Anti-α4 Antibody Treatment Blocks Virus Traffic to the Brain and Gut Early,and Stabilizes CNS Injury Late in Infection

Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab) once a week for three weeks beginning on 28 days post-infection (late). Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS), and decreased numbers of monocytes/macrophages and productive infection (SIV p28⁺, RNA⁺) in brain and gut. Antibody treatment of six SIV infected monkeys at the time of infection (early) for 3 weeks blocked monocyte/macrophage traffic and infection in the CNS, and significantly decreased leukocyte traffic and infection in the gut. SIV – RNA and p28 was absent in the CNS and the gut. SIV DNA was undetectable in brains of five of six early treated macaques, but proviral DNA in guts of treated and control animals was equivalent. Early treated animals had low-to-no plasma LPS and sCD163. These results support the notion that monocyte/macrophage traffic late in infection drives neuronal injury and maintains CNS viral reservoirs and lesions. Leukocyte traffic early in infection seeds the CNS with virus and contributes to productive infection in the gut. Leukocyte traffic early contributes to gut pathology, bacterial translocation, and activation of innate immunity.     

The role of p21-activated kinases in hepatocellular carcinoma metastasis

The p21-activated kinases (PAKs) are downstream effectors of the Rho family small GTPases as well as a wide variety of mitogenic factors and have been implicated in cancer formation, development and metastasis. PAKs phosphorylate a wide spectrum of substrates to mediate extracellular signals and regulate cytoskeletal remodeling, cell motility and survival. In this review, we aim to summarize the findings regarding the oncogenic role and the underlying mechanisms of PAKs signaling in various cancers, and in particular highlight the prime importance of PAKs in hepatocellular carcinoma (HCC) progression and metastasis. Recent studies exploring the potential therapeutic application of PAK inhibitors will also be discussed.     

A Novel Psittacine Adenovirus Identified During an Outbreak of Avian Chlamydiosis and Human Psittacosis: Zoonosis Associated with Virus-Bacterium Coinfection in Birds

Chlamydophila psittaci is found worldwide, but is particularly common among psittacine birds in tropical and subtropical regions. While investigating a human psittacosis outbreak that was associated with avian chlamydiosis in Hong Kong, we identified a novel adenovirus in epidemiologically linked Mealy Parrots, which was not present in healthy birds unrelated to the outbreak or in other animals. The novel adenovirus (tentatively named Psittacine adenovirus HKU1) was most closely related to Duck adenovirus A in the Atadenovirus genus. Sequencing showed that the Psittacine adenovirus HKU1 genome consists of 31,735 nucleotides. Comparative genome analysis showed that the Psittacine adenovirus HKU1 genome contains 23 open reading frames (ORFs) with sequence similarity to known adenoviral genes, and six additional ORFs at the 3′ end of the genome. Similar to Duck adenovirus A, the novel adenovirus lacks LH1, LH2 and LH3, which distinguishes it from other viruses in the Atadenovirus genus. Notably, fiber-2 protein, which is present in Aviadenovirus but not Atadenovirus, is also present in Psittacine adenovirus HKU1. Psittacine adenovirus HKU1 had pairwise amino acid sequence identities of 50.3–54.0% for the DNA polymerase, 64.6–70.7% for the penton protein, and 66.1–74.0% for the hexon protein with other Atadenovirus. The C. psittaci bacterial load was positively correlated with adenovirus viral load in the lung. Immunostaining for fiber protein expression was positive in lung and liver tissue cells of affected parrots, confirming active viral replication. No other viruses were found. This is the first documentation of an adenovirus-C. psittaci co-infection in an avian species that was associated with a human outbreak of psittacosis. Viral-bacterial co-infection often increases disease severity in both humans and animals. The role of viral-bacterial co-infection in animal-to-human transmission of infectious agents has not received sufficient attention and should be emphasized in the investigation of disease outbreaks in human and animals.     

ASSESSMENT OF TEMPERATURE AND NUTRIENT LIMITATION ON SEASONAL DYNAMICS AMONG SPECIES OF SARGASSUM FROM A CORAL REEF IN SOUTHERN TAIWAN1

The effects of temperature and nutrient availability on seasonal abundance were compared among Sargassum berberifolium J. Ag., S. polycystum C. Ag., S. siliquosum J. Ag., and S. sandei from a reef in southern Taiwan. Growth temperature limits and optimum were variable between species and between developmental stages. Growth temperature ranges agree with Sargassum periodicity except S. sandei. Sargassum siliquosum can tolerate high temperature as indicated by higher optimum temperature and tolerance limits. Temporal changes in tissue nutrient content and alkaline phosphatase activity and the results from nutrient enrichment bioassay show that S. sandei, S. berberifolium, and S. polycystum are P limited in the early growth period and then N limited, whereas S. siliquosum showed a contrasting trend, reflecting the type of nutrient limitation is variable by time and between species. A smaller nutrient threshold for maximum growth in S. berberifolium, S. polycystum, and S. siliquosum than in S. sandei and higher growth rate in S. berberifolium and S. polycystum indicate the higher growth vigor and nutrient utilization efficiency, the higher abundance. High N reserves in S. berberifolium and S. polycystum exposed to elevated seawater N in the early growth period supported the subsequent growth. The multiple regression analysis indicates that percent cover of S. siliquosum increased with increasing water temperature and dissolved inorganic nitrogen concentrations, whereas that of S. polycystum decreased with increasing water temperature. In conclusion, seasonal dynamics of Sargassum spp. from southern Taiwan are attributable to species and temporal variations in temperature limitation and nutrient utilization strategy.     

Enhanced inflorescence development in bougainvillea "san diego red" by removal of young leaves and cytokinin treatments

Removal of young leaves and application of the cytokinin, N-benzyla-α-(tetrahydro-2H-pyran-2yl)-adenine promote inflorescence development in Bougainvillea “San Diego Red”. Defoliation greatly increased the amount of assimilate accumulated at the shoot tip 1 to 2 days after treatment. Cytokinin applications further increased the amount accumulated and this increase was apparent 4 days before morphological changes could be detected at the inflorescence axes. Short days promoted inflorescence development and also increased assimilate accumulation at the reproductive axes; thus, it is suggested that the role of short day induction in bougainvillea may be that of redirecting the flow of assimilates, perhaps by its influence on cytokinin synthesis and distribution.     

Long non‐coding RNAs in melanoma

Melanoma is the most lethal cutaneous cancer with a highly aggressive and metastatic phenotype. While recent genetic and epigenetic studies have shed new insights into the mechanism of melanoma development, the involvement of regulatory non‐coding RNAs remain unclear. Long non‐coding RNAs (lncRNAs) are a group of endogenous non‐protein‐coding RNAs with the capacity to regulate gene expression at multiple levels. Recent evidences have shown that lncRNAs can regulate many cellular processes, such as cell proliferation, differentiation, migration and invasion. In the melanoma, deregulation of a number of lncRNAs, such as HOTAIR, MALAT1, BANCR, ANRIL, SPRY‐IT1 and SAMMSON, have been reported. Our review summarizes the functional role of lncRNAs in melanoma and their potential clinical application for diagnosis, prognostication and treatment.     

Mechanical Property Evolution of Silicon Composite Electrodes Studied by Environmental Nanoindentation

Mechanical degradation is largely responsible for the short cycle life of silicon (Si)‐based electrodes for future lithium‐ion batteries. An improved fundamental understanding of the mechanical behavior of Si electrodes, which evolves, as demonstrated in this paper, with the state of charge (SOC) and the cycle number, is a prerequisite for overcoming mechanical degradation and designing high capacity and durable Si‐based electrodes. In this study, Young's modulus (E) and hardness (H) of Si composite electrodes at different SOCs and after different cycle numbers are measured by nanoindentation under both dry and wet (liquid electrolyte) conditions. Unlike electrodes made of Si alone, E and H values of Si composite electrodes increase with increasing Li concentration. The composite electrodes under wet conditions are softer than that under dry conditions. Both E and H decrease with the cycle number. These findings highlight the effects of porosity, liquid environment, and degradation on the mechanical behavior of composite electrodes. The methods and results of this study on the mechanical property evolution of Si/polyvinylidene fluoride electrodes form a basis for exploring more effective binders for Si‐based electrodes. Furthermore, the evolving nature of the mechanical behavior of composite electrodes should be taken into consideration in future modeling efforts of porous composite electrodes.     

Identification of Ca<Superscript>2+</Superscript> signaling components in neural stem/progenitor cells during differentiation into neurons and glia in intact and dissociated zebrafish neurospheres

The development of the CNS in vertebrate embryos involves the generation of different sub-types of neurons and glia in a complex but highly-ordered spatio-temporal manner. Zebrafish are commonly used for exploring the development, plasticity and regeneration of the CNS, and the recent development of reliable protocols for isolating and culturing neural stem/progenitor cells (NSCs/NPCs) from the brain of adult fish now enables the exploration of mechanisms underlying the induction/specification/differentiation of these cells. Here, we refined a protocol to generate proliferating and differentiating neurospheres from the entire brain of adult zebrafish. We demonstrated via RT-qPCR that some isoforms of ip3r, ryr and stim are upregulated/downregulated significantly in differentiating neurospheres, and via immunolabelling that 1,4,5-inositol trisphosphate receptor (IP₃R) type-1 and ryanodine receptor (RyR) type-2 are differentially expressed in cells with neuron- or radial glial-like properties. Furthermore, ATP but not caffeine (IP₃R and RyR agonists, respectively), induced the generation of Ca²⁺ transients in cells exhibiting neuron- or glial-like morphology. These results indicate the differential expression of components of the Ca²⁺-signaling toolkit in proliferating and differentiating cells. Thus, given the complexity of the intact vertebrate brain, neurospheres might be a useful system for exploring neurodegenerative disease diagnosis protocols and drug development using Ca²⁺ signaling as a read-out.