Evolution of Influenza B Virus in Kuala Lumpur,Malaysia, between 1995 and 2008

Influenza B virus causes significant disease but remains understudied in tropical regions. We sequenced 72 influenza B viruses collected in Kuala Lumpur, Malaysia, from 1995 to 2008. The predominant circulating lineage (Victoria or Yamagata) changed every 1 to 3 years, and these shifts were associated with increased incidence of influenza B. We also found poor lineage matches with recommended influenza virus vaccine strains. While most influenza B virus lineages in Malaysia were short-lived, one circulated for 3 to 4 years.     

Apolar and polar transitions drive the conversion between amoeboid and mesenchymal shapes in melanoma cells

Melanoma cells can adopt two functionally distinct forms, amoeboid and mesenchymal, which facilitates their ability to invade and colonize diverse environments during the metastatic process. Using quantitative imaging of single living tumor cells invading three-dimensional collagen matrices, in tandem with unsupervised computational analysis, we found that melanoma cells can switch between amoeboid and mesenchymal forms via two different routes in shape space—an apolar and polar route. We show that whereas particular Rho-family GTPases are required for the morphogenesis of amoeboid and mesenchymal forms, others are required for transitions via the apolar or polar route and not amoeboid or mesenchymal morphogenesis per se. Altering the transition rates between particular routes by depleting Rho-family GTPases can change the morphological heterogeneity of cell populations. The apolar and polar routes may have evolved in order to facilitate conversion between amoeboid and mesenchymal forms, as cells are either searching for, or attracted to, particular migratory cues, respectively.     

Understory vegetation as an indicator for floodplain forest restoration in the Mississippi River Alluvial Valley,U.S.A.

In the Mississippi River Alluvial Valley (MAV), complete alteration of river‐floodplain hydrology allowed for widespread conversion of forested bottomlands to intensive agriculture, resulting in nearly 80% forest loss. Governmental programs have attempted to restore forest habitat and functions within this altered landscape by the methods of tree planting (afforestation) and local hydrologic enhancement on reclaimed croplands. Early assessments identified factors that influenced whether planting plus tree colonization could establish an overstory community similar to natural bottomland forests. The extent to which afforested sites develop typical understory vegetation has not been evaluated, yet understory composition may be indicative of restored site conditions. As part of a broad study quantifying the ecosystem services gained from restoration efforts, understory vegetation was compared between 37 afforested sites and 26 mature forest sites. Differences in vegetation attributes for species growth forms, wetland indicator classes, and native status were tested with univariate analyses; floristic composition data were analyzed by multivariate techniques. Understory vegetation of restoration sites was generally hydrophytic, but species composition differed from that of mature bottomland forest because of young successional age and differing responses of plant growth forms. Attribute and floristic variation among restoration sites was related to variation in canopy development and local wetness conditions, which in turn reflected both intrinsic site features and outcomes of restoration practices. Thus, understory vegetation is a useful indicator of functional progress in floodplain forest restoration.     

Priority threat management of invasive animals to protect biodiversity under climate change

Climate change is a major threat to global biodiversity, and its impacts can act synergistically to heighten the severity of other threats. Most research on projecting species range shifts under climate change has not been translated to informing priority management strategies on the ground. We develop a prioritization framework to assess strategies for managing threats to biodiversity under climate change and apply it to the management of invasive animal species across one‐sixth of the Australian continent, the Lake Eyre Basin. We collected information from key stakeholders and experts on the impacts of invasive animals on 148 of the region's most threatened species and 11 potential strategies. Assisted by models of current distributions of threatened species and their projected distributions, experts estimated the cost, feasibility, and potential benefits of each strategy for improving the persistence of threatened species with and without climate change. We discover that the relative cost‐effectiveness of invasive animal control strategies is robust to climate change, with the management of feral pigs being the highest priority for conserving threatened species overall. Complementary sets of strategies to protect as many threatened species as possible under limited budgets change when climate change is considered, with additional strategies required to avoid impending extinctions from the region. Overall, we find that the ranking of strategies by cost‐effectiveness was relatively unaffected by including climate change into decision‐making, even though the benefits of the strategies were lower. Future climate conditions and impacts on range shifts become most important to consider when designing comprehensive management plans for the control of invasive animals under limited budgets to maximize the number of threatened species that can be protected.     

Hurricanes accelerated the Florida–Bahamas lionfish invasion

In this study, we demonstrate how perturbations to the Florida Current caused by hurricanes are relevant to the spread of invasive lionfish from Florida to the Bahamas. Without such perturbations, this current represents a potential barrier to the transport of planktonic lionfish eggs and larvae across the Straits of Florida. We further show that once lionfish became established in the Bahamas, hurricanes significantly hastened their spread through the island chain. We gain these insights through: (1) an analysis of the direction and velocity of simulated ocean currents during the passage of hurricanes through the Florida Straits and (2) the development of a biophysical model that incorporates the tolerances of lionfish to ocean climate, their reproductive strategy, and duration that the larvae remain viable in the water column. On the basis of this work, we identify 23 occasions between the years 1992 and 2006 in which lionfish were provided the opportunity to breach the Florida Current. We also find that hurricanes during this period increased the rate of spread of lionfish through the Bahamas by more than 45% and magnified its population by at least 15%. Beyond invasive lionfish, we suggest that extreme weather events such as hurricanes likely help to homogenize the gene pool for all Caribbean marine species susceptible to transport.     

Structural importance of the C-terminal region in pig aldo-keto reductase family 1 member C1 and their effects on enzymatic activity

Background

Pig aldo-keto reductase family 1 member C1 (AKR1C1) belongs to AKR superfamily which catalyzes the NAD(P)H-dependent reduction of various substrates including steroid hormones. Previously we have reported two paralogous pig AKR1C1s, wild-type AKR1C1 (C-type) and C-terminal-truncated AKR1C1 (T-type). Also, the C-terminal region significantly contributes to the NADPH-dependent reductase activity for 5α-DHT reduction. Molecular modeling studies combined with kinetic experiments were performed to investigate structural and enzymatic differences between wild-type AKR1C1 C-type and T-type.

Results

The results of the enzyme kinetics revealed that V _max and k _cat values of the T-type were 2.9 and 1.6 folds higher than those of the C-type. Moreover, catalytic efficiency was also 1.9 fold higher in T-type compared to C-type. Since x-ray crystal structures of pig AKR1C1 were not available, three dimensional structures of the both types of the protein were predicted using homology modeling methodology and they were used for molecular dynamics simulations. The structural comparisons between C-type and T-type showed that 5α-DHT formed strong hydrogen bonds with catalytic residues such as Tyr55 and His117 in T-type. In particular, C3 ketone group of the substrate was close to Tyr55 and NADPH in T-type.

Conclusions

Our results showed that 5α-DHT binding in T-type was more favorable for catalytic reaction to facilitate hydride transfer from the cofactor, and were consistent with experimental results. We believe that our study provides valuable information to understand important role of C-terminal region that affects enzymatic properties for 5α-DHT, and further molecular mechanism for the enzyme kinetics of AKR1C1 proteins.

     

Reversible cell cycle inhibition and premature aging features imposed by conditional expression of p16Ink4a

The cyclin‐dependent kinase (Cdk) inhibitor p16^Ink4a (p16) is a canonical mediator of cellular senescence and accumulates in aging tissues, where it constrains proliferation of some progenitor cells. However, whether p16 induction in tissues is sufficient to inhibit cell proliferation, mediate senescence, and/or impose aging features has remained unclear. To address these issues, we generated transgenic mice that permit conditional p16 expression. Broad induction at weaning inhibited proliferation of intestinal transit‐amplifying and Lgr5+ stem cells and rapidly imposed features of aging, including hair loss, skin wrinkling, reduced body weight and subcutaneous fat, an increased myeloid fraction in peripheral blood, poor dentition, and cataracts. Aging features were observed with multiple combinations of p16 transgenes and transactivators and were largely abrogated by a germline Cdk4 R24C mutation, confirming that they reflect Cdk inhibition. Senescence markers were not found, and de‐induction of p16, even after weeks of sustained expression, allowed rapid recovery of intestinal cell proliferation and reversal of aging features in most mice. These results suggest that p16‐mediated inhibition of Cdk activity is sufficient to inhibit cell proliferation and impose aging features in somatic tissues of mammals and that at least some of these aging features are reversible.