Centromere regulation: new players, new rules, new questions

Centromeres support the assembly of the kinetochore on every chromosome and are therefore essential for the proper segregation of sister chromatids during cell division. Centromere identity is regulated epigenetically through the presence of the histone H3 variant CENP-A. CENP-A regulation and incorporation specifically into centromeric nucleosomes are the matter of intensive studies in many different model organisms. Here we briefly review the current knowledge in centromere biology with a focus on Drosophila melanogaster and how these insights lead to new rules and challenges.     

Holoprosencephaly: new models, new insights

Holoprosencephaly (HPE) is a common congenital malformation that is characterised by a failure to divide the forebrain into left and right hemispheres and is usually accompanied by defects in patterning of the midline of the face. HPE exists in inherited, autosomal dominant (familial) forms and mutation-associated sporadic forms, but environmental factors are also implicated. There are several features of HPE that are not well understood, including the extremely variable clinical presentation, even among obligate carriers of familial mutations, and the restriction of structural anomalies to the ventral anterior midline, despite association with defects in signal transduction pathways that regulate development of many additional body structures. The new animal models described in this review may help unravel these puzzles. Furthermore, these model systems suggest that human HPE arises from a complex interaction between the timing and strength of developmental signalling pathways, genetic variation and exposure to environmental agents.     

互惠共生微生物：新资源，新技术，新机遇，新挑战

2020年9月联合国环境规划署发布《全球生物多样性展望-5》(GBO-5)报告,助力世界实现协商一致的愿景——到2050年“与自然和谐相处”。其实,原本地球上的所有生物都是相互依存、互惠共生于地球村的,尽管存在少数“坏分子”。但由于人类的贪婪,过度扩张才导致地球“千疮百孔”的面貌,严重威胁到人类文明可持续发展。通过最近20年的研究,互惠共生微生物(mutualistic symbiotic microbes,MSM)从其丰富的群落多样性到种质新资源、从多种多样的生理生态功能到作用机制、从基础探究到新技术研发,为实现人与自然和谐相处的愿景提供了新机遇,同时也面临新挑战。令人可喜的是,中国在MSM研究领域取得了令世人瞩目的成果。《微生物学通报》于2020年11期特别推出了“互惠共生微生物专栏”,旨在展现中国MSM研究的最新进展和成果,促进生物共生学的发展壮大。     

Oral vaccines: new needs, new possibilities

Vaccination is an important tool for handling healthcare programs both in developed and developing countries. The current global scenario calls for a more-efficacious, acceptable, cost-effective and reliable method of immunization for many fatal diseases. It is hoped that the adoption of oral vaccines will help to provide an effective vaccination strategy, especially in developing countries. Mucosal immunity generated by oral vaccines can serve as a strong first line of defense against most of the pathogens infecting through the mucosal lining. Advances in elucidating the mechanism of action of oral vaccines will facilitate the design of more effective, new generation vaccines. There are promising developments in the use of different agents to effectively deliver the vaccine candidate. It is hoped that ongoing research may be able to set another cardinal point, after polio vaccine, in eradicating infectious diseases.     

Insulin substitution: new insulins, new modes of delivery

The demonstrated role of the tight control of hyperglycaemia for the prevention of long-term diabetic complications has reoriented the goals of insulin supply toward the search for restoration of the effects of physiological insulin secretion rather than the simple survival of insulin deficient patients and the reduction in the number of daily insulin injections to be performed. Normal blood glucose control requires the availability of a fast-acting insulin therapy at meal time in order to reduce hyperglycaemic excursions and a basal insulin therapy able to stabilize blood glucose between meals. Reduction of induced hypoglycaemic risk represents the secondary objective beside the main goal of avoiding hyperglycaemia. Fast-acting analogues, by a faster dissociation of their hexameric conformation after their injection or infusion in subcutaneous tissue, reduce post-meal hyperglycaemia, while their shortened duration of action versus regular insulin minimizes late post-absorptive risk of hypoglycaemia. Long-acting analogues, by their precipitation in subcutaneous tissue or their slowly reversible binding to albumin, provide a benefit on blood glucose stability versus NPH or zinc insulins. Continuous insulin therapy using pumps offers both a better blood glucose stability than multiple daily injections and a broader flexibility in life mode. Using the peritoneal route by implantable pumps is a mean to improve blood glucose stability in poorly controlled patients in spite of optimized subcutaneous insulin therapy. The development of glucose sensors provides reinforced information on blood glucose, versus self-monitoring by capillary blood measurements, that contributes to a better adaptation of insulin therapy. First trials of connections between blood glucose data and insulin delivery open a perspective toward glucose-modulated insulin therapy, at least in periods outside meals, leading to first models of semi-automated artificial endocrine pancreas. The alternative of a cellular insulin supply by pancreas or islet transplantation looked promising during recent years, but lack of transplants and adverse events related to immune suppression limit their use to very specific cases where benefit/risk ratio is positive.     

The Ordovician-Silurian boundary: new data, new concerns

Despite International Union of the Geological Sciences (IUGS) ratification of the International Commission on Stratigraphy recommendation that the base of the Parakidograptus acuminatus zone be the base of the Silurian and that the boundary stratotype be at Dob's Linn, Scotland, numerous concerns continue to be expressed over the timing of the selection as well as the boundary and its stratotype. The richness of both graptolite and non-graptolite biostratigraphic data in numerous stratigraphic sections from many areas in China published at about the same time that the boundary and stratotype were approved formally and shortly after approval suggest the possibility that boundary designation may have been somewhat premature. The new data from China document clearly the major extinction of characteristic Late Ordovician taxa significantly below the presently accepted System boundary. The new data indicate that the re-radiation of graptolites after the extinction took place in the Glyptograptus persculptus zone, the graptolite zone subjacent to the P. acuminatus zone. New geochemical data from Dob's Linn reveal a change in chemistry in strata subjacent to the base of the G. persculptus zone that could be used as an aid in correlation. The new data suggest the possibility that the base of the G. persculptus zone, the relatively traditional base of the Silurian, could be as appropriate a System boundary as the base of the P. acuminatus zone.     

PlasmoDB v5: new looks, new genomes

Version 5.1 of PlasmoDB, a resource for malaria parasite genomic and functional genomics datasets, was released in August 2006. This new release includes additional Plasmodium genomes and a newly designed website. The new site reflects the status of PlasmoDB as a member of a linked family of Apicomplexan databases.     

Malaria drug-sensitivity testing: new assays,new perspectives

Over the past five decades, the drug resistance of Plasmodium falciparum has become an issue of utmost concern. At the same time, in vitro assays for assessing antimalarial drug sensitivity have become indispensable tools for the surveillance of drug resistance and the planning of therapeutic guidelines. Several new in vitro assays have been introduced, designed to be easier to handle than previous tests and allow a faster identification of drug-resistant parasites, as well as for simple evaluation of new drugs. This review examines the various new approaches to the in vitro assessment of malaria drug sensitivity and their limitations.     

Type 2 diabetes: new genes, new understanding

Over the past two years, there has been a spectacular change in the capacity to identify common genetic variants that contribute to predisposition to complex multifactorial phenotypes such as type 2 diabetes (T2D). The principal advance has been the ability to undertake surveys of genome-wide association in large study samples. Through these and related efforts, approximately 20 common variants are now robustly implicated in T2D susceptibility. Current developments, for example in high-throughput resequencing, should help to provide a more comprehensive view of T2D susceptibility in the near future. Although additional investigation is needed to define the causal variants within these novel T2D-susceptibility regions, to understand disease mechanisms and to effect clinical translation, these findings are already highlighting the predominant contribution of defects in pancreatic beta-cell function to the development of T2D.     

Small-molecule natural products: new structures, new activities

A wide variety of novel small-molecule natural products has recently been reported. These compounds were isolated from marine and terrestrial sources, and from a variety of animals, plants and microorganisms. With the breadth of diversity represented in these bioactive small molecules, the future of natural product drug discovery looks bright.