Infection, immunoregulation, and cancer

As man has moved rapidly from the hunter-gatherer environment to the living conditions of the industrialized countries, the incidences of some cancers have increased alarmingly. Recent increases are usually attributed to dietary changes or to altered exposures to putative carcinogens associated with the modern lifestyle. However, the changes in cancer incidence parallel similar increases in non-neoplastic chronic inflammatory disorders (inflammatory bowel disease, allergies, and autoimmunity), and the epidemiology is often strikingly similar. This parallel is worth exploring, because the increases in chronic inflammatory disorders are at least partly explained by immunoregulatory defects resulting from diminished exposure to microorganisms that co-evolved with mammals and developed a role in driving immunoregulatory circuits (the hygiene hypothesis). Dysregulated chronic inflammation can drive oncogenesis and also provides growth and angiogenic factors that enhance the subsequent proliferation and spread of tumor cells. Thus, a modern failure to downregulate inappropriate inflammation could underlie increases in some cancers in parallel with the increases in chronic inflammatory disorders. This possibility is supported by recent work showing that in some circumstances regulatory T cells protect against cancer, rather than aggravating it, as previously assumed. A greater understanding of these interactions might pave the way to improved microbe-based immunotherapies.     

Conserved and variable structural elements in the 5' untranslated region of two hypoviruses from the filamentous fungus Cryphonectria parasitica

Virulence-attenuating viruses (hypoviruses) of the filamentous fungus Cryphonectria parasitica, the causative agent of chestnut blight, have become a premier model for understanding the molecular biology of mycoviruses. However, a major gap exists in current understanding of structure and function of the untranslated regions (UTRs) of the hypovirus RNA genome, despite considerable evidence that secondary and tertiary UTR structure plays a crucial role in the control of translation and genome replication in other systems. In this study we have used structure prediction software coupled with RNase digestion studies to develop validated structural models for the 5′ UTRs of the two best-characterized members of the Hypoviridae, CHV1-EP713 and CHV1-Euro7. These two hypovirus strains exhibit significant variation in virulence attenuation despite sharing >90% sequence identity. Our models reveal highly structured regions in the 5′ UTR of both strains, with numerous stem-loops suggestive of internal ribosome entry sites. However, considerable differences in the size and complexity of structural elements exist between the two strains. These data will guide future, mutagenesis-based studies of the structural requirements for hypovirus genome replication and translation.     

Identification of a Series of Compounds with Potent Antiviral Activity for the Treatment of Enterovirus Infections

相似文献   

The Narrowing of Theoretical Orientations in Clinical Psychology Doctoral Training

The focus of this article is the increasingly narrow range of therapeutic orientations represented in clinical psychology graduate training programs, particularly within the most research‐oriented programs. Data on the self‐reported therapeutic orientations of faculty at “clinical science” Ph.D. programs, Ph.D. programs at comprehensive universities in clinical and in counseling psychology, Psy.D. programs at comprehensive universities, and Ph.D. or Psy.D. programs at freestanding specialized institutions reveal a strong predominance of faculty with cognitive‐behavioral orientations at the more science‐focused programs, and a narrower range of orientations than in the more practice‐focused programs. We discuss the implications of this trend for the future development of clinical psychology and provide suggestions for addressing the attendant concerns.     

Variation in human genes encoding adhesion and proinflammatory molecules are associated with severe malaria in the Vietnamese

The genetic basis for susceptibility to malaria has been studied widely in African populations but less is known of the contribution of specific genetic variants in Asian populations. We genotyped 67 single-nucleotide polymorphisms (SNPs) in 1030 severe malaria cases and 2840 controls from Vietnam. After data quality control, genotyping data of 956 cases and 2350 controls were analysed for 65 SNPs (3 gender confirmation, 62 positioned in/near 42 malarial candidate genes). A total of 14 SNPs were monomorphic and 2 (rs8078340 and rs33950507) were not in Hardy-Weinberg equilibrium in controls (P<0.01). In all, 7/46 SNPs in 6 genes (ICAM1, IL1A, IL17RC, IL13, LTA and TNF) were associated with severe malaria, with 3/7 SNPs in the TNF/LTA region. Genotype-phenotype correlations between SNPs and clinical parameters revealed that genotypes of rs708567 (IL17RC) correlate with parasitemia (P=0.028, r(2)=0.0086), with GG homozygotes having the lowest parasite burden. Additionally, rs708567 GG homozygotes had a decreased risk of severe malaria (P=0.007, OR=0.78 (95% CI; 0.65-0.93)) and death (P=0.028, OR=0.58 (95% CI; 0.37-0.93)) than those with AA and AG genotypes. In summary, variants in six genes encoding adhesion and proinflammatory molecules are associated with severe malaria in the Vietnamese. Further replicative studies in independent populations will be necessary to confirm these findings.     

The importance of influenza prevention for public health

Annual epidemics of seasonal (inter-pandemic) influenza represent a significant burden on society in terms of morbidity, mortality, hospitalizations and lost working time. The impact of influenza depends on a mix of direct and indirect effects and is not easy to assess. Nevertheless there is a consensus in considering influenza prevention and mitigation high priorities for public health. We review the available evidence to assess the impact of influenza prevention focusing especially on vaccines and immunization strategies.