Rac interacts with Abi-1 and WAVE2 to promote an Arp2/3-dependent actin recruitment during chlamydial invasion

Chlamydiae are Gram-negative obligate intracellular pathogens to which access to an intracellular environment is fundamental to their development. Chlamydial attachment to host cells induces the activation of the Rac GTPase, which is required for the localization of WAVE2 at the sites of chlamydial entry. Co-immunoprecipitation experiments demonstrated that Chlamydia trachomatis infection promoted the interaction of Rac with WAVE2 and Abi-1, but not with IRSp53. siRNA depletion of WAVE2 and Abi-1 abrogated chlamydia-induced actin recruitment and significantly reduced the uptake of the pathogen by the depleted cells. Chlamydia invasion also requires the Arp2/3 complex as demonstrated by its localization to the sites of chlamydial attachment and the reduced efficiency of chlamydial invasion in cells overexpressing the VCA domain of the neural Wiskott-Aldrich syndrome protein. Thus, C. trachomatis activates Rac and promotes its interaction with WAVE2 and Abi-1 to activate the Arp2/3 complex resulting in the induction of actin cytoskeletal rearrangements that are required for invasion.     

WIPI2B links PtdIns3P to LC3 lipidation through binding ATG16L1

WIPI proteins, phosphatidylinositol 3-phosphate (PtdIns3P) binding proteins with β-propeller folds, are recruited to the omegasome following PtdIns3P production. The functions of the WIPI proteins in autophagosome formation are poorly understood. In a recent study, we reported that WIPI2B directly binds ATG16L1 and functions by recruiting the ATG12–ATG5-ATG16L1 complex to forming autophagosomes during starvation- or pathogen-induced autophagy. Our model of WIPI2 function provides an explanation for the PtdIns3P-dependent recruitment of the ATG12–ATG5-ATG16L1 complex during initiation of autophagy.     

An Ion‐Exchange Promoted Phase Transition in a Li‐Excess Layered Cathode Material for High‐Performance Lithium Ion Batteries

A new approach to intentionally induce phase transition of Li‐excess layered cathode materials for high‐performance lithium ion batteries is reported. In high contrast to the limited layered‐to‐spinel phase transformation that occurred during in situ electrochemical cycles, a Li‐excess layered Li[Li_0.2Mn_0.54Ni_0.13Co_0.13]O₂ is completely converted to a Li₄Mn₅O₁₂‐type spinel product via ex situ ion‐exchanges and a post‐annealing process. Such a layered‐to‐spinel phase conversion is examined using in situ X‐ray diffraction and in situ high‐resolution transmission electron microscopy. It is found that generation of sufficient lithium ion vacancies within the Li‐excess layered oxide plays a critical role for realizing a complete phase transition. The newly formed spinel material exhibits initial discharge capacities of 313.6, 267.2, 204.0, and 126.3 mAh g^?1 when cycled at 0.1, 0.5, 1, and 5 C (1 C = 250 mA g^?1), respectively, and can retain a specific capacity of 197.5 mAh g^?1 at 1 C after 100 electrochemical cycles, demonstrating remarkably improved rate capability and cycling stability in comparison with the original Li‐excess layered cathode materials. This work sheds light on fundamental understanding of phase transitions within Li‐excess layered oxides. It also provides a novel route for tailoring electrochemical performance of Li‐excess layered cathode materials for high‐capacity lithium ion batteries.     

Cryptosporidium

This review discusses characteristics of the genus Cryptosporidium and addresses the pathogenesis, reservoirs, public health significance and current applications for the detection and typing of this important pathogen. By increasing knowledge in key areas of Cryptosporidium research such as aetiology, epidemiology, transmission and host interactions, the numbers of cases of human cryptosporidiosis should be reduced.     

Under the microscope: Arcobacter

This review describes characteristics of the genus Arcobacter. Unlike its close phenotypically related neighbour Campylobacter, Arcobacter is not currently a major public health concern, but is considered as an emerging human pathogen, and is of significance towards animal health. This review focuses on the public health significance, culturing and typing, reservoirs, and antimicrobial studies of Arcobacter. Collectively, increasing knowledge in these areas will help to develop measures, which can be used to control this emerging pathogen.     

3-(Arylamino)-3-phenylpropan-2-olamines as a new series of dual norepinephrine and serotonin reuptake inhibitors

A series of 3-(arylamino)-3-phenylpropan-2-olamines was prepared and screened for their ability to inhibit monoamine reuptake. A number of analogues displayed significant dual norepinephrine and serotonin reuptake inhibition. Compounds in this class exhibited minimal affinity for the dopamine transporter.     

Differential inhibition of six copper amine oxidases by a family of 4-(aryloxy)-2-butynamines: evidence for a new mode of inactivation

A series of compounds derived from a previously identified substrate analogue of copper amine oxidases (CuAOs) (Shepard et al. (2002) Eur. J. Biochem. 269, 3645-3658) has been screened against six different CuAOs with a view to designing potent and selective inhibitors. The substrate analogues investigated were 4-(1-naphthyloxy)-2-butyn-1-amine, 4-(2-methylphenoxy)-2-butyn-1-amine, 4-(3-methylphenoxy)-2-butyn-1-amine, 4-(4-methylphenoxy)-2-butyn-1-amine, and 4-phenoxy-2-butyn-1-amine. These compounds were screened against equine plasma amine oxidase (EPAO), Pisum sativum amine oxidase (PSAO), Pichia pastoris lysyl oxidase (PPLO), bovine plasma amine oxidase (BPAO), human kidney diamine oxidase (KDAO), and Arthrobacter globiformis amine oxidase (AGAO) to examine the effect of different substituent groups on potency. Despite the similar structures of the 4-aryloxy analogues evaluated, striking differences in potency were observed. In addition, crystal structures of AGAO derivitized with 4-(2-naphthyloxy)-2-butyn-1-amine and 4-(4-methylphenoxy)-2-butyn-1-amine were obtained at a resolution of 1.7 A. The structures reveal a novel and unprecedented reaction mechanism involving covalent attachment of the alpha,beta-unsaturated aldehyde turnover product to the amino group of the reduced 2,4,5-trihydroxyphenylalanine quinone (TPQ) cofactor. Collectively, the structural and inhibition results support the feasibility of designing selective mechanism-based inhibitors of copper amine oxidases.