isoforms in MDA-MB-231 Breast Cancer Cells

Plasma membrane calcium ATPases (PMCAs) actively extrude Ca(2+) from the cell and are essential components in maintaining intracellular Ca(2+) homeostasis. There are four PMCA isoforms (PMCA1-4), and alternative splicing of the PMCA genes creates a suite of calcium efflux pumps. The role of these different PMCA isoforms in the control of calcium-regulated cell death pathways and the significance of the expression of multiple isoforms of PMCA in the same cell type are not well understood. In these studies, we assessed the impact of PMCA1 and PMCA4 silencing on cytoplasmic free Ca(2+) signals and cell viability in MDA-MB-231 breast cancer cells. The PMCA1 isoform was the predominant regulator of global Ca(2+) signals in MDA-MB-231 cells. PMCA4 played only a minor role in the regulation of bulk cytosolic Ca(2+), which was more evident at higher Ca(2+) loads. Although PMCA1 or PMCA4 knockdown alone had no effect on MDA-MB-231 cell viability, silencing of these isoforms had distinct consequences on caspase-independent (ionomycin) and -dependent (ABT-263) cell death. PMCA1 knockdown augmented necrosis mediated by the Ca(2+) ionophore ionomycin, whereas apoptosis mediated by the Bcl-2 inhibitor ABT-263 was enhanced by PMCA4 silencing. PMCA4 silencing was also associated with an inhibition of NFκB nuclear translocation, and an NFκB inhibitor phenocopied the effects of PMCA4 silencing in promoting ABT-263-induced cell death. This study demonstrates distinct roles for PMCA1 and PMCA4 in the regulation of calcium signaling and cell death pathways despite the widespread distribution of these two isoforms. The targeting of some PMCA isoforms may enhance the effectiveness of therapies that act through the promotion of cell death pathways in cancer cells.     

中华绒螯蟹（Eriocheir sinensis）肌肉中粗脂肪含量与死亡,产 …

本文报道了中华螯蟹越冬时,越冬后不同性别、不同生活状况肌肉中粗脂肪含量及变化。越冬时、越冬后死亡的♂♀河蟹肌肉中粗脂肪的含量均不到８％,而同时越冬成活的♂♀蟹肌肉中粗脂肪含量均高于１０％。顺利越冬并能产卵的雌蟹肌肉中粗脂肪含量为４．９６％,顺利越冬并交配的♂性肌肉中粗脂肪含量为４．１８％。产卵并抱卵孵化的♀蟹肌肉中粗脂肪含量为５．８５％,产卵但♀蟹中途死亡的其肌肉中粗脂肪的含量为５．４７％。交配不     

Death and NF-kappaB in T cell activation: life at the edge

Nuclear Factor kappa-B appears to be required to prevent p73-induced apoptosis triggered by primary T cell activation. Here we explore what this state of affairs might do for the regulation of the immune system.     

Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) Signaling and Cell Death in the Immature Central Nervous System after Hypoxia-Ischemia and Inflammation

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family. The interaction of TRAIL with death receptor 4 (DR4) and DR5 can trigger apoptotic cell death. The aim of this study was to investigate the role of TRAIL signaling in neonatal hypoxia-ischemia (HI). Using a neonatal mouse model of HI, mRNA, and protein expression of TRAIL, DR5 and the TRAIL decoy receptors osteoprotegerin (OPG), mDcTRAILR1, and mDcTRAILR2 were determined. In vitro, mRNA expression of these genes was measured in primary neurons and oligodendrocyte progenitor cells (OPCs) after inflammatory cytokine (TNF-α/IFN-γ) treatment and/or oxygen and glucose deprivation (OGD). The toxicity of these various paradigms was also measured. The expression of TRAIL, DR5, OPG, and mDcTRAILR2 was significantly increased after HI. In vitro, inflammatory cytokines and OGD treatment significantly induced mRNAs for TRAIL, DR5, OPG, and mDcTRAILR2 in primary neurons and of TRAIL and OPG in OPCs. TRAIL protein was expressed primarily in microglia and astroglia, whereas DR5 co-localized with neurons and OPCs in vivo. OGD enhanced TNF-α/IFN-γ toxicity in both neuronal and OPC cultures. Recombinant TRAIL exerted toxicity alone or in combination with OGD and TNF-α/IFN-γ in primary neurons but not in OPC cultures. The marked increases in the expression of TRAIL and its receptors after cytokine exposure and OGD in primary neurons and OPCs were similar to those found in our animal model of neonatal HI. The toxicity of TRAIL in primary neurons suggests that TRAIL signaling participates in neonatal brain injury after inflammation and HI.     

Reconstruction of the Sudden Oak Death epidemic in California through microsatellite analysis of the pathogen Phytophthora ramorum

The genetic structure of the clonally reproducing Sudden Oak Death (SOD) pathogen in California was investigated using seven variable microsatellites. A total of 35 multilocus genotypes were identified among 292 samples representative of populations from 14 forest sites and of the nursery trade. amova indicated significant genetic variability both within (44.34%) and among populations (55.66%). Spatial autocorrelation analyses indicated that Moran's index of similarity reached a minimum of 0.1 at 350 m, increased to 0.4 at 1500 m and then decreased to zero at 10 km. These results suggest a bimodal pattern of spread, with medium range dispersal (1500–10 000 m) putatively attributed to the presence of strong winds. Lack of genetic structure was identified for three groups of populations. One group notably included the nurseries' population and two forest populations, both linked to early reports of the pathogen. A neighbour-joining analysis based on pairwise Φ_ST values indicated that the clade inclusive of the nurseries' populations is basal to all California populations. A network analysis identified three common genotypes as the likely founders of the California infestation and proposes a stepwise model for local evolution of novel genotypes. This was supported by the identification in the same locations of novel genotypes and of their 1- or 2-step parents. We hypothesize that the few undifferentiated population groups indicate historical human spread of the pathogen, while the general presence of genetically structured populations indicates that new infestations are currently generated by rare medium or long-range natural movement of the pathogen, followed by local generation of new genotypes.     

Social inequality and obesity in Czech school children

This study uses logistic regressions to consider the effect of social factors, physical activity, meal frequency and BMI of parents on children's body mass index (BMI) values. Three thousand three hundred and sixty-two children aged 7-11 years were examined in 38 schools in the Czech Republic. Six anthropometric characteristics were assessed in 1999-2000. Most important factors influencing children's BMI values were: obesity of both or at least one of the parents, being an only child, residence in small communities, and irregular breakfasts.     

Death receptors: Targets for cancer therapy

Apoptosis is the cell's intrinsic program to death, which plays an important role in physiologic growth control and homeostasis. Apoptosis can be triggered by death receptors (DRs), without any adverse effects. DRs are the members of tumor necrosis factor (TNF) receptor superfamily, known to be involved in apoptosis signaling, independent of p53 tumor-supressor gene. Selective triggering of DR-mediated apoptosis in cancer cells is a novel approach in cancer therapy. So far, the best characterized DRs are CD95 (Fas/Apo1), TNF-related apoptosis-inducing ligand receptor (TRAILR) and tumor necrosis factor receptor (TNFR). Among these, TRAILR is emerging as most promising agent for cancer therapy, because it induces apoptosis in a variety of tumor and transformed cells without any toxicity to normal cells. TRAIL treatment in combination with chemotherapy or radiotherapy enhances TRAIL sensitivity or reverses TRAIL resistance by regulating downstream effectors. This review covers the current knowledge about the DRs, summarizes main signaling in DRs and also summarizes the preclinical approaches of these DRs in cancer therapy.     

Death rates from stroke in England and Wales predicted from past maternal mortality.

Geographical differences in maternal mortality in England and Wales during 1911-4 correlate closely with death rates from stroke in the generation born around that time. The geographical distribution of stroke is more closely related to past maternal mortality than to any leading cause of death, past or present, except ischaemic heart disease, for which correlation coefficients with stroke are similar. This relation is new evidence that poor health and physique of mothers are important determinants of the risk of stroke among their offspring.     

Artesunate Induces Cell Death in Human Cancer Cells via Enhancing Lysosomal Function and Lysosomal Degradation of Ferritin

Artesunate (ART) is an anti-malaria drug that has been shown to exhibit anti-tumor activity, and functional lysosomes are reported to be required for ART-induced cancer cell death, whereas the underlying molecular mechanisms remain largely elusive. In this study, we aimed to elucidate the molecular mechanisms underlying ART-induced cell death. We first confirmed that ART induces apoptotic cell death in cancer cells. Interestingly, we found that ART preferably accumulates in the lysosomes and is able to activate lysosomal function via promotion of lysosomal V-ATPase assembly. Furthermore, we found that lysosomes function upstream of mitochondria in reactive oxygen species production. Importantly, we provided evidence showing that lysosomal iron is required for the lysosomal activation and mitochondrial reactive oxygen species production induced by ART. Finally, we showed that ART-induced cell death is mediated by the release of iron in the lysosomes, which results from the lysosomal degradation of ferritin, an iron storage protein. Meanwhile, overexpression of ferritin heavy chain significantly protected cells from ART-induced cell death. In addition, knockdown of nuclear receptor coactivator 4, the adaptor protein for ferritin degradation, was able to block ART-mediated ferritin degradation and rescue the ART-induced cell death. In summary, our study demonstrates that ART treatment activates lysosomal function and then promotes ferritin degradation, subsequently leading to the increase of lysosomal iron that is utilized by ART for its cytotoxic effect on cancer cells. Thus, our data reveal a new mechanistic action underlying ART-induced cell death in cancer cells.     

Effect of elevated temperature on osmotic and ionic regulation in a salt-tolerant caddisfly from Death Valley,California

The effects of temperature (8–10 or 20°C) on regulation of haemolymph osmotic and ionic concentrations were investigated over a range of salinities (0–25‰) in fifth-instar larvae of the Death Valley caddisfly Limnephilus assimilis. At low temperatures, levels of chloride and sodium in the haemolymph are regulated over a wide range of salinities corresponding to the salinities at which larvae occur in nature and at which they can complete development into adults. In contrast, haemolymph osmolality is constant at low salinities (<14‰) but approaches conformity with the medium at higher salinities. High temperature reduces the larva's ability to maintain low chloride concentrations in its haemolymph and also leads to a reduction in haemolymph osmotic pressure; thus, at high temperatures ions account for more of the haemolymph osmotic concentration than at low temperatures. These data suggest that the absence of larvae from thermal pools and from all Death Valley waters in summer can be explained by the effects of high water temperatures on hydromineral regulation.     

A Novel Initiation Mechanism of Death in Streptococcus pneumoniae Induced by the Human Milk Protein-Lipid Complex HAMLET and Activated during Physiological Death

To cause colonization or infection, most bacteria grow in biofilms where differentiation and death of subpopulations is critical for optimal survival of the whole population. However, little is known about initiation of bacterial death under physiological conditions. Membrane depolarization has been suggested, but never shown to be involved, due to the difficulty of performing such studies in bacteria and the paucity of information that exists regarding ion transport mechanisms in prokaryotes. In this study, we performed the first extensive investigation of ion transport and membrane depolarization in a bacterial system. We found that HAMLET, a human milk protein-lipid complex, kills Streptococcus pneumoniae (the pneumococcus) in a manner that shares features with activation of physiological death from starvation. Addition of HAMLET to pneumococci dissipated membrane polarity, but depolarization per se was not enough to trigger death. Rather, both HAMLET- and starvation-induced death of pneumococci specifically required a sodium-dependent calcium influx, as shown using calcium and sodium transport inhibitors. This mechanism was verified under low sodium conditions, and in the presence of ionomycin or monensin, which enhanced pneumococcal sensitivity to HAMLET- and starvation-induced death. Pneumococcal death was also inhibited by kinase inhibitors, and indicated the involvement of Ser/Thr kinases in these processes. The importance of this activation mechanism was made evident, as dysregulation and manipulation of physiological death was detrimental to biofilm formation, a hallmark of bacterial colonization. Overall, our findings provide novel information on the role of ion transport during bacterial death, with the potential to uncover future antimicrobial targets.