Observed trends of soil fauna in the Antarctic Dry Valleys: early signs of shifts predicted under climate change.

Long-term observations of ecological communities are necessary for generating and testing predictions of ecosystem responses to climate change. We investigated temporal trends and spatial patterns of soil fauna along similar environmental gradients in three sites of the McMurdo Dry Valleys, Antarctica, spanning two distinct climatic phases: a decadal cooling trend from the early 1990s through the austral summer of February 2001, followed by a shift to the current trend of warming summers and more frequent discrete warming events. After February 2001, we observed a decline in the dominant species (the nematode Scottnema lindsayae) and increased abundance and expanded distribution of less common taxa (rotifers, tardigrades, and other nematode species). Such diverging responses have resulted in slightly greater evenness and spatial homogeneity of taxa. However, total abundance of soil fauna appears to be declining, as positive trends of the less common species so far have not compensated for the declining numbers of the dominant species. Interannual variation in the proportion of juveniles in the dominant species was consistent across sites, whereas trends in abundance varied more. Structural equation modeling supports the hypothesis that the observed biological trends arose from dissimilar responses by dominant and less common species to pulses of water availability resulting from enhanced ice melt. No direct effects of mean summer temperature were found, but there is evidence of indirect effects via its weak but significant positive relationship with soil moisture. Our findings show that combining an understanding of species responses to environmental change with long-term observations in the field can provide a context for validating and refining predictions of ecological trends in the abundance and diversity of soil fauna.

Pharmacological interrogation of a rodent forced ambulation model: leveraging gait impairment as a measure of pain behavior pre-clinically.

OBJECTIVE: The aim of this study was to investigate whether inflammogen-induced temporal and spatial gait changes in a rodent forced-ambulation paradigm were sensitive to pharmacological intervention with both clinically validated and novel analgesics. METHODS: Using the GaitScan (CleverSys Inc., Reston, VA) treadmill system, we identified four functional endpoints inspired by clinical literature and sensitive to unilateral joint injury induced by intra-articular Complete Freund's Adjuvant (CFA). These endpoints included: range of motion, normalized stance distance, stance/swing ratio, and paw print size as a measure of guarding; collectively, these measures are proposed to serve as a high fidelity index of joint pain. We then examined the ability of known analgesic mechanisms to attenuate gait impairment as measured by this index. RESULTS: Clinically efficacious opioids, Nonsteroidal anti-inflammatory drugs (NSAIDs), and the yet unapproved anti-NGF antibody dose-dependently attenuated the CFA)-induced gait deficits, while a TNF-alpha fusion protein blocker had no effect on gait, but did produce a reduction in swelling. As well, the time course for gait impairment in the model appears to be distinct from the traditional endpoint of tactile hypersensitivity, offering the potential to assess a novel functional pain phenotype. CONCLUSIONS: In response to the call for more functional pain measures, we submit this composite gait score as a novel endpoint to interrogate joint pain pre-clinically. As the etiology of human osteoarthritis (OA) remains unclear, this model/endpoint cannot attempt to improve construct validity, but may provide an additional dimension to interrogate pain-induced gait deficits.

Pump-probe spectrometer for measuring x-ray induced strain.

A hard x-ray pump-probe spectrometer using a multi-crystal Bragg reflector is demonstrated at a third generation synchrotron source. This device derives both broadband pump and monochromatic probe pulses directly from a single intense, broadband x-ray pulse centered at 8.767 keV. We present a proof-of-concept experiment which directly measures x-ray induced crystalline lattice strain.

Nuclear cyclophilins affect spliceosome assembly and function in vitro.

Cyclophilins are ubiquitously expressed proteins that bind to prolines and can catalyse cis/trans isomerization of proline residues. There are 17 annotated members of the cyclophilin family in humans, ubiquitously expressed and localized variously to the cytoplasm, nucleus or mitochondria. Surprisingly, all eight of the nuclear localized cyclophilins are found associated with spliceosomal complexes. However, their particular functions within this context are unknown. We have therefore adapted three established assays for in vitro pre-mRNA splicing to probe the functional roles of nuclear cyclophilins in the context of the human spliceosome. We find that four of the eight spliceosom-associated cyclophilins exert strong effects on splicing in vitro. These effects are dose-dependent and, remarkably, uniquely characteristic of each cyclophilin. Using both qualitative and quantitative means, we show that at least half of the nuclear cyclophilins can act as regulatory factors of spliceosome function in vitro. The present work provides the first quantifiable evidence that nuclear cyclophilins are splicing factors and provides a novel approach for future work into small molecule-based modulation of pre-mRNA splicing.

The exclusion problem in seasonally forced epidemiological systems.

The pathogen exclusion problem is the problem of finding control measures that will exclude a pathogen from an ecological system or, if the system is already disease-free, maintain it in that state. To solve this problem we work within a holistic control theory framework which is consistent with conventional theory for simple systems (where there is no external forcing and constant controls) and seamlessly generalises to complex systems that are subject to multiple component seasonal forcing and targeted variable controls. We develop, customise and integrate a range of numerical and algebraic procedures that provide a coherent methodology powerful enough to solve the exclusion problem in the general case. An important aspect of our solution procedure is its two-stage structure which reveals the epidemiological consequences of the controls used for exclusion. This information augments technical and economic considerations in the design of an acceptable exclusion strategy. Our methodology is used in two examples to show how time-varying controls can exploit the interference and reinforcement created by the external and internal lag structure and encourage the system to 'take over' some of the exclusion effort. On-off control switching, resonant amplification, optimality and controllability are important issues that emerge in the discussion.

The Impact of Simulated Corn Earworm (Lepidoptera: Noctuidae) Damage in Indeterminate Soybean.

Field experiments were conducted in Starkville and Stoneville, MS, during 2012 and 2013 to evaluate fruit removal level and timing on soybean growth, crop maturity, and yield. Fruit removal treatments consisted of 0, 50, and 100% of all fruit removed at specified growth stages (R2, R3, R4, and R5.5). Plant heights were determined at least biweekly from the time damage was imposed until R7. The impact of fruit removal level and timing on crop maturity was determined by estimating the percentage of naturally abscised leaves at 137 days after planting (DAP) when control plots were ∼10-15 d from harvest and the percentage of nonsenesced main stems at 139 DAP. There was no significant impact of fruit removal timing or fruit removal level on plant height or canopy width. Significant delays in crop maturity were observed when fruit removal was imposed at the R5.5 growth stage. Significant reductions in yield and crop value were observed as early as R3 and R4 when 100% of fruit was removed. Both fruit removal levels at R5.5 resulted in a significant reduction in yield and crop value compared with the nontreated control. Indeterminate soybeans appear to have the ability to compensate for some fruit loss during the early to middle reproductive growth stages without delaying maturity. However, severe fruit loss causes increasingly more yield loss as the plant approached maturity. Thresholds and economic injury levels therefore need to be adjusted accordingly to account for the dynamic nature of yield losses and crop maturity delays.

Assessment of the purity of isolated cell populations for lineage-specific chimerism monitoring post haematopoietic stem cell transplantation.

Following haematopoietic stem cell transplantation, monitoring the proportion of donor and recipient haematopoiesis in the patient (chimerism) is an influential tool in directing further treatment choices. Short tandem repeat (STR) analysis is a method of chimerism monitoring using DNA isolated from peripheral blood, bone marrow or specific isolated cell lineages such as CD3+ T cells. For lineage-specific STR analysis on cell populations isolated from peripheral blood, a qualitative estimation of the purity of each isolated population is essential for the correct interpretation of the test data. We describe a rapid, inexpensive method for the determination of purity using a simple flow cytometry method. The method described for assessing the purity of sorted CD3+ cells can be applied to any cell population isolated using the same technology. Data obtained were comparable to results from a commercial polymerase chain reaction (PCR)-based method for the assessment of purity (Non-T Genomic Detection Kit, Accumol, Calgary, AB, Canada) (P = 0.59). Of the 303 samples tested by flow cytometry, 290 (95.7%) exceeded 90% purity, and 215 (70.95%) were over 99% pure. There were some outlying samples, showing diversity between samples and the unpredictability of purity of isolated cell populations. This flow cytometry method can be easily assimilated into routine testing protocols, allowing purity assessment in multiple-sorted cell populations for lineage-specific chimerism monitoring using a single secondary antibody and giving results comparable to a PCR-based method. As purity of isolated cell lineages is affected by time after venepuncture and storage temperature, assessment of each sample is recommended to give a reliable indication of sample quality and confidence in the interpretation of the results.

Denosumab and giant cell tumour of bone-a review and future management considerations.

Giant cell tumour of bone (gctb) is one type of giant-cell-rich bone lesion characterized by the presence of numerous multinucleated osteoclast-type giant cells. Giant cells are known to express rankl (receptor activator of nuclear factor κB ligand) and are responsible for the aggressive osteolytic nature of the tumour. No available treatment option is definitively effective in curing this disease, especially in surgically unsalvageable cases. In recent years, several studies of denosumab in patients with advanced or unresectable gctb have shown objective changes in tumour composition, reduced bony destruction, and clinical benefit. Denosumab is a fully human monoclonal antibody that targets and binds with high affinity and specificity to rankl. Several large phase iii studies have shown that denosumab is more effective than bisphosphonates in reducing skeletal morbidity arising from a wide range of tumours and that it can delay bone metastasis. The relevant articles are reviewed here. The controversies related to the future use of denosumab in the treatment of gctb are discussed.

High contrast x-ray speckle from atomic-scale order in liquids and glasses.

The availability of ultrafast pulses of coherent hard x rays from the Linac Coherent Light Source opens new opportunities for studies of atomic-scale dynamics in amorphous materials. Here, we show that single ultrafast coherent x-ray pulses can be used to observe the speckle contrast in the high-angle diffraction from liquid Ga and glassy Ni(2)Pd(2)P and B(2)O(3). We determine the thresholds above which the x-ray pulses disturb the atomic arrangements. Furthermore, high contrast speckle is observed in scattering patterns from the glasses integrated over many pulses, demonstrating that the source and optics are sufficiently stable for x-ray photon correlation spectroscopy studies of dynamics over a wide range of time scales.

Scoping review protocol on the health of sub-Saharan African migrants in the Asia-Pacific region.

INTRODUCTION: Increasing economic opportunities have attracted people from sub-Saharan Africa to migrate to the Asia-Pacific region in the last two decades. The information on the health situation of these migrants is limited. We aim to assess scientific evidence on the health of sub-Saharan African migrants in the Asia-Pacific region using a scoping review. METHODS AND ANALYSIS: The review will be conducted according to the JBI guide on evidence synthesis, and the final results will be organised and reported in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for scoping reviews. Search strategies have been developed centred on population-concept-context elements including sub-Saharan Africa, Asia-Pacific, migration and health. A total of eight databases will be searched, including PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, ProQuest, Scopus, Web of Science, Wanfang and CNKI. Title and abstract screening and full-text screening will be conducted by two researchers independently. Data will be charted according to predesigned form. ETHICS AND DISSEMINATION: This study involves neither human participants nor unpublished secondary data. Institutional review board approval is therefore not required. Findings of this scoping review will be disseminated through publication in a peer-reviewed journal, through academic network and project report.

Wastewater-based epidemiology in hazard forecasting and early-warning systems for global health risks.

With the advent of the SARS-CoV-2 pandemic, Wastewater-Based Epidemiology (WBE) has been applied to track community infection in cities worldwide and has proven succesful as an early warning system for identification of hotspots and changingprevalence of infections (both symptomatic and asymptomatic) at a city or sub-city level. Wastewater is only one of environmental compartments that requires consideration. In this manuscript, we have critically evaluated the knowledge-base and preparedness for building early warning systems in a rapidly urbanising world, with particular attention to Africa, which experiences rapid population growth and urbanisation. We have proposed a Digital Urban Environment Fingerprinting Platform (DUEF) - a new approach in hazard forecasting and early-warning systems for global health risks and an extension to the existing concept of smart cities. The urban environment (especially wastewater) contains a complex mixture of substances including toxic chemicals, infectious biological agents and human excretion products. DUEF assumes that these specific endo- and exogenous residues, anonymously pooled by communities' wastewater, are indicative of community-wide exposure and the resulting effects. DUEF postulates that the measurement of the substances continuously and anonymously pooled by the receiving environment (sewage, surface water, soils and air), can provide near real-time dynamic information about the quantity and type of physical, biological or chemical stressors to which the surveyed systems are exposed, and can create a risk profile on the potential effects of these exposures. Successful development and utilisation of a DUEF globally requires a tiered approach including: Stage I: network building, capacity building, stakeholder engagement as well as a conceptual model, followed by Stage II: DUEF development, Stage III: implementation, and Stage IV: management and utilization. We have identified four key pillars required for the establishment of a DUEF framework: (1) Environmental fingerprints, (2) Socioeconomic fingerprints, (3) Statistics and modelling and (4) Information systems. This manuscript critically evaluates the current knowledge base within each pillar and provides recommendations for further developments with an aim of laying grounds for successful development of global DUEF platforms.

Expansion of regulatory CD8+ CD25+ T cells after neonatal alloimmunization.

Transplantation tolerance induced by neonatal injection of semi-allogeneic spleen cells is associated with a pathological syndrome caused by T helper type 2 (Th2) differentiation of donor-specific CD4(+) T lymphocytes. We have shown previously that this Th2-biased response is inhibited by host CD8(+) T cells. Herein, we demonstrate that upon neonatal immunization with (A/J × BALB/c)F(1) spleen cells, BALB/c mice expand a population of CD8(+) T cells expressing both CD25 and forkhead box P3 (FoxP3) markers. In this setting, CD8(+) CD25(+) T cells predominantly produce interferon (IFN)-γ and interleukin (IL)-10 and are efficient in controlling IL-4, IL-5 and IL-13 production by donor-specific CD4(+) T cells in vitro. CD8(+) FoxP3(-) T cells are single producers of IFN-γ or IL-10, whereas CD8(+) FoxP3(+) T cells are double producers of IFN-γ and IL-10. We further demonstrate that IFN-γ and IL-10 are two major cytokines produced by CD8(+) T cells involved in the in vivo regulation of Th2-type pathology. In this setting, we conclude that neonatal alloimmunization induces the expansion of several regulatory CD8(+) T cells which may control Th2 activities via IFN-γ and IL-10.

Endovascular repair of an acute, mycotic, ascending aortic pseudoaneurysm.

This report describes endovascular stenting of an acute mycotic ascending aortic aneurysm. An eighty-three year old lady presented nine weeks after aortic valve surgery and subsequent thyroidectomy with sternal pain secondary to a mycotic ascending aortic pseudoaneurysm. The pseudoaneurysm was visible through the unhealed sternum. Open repair was considered too high a mortality risk. Endovascular stenting was performed using two covered infrarenal proximal extension devices (GORE Excluder Aortic Extender(®), W. L. Gore & Associates, Flagstaff, Arizona, USA) deployed from a right axillary approach utilising overdrive cardiac pacing. Post procedure imaging revealed shrinkage of the pseudoaneurysm sac.

Low-Dose High-Resolution TOF-PET Using Ionization-activated Multi-State Low-Z Detector Media.

We propose PET scanners using low atomic number media that undergo a persistent local change of state along the paths of the Compton recoil electrons. Measurement of the individual scattering locations and angles, deposited energies, and recoil electron directions allows using the kinematical constraints of the 2-body Compton scattering process to perform a statistical time-ordering of the scatterings, with a high probability of precisely identifying where the gamma first interacted in the detector. In these cases the Line-of-Response is measured with high resolution, determined by the underlying physics processes and not the detector segmentation. There are multiple such media that act through different mechanisms. As an example in which the change of state is quantum-mechanical through a change in molecular configuration, rather than thermodynamic, as in a bubble chamber, we present simulations of a two-state photoswitchable organic dye, a 'Switchillator', that is activated to a fluorescent-capable state by the ionization of the recoil electrons. The activated state is persistent, and can be optically excited multiple times to image individual activated molecules. Energy resolution is provided by counting the activated molecules. Location along the LOR is implemented by large-area time-of-flight MCP-PMT photodetectors with single photon time resolution in the tens of ps and sub-mm spatial resolution. Simulations indicate a large reduction of dose.

Climate controls on erosion in tectonically active landscapes.

The ongoing debate about the nature of coupling between climate and tectonics in mountain ranges derives, in part, from an imperfect understanding of how topography, climate, erosion, and rock uplift are interrelated. Here, we demonstrate that erosion rate is nonlinearly related to fluvial relief with a proportionality set by mean annual rainfall. These relationships can be quantified for tectonically active landscapes, and calculations based on them enable estimation of erosion where observations are lacking. Tests of the predictive power of this relationship in the Himalaya, where erosion is well constrained, affirm the value of our approach. Our model allows estimation of erosion rates in fluvial landscapes using readily available datasets, and the underlying relationship between erosion and rainfall offers the promise of a deeper understanding of how climate and tectonic evolution affect erosion and topography in space and time and of the potential influence of climate on tectonics.

Air-transfer production method for large-area picosecond photodetectors.

We have designed and prototyped the process steps for the batch production of large-area micro-channel-plate photomultipliers (MCP-PMT) using the "air-transfer" assembly process developed with single LAPPDTM modules. Results are presented addressing the challenges of designing a robust package that can transmit large numbers of electrical signals for pad or strip readout from inside the vacuum tube and of hermetically sealing the large-perimeter window-body interface. We have also synthesized a photocathode in a large-area low-aspect-ratio volume and have shown that the micro-channel plates recover their functionality after cathode synthesis. These steps inform a design for a multi-module batch facility employing dual nested low-vacuum and ultra-high-vacuum systems in a small-footprint. The facility design provides full access to multiple MCP-PMT modules prior to hermetic pinch-off for leak-checking and real-time photocathode optimization.

Reversal of phencyclidine effects by a group II metabotropic glutamate receptor agonist in rats.

Glutamatergic abnormalities have been associated with several psychiatric disorders, including schizophrenia and addiction. Group II metabotropic glutamate receptors were targeted to normalize glutamatergic disruptions associated with an animal model of schizophrenia, the phencyclidine model. An agonist of this group of receptors, at a dose that was without effects on spontaneous activity and corticolimbic dopamine neurotransmission, attenuated the disruptive effects of phencyclidine on working memory, stereotypy, locomotion, and cortical glutamate efflux. This behavioral reversal occurred in spite of sustained dopamine hyperactivity. Thus, targeting this group of receptors may present a nondopaminergic therapeutic strategy for treatment of psychiatric disorders.