Molecular insight into invasive group A streptococcal disease

Streptococcus pyogenes is also known as group A Streptococcus (GAS) and is an important human pathogen that causes considerable morbidity and mortality worldwide. The GAS serotype M1T1 clone is the most frequently isolated serotype from life-threatening invasive (at a sterile site) infections, such as streptococcal toxic shock-like syndrome and necrotizing fasciitis. Here, we describe the virulence factors and newly discovered molecular events that mediate the in vivo changes from non-invasive GAS serotype M1T1 to the invasive phenotype, and review the invasive-disease trigger for non-M1 GAS. Understanding the molecular basis and mechanism of initiation for streptococcal invasive disease may expedite the discovery of novel therapeutic targets for the treatment and control of severe invasive GAS diseases.     

The classification of streptococci and human streptococcal diseases

The modern nomenclature, phenotypic, medical, ecological and phylogenetic classification of streptococci and different classification of streptococcal human diseases are presented. All phylogenetic groups of streptococci have been shown to contain species causing diseases in man. The most medically significant groups are the phylogenetic groups Pyogenes and Mitis. Directions of the improvement of the classification of streptococci and streptococcal human diseases on the basis of modern concepts on the taxonomy of streptococci, the biological properties and ecology of the infective agents, as well as the genesis and clinical picture of diseases induced by them, have been determined.     

The mysteries of the diatoms

Understanding the physiology of these unique and spectacularly successful algal species could lead to substantial benefits in a wide range of areas from nanotechnology to climate change. Michael Gross reports.     

Bioeconomic management of invasive vector-borne diseases

Invasive insects, arthropods, and other invertebrates are of concern due to the role some play in introducing and transmitting pathogens via a pathogen–vector relationship. Indeed, vector-borne diseases represent a significant portion of emerging diseases. We compare and contrast three strategic approaches to managing a vector-borne pathogen: conventional strategies based on disease ecology without regard to economic tradeoffs and cost-effective strategies based on a bioeconomic framework. Conventional strategies entail managing the vector population below a threshold value based on R ₀—the basic reproductive ratio of the pathogen, which measures a pathogen’s ability to invade uninfected systems. This does not account for post-infection dynamics, nor does it balance ecological and economic tradeoffs. Thresholds take on a more profound role under a bioeconomic paradigm: rather than unilaterally determining vector control choices, thresholds inform control choices and are influenced by them. Simulation results show cost-effective strategies can lower overall program costs and may be less sensitive to parameter estimation.     

Addressing the mysteries of perforin function

Perforin is a cytolytic protein stored in secretory granules of CTL and NK cells. It synergizes with proapoptotic serine proteases, granzymes, to deliver the lethal hit to virus-infected or transformed target cells. The mechanism of perforin action has not been described beyond its original characterization in the 1980s, and its role in human disease has remained elusive. This article addresses recent key advances in genetic, clinical and biochemical studies that have reignited the current interest in perforin biology.     

Unraveling the mysteries of dog evolution

The increased battery of molecular markers, derived from comparative genomics, is aiding our understanding of the genetics of domestication. The recent BMC Biology article pertaining to the evolution of small size in dogs is an example of how such methods can be used to study the origin and diversification of the domestic dog. We are still challenged, however, to appreciate the genetic mechanisms responsible for the phenotypic diversity seen in 'our best friend'.     

Inter-species genetic movement may blur the epidemiology of streptococcal diseases in endemic regions

Streptococcus dysgalactiae subsp. equisimilis (human group G streptococcus, GGS) is generally regarded as a commensal organism but can cause a spectrum of human diseases very similar to that caused by S. pyogenes (group A streptococcus, GAS). Lateral acquisition of genes between these two phylogenetically closely related species is well documented. However, the extent and mechanisms of lateral acquisitions is not known. We report here genomic subtraction between a pathogenic GGS isolate and a community GGS isolate and analyses of the gene sequences unique to the pathovar. Our results show that cross-species genetic transfers are common between GGS and two closely related human pathogens, GAS and the group B streptococcus. We also demonstrate that mobile genetic elements, such as phages and transposons, play an important role in the ongoing inter-species transfers of genetic traits between extant organisms in the community. Furthermore, lateral gene transfers between GAS and GGS may occur more frequently in geographical regions of high GAS endemicity. These observations may have important implications in understanding the epidemiology of streptococcal diseases in such regions.     

Lingering mysteries of ubiquitin-chain assembly

The small protein ubiquitin is often linked to substrates as a polymer. Such polymers vary in both linkage and length, which has important consequences for their function. Surprisingly, the mechanisms of ubiquitin-chain assembly are still not known. Deciphering them will shed light on why substrates differ in the extent and timing of polyubiquitin modification and how ancillary ubiquitination factors function.     

诚恳做人 实在做事 为衰老之谜解扣

童坦君教授是我国老年医学基础专家,中国科学院院士。他致力于衰老机制的研究,在国内率先建立衰老分子机理研究室,将应用于肿瘤研究方面的分子生物学与细胞生物学技术引入衰老机制研究,取得享有国际声誉的创新性研究成果。童教授对科教事业的真知灼见和执著追求,以及他为人谦和的品质,令人钦敬。     

Unraveling the mysteries of protein folding and misfolding

This mini-review focuses on the processes and consequences of protein folding and misfolding. The latter process often leads to protein aggregation and precipitation with the aggregates adopting either highly ordered (amyloid fibril) or disordered (amorphous) forms. In particular, the amyloid fibril is discussed because this form has gained considerable notoriety due to its close links to a variety of debilitating diseases including Alzheimer's, Parkinson's, Huntington's, and Creutzfeldt-Jakob diseases, and type-II diabetes. In each of these diseases a different protein forms fibrils, yet the fibrils formed have a very similar structure. The mechanism by which fibrils form, fibril structure, and the cytotoxicity associated with fibril formation are discussed. The generic nature of amyloid fibril structure suggests that a common target may be accessible to treat amyloid fibril-associated diseases. As such, the ability of some molecules, for example, the small heat-shock family of molecular chaperone proteins, to inhibit fibril formation is of interest due to their therapeutic potential.     

Uncovering the Nutritional Landscape of Food

Recent progresses in data-driven analysis methods, including network-based approaches, are revolutionizing many classical disciplines. These techniques can also be applied to food and nutrition, which must be studied to design healthy diets. Using nutritional information from over 1,000 raw foods, we systematically evaluated the nutrient composition of each food in regards to satisfying daily nutritional requirements. The nutrient balance of a food was quantified and termed nutritional fitness; this measure was based on the food’s frequency of occurrence in nutritionally adequate food combinations. Nutritional fitness offers a way to prioritize recommendable foods within a global network of foods, in which foods are connected based on the similarities of their nutrient compositions. We identified a number of key nutrients, such as choline and α-linolenic acid, whose levels in foods can critically affect the nutritional fitness of the foods. Analogously, pairs of nutrients can have the same effect. In fact, two nutrients can synergistically affect the nutritional fitness, although the individual nutrients alone may not have an impact. This result, involving the tendency among nutrients to exhibit correlations in their abundances across foods, implies a hidden layer of complexity when exploring for foods whose balance of nutrients within pairs holistically helps meet nutritional requirements. Interestingly, foods with high nutritional fitness successfully maintain this nutrient balance. This effect expands our scope to a diverse repertoire of nutrient-nutrient correlations, which are integrated under a common network framework that yields unexpected yet coherent associations between nutrients. Our nutrient-profiling approach combined with a network-based analysis provides a more unbiased, global view of the relationships between foods and nutrients, and can be extended towards nutritional policies, food marketing, and personalized nutrition.