The state and conservation of Southeast Asian biodiversity

Southeast Asia is a region of conservation concern due to heavy losses of its native habitats. In this overview, we highlight the conservation importance of Southeast Asia by comparing its degree of species endemism and endangerment, and its rate of deforestation with other tropical regions (i.e., Meso-America, South America, and Sub-Saharan Africa). Southeast Asia contains the highest mean proportion of country-endemic bird (9%) and mammal species (11%). This region also has the highest proportion of threatened vascular plant, reptile, bird, and mammal species. Furthermore, not only is Southeast Asia’s annual deforestation rate the highest in the tropics, but it has also increased between the periods 1990–2000 and 2000–2005. This could result in projected losses of 13–85% of biodiversity in the region by 2100. Secondary habitat restoration, at least in certain countries, would allow for some amelioration of biodiversity loss and thus potentially lower the currently predicted extinction rates. Nonetheless, urgent conservation actions are needed. Conservation initiatives should include public education, sustaining livelihoods, and ways to enhance the sustainability of agriculture and increase the capacity of conservation institutions. Furthermore, these actions should be country-specific and not ignore areas heavily populated by humans, as they can also harbour high numbers of threatened species. We urge that cooperative conservation initiatives be undertaken and support (e.g., capacity-building) be given by more developed countries in the region and beyond.     

Unreported yet massive deforestation driving loss of endemic biodiversity in Indian Himalaya

Deforestation is a primary driver of biotic extinctions in the tropics. The impacts of deforestation in tropical biodiversity hotspots are of particular concern because these regions contain high concentrations of globally endemic species. However, the effects of large-scale deforestation on native biotas within the biodiversity hotspot of Himalaya remain poorly documented. Here we report on an alarming trend of deforestation in the Indian Himalaya and project the likely consequential extinctions of endemic taxa (species and subspecies) by 2100 across a broad range of taxonomic groups, including gymnosperms, angiosperms, fishes, amphibians, reptiles, birds, and mammals. With the current level of deforestation, by 2100 only about 10% of the land area of the Indian Himalaya will be covered by dense forest (>40% canopy cover)—a scenario in which almost a quarter of the endemic species could be wiped out, including 366 endemic vascular plant taxa and 35 endemic vertebrate taxa. We also show that inaccurate reporting of forest cover data by governmental institutions can result in underestimations of the biological impacts of deforestation, as well as potential miscalculations in land-use decisions (e.g., the construction of hydroelectric dams). Large-scale conservation efforts, including forest protection and reforestation, are urgently needed to avoid the impending deforestation-driven biodiversity losses in the Himalaya.     

Validation of an optical encoder during free weight resistance movements and analysis of bench press sticking point power during fatigue

During the concentric movement of the bench press, there is an initial high-power push after chest contact, immediately followed by a characteristic area of low power, the so-called "sticking region." During high-intensity lifting, a decline in power can result in a failed lift attempt. The purpose of this study was to determine the validity of an optical encoder to measure power and then employ this device to determine power changes during the initial acceleration and sticking region during fatiguing repeated bench press training. Twelve subjects performed a free weight bench press, a Smith Machine back squat, and a Smith Machine 40-kg bench press throw for power validation measures. All barbell movements were simultaneously monitored using cinematography and an optical encoder. Eccentric and concentric mean and peak power were calculated using time and position data derived from each method. Validity of power measures between the video (criterion) and optical encoder scores were evaluated by standard error of the estimate (SEE) and coefficient of variation (CV). Seven subjects then performed 4 sets of 6 free weight bench press repetitions progressively increasing from 85 to 95% of their 6 repetition maximum, with each repetition continually monitored by an optical encoder. The SEE for power ranged from 3.6 to 14.4 W (CV, 1.0-3.0%; correlation, 0.97-1.00). During the free weight bench press training, peak power declined by approximately 55% (p < 0.01) during the initial acceleration phase of the final 2 repetitions of the final set. Although decreases in power of the sticking point were significant (p < 0.01), as early as repetition 5 (-40%) they reached critically low levels in the final 2 repetitions (>-95%). In conclusion, the optical encoder provided valid measures of kinetics during free weight resistance training movements. The decline in power during the initial acceleration phase appears a factor in a failed lift attempt at the sticking point.     

Endemic predators, invasive prey and native diversity

Interactions between native diversity and invasive species can be more complex than is currently understood. Invasive ant species often substantially reduce diversity in the native ants diversity that act as natural control agents for pest insects. In Indonesia (on the island of Sulawesi), the third largest cacao producer worldwide, we show that a predatory endemic toad (Ingerophrynus celebensis) controls invasive ant (Anoplolepis gracilipes) abundance, and positively affects native ant diversity. We call this the invasive-naivety effect (an opposite of enemy release), whereby alien species may not harbour anti-predatory defences against a novel native predator. A positive effect of the toads on native ants may facilitate their predation on insect vectors of cacao diseases. Hence, toads may increase crop yield, but further research is needed on this aspect. Ironically, amphibians are globally the most threatened vertebrate class and are strongly impacted by the conversion of rainforest to cacao plantations in Sulawesi. It is, therefore, crucial to manage cacao plantations to maintain these endemic toads, as they may provide critical ecosystem services, such as invasion resistance and preservation of native insect diversity.     

Repeated assessment of exploration and novelty seeking in the human behavioral pattern monitor in bipolar disorder patients and healthy individuals

Background

Exploration and novelty seeking are cross-species adaptive behaviors that are dysregulated in bipolar disorder (BD) and are critical features of the illness. While these behaviors have been extensively quantified in animals, multivariate human paradigms of exploration are lacking. The human Behavioral Pattern Monitor (hBPM), a human version of the animal open field, identified a signature pattern of hyper-exploration in manic BD patients, but whether exploratory behavior changes with treatment is unknown. The objective of this study was to assess the sensitivity of the hBPM to changes in manic symptoms, a necessary step towards elucidating the neurobiology underlying BD.

Methodology and Principal Findings

Twelve acutely hospitalized manic BD subjects and 21 healthy volunteers were tested in the hBPM over three sessions; all subjects were retested one week after their first session and two weeks after their second session. Motor activity, spatial and entropic (degree of unpredictability) patterns of exploration, and interactions with novel objects were quantified. Manic BD patients demonstrated greater motor activity, extensive and more unpredictable patterns of exploration, and more object interactions than healthy volunteers during all three sessions. Exploration and novelty-seeking slightly decreased in manic BD subjects over the three sessions as their symptoms responded to treatment, but never to the level of healthy volunteers. Among healthy volunteers, exploration did not significantly decrease over time, and hBPM measures were highly correlated between sessions.

Conclusions/Significance

Manic BD patients showed a modest reduction in symptoms yet still demonstrated hyper-exploration and novelty seeking in the hBPM, suggesting that these illness features may be enduring characteristics of BD. Furthermore, behavior in the hBPM is not subject to marked habituation effects. The hBPM can be reliably used in a repeated-measures design to characterize exploration and novelty seeking and, in parallel with animal studies, can contribute to developing treatments that target neuropsychiatric disease.     

Pathways for compartmentalizing protein synthesis in eukaryotic cells: the template-partitioning model.

mRNAs encoding signal sequences are translated on endoplasmic reticulum (ER) -- bound ribosomes, whereas mRNAs encoding cytosolic proteins are translated on cytosolic ribosomes. The partitioning of mRNAs to the ER occurs by positive selection; cytosolic ribosomes engaged in the translation of signal-sequence-bearing proteins are engaged by the signal-recognition particle (SRP) pathway and subsequently trafficked to the ER. Studies have demonstrated that, in addition to the SRP pathway, mRNAs encoding cytosolic proteins can also be partitioned to the ER, suggesting that RNA partitioning in the eukaryotic cell is a complex process requiring the activity of multiple RNA-partitioning pathways. In this review, key findings on this topic are discussed, and the template-partitioning model, describing a hypothetical mechanism for RNA partitioning in the eukaryotic cell, is proposed.     

Poly(A)-Binding Protein 1 Partially Relocalizes to the Nucleus during Herpes Simplex Virus Type 1 Infection in an ICP27-Independent Manner and Does Not Inhibit Virus Replication

Infection of cells by herpes simplex virus type 1 (HSV-1) triggers host cell shutoff whereby mRNAs are degraded and cellular protein synthesis is diminished. However, virus protein translation continues because the translational apparatus in HSV-infected cells is maintained in an active state. Surprisingly, poly(A)-binding protein 1 (PABP1), a predominantly cytoplasmic protein that is required for efficient translation initiation, is partially relocated to the nucleus during HSV-1 infection. This relocalization occurred in a time-dependent manner with respect to virus infection. Since HSV-1 infection causes cell stress, we examined other cell stress inducers and found that oxidative stress similarly relocated PABP1. An examination of stress-induced kinases revealed similarities in HSV-1 infection and oxidative stress activation of JNK and p38 mitogen-activated protein (MAP) kinases. Importantly, PABP relocalization in infection was found to be independent of the viral protein ICP27. The depletion of PABP1 by small interfering RNA (siRNA) knockdown had no significant effect on viral replication or the expression of selected virus late proteins, suggesting that reduced levels of cytoplasmic PABP1 are tolerated during infection.The lytic replication cycle of herpes simplex virus type 1 (HSV-1) can be divided into three phases, immediate-early (IE), early (E), and late (L), that occur in a coordinated sequential gene expression program. IE proteins can regulate E and L gene expression, which produces proteins involved in DNA replication, capsid production, and virion assembly. HSV infection results in host cell shutoff to facilitate the efficient production of viral proteins. First, mRNA is degraded by the virion-associated vhs protein, and then ICP27, a multifunctional regulator of gene expression, inhibits pre-mRNA splicing. As most viral mRNAs are intronless, this abrogates the production of stable cellular mRNAs that can be exported to the cytoplasm and compete for translation with viral mRNAs (44).HSV mRNAs are capped and polyadenylated and so are translated via a normal cap-dependent mechanism. Translation initiation, during which translationally active ribosomes are assembled, is a tightly regulated process (21). Eukaryotic initiation factor 4F (eIF4F) (composed of eIF4E, eIF4G, and eIF4A) that binds the cap at the 5′ end of the mRNA promotes the recruitment of the 40S ribosomal subunit and associated factors, including eIF2-GTP initiator tRNA. The recognition of the start codon then promotes large ribosomal subunit joining. Poly(A)-binding protein 1 (PABP1), which binds and multimerizes on mRNA poly(A) tails, enhances translation initiation through interactions with the eIF4G component of the eIF4F cap-binding complex (20, 29, 32, 51) to circularize the mRNA in a “closed-loop” conformation (24). Key protein-RNA and protein-protein interactions in the translation initiation complex are strengthened by this PABP1-mediated circularization (12).HSV-1 maintains active viral translation in the face of host translational shutoff. Infection activates protein kinase R (PKR), which phosphorylates eIF2α, resulting in translation inhibition. However, HSV-1 ICP34.5 redirects protein phosphatase 1α to reverse eIF2α phosphorylation, abrogating the block to translation (17, 38). In addition, the HSV-1 US11 protein inhibits PKR and may also block PKR-mediated eIF2α phosphorylation (40, 42). HSV-1 infection also enhances eIF4F assembly in quiescent cells by the phosphorylation and proteasome-mediated degradation of the eIF4E-binding protein (4E-BP), which, when hypophosphorylated, can negatively regulate eIF4F complex formation (54). However, ICP6 may also contribute to eIF4F assembly by binding to eIF4G (55). Finally, ICP6 is required for Mnk-1 phosphorylation of eIF4E, but the mechanisms behind this remain unclear (54). ICP27 has also been implicated in translation regulation during HSV infection (6, 8, 10, 30) and may also activate p38 mitogen-activated protein (MAP) kinase that can phosphorylate eIF4E (16, 59).PABP1 appears to be a common cellular target of RNA and DNA viruses. PABP1 can undergo proteolysis, intracellular relocalization, or modification of its interaction with other translation factors in response to infection. For example, poliovirus induces host cell shutoff by cleaving PABP1, thus disrupting certain PABP1-containing complexes (28, 29). The rotavirus NSP3 protein can displace PABP1 from translation initiation complexes (41). However, NSP3 also interacts with a cellular protein, RoXaN, which is required to relocate PABP1 to the nucleus (13). Similarly, the Kaposi''s sarcoma herpesvirus (KSHV) SOX protein plays a role in relocating PABP1, its cofactor in cellular mRNA decay, to the nucleus (33). Although steady-state levels of PABP1 are highest in the cytoplasm of normal cells, where it has cytoplasmic functions, it is a nucleocytoplasmic shuttling protein (1). However, it is unclear how PABP1 enters or exits the nucleus, as it contains neither a canonical nuclear export nor an import signal.Here we describe the loss of PABP1 from cap-binding complexes and the partial relocation of PABP1 to the nucleus in HSV-1-infected cells in a time-dependent manner. Relocation is specific for PABP1, as other translation factors remained in the cytoplasm. Cells undergo stress during HSV-1 infection, and analysis of a variety of cell stresses revealed that PABP relocalization was also observed upon oxidative stress. Paxillin, a potential PABP1 nuclear chaperone, was phosphorylated, and the paxillin-PABP1 interaction was reduced during virus infection. However, the interaction was weak and cell type dependent, indicating that other effectors of PABP1 relocation in the infected cell must exist. Recently, the HSV-1 ICP27 protein was suggested to alter the PABP1 cellular location (6). However, infections with ICP27-null mutant viruses clearly demonstrated that ICP27 is not required for PABP1 nuclear relocation in the context of infection. Although HSV-1 mRNAs are translated by a normal cap-dependent mechanism known to be enhanced by PABP1, small interfering RNA (siRNA) knockdown of PABP1 indicated that at late times of infection, the translation of certain virus late proteins tolerates very low levels of PABP1.     

Heterotachy and tree building: a case study with plastids and eubacteria

The nature of heterotachy at the center of recent controversy over the relative performance of tree-building methods is different from the form of heterotachy that has been inferred in empirical studies. The latter have suggested that proportions of variable sites (p(var)) vary among orthologues and among paralogues. However, the strength of this inference, describing what may be one of the most important evolutionary properties of sequence data, has remained weak. Consequently, other models of sequence evolution have been proposed to explain some long-branch attraction (LBA) problems that could be attributed to differences in p(var). For an empirical case with plastid and eubacterial RNA polymerase sequences, we confirm using capture-recapture estimates and simulations that p(var) can differ among orthologues in anciently diverged evolutionary lineages. We find that parsimony and a least squares distance method that implements an overly simple model of sequence evolution are susceptible to LBA induced by this form of heterotachy. Although homogeneous maximum likelihood inference was found to be robust to model misspecification in our specific example, we caution against assuming that it will always be so.     

Effector and memory CD8+ T cells can be generated in response to alloantigen independently of CD4+ T cell help

There is now considerable evidence suggesting that CD8(+) T cells are able to generate effector but not functional memory T cells following pathogenic infections in the absence of CD4(+) T cells. We show that following transplantation of allogeneic skin, in the absence of CD4(+) T cells, CD8(+) T cells become activated, proliferate, and expand exclusively in the draining lymph nodes and are able to infiltrate and reject skin allografts. CD44(+)CD8(+) T cells isolated 100 days after transplantation rapidly produce IFN-gamma following restimulation with alloantigen in vitro. In vivo CD44(+)CD8(+) T cells rejected donor-type skin allografts more rapidly than naive CD8(+) T cells demonstrating the ability of these putative memory T cells to mount an effective recall response in vivo. These data form the first direct demonstration that CD8(+) T cells are able to generate memory as well as effector cells in response to alloantigen during rejection in the complete absence of CD4(+) T cells. These data have important implications for the design of therapies to combat rejection and serve to reinforce the view that CD8(+) T cell responses to allografts require manipulation in addition to CD4(+) T cell responses to completely prevent the rejection of foreign organ transplants.