Evolution of an obligate social cheater to a superior cooperator

Obligate relationships have evolved many times and can be parasitic or mutualistic. Obligate organisms rely on others to survive and thus coevolve with their host or partner. An important but little explored question is whether obligate status is an evolutionarily terminal condition or whether obligate lineages can evolve back to an autonomous lifestyle. The bacterium Myxococcus xanthus survives starvation by the social development of spore-bearing fruiting bodies. Some M. xanthus genotypes defective at fruiting body development in isolation can nonetheless exploit proficient genotypes in chimaeric groups. Here we report an evolutionary transition from obligate dependence on an altruistic host to an autonomous mode of social cooperation. This restoration of social independence was caused by a single mutation of large effect that confers fitness superiority over both ancestral genotypes, including immunity from exploitation by the ancestral cheater. Thus, a temporary state of obligate cheating served as an evolutionary stepping-stone to a novel state of autonomous social dominance.     

Pathogen-induced human TH17 cells produce IFN-γ or IL-10 and are regulated by IL-1β

IL-17-producing CD4+ T helper cells (TH17) have been extensively investigated in mouse models of autoimmunity. However, the requirements for differentiation and the properties of pathogen-induced human TH17 cells remain poorly defined. Using an approach that combines the in vitro priming of naive T cells with the ex vivo analysis of memory T cells, we describe here two types of human TH17 cells with distinct effector function and differentiation requirements. Candida albicans-specific TH17 cells produced IL-17 and IFN-γ, but no IL-10, whereas Staphylococcus aureus-specific TH17 cells produced IL-17 and could produce IL-10 upon restimulation. IL-6, IL-23 and IL-1β contributed to TH17 differentiation induced by both pathogens, but IL-1β was essential in C. albicans-induced TH17 differentiation to counteract the inhibitory activity of IL-12 and to prime IL-17/IFN-γ double-producing cells. In addition, IL-1β inhibited IL-10 production in differentiating and in memory TH17 cells, whereas blockade of IL-1β in vivo led to increased IL-10 production by memory TH17 cells. We also show that, after restimulation, TH17 cells transiently downregulated IL-17 production through a mechanism that involved IL-2-induced activation of STAT5 and decreased expression of ROR-γt. Taken together these findings demonstrate that by eliciting different cytokines C. albicans and S. aureus prime TH17 cells that produce either IFN-γ or IL-10, and identify IL-1β and IL-2 as pro- and anti-inflammatory regulators of TH17 cells both at priming and in the effector phase.     

A resolved outflow of matter from a brown dwarf

The birth of stars involves not only accretion but also, counter-intuitively, the expulsion of matter in the form of highly supersonic outflows. Although this phenomenon has been seen in young stars, a fundamental question is whether it also occurs among newborn brown dwarfs: these are the so-called 'failed stars', with masses between stars and planets, that never manage to reach temperatures high enough for normal hydrogen fusion to occur. Recently, evidence for accretion in young brown dwarfs has mounted, and their spectra show lines that are suggestive of outflows. Here we report spectro-astrometric data that spatially resolve an outflow from a brown dwarf. The outflow's characteristics appear similar to, but on a smaller scale than, outflows from normal young stars. This result suggests that the outflow mechanism is universal, and perhaps relevant even to the formation of planets.     

ATM controls meiotic double-strand-break formation

In many organisms, developmentally programmed double-strand breaks (DSBs) formed by the SPO11 transesterase initiate meiotic recombination, which promotes pairing and segregation of homologous chromosomes. Because every chromosome must receive a minimum number of DSBs, attention has focused on factors that support DSB formation. However, improperly repaired DSBs can cause meiotic arrest or mutation; thus, having too many DSBs is probably as deleterious as having too few. Only a small fraction of SPO11 protein ever makes a DSB in yeast or mouse and SPO11 and its accessory factors remain abundant long after most DSB formation ceases, implying the existence of mechanisms that restrain SPO11 activity to limit DSB numbers. Here we report that the number of meiotic DSBs in mouse is controlled by ATM, a kinase activated by DNA damage to trigger checkpoint signalling and promote DSB repair. Levels of SPO11-oligonucleotide complexes, by-products of meiotic DSB formation, are elevated at least tenfold in spermatocytes lacking ATM. Moreover, Atm mutation renders SPO11-oligonucleotide levels sensitive to genetic manipulations that modulate SPO11 protein levels. We propose that ATM restrains SPO11 via a negative feedback loop in which kinase activation by DSBs suppresses further DSB formation. Our findings explain previously puzzling phenotypes of Atm-null mice and provide a molecular basis for the gonadal dysgenesis observed in ataxia telangiectasia, the human syndrome caused by ATM deficiency.     

Functions of FGF signalling from the apical ectodermal ridge in limb development

To determine the role of fibroblast growth factor (FGF) signalling from the apical ectodermal ridge (AER), we inactivated Fgf4 and Fgf8 in AER cells or their precursors at different stages of mouse limb development. We show that FGF4 and FGF8 regulate cell number in the nascent limb bud and are required for survival of cells located far from the AER. On the basis of the skeletal phenotypes observed, we conclude that these functions are essential to ensure that sufficient progenitor cells are available to form the normal complement of skeletal elements, and perhaps other limb tissues. In the complete absence of both FGF4 and FGF8 activities, limb development fails. We present a model to explain how the mutant phenotypes arise from FGF-mediated effects on limb bud size and cell survival.     

夏季黄连木排放萜烯类化合物浓度日变化及排放速率的研究

采用流动式采样与气相色谱 质谱联用法研究了意大利撒丁岛Noak’sArk自然生态区主要灌木黄连木 (Pistacialentiscus)萜烯类化合物排放特征、排放速率及其日变化。排放物种包括α 蒎烯、β 蒎烯、桧烯、苎烯、戊花烃、莰烯、β 水芹烯、β 香叶烯、α 松油烯、α 水芹烯和 3 蒈烯 ,以及少量异戊二烯。萜烯类化合物占总排放的 99 4%,异戊二烯仅占 0 6%。在萜烯类化合物中 ,主要排放物为α 蒎烯、β 蒎烯、桧烯和苎烯 ,分别占总排放的 64 5 %、18 4%、6 0 %和 5 9%。萜烯排放速率随温度的升高而增加 ,呈指数相关。在标准条件下 ( 30 3K) ,黄连木树种的排放速率为 2 72±0 72 μg g·h。黄连木排放速率公式中 β值为 0 12 8K-1,与文献值 0 0 5 7～ 0 144K-1相一致。     

Haemoglobin F intalassemia minor. amino-acid composition

Riassunto Dal sangue di un soggetto affetto daTalassemiaMinor si sono ottenuti cristalli tipici di Hb F.L'analisi della composizione in aminoacidi di tali cristalli porta a concludere che la frazione di Hb alcaliresistente presente in questa malattia e l'Hb F sono identiche.     

The multifaceted role of glial cells in amyotrophic lateral sclerosis

Despite indisputable progress in the molecular and genetic aspects of amyotrophic lateral sclerosis (ALS), a mechanistic comprehension of the neurodegenerative processes typical of this disorder is still missing and no effective cures to halt the progression of this pathology have yet been developed. Therefore, it seems that a substantial improvement of the outcome of ALS treatments may depend on a better understanding of the molecular mechanisms underlying neuronal pathology and survival as well as on the establishment of novel etiological therapeutic strategies. Noteworthy, a convergence of recent data from multiple studies suggests that, in cellular and animal models of ALS, a complex pathological interplay subsists between motor neurons and their non-neuronal neighbours, particularly glial cells. These observations not only have drawn attention to the physiopathological changes glial cells undergo during ALS progression, but they have moved the focus of the investigations from intrinsic defects and weakening of motor neurons to glia–neuron interactions. In this review, we summarize the growing body of evidence supporting the concept that different glial populations are critically involved in the dreadful chain of events leading to motor neuron sufferance and death in various forms of ALS. The outlined observations strongly suggest that glial cells can be the targets for novel therapeutic interventions in ALS.