Has the Time Come for Big Science in Wildlife Health?

The consequences of wildlife emerging diseases are global and profound with increased burden on the public health system, negative impacts on the global economy, declines and extinctions of wildlife species, and subsequent loss of ecological integrity. Examples of health threats to wildlife include Batrachochytrium dendrobatidis, which causes a cutaneous fungal infection of amphibians and is linked to declines of amphibians globally; and the recently discovered Pseudogymnoascus (Geomyces) destructans, the etiologic agent of white nose syndrome which has caused precipitous declines of North American bat species. Of particular concern are the novel pathogens that have emerged as they are particularly devastating and challenging to manage. A big science approach to wildlife health research is needed if we are to make significant and enduring progress in managing these diseases. The advent of new analytical models and bench assays will provide us with the mathematical and molecular tools to identify and anticipate threats to wildlife, and understand the ecology and epidemiology of these diseases. Specifically, new molecular diagnostic techniques have opened up avenues for pathogen discovery, and the application of spatially referenced databases allows for risk assessments that can assist in targeting surveillance. Long-term, systematic collection of data for wildlife health and integration with other datasets is also essential. Multidisciplinary research programs should be expanded to increase our understanding of the drivers of emerging diseases and allow for the development of better disease prevention and management tools, such as vaccines. Finally, we need to create a National Fish and Wildlife Health Network that provides the operational framework (governance, policies, procedures, etc.) by which entities with a stake in wildlife health cooperate and collaborate to achieve optimal outcomes for human, animal, and ecosystem health.     

Freezing of Gait in Parkinson’s Disease: An Overload Problem?

Freezing of gait (FOG) is arguably the most severe symptom associated with Parkinson’s disease (PD), and often occurs while performing dual tasks or approaching narrowed and cluttered spaces. While it is well known that visual cues alleviate FOG, it is not clear if this effect may be the result of cognitive or sensorimotor mechanisms. Nevertheless, the role of vision may be a critical link that might allow us to disentangle this question. Gaze behaviour has yet to be carefully investigated while freezers approach narrow spaces, thus the overall objective of this study was to explore the interaction between cognitive and sensory-perceptual influences on FOG. In experiment #1, if cognitive load is the underlying factor leading to FOG, then one might expect that a dual-task would elicit FOG episodes even in the presence of visual cues, since the load on attention would interfere with utilization of visual cues. Alternatively, if visual cues alleviate gait despite performance of a dual-task, then it may be more probable that sensory mechanisms are at play. In compliment to this, the aim of experiment#2 was to further challenge the sensory systems, by removing vision of the lower-limbs and thereby forcing participants to rely on other forms of sensory feedback rather than vision while walking toward the narrow space. Spatiotemporal aspects of gait, percentage of gaze fixation frequency and duration, as well as skin conductance levels were measured in freezers and non-freezers across both experiments. Results from experiment#1 indicated that although freezers and non-freezers both walked with worse gait while performing the dual-task, in freezers, gait was relieved by visual cues regardless of whether the cognitive demands of the dual-task were present. At baseline and while dual-tasking, freezers demonstrated a gaze behaviour that neglected the doorway and instead focused primarily on the pathway, a strategy that non-freezers adopted only when performing the dual-task. Interestingly, with the combination of visual cues and dual-task, freezers increased the frequency and duration of fixations toward the doorway, compared to non-freezers. These results suggest that although increasing demand on attention does significantly deteriorate gait in freezers, an increase in cognitive demand is not exclusively responsible for freezing (since visual cues were able to overcome any interference elicited by the dual-task). When vision of the lower limbs was removed in experiment#2, only the freezers’ gait was affected. However, when visual cues were present, freezers’ gait improved regardless of the dual-task. This gait behaviour was accompanied by greater amount of time spent looking at the visual cues irrespective of the dual-task. Since removing vision of the lower-limbs hindered gait even under low attentional demand, restricted sensory feedback may be an important factor to the mechanisms underlying FOG.     

Has the code for protein translocation been broken?

Polypeptides chains are segregated by the translocon channel into secreted or membrane-inserted proteins. Recent reports claim that an in vivo system has been used to break the "amino acid code" used by translocons to make the determination of protein type (i.e. secreted or membrane-inserted). However, the experimental setup used in these studies could have confused the derivation of this code, in particular for polar amino acids. These residues are likely to undergo stabilizing interactions with other protein components in the experiment, shielding them from direct contact with the inhospitable membrane. Hence, it is our view that the "code" for protein translocation has not yet been deciphered and that further experiments are required for teasing apart the various energetic factors contributing to protein translocation.     

Tau Aggregation in Alzheimer's Disease: What Role for Phosphorylation?

The crucial role of the neuronal Tau protein in microtubule stabilization and axonal transport suggests that too little or too much Tau might lead to neuronal dysfunction. The presence of a hyper phosphorylated but non aggregated molecule as a toxic species that might sequester normal Tau is discussed. We present recent in vitro results that might allow us to dissect the role of individual phosphorylation sites on its structure and function. We also discuss in this review the role of phosphorylation for the aggregation of the neuronal Tau protein, and compare it to the aggregation induced by external poly anions.Key Words: Tau, phosphorylation, paired helical filaments, microtubule, Alzheimer''s diseaseAlzheimer''s disease and its concomitant cognitive decline form a grim perspective for society, especially as the average life span of our population is expected to increase. This is even more the case as part of the basic knowledge concerning the disease is still under discussion. Indeed, contrary to other major disease classes such as cancer where a number of biological players have been well defined and have turned into potential targets for drug development, the molecular events leading to neuronal degeneration and ensuing cognitive decline are not completely understood. Even more, in a remarkable paradigm shift, both the extracellular β amyloid plaques and intracellular neuronal filaments and tangles, previously thought of as the main molecular markers and also the main culprits for the disease, are now considered as an ultimate rescue mechanism of the diseased brain.¹ This change in perception, equally found in other neuronal diseases such as Huntington''s disease,² deprives us from an obvious pharmacological target, even though it is not clear what we get in exchange. Alzheimer derived diffusible ligands (ADDLs) are β amyloid peptide oligomers,³ without a clear definition though of their precise molecular content and conformation. As for Tau, the major component of the neuronal filaments and tangles,⁴ a hyperphosphorylated but soluble form rather than the aggregated protein might be the toxic species. Finally, even the two opposing viewpoints of “gain of toxic function” versus “loss of physiological function” have not yet been sorted out for neither molecular marker, be it for β amyloid⁵ or Tau.⁶ The functional overlap between Tau and other microtubule associated proteins (MAPs), leading to the absence of a clear phenotype for Tau knockout mice, does not even lead to a clear cut answer to this question. However, both an overproduction of the longer β amyloid [1–42] peptide and an abnormal (hyper)phosphorylation of Tau seem related to the disease, and it remains a major challenge to tease out the precise role of these components in the disease progression.From a clinical perspective, Alzheimer''s diseased neurofibrillary pathology has been post mortem scored according to the Braak rules.⁷ This latter staging is based upon quantifying the neurofibrillary lesions in distinct regions from the brain using a silver iodate technique originally proposed by Gallyas.⁸ Technical constraints, however, have limited this staging to research centers, and have prompted the same group to develop a more routinely accessible immunochemical method.⁹ The latter uses the AT8 antibody, that immunostains a hyperphosphorylated Tau form, be it in its soluble or aggregated form.¹⁰ Importantly, the comparative imaging of brain slices with silver or with the antibody allow a nearly identical staging, establishing an unambiguous link between hyperphosphorylation and the presence of tangles. In this review, we want to focus on the link between (hyper)phosphorylation and disease related aspects of Tau, and want to discuss how in vitro studies might shed further light on the link between Tau post translational modifications, its aggregation and the general modulation of its functional aspects.A first question concerns a clear definition of “hyper ” and “abnormal” phosphorylation. Normal Tau contains 2–3 phosphate groups, assuring the dynamic character of the microtubule network (see below). Tau in its aggregated form (as Paired Helical Filaments (PHFs) or Straight Filaments (SF)) contains 5–9 moles of phosphate/ mole of the protein, defining it as hyper phosphorylated.¹¹ Overlap exists between the AD and normal adult patterns of phosphorylation, making the quantitative differences in the level of phosphate incorporation one of the decisive parameters.¹² Specific phosphorylation patterns also seem generated in the disease, and these form the basis for a large class of AD specific antibodies, including the above mentioned AT-8 antibody¹⁰ with specificity for both phospho-Ser199/phospho-Ser202 and phosphoThr205. All these data indicate that some phospho “bar code” might exist, whereby some sites are important for its physiological role of microtubule dynamics regulator, whereas another set (overlapping or not with the previous one) leads to aggregation into PHFs, degradation and/or toxic function.Untangling this code will be a major enterprise, largely due to the large number of phosphorylation sites on Tau together with the complex interplay of the different kinases involved. Underlying many of the difficulties is the analytical problem of characterizing samples at a qualitative (what sites?) and quantitative (what degree of phosphate incorporation?) level. Both mass spectrometry and immunochemistry have well recognized advantages of sensitivity for characterizing a phosphorylation pattern of Tau samples derived from in vivo material, and the recent demonstration of top down mass spectrometry for the characterization of complex protein molecules without previous digestion has the potential of opening up a novel observation window for such complex patterns.¹³ We recently have demonstrated that NMR spectroscopy equally might play a role in characterizing a complex phosphorylation pattern.¹⁴ Although plagued by an extremely low sensitivity compared to the above mentioned methods and requiring a stable isotope labelled substrate protein, it has the potential to answer both questions of what site(s) are modified and to what extent, and its non destructive character leads to well-characterized samples that then can be used for structural and functional assays. As an example, after a full characterization of the cAMP dependent kinase (PKA) generated phospho-pattern (Fig. 1A), we acrylodan labelled the same sample and used it to quantify the binding parameters to taxol-stabilized microtubules. This allowed us to demonstrate that phosphorylation of the Ser214 position causes an affinity drop by two orders of magnitude (Fig. 1B), without detaching this part of the protein from the microtubule surface. Despite this, the protein is not completely devoid of polymerization activity (Fig. 1c), underscoring the complexity of relationship between phosphorylation status and activity.Open in a separate windowFigure 1(Left) NMR assignment of the phosphorylation pattern of Tau after incubation with PKA¹⁴. (Right) Effect of a single phosphorylation event at Ser214 on the microtubule binding properties¹⁵ (right, top) or on its tubulin polymerizing capacity (right, bottom). In both panes, the upper curve is Tau, and the lower one pSer214 Tau. The affinity of acrylodan labeled Tau towards taxol stabilzed microtubules was measured by FRET for Tau (solid curve) or pSer214 Tau (dotted line), whereas turbidity was used to evaluate the polymerization of tubulin into microtubules.The axon of the mature neuron is characterized by a polarized microtubule orientation, while dendrites contain microtubules of mixed polarity.¹⁶ At the core of the complex neuronal transport machinery that assures correct subcellular localization of organelles, mRNAs and proteins, the dynamic stability of the microtubular network is of uttermost importance for the correct functioning of the neuron.¹⁷ Tau localizes mostly to axons, whereas MAP2 localization is largely restriced to the somatodendritic compartment. As long-distance trafficking uses mainly the axonal microtubule railway and Tau does (de)stabilize this network, it is of no surprise that a deregulation of its expression and/or phosphorylation level can lead to defects in axonal transport such as found in the early stages of AD¹⁸ or even at the later stages of the disease.¹⁹ Overexpression of the longest human tau isoform in wild-type mice leads to motor defects similar to those observed in progressive supranuclear palsy, another tauopathy,²⁰ but crossing these mice with constitutively active Gsk3β transgenic mice reduces importantly the number of axonal dilatations in brain and spinal cord, the axonal degeneration and muscular atrophy, and alleviates practically all motor problems.²¹ The amount of Tau associated with microtubules was reduced by 50% in preparations from brain and spinal cord of these mice that overexpress both human Tau and Gsk3β compared to the hTau transgenic mice. In vitro, Tau accumulation at the surface of taxol stabilized microtubules has been observed, albeit with a lower affinity than the direct interaction,²² and these aggregates might correspond to the traffick deregulating patches of Tau causing the axonopathy. In the hTau/Gsk3β mouse model, however, the authors did not detect true Tau filaments or neurofibrillary tangles, suggesting that the phosphorylation by this sole enzyme is enough to create a phosphorylation pattern of Tau that avoids its accumulation on the microtubule surface, but that does not lead to its aggregation into PHFs. Using a different mouse model overexpressing the naturally aggregating P301L hTau mutant, Le Corre et al. tested a small molecule inhibitor of the Erk2 kinase (with, however, a similar inhibition for other kinases such as cdc2, Gsk3β, PKA and PKC), and found that this compound does reduce motor impairments in a P301L Tau transgenic mouse model.²³ Without affecting tangle counts, the inhibitor causes a reduction of soluble aggregated hyperphosphorylated tau, although the exact nature of this species remains to be defined. The conclusions of this study with the kinase inhibitor build upon previous work by the group of Iqbal, who showed that (i) a hyperphosphorylated but soluble form of Tau (AD P-Tau) exists¹¹ (ii) it interacts with normal Tau,²⁴ and (iii) aggregation of this AD P-Tau into filaments neutralizes this interaction.²⁵ This species would not interact with tubulin, but even when present in a minor concentration, it would form a sink for the normal Tau, thereby leading to disruption of the microtubular network. When the disease progresses, the concentration of AD P-Tau increases, leading eventually to its aggregated form. Using an inducible model of the same hTau (P301L) transgenic mouse, Santa Cruz et al. showed that the soluble hyperphosphorylated species leads to neuronal degeneration, and this irrespective of ongoing tangle formation after the shutting off of the transgene.²⁶Whereas these studies tend to indicate that the filaments of aggregated Tau are not the main culprit, questions remain as for the identity of the species that would be responsible for the sequestration of normal Tau, and hence lead to microtubule impairment. In vitro studies hereby can play an important role, as they can hopefully reproduce and subsequently allow the identification of the molecular features that define these species. We have thus set out to identify the kinase(s) that might lead to a species that (i) interacts with normal Tau with such an affinity that it might disrupt the Tau:microtubule interaction, and (ii) that might lead to the formation of amyloid aggregates without the addition of any anionic cofactors. As for the first requirement, recent data by FRET spectroscopy using an acrylodan labelled Tau and taxol stabilized microtubules have shown that the affinity of Tau for the microtubular surface is high, with a dissociation constant K_D of the order of 20 nM.^15,27 When Tau is the polymerizing agent, the binding is even characterized by a quasi irreversible component.²⁷ Finally, the tubulin concentration in the neuronal axon is high, so for P-Tau to compete successfully for this MT associated Tau, one would need a very high affinity constant. Alternatively, two aspects of the same phosphorylation event(s) might reinforce this scenario, whereby a given subset of kinases generates the AD P-Tau species, and another one leads to destabilization of the Tau:MT interaction. In this aspect, it is interesting to note that the sole phosphorylation of Ser214 by PKA can lead to a hundred fold decrease in affinity for the MT surface (Fig. 1B).As for the molecular aspects of Tau aggregation, most if not all of the present work has followed up on the initial observation that the addition of poly anions such as heparin can promote the aggregation of Tau into PHFs that under the electron microscope have the same aspect as those fibers isolated form the brains of AD patients.²⁸ Because later on, other poly anions such as the surface of arachidonic acid micelles or RNA equally were found to promote the fibrilization process,^29,30 charge compensation rather than the precise anion seems to play an important role in the process. Following up on earlier mapping studies of the core region with proteases,³¹ we have recently NMR spectroscopy to (i) define the immobile core region with a per-residue precision³² and (ii) map the interaction between heparin fragments and Tau.³³ We confirmed the pronounced interaction of heparin with both the regions up and downstream of the microtubule binding repeats (MTBRs), but observed equally a strong interaction with the second and third repeat.³³ Of special interest was the observation that all heparin seems integrated in the fiber, as all visible signals of mobility retaining regions resonated at exactly the same frequency as the free Tau protein. EPR data on full length Tau PHF suggested a model for the fibers with a parallel in-register stacking of β strand,³⁴ similar to the recently obtained high resolution data on crystals³⁵ or fibers³⁶ derived from a prion peptide, or of fibers from β amyloid peptide.³⁷ Those peptide arrangements show a “dry” interface where the shape complementarity of facing side chains leaves little room even for water molecules,³⁵ further excluding the possibility that heparin intercalates between the facing β sheets. Considering that the NMR invisible solid like core region in the heparin induced PHFs spanning over hundred amino acids is not necessarily the true amyloid region, we can imagine that this region consists both of immobilized but disordered regions, and of genuine amyloid regions defined by some regular stacking. In other systems, this amyloid region consists of rather small peptides, and if we consider the R2 and R3 repeats, we can imagine that they would be no longer than the V₂₇₅QIINK₂₈₀ (in PHF6*) or V₃₀₆QIVYK₃₁₁ (in PHF6) hexapeptides, previously identified by peptide mapping studies as the aggregation nuclei.^38,39 Stacking of these peptides into parallel in register β sheets would however lead to the formation of ladder-like intermolecular stretches of the same residues. The K₂₈₀–K₂₈₁ and K₃₁₁P₃₁₂ motifs would create a continuous stretch of positive charges with accompanying strong electrostatic repulsion, unless a mechanism of charge neutralization is provided. One of such mechanisms is the deletion of at least one lysine, and ΔK₂₈₀ indeed is a mutant which aggregates more rapidly.⁴⁰ The in vitro study suggests a model where the heparin polymer wraps tightly around the outer surface of the (double) pleated sheets, and thereby neutralizes the inhibitory charge repulsions that would occur in a continuous but intermolecularly formed polylysine stretch. The heterogeneous nature of most heparin preparations thereby might lead to fibers of lesser regularity than those formed by isolated synthetic peptides. Solid state NMR and/or crystallography, as techniques that might resolve the recent controversy concerning the structure of the core region—only cross β strands^41,42 or equally some α helical structure^43,44—will require homogeneous preparations of filaments, and will have to distinguish between the amorphous and truly amyloid phases in this core. Our finding that subtle variations in size and/or charge distribution between two batches of the same commercial heparin can lead to fiber formation of all Tau molecules^32,45 or only less than 30% (Sillen A, Lippens G, unpublished data) suggests that other poly anions might be better suited to prepare fibers for structural biology. Careful dosing and characterization of the fibers through a combination of biochemical and low resolution spectroscopic methods will thereby be one of the corner stones for the structural elucidation of the PHF core region.Can phosphorylation lead to an equivalent charge compensation mechanisms, or are other structural factors in play? The AD P-Tau was shown to form filaments upon incubation at physiologically relevant conditions.⁴⁶ Upon dephosphorylation, however, all isoforms loose this capacity, suggesting that time wise, phosphorylation comes before aggregation. However, the same study revealed that the three or four microtubule binding domains cannot be phosphorylated for aggregation to occur, limiting the role of phosphorylation to charge compensation of the inhibitory regions up- and downstream of the MTBRs. Although in agreement with the finding that the isolated MTBRs aggregate more readily than the full length protein, this seems in contradiction with the aggregation model induced by exogeneous poly anions (Fig. 2), where charge compensation is not limited to the MTBR flanking regions, but also within the repeats itself. We are presently working with recombinant Tau and different kinases to reproduce the aggregation without additional poly anions. This should allow us to apply our structural biology tools to the fiber formation induced by the sole event of phosphorylation, and hence get better insight in the physiological aggregation mechanism. At the same time, we hope to get insight in the important but unanswered question to what certain AD specific antibodies really detect. Indeed, some of these have been classified as “conformational antibodies.” Structural elucidation of the antibody in complex with its phosphorylated Tau antigen could be a major step forward in the understanding of the distinguishing features of PHF-Tau, and hence in the aggregation mechanism.Open in a separate windowFigure 2(Left) Electron microscopy picture of a Tau PHF promoted by incubation with heparin. (Right) Model for the amyloid core of the fiber, with heparin providing for the negative charges essential to compensate for the positive stretch formed by parallel in register stacking of lysine containing peptides.³³Phosphorylation is evidently not only a signal for aggregation, but is present in very many physiological processes. Just to mention a few aspects concerning Tau, it promotes equally the interaction with Hsc70, which acts as a linker of the CHIP E3 ligase, thereby establishing a link with its degradation.⁴⁷ Other protein components such as the prolyl cis/trans isomerase Pin1 equally interact with the phosphorylated Tau, and might even restore its incapacity of microtubule formation.⁴⁸ Very recently, phosphorylated Tau was shown to interact with actin filaments, thereby influencing their bundling and association into so-called Hirano bodies.⁴⁹ A detailed biochemical/biophysical study of these different pathways might lead to a better understanding of Tau''s role in Alzheimer''s disease, and hopefully open a novel therapeutic window on this disease.     

Psychocultural Studies: Has the Time Come?

Handbook of Cross-Cultural Psychology. Perspectives. Volume 1 . Harry C. Triandis and Willliam Wilson Lambert , eds.
Handbook of Cross-Cultural Psychology. Methodology. Volume 2 . Harry C. Triandis and John W. Berry eds.
Handbook of Cross-Cultural Psychology. Basic Processes. Volume 1 . Harry C. Triandis and Walter Lonner , eds.
Handbook of Cross-Cultural Psychology. Developmental Psychology. Volume 4 . Harry C. Triandis and Alastair Heron , eds.
Handbook of Cross-Cultural Psychology. Social Psychology. Volume 5 . Harry C. Triandis and Richard W. Brislin eds.
Handbook of Cross-Cultural Psychology. Psychopathology, Volume 6 . Harry C. Triandis and Juris G. Draguns eds.
Cross-cultural Contributions of Psychology . Lutz H. Echkensberger, Walter J. Lonner and Ype H. Poortinga eds.
Perspectives on Cross-Cultural Psychology . Anthony J. Marsella. Roland G. Tharp and Thomas J. Ciborowski. eds.
Studies in Cross-Culturla Psychology. Volume 2 . Neil Warren , ed.     

Genetic Testing for Huntington's Disease: How Is the Decision Taken?

Research on genetic decision-making normally constructs the decision as an opportunity for choice. However, minimal research investigates how these decisions are taken and whether those who live with genetic risk perceive the test as an opportunity for choice. Employing semistructured interviews with at-risk persons, this study explored decisions about genetic testing for Huntington's disease (HD)--a fatal genetic disorder. A primary aim was to understand how test decisions were perceived. Qualitative data analysis revealed four decision pathways: (1) no decision to be made, (2) constrained decisions, (3) reevaluating the decision, and (4) indicators of HD. Contrary to the rational, "information-processor" approach to decision making, some test decisions were immediate and automatic. These stories challenged the conventional construction of a genetic-test decision as an opportunity for choice. Participant narratives suggested that this construction may be inadequate, at least for some people who live with genetic risk. Test decisions were sometimes constrained by perceived responsibility to other family members, notably offspring. For others at risk, the test decision was a dynamic process of critical thought and evaluation. Finally, behaviors that could be symptoms of HD were the catalyst for testing.     

Influenza Seasonality in the Tropics and Subtropics – When to Vaccinate?

BackgroundThe timing of the biannual WHO influenza vaccine composition selection and production cycle has been historically directed to the influenza seasonality patterns in the temperate regions of the northern and southern hemispheres. Influenza activity, however, is poorly understood in the tropics with multiple peaks and identifiable year-round activity. The evidence-base needed to take informed decisions on vaccination timing and vaccine formulation is often lacking for the tropics and subtropics. This paper aims to assess influenza seasonality in the tropics and subtropics. It explores geographical grouping of countries into vaccination zones based on optimal timing of influenza vaccination.MethodsInfluenza seasonality was assessed by different analytic approaches (weekly proportion of positive cases, time series analysis, etc.) using FluNet and national surveillance data. In case of discordance in the seasonality assessment, consensus was built through discussions with in-country experts. Countries with similar onset periods of their primary influenza season were grouped into geographical zones.ResultsThe number and period of peak activity was ascertained for 70 of the 138 countries in the tropics and subtropics. Thirty-seven countries had one and seventeen countries had two distinct peaks. Countries near the equator had secondary peaks or even identifiable year-round activity. The main influenza season in most of South America and Asia started between April and June. The start of the main season varied widely in Africa (October and December in northern Africa, April and June in Southern Africa and a mixed pattern in tropical Africa). Eight “influenza vaccination zones” (two each in America and Asia, and four in Africa and Middle East) were defined with recommendations for vaccination timing and vaccine formulation. The main limitation of our study is that FluNet and national surveillance data may lack the granularity to detect sub-national variability in seasonality patterns.ConclusionDistinct influenza seasonality patterns, though complex, could be ascertained for most countries in the tropics and subtropics using national surveillance data. It may be possible to group countries into zones based on similar recommendations for vaccine timing and formulation.     

Problem-Elephant Translocation: Translocating the Problem and the Elephant?

Human-elephant conflict (HEC) threatens the survival of endangered Asian elephants (Elephas maximus). Translocating “problem-elephants” is an important HEC mitigation and elephant conservation strategy across elephant range, with hundreds translocated annually. In the first comprehensive assessment of elephant translocation, we monitored 16 translocations in Sri Lanka with GPS collars. All translocated elephants were released into national parks. Two were killed within the parks where they were released, while all the others left those parks. Translocated elephants showed variable responses: “homers” returned to the capture site, “wanderers” ranged widely, and “settlers” established home ranges in new areas soon after release. Translocation caused wider propagation and intensification of HEC, and increased elephant mortality. We conclude that translocation defeats both HEC mitigation and elephant conservation goals.     

Does the Establishment of Sustainable Use Reserves Affect Fire Management in the Humid Tropics?

Tropical forests are experiencing a growing fire problem driven by climatic change, agricultural expansion and forest degradation. Protected areas are an important feature of forest protection strategies, and sustainable use reserves (SURs) may be reducing fire prevalence since they promote sustainable livelihoods and resource management. However, the use of fire in swidden agriculture, and other forms of land management, may be undermining the effectiveness of SURs in meeting their conservation and sustainable development goals. We analyse MODIS derived hot pixels, TRMM rainfall data, Terra-Class land cover data, socio-ecological data from the Brazilian agro-census and the spatial extent of rivers and roads to evaluate whether the designation of SURs reduces fire occurrence in the Brazilian Amazon. Specifically, we ask (1) a. Is SUR location (i.e., de facto) or (1) b. designation (i.e. de jure) the driving factor affecting performance in terms of the spatial density of fires?, and (2), Does SUR creation affect fire management (i.e., the timing of fires in relation to previous rainfall)? We demonstrate that pre-protection baselines are crucial for understanding reserve performance. We show that reserve creation had no discernible impact on fire density, and that fires were less prevalent in SURs due to their characteristics of sparser human settlement and remoteness, rather than their status de jure. In addition, the timing of fires in relation to rainfall, indicative of local fire management and adherence to environmental law, did not improve following SUR creation. These results challenge the notion that SURs promote environmentally sensitive fire-management, and suggest that SURs in Amazonia will require special attention if they are to curtail future accidental wildfires, particularly as plans to expand the road infrastructure throughout the region are realised. Greater investment to support improved fire management by farmers living in reserves, in addition to other fire users, will be necessary to help ameliorate these threats.     

Has the adipokine profile an influence on the catch-up growth type in small for gestational age infants?

Journal of Physiology and Biochemistry - Infants born small for gestational age (SGA) are at increased risk of perinatal morbidity, persistent short stature, and metabolic alterations in later...     

Disease mutations in disordered regions--exception to the rule?

Intrinsically disordered proteins (IDPs) have been implicated in a number of human diseases, including cancer, diabetes, neurodegenerative and cardiovascular disorders. Although for some of these conditions molecular mechanisms are now better understood, the big picture connecting distinct structural properties and functional repertoire of IDPs to pathogenesis and disease progression is still incomplete. Recent studies suggest that signaling and regulatory roles carried out by IDPs require them to be tightly regulated, and that altered IDP abundance may lead to disease. Here, we propose another link between IDPs and disease that takes into account disease-associated missense mutations located in the intrinsically disordered regions. We argue that such mutations are more prevalent and have larger functional impact than previously thought. In addition, we demonstrate that deleterious amino acid substitutions that cause disorder-to-order transitions are particularly enriched among disease mutations compared to neutral polymorphisms. Finally, we discuss potential differences in functional outcomes between disease mutations in ordered and disordered regions, and challenge the conventional structure-centric view of missense mutations.     

Is There an Association between Dryland Salinity and Ross River Virus Disease in Southwestern Australia?

Land use change has the potential to cause severe ecosystem degradation and drive changes in disease transmission and emergence. Broadscale clearing of native vegetation for agriculture in southwestern Australia has resulted in severe ecosystem degradation, which has been compounded by the subsequent development of large areas of dryland salinity. The mosquito-borne disease, Ross River virus (RRV), has been noted as a potential adverse human health outcome in these salinity affected regions. The association between dryland salinity and RRV disease was therefore tested by undertaking a spatial analysis of disease notification records using standard and Bayesian techniques. To overcome inherent limitations with notification data, serological RRV antibody prevalence was also investigated. Neither method revealed a significant association with dryland salinity, however, the spatial scale imposed limited the sensitivity of both studies. Thus, further multidisciplinary studies are required to overcome these limitations and advance understanding of this ecosystem health issue, particularly using variables that can be investigated on a finer scale.