First report of gastrocotylinean post-oncomiracidia (Platyhelminthes: Monogenoidea: Heteronchoinea) on gills of flyingfish (Exocoetidae), snapper (Lutjanidae), dolphinfish (Coryphaenidae), and amberjack (Carangidae) from the Gulf of Mexico: decoy hosts and the dilution effect

Larvae, identified as post-oncomiracidia of the suborder Gastrocotylinea (Monogenoidea), were collected from formalin-fixed gills excised from six species of marine fishes captured from the Gulf of Mexico off Mississippi and Florida: common dolphinfish, Coryphaena hippurus and pompano dolphinfish, Coryphaena equiselis (both Perciformes, Coryphaenidae); gray snapper, Lutjanus griseus (Perciformes, Lutjanidae); greater amberjack, Seriola dumerili (Perciformes, Carangidae); and Atlantic flyingfish, Cheilopogon melanurus and sailfin flyingfish, Parexocoetus hillianus (both Beloniformes and Exocoetidae). Based on a combination of diagnostic morphological features, the specimens were divided into two basic forms, each of which was further subdivided into two morphotypes. No gastrocotylinean post-oncomiracidium had been reported previously from these hosts. Of the six host species, only C. hippurus serves as a host (unconfirmed) for the adult of a gastrocotylinean species, suggesting that the recorded fishes from the Gulf of Mexico comprise dead-end hosts acting as decoys for the oncomiracidia. These comparatively non-susceptible “decoy hosts” apparently dilute the susceptible fish-host population and by intercepting infective larvae (oncomiracidia) decrease the abundance of parasites on their typical hosts.     

Amino acid signaling to mTOR mediated by inositol polyphosphate multikinase

mTOR complex 1 (mTORC1; mammalian target of rapamycin [mTOR] in complex with raptor) is a key regulator of protein synthesis and cell growth in response to nutrient amino acids. Here we report that inositol polyphosphate multikinase (IPMK), which possesses both inositol phosphate kinase and lipid kinase activities, regulates amino acid signaling to mTORC1. This regulation is independent of IPMK's catalytic function, instead reflecting its binding with mTOR and raptor, which maintains the mTOR-raptor association. Thus, IPMK appears to be a physiologic mTOR cofactor, serving as a determinant of mTORC1 stability and amino acid-induced mTOR signaling. Substances that block IPMK-mTORC1 binding may afford therapeutic benefit in nutrient amino acid-regulated conditions such as obesity and diabetes.     

H3N2 influenza infection elicits more cross-reactive and less clonally expanded anti-hemagglutinin antibodies than influenza vaccination

Background

During the recent H1N1 influenza pandemic, excess morbidity and mortality was seen in young but not older adults suggesting that prior infection with influenza strains may have protected older subjects. In contrast, a history of recent seasonal trivalent vaccine in younger adults was not associated with protection.

Methods and Findings

To study hemagglutinin (HA) antibody responses in influenza immunization and infection, we have studied the day 7 plasma cell repertoires of subjects immunized with seasonal trivalent inactivated influenza vaccine (TIV) and compared them to the plasma cell repertoires of subjects experimentally infected (EI) with influenza H3N2 A/Wisconsin/67/2005. The majority of circulating plasma cells after TIV produced influenza-specific antibodies, while most plasma cells after EI produced antibodies that did not react with influenza HA. While anti-HA antibodies from TIV subjects were primarily reactive with single or few HA strains, anti-HA antibodies from EI subjects were isolated that reacted with multiple HA strains. Plasma cell-derived anti-HA antibodies from TIV subjects showed more evidence of clonal expansion compared with antibodies from EI subjects. From an H3N2-infected subject, we isolated a 4-member clonal lineage of broadly cross-reactive antibodies that bound to multiple HA subtypes and neutralized both H1N1 and H3N2 viruses. This broad reactivity was not detected in post-infection plasma suggesting this broadly reactive clonal lineage was not immunodominant in this subject.

Conclusion

The presence of broadly reactive subdominant antibody responses in some EI subjects suggests that improved vaccine designs that make broadly reactive antibody responses immunodominant could protect against novel influenza strains.     

Thrombin-mediated Proteoglycan Synthesis Utilizes Both Protein-tyrosine Kinase and Serine/Threonine Kinase Receptor Transactivation in Vascular Smooth Muscle Cells

G protein-coupled receptor signaling is mediated by three main mechanisms of action; these are the classical pathway, β-arrestin scaffold signaling, and the transactivation of protein-tyrosine kinase receptors such as those for EGF and PDGF. Recently, it has been demonstrated that G protein-coupled receptors can also mediate signals via transactivation of serine/threonine kinase receptors, most notably the transforming growth factor-β receptor family. Atherosclerosis is characterized by the development of lipid-laden plaques in blood vessel walls. Initiation of plaque development occurs via low density lipoprotein retention in the neointima of vessels due to binding with modified proteoglycans secreted by vascular smooth muscle cells. Here we show that transactivation of protein-tyrosine kinase receptors is mediated by matrix metalloproteinase triple membrane bypass signaling. In contrast, serine/threonine kinase receptor transactivation is mediated by a cytoskeletal rearrangement-Rho kinase-integrin system, and both protein-tyrosine kinase and serine/threonine kinase receptor transactivation concomitantly account for the total proteoglycan synthesis stimulated by thrombin in vascular smooth muscle. This work provides evidence of thrombin-mediated proteoglycan synthesis and paves the way for a potential therapeutic target for plaque development and atherosclerosis.     

Alkaline Water Electrolysis at 25 A cm−2 with a Microfibrous Flow‐through Electrode

The generation of renewable electricity is variable, leading to periodic oversupply. Excess power can be converted to H₂ via water electrolysis, but the conversion cost is currently too high. One way to decrease the cost of electrolysis is to increase the maximum productivity of electrolyzers. This study investigates how nano‐ and microstructured porous electrodes can improve the productivity of H₂ generation in a zero‐gap, flow‐through alkaline water electrolyzer. Three nickel electrodes—foam, microfiber felt, and nanowire felt—are studied to examine the tradeoff between surface area and pore structure on the performance of alkaline electrolyzers. Although the nanowire felt with the highest surface area initially provides the highest performance, this performance quickly decreases as gas bubbles are trapped within the electrode. The open structure of the foam facilitates bubble removal, but its small surface area limits its maximum performance. The microfiber felt exhibits the best performance because it balances high surface area with the ability to remove bubbles. The microfiber felt maintains a maximum current density of 25 000 mA cm^?2 over 100 h without degradation, which corresponds to a hydrogen production rate 12.5‐ and 50‐times greater than conventional proton‐exchange membrane and alkaline electrolyzers, respectively.     

c-MET Regulates Myoblast Motility and Myocyte Fusion during Adult Skeletal Muscle Regeneration

Adult muscle stem cells, satellite cells (SCs), endow skeletal muscle with tremendous regenerative capacity. Upon injury, SCs activate, proliferate, and migrate as myoblasts to the injury site where they become myocytes that fuse to form new muscle. How migration is regulated, though, remains largely unknown. Additionally, how migration and fusion, which both require dynamic rearrangement of the cytoskeleton, might be related is not well understood. c-MET, a receptor tyrosine kinase, is required for myogenic precursor cell migration into the limb for muscle development during embryogenesis. Using a genetic system to eliminate c-MET function specifically in adult mouse SCs, we found that c-MET was required for muscle regeneration in response to acute muscle injury. c-MET mutant myoblasts were defective in lamellipodia formation, had shorter ranges of migration, and migrated slower compared to control myoblasts. Surprisingly, c-MET was also required for efficient myocyte fusion, implicating c-MET in dual functions of regulating myoblast migration and myocyte fusion.     

Design and evaluation of novel 8-oxo-pyridopyrimidine Jak1/2 inhibitors

A highly ligand efficient, novel 8-oxo-pyridopyrimidine containing inhibitor of Jak1 and Jak2 isoforms with a pyridone moiety as the hinge-binding motif was discovered. Structure-based design strategies were applied to significantly improve enzyme potency and the polarity of the molecule was adjusted to gain cellular activity. The crystal structures of two representative inhibitors bound to Jak1 were obtained to enable SAR exploration.     

DNA barcoding and species delimitation of butterflies (Lepidoptera) from Nigeria

Molecular Biology Reports - Accurate identification of species is a prerequisite for successful biodiversity management and further genetic studies. Species identification techniques often require...