Lipid acquisition by intracellular Chlamydiae

Chlamydia species are obligate intracellular pathogens that are important causes of human genital tract, ocular and respiratory infections. The bacteria replicate within a specialized membrane-bound compartment termed the inclusion and require host-derived lipids for intracellular growth and development. Emerging evidence indicates that Chlamydia has evolved clever strategies to fulfil its lipid needs by interacting with multiple host cell compartments and redirecting trafficking pathways to its intracellular niche. In this review, we highlight recent findings that have significantly expanded our understanding of how Chlamydia exploit lipid trafficking pathways to ensure the survival of this important human pathogen.     

On the blink: the importance of target-distractor similarity in eliciting an attentional blink with faces

Temporal allocation of attention is often investigated with a paradigm in which two relevant target items are presented in a rapid sequence of irrelevant distractors. The term Attentional Blink (AB) denotes a transient impairment of awareness for the second of these two target items when presented close in time. Experimental studies reported that the AB is reduced when the second target is emotionally significant, suggesting a modulation of attention allocation. The aim of the present study was to systematically investigate the influence of target-distractor similarity on AB magnitude for faces with emotional expressions under conditions of limited attention in a series of six rapid serial visual presentation experiments. The task on the first target was either to discriminate the gender of a neutral face (Experiments 1, 3-6) or an indoor/outdoor visual scene (Experiment 2). The task on the second target required either the detection of emotional expressions (Experiments 1-5) or the detection of a face (Experiment 6). The AB was minimal or absent when targets could be easily discriminated from each other. Three successive experiments revealed that insufficient masking and target-distractor similarity could account for the observed immunity of faces against the AB in the first two experiments. An AB was present but not increased when the facial expression was irrelevant to the task suggesting that target-distractor similarity plays a more important role in eliciting an AB than the attentional set demanded by the specific task. In line with previous work, emotional faces were less affected by the AB.     

Cofactors required for TLR7- and TLR9-dependent innate immune responses

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Highlights? RNAi and systems-based analysis identified 190 TLR7/9 signaling cofactors ? Pathway crossprofiling enabled mapping cofactors to specific NFκB signaling modules ? HRS is a mediator of ubiquitin-dependent nondegradative endosomal TLR sorting     

Embryonic lethality and fetal liver apoptosis in mice lacking all three small Maf proteins

Embryogenesis is a period during which cells are exposed to dynamic changes of various intracellular and extracellular stresses. Oxidative stress response genes are regulated by heterodimers composed of Cap'n'Collar (CNC) and small Maf proteins (small Mafs) that bind to antioxidant response elements (ARE). Whereas CNC factors have been shown to contribute to the expression of ARE-dependent cytoprotective genes during embryogenesis, the specific contribution of small Maf proteins to such gene regulation remains to be fully examined. To delineate the small Maf function in vivo, in this study we examined mice lacking all three small Mafs (MafF, MafG, and MafK). The small Maf triple-knockout mice developed normally until embryonic day 9.5 (E9.5). Thereafter, however, the triple-knockout embryos showed severe growth retardation and liver hypoplasia, and the embryos died around E13.5. ARE-dependent cytoprotective genes were expressed normally in E10.5 triple-knockout embryos, but the expression was significantly reduced in the livers of E13.5 mutant embryos. Importantly, the embryonic lethality could be completely rescued by transgenic expression of exogenous MafG under MafG gene regulatory control. These results thus demonstrate that small Maf proteins are indispensable for embryonic development after E9.5, especially for liver development, but early embryonic development does not require small Mafs.     

Looking for novel functions of tau

The lack or excess of the protein tau can be deleterious for neurons. The absence of tau can result in retarded neurogenesis and neuronal differentiation, although adult mice deficient in tau are viable, probably because of the compensation of the loss of tau by other MAPs (microtubule-associated proteins). On the contrary, the overexpression of tau can be toxic for the cell. One way to reduce intracellular tau levels can be achieved by its secretion through microvesicles to the extracellular space. Furthermore, tau can be found in the extracellular space because of the neuronal cell death occurring in neurodegenerative disorders such as Alzheimer's disease. The presence of toxic extracellular tau could be the mechanism for the spreading of tau pathology in these neurodegenerative disorders.     

Behaviour and welfare of veal calves fed different amounts of solid feed supplemented to a milk replacer ration adjusted for similar growth

Veal calves in Europe are typically fed large quantities of milk replacer and small amounts of solid feed, a diet known to lead to the development of abnormal oral behaviours in these animals. These abnormal oral behaviours are thought to be an indication of frustration, chronic stress, and hence poor welfare. The present study investigated how different feeding strategies, differing in solid feed and milk replacer provision, affected the behaviour and welfare of veal calves across time. Four treatment groups (A–D) comprising of 12 Holstein–Friesian bull calves each (7.6 ± 0.1 weeks old and 54.7 ± 0.3 kg at arrival), penned in groups of three, were fed one of four amounts of a solid feed mixture, i.e. 50% concentrates, 25% fresh maize silage, and 25% wheat straw (on dry matter [DM] basis): A = 0, B = 9, C = 18, and D = 27 g DM/kg^0.75/d. Provision of milk replacer was adjusted to achieve similar average daily gain across treatments. Behaviour was recorded around feeding (10 min continuous focal observations of individual calves) and throughout the day (7 sessions of 30 min scan sampling at 5 min interval every 2 h from 06:30 h) every week for four months. In an attempt to find an easy practical method to measure behavioural response to feeding strategy, two 3-min behavioural tests were carried out: (1) in months 1 and 3, calves were presented with a ball and latency to make oral contact with it was recorded; and (2) in month 1, calves were presented with an overall and time spent orally manipulating (i.e. chewing or licking) it was recorded using scan sampling every 10 s. Calves in treatment D displayed less abnormal oral behaviours around feeding, less tongue playing throughout the day, and more chewing in the first two months, compared to treatment A. Treatment B only led to lower tongue playing levels compared to A and treatment C had no benefit in terms of reducing abnormal oral behaviours. Although a solid feed dose–response was expected on the display of abnormal behaviours in veal calves, treatment C did not fit within this expectation. These findings point to a more complex relationship between solid feed and abnormal oral behaviour frequency in veal calves. The two behavioural tests distinguished the different treatments as expected, and thus showed a solid feed dose–response. Because of an increase in chewing and ruminating efficiency over time, amounts of solid feed should be increased with age to maintain high levels of chewing and ruminating. Moreover, high levels of chewing and ruminating may have to be maintained long enough at the beginning of the fattening period to lead to a reduction in abnormal oral behaviours.     

Microbial community structure elucidates performance of Glyceria maxima plant microbial fuel cell

The plant microbial fuel cell (PMFC) is a technology in which living plant roots provide electron donor, via rhizodeposition, to a mixed microbial community to generate electricity in a microbial fuel cell. Analysis and localisation of the microbial community is necessary for gaining insight into the competition for electron donor in a PMFC. This paper characterises the anode–rhizosphere bacterial community of a Glyceria maxima (reed mannagrass) PMFC. Electrochemically active bacteria (EAB) were located on the root surfaces, but they were more abundant colonising the graphite granular electrode. Anaerobic cellulolytic bacteria dominated the area where most of the EAB were found, indicating that the current was probably generated via the hydrolysis of cellulose. Due to the presence of oxygen and nitrate, short-chain fatty acid-utilising denitrifiers were the major competitors for the electron donor. Acetate-utilising methanogens played a minor role in the competition for electron donor, probably due to the availability of graphite granules as electron acceptors.     

Pseudomonas aeruginosa Pili and Flagella Mediate Distinct Binding and Signaling Events at the Apical and Basolateral Surface of Airway Epithelium

Pseudomonas aeruginosa, an important opportunistic pathogen of man, exploits numerous factors for initial attachment to the host, an event required to establish bacterial infection. In this paper, we rigorously explore the role of two major bacterial adhesins, type IV pili (Tfp) and flagella, in bacterial adherence to distinct host receptors at the apical (AP) and basolateral (BL) surfaces of polarized lung epithelial cells and induction of subsequent host signaling and pathogenic events. Using an isogenic mutant of P. aeruginosa that lacks flagella or utilizing beads coated with purified Tfp, we establish that Tfp are necessary and sufficient for maximal binding to host N-glycans at the AP surface of polarized epithelium. In contrast, experiments utilizing a P. aeruginosa isogenic mutant that lacks Tfp or using beads coated with purified flagella demonstrate that flagella are necessary and sufficient for maximal binding to heparan sulfate (HS) chains of heparan sulfate proteoglycans (HSPGs) at the BL surface of polarized epithelium. Using two different cell-free systems, we demonstrate that Tfp-coated beads show highest binding affinity to complex N-glycan chains coated onto plastic plates and preferentially aggregate with beads coated with N-glycans, but not with single sugars or HS. In contrast, flagella-coated beads bind to or aggregate preferentially with HS or HSPGs, but demonstrate little binding to N-glycans. We further show that Tfp-mediated binding to host N-glycans results in activation of phosphatidylinositol 3-kinase (PI3K)/Akt pathway and bacterial entry at the AP surface. At the BL surface, flagella-mediated binding to HS activates the epidermal growth factor receptor (EGFR), adaptor protein Shc, and PI3K/Akt, and induces bacterial entry. Remarkably, flagella-coated beads alone can activate EGFR and Shc. Together, this work provides new insights into the intricate interactions between P. aeruginosa and lung epithelium that may be potentially useful in the development of novel treatments for P. aeruginosa infections.