Lung underdevelopment: case reports and a literature review

Lung underdevelopment is a rare congenital anomaly with variable clinical significance and presenting symptoms. It usually manifests during childhood. We present two cases of developmental lung anomaly subtypes and discuss clinical presentation and outcomes in such patient populations

A variant of KCC2 from patients with febrile seizures impairs neuronal Cl- extrusion and dendritic spine formation

Genetic variation in SLC12A5 which encodes KCC2, the neuron‐specific cation‐chloride cotransporter that is essential for hyperpolarizing GABAergic signaling and formation of cortical dendritic spines, has not been reported in human disease. Screening of SLC12A5 revealed a co‐segregating variant (KCC2‐R952H) in an Australian family with febrile seizures. We show that KCC2‐R952H reduces neuronal Cl− extrusion and has a compromised ability to induce dendritic spines in vivo and in vitro. Biochemical analyses indicate a reduced surface expression of KCC2‐R952H which likely contributes to the functional deficits. Our data suggest that KCC2‐R952H is a bona fide susceptibility variant for febrile seizures.Peer reviewe

A variant of KCC2 from patients with febrile seizures impairs neuronal Cl- extrusion and dendritic spine formation

Genetic variation in SLC12A5 which encodes KCC2, the neuron‐specific cation‐chloride cotransporter that is essential for hyperpolarizing GABAergic signaling and formation of cortical dendritic spines, has not been reported in human disease. Screening of SLC12A5 revealed a co‐segregating variant (KCC2‐R952H) in an Australian family with febrile seizures. We show that KCC2‐R952H reduces neuronal Cl− extrusion and has a compromised ability to induce dendritic spines in vivo and in vitro. Biochemical analyses indicate a reduced surface expression of KCC2‐R952H which likely contributes to the functional deficits. Our data suggest that KCC2‐R952H is a bona fide susceptibility variant for febrile seizures.Peer reviewe

Can the natural turf pitch be viewed as a risk factor for injury within Association Football?

OBJECTIVES: A review of the current literature is used to propose a 'conceptual model for relative pitch hardness' and how this may affect incidence of injury within Association Football. Based upon the injury risk and causation model of Meeuwisse et al. (Clin J Sport Med 2007; 17(3):215), it may provide researchers a necessary framework to guide future research investigations. DESIGN: A literature review. METHODS: A comprehensive search of electronic databases available until October 2014, and supplemental hand searching was conducted to identify relevant studies. Studies were deemed relevant if they met the following criteria: published in English, presented or referenced in an epidemiological study or provided data directly and/or related to the surface of the football pitch, ball or boot to surface interaction and injury. Further information was sourced on surface hardness, players' movement patterns and physiological demands within football. RESULTS: Papers varied in methodological quality, with comparative studies examining injury rates on artificial versus natural turf pitches being most prevalent. No prospective studies were found that objectively measured the relationship between hardness of natural turf and injury risk within football. CONCLUSIONS: The literature review into natural turf pitches and injury within football has largely been unable to confirm that pitch hardness can be viewed as a significant extrinsic risk factor. Methodological concerns, including objectivity in pitch assessment and uniformity in defining injuries undermine the efficacy of available work. Future studies are needed utilising objective assessment tools to draw more definitive conclusions regarding pitch hardness as an extrinsic factor for injury within football

Ih-mediated depolarization enhances the temporal precision of neuronal integration

Feed-forward inhibition mediated by ionotropic GABAA receptors contributes to the temporal precision of neuronal signal integration. These receptors exert their inhibitory effect by shunting excitatory currents and by hyperpolarizing neurons. The relative roles of these mechanisms in neuronal computations are, however, incompletely understood. In this study, we show that by depolarizing the resting membrane potential relative to the reversal potential for GABAA receptors, the hyperpolarization-activated mixed cation current (Ih) maintains a voltage gradient for fast synaptic inhibition in hippocampal pyramidal cells. Pharmacological or genetic ablation of Ih broadens the depolarizing phase of afferent synaptic waveforms by hyperpolarizing the resting membrane potential. This increases the integration time window for action potential generation. These results indicate that the hyperpolarizing component of GABAA receptor-mediated inhibition has an important role in maintaining the temporal fidelity of coincidence detection and suggest a previously unrecognized mechanism by which Ih modulates information processing in the hippocampus

Phosphorus speciation in cultivated organic soils revealed by P K-edge XANES spectroscopy

Cultivated organic soils make a significant contribution to phosphorus (P) leaching losses from agricultural land, despite occupying a small proportion of cultivated area. However, less is known about P mobilisation processes and the P forms present in peat soils compared with mineral soils. In this study, P forms and their distribution with depth were investigated in two cultivated Histosol profiles, using a combination of wet chemical extraction and P K-edge X-ray absorption near-edge structure (XANES) spectroscopy.Both profiles had elevated P content in the topsoil, amounting to around 40 mmol kg(-1), and P speciation in both profiles was strongly dominated by organic P. Topsoils were particularly rich in organic P (P-org), with relative proportions of up to 80%. Inorganic P in the profiles was almost exclusively adsorbed to surface reactive aluminium (Al) and iron (Fe) minerals. In one of the pro-files, small contributions of Ca-phosphates were detected.A commonly used P saturation index (PSI) based on ammonium-oxalate extraction indicated a low to moderate risk of P leaching from both profiles. However, the capacity of soil Al and Fe to retain P in organic soils could be reduced by high competition from organic compounds for sorption sites. This is not directly accounted for in PSI and similar indices.Accumulation of P-org in the topsoil may be attributable by microbial peat decomposition and transformation of mineral fertiliser P by both microbiota and crops. Moreover, high carbon-phosphorus ratio in the surface peat material in both profiles suggests reduced net mineralisation of P-org in the two soils. However, advancing microbial peat decomposition will eventually lead to complete loss of peat horizons and to mineralisation of P-org. Hence, P-org in both profiles represents a huge potentially mobilised P pool

GPVI and GPIbα Mediate Staphylococcal Superantigen-Like Protein 5 (SSL5) Induced Platelet Activation and Direct toward Glycans as Potential Inhibitors

Background Staphylococcus aureus (S. aureus) is a common pathogen capable of causing life-threatening infections. Staphylococcal superantigen-like protein 5 (SSL5) has recently been shown to bind to platelet glycoproteins and induce platelet activation. This study investigates further the interaction between SSL5 and platelet glycoproteins. Moreover, using a glycan discovery approach, we aim to identify potential glycans to therapeutically target this interaction and prevent SSL5-induced effects. Methodology/Principal Findings In addition to platelet activation experiments, flow cytometry, immunoprecipitation, surface plasmon resonance and a glycan binding array, were used to identify specific SSL5 binding regions and mediators. We independently confirm SSL5 to interact with platelets via GPIbα and identify the sulphated-tyrosine residues as an important region for SSL5 binding. We also identify the novel direct interaction between SSL5 and the platelet collagen receptor GPVI. Together, these receptors offer one mechanistic explanation for the unique functional influences SSL5 exerts on platelets. A role for specific families of platelet glycans in mediating SSL5-platelet interactions was also discovered and used to identify and demonstrate effectiveness of potential glycan based inhibitors in vitro. Conclusions/Significance These findings further elucidate the functional interactions between SSL5 and platelets, including the novel finding of a role for the GPVI receptor. We demonstrate efficacy of possible glycan-based approaches to inhibit the SSL5-induced platelet activation. Our data warrant further work to prove SSL5-platelet effects in viv

Pheromone production, male abundance, body size, and the evolution of elaborate antennae in moths

The males of some species of moths possess elaborate feathery antennae. It is widely assumed that these striking morphological features have evolved through selection for males with greater sensitivity to the female sex pheromone, which is typically released in minute quantities. Accordingly, females of species in which males have elaborate (i.e., pectinate, bipectinate, or quadripectinate) antennae should produce the smallest quantities of pheromone. Alternatively, antennal morphology may be associated with the chemical properties of the pheromone components, with elaborate antennae being associated with pheromones that diffuse more quickly (i.e., have lower molecular weights). Finally, antennal morphology may reflect population structure, with low population abundance selecting for higher sensitivity and hence more elaborate antennae. We conducted a phylogenetic comparative analysis to test these explanations using pheromone chemical data and trapping data for 152 moth species. Elaborate antennae are associated with larger body size (longer forewing length), which suggests a biological cost that smaller moth species cannot bear. Body size is also positively correlated with pheromone titre and negatively correlated with population abundance (estimated by male abundance). Removing the effects of body size revealed no association between the shape of antennae and either pheromone titre, male abundance, or mean molecular weight of the pheromone components. However, among species with elaborate antennae, longer antennae were typically associated with lower male abundances and pheromone compounds with lower molecular weight, suggesting that male distribution and a more rapidly diffusing female sex pheromone may influence the size but not the general shape of male antennae

Cryo-EM structures of complex I from mouse heart mitochondria in two biochemically defined states.

Complex I (NADH:ubiquinone oxidoreductase) uses the reducing potential of NADH to drive protons across the energy-transducing inner membrane and power oxidative phosphorylation in mammalian mitochondria. Recent cryo-EM analyses have produced near-complete models of all 45 subunits in the bovine, ovine and porcine complexes and have identified two states relevant to complex I in ischemia-reperfusion injury. Here, we describe the 3.3-Å structure of complex I from mouse heart mitochondria, a biomedically relevant model system, in the 'active' state. We reveal a nucleotide bound in subunit NDUFA10, a nucleoside kinase homolog, and define mechanistically critical elements in the mammalian enzyme. By comparisons with a 3.9-Å structure of the 'deactive' state and with known bacterial structures, we identify differences in helical geometry in the membrane domain that occur upon activation or that alter the positions of catalytically important charged residues. Our results demonstrate the capability of cryo-EM analyses to challenge and develop mechanistic models for mammalian complex I