TgPL2, a patatin‐like phospholipase domain‐containing protein,is involved in the maintenance of apicoplast lipids homeostasis in Toxoplasma

Patatin‐like phospholipases are involved in numerous cellular functions, including lipid metabolism and membranes remodeling. The patatin‐like catalytic domain, whose phospholipase activity relies on a serine‐aspartate dyad and an anion binding box, is widely spread among prokaryotes and eukaryotes. We describe TgPL2, a novel patatin‐like phospholipase domain‐containing protein from the parasitic protist Toxoplasma gondii. TgPL2 is a large protein, in which the key motifs for enzymatic activity are conserved in the patatin‐like domain. Using immunofluorescence assays and immunoelectron microscopy analysis, we have shown that TgPL2 localizes to the apicoplast, a non‐photosynthetic plastid found in most apicomplexan parasites. This plastid hosts several important biosynthetic pathways, which makes it an attractive organelle for identifying new potential drug targets. We thus addressed TgPL2 function by generating a conditional knockdown mutant and demonstrated it has an essential contribution for maintaining the integrity of the plastid. In absence of TgPL2, the organelle is rapidly lost and remaining apicoplasts appear enlarged, with an abnormal accumulation of membranous structures, suggesting a defect in lipids homeostasis. More precisely, analyses of lipid content upon TgPL2 depletion suggest this protein is important for maintaining levels of apicoplast‐generated fatty acids, and also regulating phosphatidylcholine and lysophosphatidylcholine levels in the parasite.     

Nebulized Liposomal Amphotericin B for Treatment of Pulmonary Infection Caused by <Emphasis Type="Italic">Hormographiella aspergillata</Emphasis>: Case Report and Literature Review

Invasive fungal infection is a serious complication following allogeneic hematopoietic stem cell transplantation. Pulmonary infection due to Hormographiella aspergillata is an uncommon condition associated with a high mortality rate. The susceptibility of H. aspergillata to available antifungal agents is not well established. We report for the first time a case of H. aspergillata lung infection that responded poorly to conventional treatment with liposomal amphotericin B (LAmB; 3 mg kg^?1 of body weight per day) with renal damage at higher posology (5 mg kg^?1 of body weight per day), but improved rapidly after addition of nebulized LAmB to intravenous LAmB (3 mg kg^?1 of body weight per day). Successful treatment of our patient using nebulized LAmB would be worth evaluating in cases refractory to standard treatment or when the reference treatment may not be extended due to interaction or side effects.     

AMPKα1‐LDH pathway regulates muscle stem cell self‐renewal by controlling metabolic homeostasis

Control of stem cell fate to either enter terminal differentiation versus returning to quiescence (self‐renewal) is crucial for tissue repair. Here, we showed that AMP‐activated protein kinase (AMPK), the master metabolic regulator of the cell, controls muscle stem cell (MuSC) self‐renewal. AMPKα1^?/? MuSCs displayed a high self‐renewal rate, which impairs muscle regeneration. AMPKα1^?/? MuSCs showed a Warburg‐like switch of their metabolism to higher glycolysis. We identified lactate dehydrogenase (LDH) as a new functional target of AMPKα1. LDH, which is a non‐limiting enzyme of glycolysis in differentiated cells, was tightly regulated in stem cells. In functional experiments, LDH overexpression phenocopied AMPKα1^?/? phenotype, that is shifted MuSC metabolism toward glycolysis triggering their return to quiescence, while inhibition of LDH activity rescued AMPKα1^?/? MuSC self‐renewal. Finally, providing specific nutrients (galactose/glucose) to MuSCs directly controlled their fate through the AMPKα1/LDH pathway, emphasizing the importance of metabolism in stem cell fate.     

Bat rabies surveillance in France: first report of unusual mortality among serotine bats

Background

Rabies is a fatal viral encephalitic disease that is caused by lyssaviruses which can affect all mammals, including human and bats. In Europe, bat rabies cases are attributed to five different lyssavirus species, the majority of rabid bats being attributed to European bat 1 lyssavirus (EBLV-1), circulating mainly in serotine bats (Eptesicus serotinus). In France, rabies in bats is under surveillance since 1989, with 77 positive cases reported between 1989 and 2016.

Case presentation

In the frame of the bat rabies surveillance, an unusual mortality of serotine bats was reported in 2009 in a village in North-East France. Six juvenile bats from an E. serotinus maternity colony counting ~200 individuals were found to be infected with EBLV-1. The active surveillance of the colony by capture sessions of bats from July to September 2009 showed a high detection rate of neutralising EBLV-1 antibodies (≈ 50%) in the colony. Moreover, one out of 111 animals tested was found to shed viable virus in saliva, while lyssavirus RNA was detected by RT-PCR for five individuals.

Conclusion

This study demonstrated that the lyssavirus infection in the serotine maternity colony was followed by a high rate of bat rabies immunity after circulation of the virus in the colony. The ratio of seropositive bats is probably indicative of an efficient virus transmission coupled to a rapid circulation of EBLV-1 in the colony.

     

Inner structural organization of the distal humerus in Paranthropus and Homo

The taxonomic attribution of isolated hominin distal humeri has been a matter of uncertainty and disagreement notwithstanding their relative abundance in the fossil record. Four taxonomically-based morphotypes, respectively representing P. boisei, P. robustus, non-erectus early Homo and H. erectus, have been identified based on the cross-sectional outer shape variation of an assemblage of Plio-Pleistocene eastern and southern African specimens (Lague, 2015). However, the existence of possible differences between Paranthropus and Homo in the inner structural organisation at this skeletal site remains unexplored. We used noninvasive imaging techniques to tentatively characterize the endostructural organization of five early Pleistocene distal humeri from South Africa (TM 1517g, SK 24600, SKX 10924, SKX 34805) and Ethiopia (Gombore IB), which have been variably attributed to Paranthropus or Homo. While the investigated specimens reveal diverse degrees of inner preservation related to their taphonomic and diagenetic history, in all but SK 24600 from Swartkrans we could comparatively assess some geometric properties at the most distal cross-sectional level (%CA, I_x/I_y, I_max/I_min) and quantify cortical bone thickness topographic variation across the preserved shaft portions by means of a 2-3D Relative Cortical Thickness index. Whenever possible, we also provided details about the site-specific organization of the cancellous network and measured the same parameters in a comparative sample of twelve adult extant humans. For most features, our results indicate two main patterns: the first includes the specimens TM 1517g, SKX 10924 and SKX 34805, while the second endostructural morphotype sets apart the robust Homo aff. erectus Gombore IB specimen from Melka Kunture, which more closely resembles the condition displayed by our comparative human sample. Notably, marked differences in the amount and pattern of proximodistal cortical bone distribution have been detected between Gombore IB and SKX 34805 from Swartkrans. Given its discordant outer and inner signatures, we conclude that the taxonomic status of SKX 34805 deserves further investigations.     

Identification of a GTP-bound Rho specific scFv molecular sensor by phage display selection

Background  

The Rho GTPases A, B and C proteins, members of the Rho family whose activity is regulated by GDP/GTP cycling, function in many cellular pathways controlling proliferation and have recently been implicated in tumorigenesis. Although overexpression of Rho GTPases has been correlated with tumorigenesis, only their GTP-bound forms are able to activate the signalling pathways implicated in tumorigenesis. Thus, the focus of much recent research has been to identify biological tools capable of quantifying the level of cellular GTP-bound Rho, or determining the subcellular location of activation. However useful, these tools used to study the mechanism of Rho activation still have limitations. The aim of the present work was to employ phage display to identify a conformationally-specific single chain fragment variable (scFv) that recognizes the active, GTP-bound, form of Rho GTPases and is able to discriminate it from the inactive, GDP-bound, Rho in endogenous settings.     

渤海中、南部大型底栖动物物种多样性的研究

以1997年 6月、1998年9月和1999年4月共3个航次,覆盖渤海中、南部大部分海区的大型底栖动物丰度、生物量和生产力的研究为基础,进一步对其物种多样性进行了分析。结果表明：研究海域的大型底栖动物物种多样性没有明显的平面分布规律;物种多样性指数与沉积物因子的相关性高于其与底层水因子的相关性;沉积物中污染物含量的确会对大型底栖动物的多样性造成影响。通过对3个航次中3个相同站位的比较,发现不同年份之3个季节的平均Shannon Wiener指数无显著差异（P>0.05）;而1998年9月和1999年4月2个航次中20个相同站位的平均Shannon Wiener指数同样也未表现出明显的差异（P>0.05）。此外,渤海的物种数量要明显地高于胶州湾。     

The essential role of lipids in Alzheimer's disease

In the absence of efficient diagnostic and therapeutic tools, Alzheimer's disease (AD) is a major public health concern due to longer life expectancy in the Western countries. Although the precise cause of AD is still unknown, soluble β-amyloid (Aβ) oligomers are considered the proximate effectors of the synaptic injury and neuronal death occurring in the early stages of AD. Aβ oligomers may directly interact with the synaptic membrane, leading to impairment of synaptic functions and subsequent signalling pathways triggering neurodegeneration. Therefore, membrane structure and lipid status should be considered determinant factors in Aβ-oligomer-induced synaptic and cell injuries, and therefore AD progression. Numerous epidemiological studies have highlighted close relationships between AD incidence and dietary patterns. Among the nutritional factors involved, lipids significantly influence AD pathogenesis. It is likely that maintenance of adequate membrane lipid content could prevent the production of Aβ peptide as well as its deleterious effects upon its interaction with synaptic membrane, thereby protecting neurons from Aβ-induced neurodegeneration. As major constituents of neuronal lipids, n-3 polyunsaturated fatty acids are of particular interest in the prevention of AD valuable diet ingredients whose neuroprotective properties could be essential for designing preventive nutrition-based strategies. In this review, we discuss the functional relevance of neuronal membrane features with respect to susceptibility to Aβ oligomers and AD pathogenesis, as well as the prospective capacities of lipids to prevent or to delay the disease.