Primary moult of continental Black-tailed Godwits Limosa limosa limosa in the Doñana wetlands,Spain

Capsule: Most Continental Black-tailed Godwits Limosa limosa limosa using the Doñana wetlands during post-breeding migration appear to begin moult before they arrive and suspend moult before they migrate onwards to West Africa.

Aims: We aim to describe the primary moult strategies and patterns in the Continental Black-tailed Godwits using the Doñana wetlands, a major passage and wintering area for waterbirds in southern Spain.

Methods: Individual godwits were captured, marked and their primary moult was scored in Doñana during the non-breeding season (June–March) in 2011 and 2012. Data from resightings of colour-marked godwits and birds equipped with satellite transmitters were used to estimate stopover duration during post-breeding migration (June–September) to determine if godwits move to West Africa before completing their primary moult.

Results: Average primary moult duration was estimated to be 84 days?±?9 se, during 29 June–21 September and did not differ between sexes. Only 2% of individuals were observed with suspended moult. We estimated stopover duration in Doñana to be 13 days?±?2 se before migrating to West Africa.

Conclusions: Most godwits stage for about two weeks in the Doñana wetlands during southward migration, moult their primaries and appear to suspend moult before crossing the Sahara. Others may complete their primary moult in Doñana, or elsewhere in Europe and overwinter in Doñana where increasing numbers of godwits have been detected in recent years. A few individuals may finish the moult in Doñana and migrate to West Africa late in the post-breeding season.     

High Frequency Stimulation of the Subthalamic Nucleus Leads to Presynaptic GABA(B)-Dependent Depression of Subthalamo-Nigral Afferents

Patients with akinesia benefit from chronic high frequency stimulation (HFS) of the subthalamic nucleus (STN). Among the mechanisms contributing to the therapeutic success of HFS-STN might be a suppression of activity in the output region of the basal ganglia. Indeed, recordings in the substantia nigra pars reticulata (SNr) of fully adult mice revealed that HFS-STN consistently produced a reduction of compound glutamatergic excitatory postsynaptic currents at a time when the tetrodotoxin-sensitive components of the local field potentials had already recovered after the high frequency activation. These observations suggest that HFS-STN not only alters action potential conduction on the way towards the SNr but also modifies synaptic transmission within the SNr. A classical conditioning-test paradigm was then designed to better separate the causes from the indicators of synaptic depression. A bipolar platinum-iridium macroelectrode delivered conditioning HFS trains to a larger group of fibers in the STN, while a separate high-ohmic glass micropipette in the rostral SNr provided test stimuli at minimal intensity to single fibers. The conditioning-test interval was set to 100 ms, i.e. the time required to recover the excitability of subthalamo-nigral axons after HFS-STN. The continuity of STN axons passing from the conditioning to the test sites was examined by an action potential occlusion test. About two thirds of the subthalamo-nigral afferents were occlusion-negative, i.e. they were not among the fibers directly activated by the conditioning STN stimulation. Nonetheless, occlusion-negative afferents exhibited signs of presynaptic depression that could be eliminated by blocking GABA(B) receptors with {"type":"entrez-protein","attrs":{"text":"CGP55845","term_id":"875097176","term_text":"CGP55845"}}CGP55845 (1 µM). Further analysis of single fiber-activated responses supported the proposal that the heterosynaptic depression of synaptic glutamate release during and after HFS-STN is mainly caused by the tonic release of GABA from co-activated striato-nigral afferents to the SNr. This mechanism would be consistent with a gain-of-function hypothesis of DBS.     

Receptor for advanced glycation endproducts mediates neutrophil migration across intestinal epithelium

Receptor for advanced glycation endproducts (RAGE) is an Ig superfamily cell surface receptor that interacts with a diverse array of ligands associated with inflammatory responses. In this study, we provide evidence demonstrating that RAGE is involved in inflammatory responses in the intestines. We showed that RAGE is expressed in intestinal epithelial cells, primarily concentrated at the lateral membranes close to the apical cell junction complexes. Although RAGE expression was low in epithelium under normal conditions, this protein was up-regulated after treatment with the inflammatory cytokines IFN-gamma and/or TNF-alpha. RAGE expression was also elevated in colon tissue samples from patients with inflammatory bowel diseases. Using in vitro transmigration assays, we found that RAGE mediates neutrophil (polymorphonuclear leukocytes (PMN)) adhesion to, and subsequent migration across, intestinal epithelial monolayers. This activity appears to be mediated by the binding of RAGE to the PMN-specific beta(2) integrin CD11b/CD18. Thus, these results provide a novel mechanism for the regulation of PMN transepithelial migration and may suggest a new therapeutic target for intestinal inflammation.     

Assessment and Evaluation of the High Risk Neonate: The NICU Network Neurobehavioral Scale

There has been a long-standing interest in the assessment of the neurobehavioral integrity of the newborn infant. The NICU Network Neurobehavioral Scale (NNNS) was developed as an assessment for the at-risk infant. These are infants who are at increased risk for poor developmental outcome because of insults during prenatal development, such as substance exposure or prematurity or factors such as poverty, poor nutrition or lack of prenatal care that can have adverse effects on the intrauterine environment and affect the developing fetus. The NNNS assesses the full range of infant neurobehavioral performance including neurological integrity, behavioral functioning, and signs of stress/abstinence. The NNNS is a noninvasive neonatal assessment tool with demonstrated validity as a predictor, not only of medical outcomes such as cerebral palsy diagnosis, neurological abnormalities, and diseases with risks to the brain, but also of developmental outcomes such as mental and motor functioning, behavior problems, school readiness, and IQ. The NNNS can identify infants at high risk for abnormal developmental outcome and is an important clinical tool that enables medical researchers and health practitioners to identify these infants and develop intervention programs to optimize the development of these infants as early as possible. The video shows the NNNS procedures, shows examples of normal and abnormal performance and the various clinical populations in which the exam can be used.     

Extensive Rearrangements in the Chloroplast Genome of <Emphasis Type="Italic">Trachelium caeruleum</Emphasis> Are Associated with Repeats and tRNA Genes

Chloroplast genome organization, gene order, and content are highly conserved among land plants. We sequenced the chloroplast genome of Trachelium caeruleum L. (Campanulaceae), a member of an angiosperm family known for highly rearranged genomes. The total genome size is 162,321 bp, with an inverted repeat (IR) of 27,273 bp, large single-copy (LSC) region of 100,114 bp, and small single-copy (SSC) region of 7,661 bp. The genome encodes 112 different genes, with 17 duplicated in the IR, a tRNA gene (trnI-cau) duplicated once in the LSC region, and a protein-coding gene (psbJ) with two duplicate copies, for a total of 132 putatively intact genes. ndhK may be a pseudogene with internal stop codons, and clpP, ycf1, and ycf2 are so highly diverged that they also may be pseudogenes. ycf15, rpl23, infA, and accD are truncated and likely nonfunctional. The most conspicuous feature of the Trachelium genome is the presence of 18 internally unrearranged blocks of genes inverted or relocated within the genome relative to the ancestral gene order of angiosperm chloroplast genomes. Recombination between repeats or tRNA genes has been suggested as a mechanism of chloroplast genome rearrangements. The Trachelium chloroplast genome shares with Pelargonium and Jasminum both a higher number of repeats and larger repeated sequences in comparison to eight other angiosperm chloroplast genomes, and these are concentrated near rearrangement endpoints. Genes for tRNAs occur at many but not all inversion endpoints, so some combination of repeats and tRNA genes may have mediated these rearrangements.     

Homeostasis of peripheral FoxP3+ CD4+ regulatory T cells in patients with early and late stage breast cancer

FoxP3 ⁺ CD4 ⁺ regulatory T cells (Tregs) are important mediators of peripheral immune tolerance, acting via multiple mechanisms to suppress cellular immunity including antitumor responses. Although therapeutic strategies have been proposed to deplete Tregs in patients with breast cancer and other malignancies, dynamic changes in the Treg compartment as a function of stage and treatment of breast cancer remain poorly understood. Here, we evaluated peripheral blood CD4⁺ T cells and FoxP3⁺ CD4⁺ T cells from 45 patients with early or late stage breast cancer and compared percentages, absolute counts, and Treg function to those from healthy volunteers (HV) of comparable age. Patients having completed adjuvant chemotherapy and patients with metastatic cancer exhibited significantly lower absolute CD4 counts and significantly higher percentages of FoxP3⁺ CD4⁺ T cells. In contrast, the absolute counts of circulating FoxP3⁺ CD4⁺ T cells did not differ significantly among early stage patients, late stage patients, or HV. Functionally, FoxP3⁺ CD4⁺ T cells from all donor groups similarly expressed CTLA-4 and failed to secrete IFN-γ in response to stimulation. Thus, although Tregs comprise an increased percentage of circulating CD4⁺ T cells in patients with metastatic breast cancer and patients in remission after completing the adjuvant chemotherapy, the systemic Treg pool, as measured by absolute counts, appears relatively constant regardless of disease stage or treatment status. Total CD4⁺ T cell counts are not constant, however, suggesting that homeostatic mechanisms, or susceptibility to cytotoxic or malignant insults, fundamentally differ for regulatory and non-regulatory CD4⁺ T cells.     

Human Immunodeficiency Virus Type 1 Escapes from Interleukin-2-Producing CD4+ T-Cell Responses without High-Frequency Fixation of Mutations

The presence of interleukin-2 (IL-2)-producing human immunodeficiency virus type 1 (HIV-1)-specific CD4⁺ T-cell responses has been associated with the immunological control of HIV-1 replication; however, the causal relationship between these factors remains unclear. Here we show that IL-2-producing HIV-1-specific CD4⁺ T cells can be cloned from acutely HIV-1-infected individuals. Despite the early presence of these cells, each of the individuals in the present study exhibited progressive disease, with one individual showing rapid progression. In this rapid progressor, three IL-2-producing HIV-1 Gag-specific CD4⁺ T-cell responses were identified and mapped to the following optimal epitopes: HIVWASRELER, REPRGSDIAGT, and FRDYVDRFYKT. Responses to these epitopes in peripheral blood mononuclear cells were monitored longitudinally to >1 year postinfection, and contemporaneous circulating plasma viruses were sequenced. A variant of the FRDYVDRFYKT epitope sequence, FRDYVDQFYKT, was observed in 1/21 plasma viruses sequenced at 5 months postinfection and 1/10 viruses at 7 months postinfection. This variant failed to stimulate the corresponding CD4⁺ T-cell clone and thus constitutes an escape mutant. Responses to each of the three Gag epitopes were rapidly lost, and this loss was accompanied by a loss of antigen-specific cells in the periphery as measured by using an FRDYVDRFYKT-presenting major histocompatibility complex class II tetramer. Highly active antiretroviral therapy was associated with the reemergence of FRDYVDRFYKT-specific cells by tetramer. Thus, our data support that IL-2-producing HIV-1-specific CD4⁺ T-cell responses can exert immune pressure during early HIV-1 infection but that the inability of these responses to enforce enduring control of viral replication is related to the deletion and/or dysfunction of HIV-1-specific CD4⁺ T cells rather than to the fixation of escape mutations at high frequencies.In the typical course of acute human immunodeficiency virus type 1 (HIV-1) infection an initial burst of high-level viremia is reduced by at least 100-fold to a set point level (11, 12). This precipitous drop in viral load is suggestive of a partially effective host immune response to primary HIV-1 infection. Several lines of evidence support an important role for CD8⁺ T cells in suppressing HIV-1 replication in acute infection: principally, the decline in HIV-1 viremia is temporally associated with the emergence of an HIV-1-specific CD8⁺ T-cell response, and the in vivo depletion of CD8⁺ T cells in simian immunodeficiency virus-infected macaques consistently results in elevated viral loads (7, 24, 30). Consistent with the application of effective immune pressure, it has been well established that HIV-1- and simian immunodeficiency virus-specific CD8⁺ T cells drive the emergence and fixation of escape mutations in the epitopes that they target (1, 3, 8, 18, 31, 33, 34). This evidence has contributed to the prioritization of vaccine candidates that elicit potent HIV-1-specific CD8⁺ T-cell responses.The role of CD4⁺ T-cell responses in the response to acute HIV-1 infection is less clear. There is compelling evidence that CD4⁺ T-cell help may be critical for the establishment of a qualitatively and quantitatively robust CD8⁺ T-cell memory pool for persistent virus infections (4, 9, 17, 37, 39). Furthermore, an important role for CD4⁺ help in maintaining an effective CD8⁺ T-cell response has been established in the lymphocytic choriomeningitis virus model of chronic viral infection (28, 45). Evidence in support of a role for the CD4⁺ T-cell response to HIV-1 infection in suppressing viral replication is derived from studies which demonstrated that a CD4⁺ T-cell response characterized by vigorous proliferation and production of interleukin-2 (IL-2) is associated with control of viremia (6, 35). It has further been demonstrated that the functional defect of CD8⁺ T cells observed in chronic HIV-1 infection can be induced in vitro by the depletion of CD4⁺ T cells or the addition of IL-2-neutralizing antibodies and can be corrected in vivo by vaccine-mediated augmentation of HIV-1-specific CD4⁺ T-cell responses (26). These observations have suggested that an IL-2-producing response may be necessary for controlling viremia. However, in the majority of HIV-1-infected individuals, a qualitative impairment of the HIV-1-specific CD4⁺ T-cell response occurs early after infection, resulting in the loss of proliferative capacity as well as the ability to produce IL-2 (43). This impairment correlates well with levels of antigen and viremia (29). The relationship between viral control and the presence of IL-2-producing HIV-specific CD4⁺ T-cell responses must be interpreted with caution, however, as the causal relationship between these two factors is unclear. The maintenance of an IL-2-producing HIV-1-specific CD4⁺ T-cell proliferative response could simply be the result of control of viremia achieved through another means, rather than causal in the association. Therapeutic administration of IL-2 to chronically infected individuals failed to reveal any clinical benefit, perhaps supporting that IL-2 is a marker, rather than a driver, of immunological control (25). However, it is unclear whether the systemic administration of IL-2 effectively substitutes for the targeted production of IL-2 by HIV-1-specific CD4⁺ T cells.The fixation of escape mutations in CD4⁺ T-cell epitopes during acute infection would provide direct evidence that CD4⁺ T cells apply immunological pressure against HIV-1. Harcourt et al. identified epitopes targeted by proliferative CD4⁺ T-cell responses in chronically infected individuals and sequenced these epitopes from proviral DNA at multiple time points (16). Variations in these epitope sequences were observed over time, and a minority of these variants failed to stimulate CD4⁺ T-cell lines raised against the index peptide. This study indicated the potential for HIV-1 virus to escape within proviral populations. However, the observation that the majority of emergent variants were still able to stimulate CD4⁺ T-cell responses argues against potent selective pressure for escape mutants (16). A second study examined gamma interferon (IFN-γ)-producing CD4⁺ T-cell responses and contemporaneous circulating virus epitopes in a cohort of chronically infected, untreated, HIV-1-infected individuals. A lack of intrapatient variability within CD4⁺ T-cell epitopes was observed in this study, and while two of four subjects exhibited epitope sequences that differed from the consensus HIV-1 sequence, there was a trend to greater sequence variability outside of epitopic regions, arguing against potent immune pressure (23). These studies support that HIV-1-specific CD4⁺ T-cell responses fail to exert potent selective pressure against cognate epitopes in chronic infection; however, it is difficult to determine whether or not the observed epitopic variations are indicative of relatively weak selective pressures. Since the overall cellular immune response to HIV-1 infection is particularly robust and effective during the acute phase of infection, we examined the kinetics of the HIV-1-specific IL-2-secreting CD4⁺ T-cell-mediated immune response during acute/early HIV-1 infection and studied the effects of this response on circulating plasma viruses.     

Spatial patterns in age- and colony-specific survival in a long-lived seabird across 14 contrasting colonies

Demographic rates such as recruitment and survival probability can vary considerably among populations of the same species due to variation in underlying environmental processes. If environmental processes are spatially correlated, nearby populations are expected to have more similar demographic rates than those further apart. Breeding populations and foraging ranges are spatially segregated in colonial seabirds, making them ideal for studying spatial patterns in demographic rates and their effects on local population dynamics. Here we explored variation in age-dependent survival probabilities across 14 colonies of Herring Gulls Larus argentatus breeding along the Dutch North Sea coast. We used long-term mark–recapture data of marked fledglings to estimate survival, and estimated spatial autocorrelation of survival probabilities. We assessed whether survival until recruitment age or until 10 years old (close to their expected lifespan) explained variation in population trajectories of each colony. Juvenile and adult survival showed a strong, but different, north-to-south gradient in survival probability, with lower juvenile but higher adult survival in northern colonies than southern colonies, whereas the spatial pattern of immature survival was less distinct. Neither recruitment nor the proportion of 10-year-old adults alive predicted whether a colony collapsed, declined, remained stable or increased. The distinct spatial pattern in survival suggests variation in regional food availability, which do not seem to drive local population dynamics. The absence of a link between survival and colony trajectories implies that connectivity between populations plays an important role affecting population dynamics.     

Assessing German farmers’ attitudes regarding nature conservation set-aside in regions dominated by arable farming

This paper presents an analysis of the attitudes of farmers towards a policy approach that combines the instrument of set-aside of farmland with agri-environmental measures under the Common Agricultural Policy (CAP) for achieving nature goals. One of the stated objectives of current agricultural and environmental policies is to give greater consideration to issues of nature conservation in agricultural landscapes. To fulfil this objective, there is an urgent need to develop approaches that, on the one hand, are capable of delivering tangible improvements in the ecological situation and nature conservation in agriculture and, on the other hand, are structured in such a way that farmers are willing to put them into practice. In addition, such approaches need to be economical and affordable for society. The Leibniz-Centre for Agricultural Landscape Research (ZALF) has developed the concept of ‘nature-conservation set-aside’, especially for landscapes that are under predominantly arable use. Conservation set-aside refers to parts of arable farmland especially well suited to nature conservation, which are mandatorily withdrawn from agricultural production (for those who claim payment) and on which ecologically valuable habitats are created through specific management activities. To determine what kind of problems might arise for farmers in the course of implementing this concept as an agri-environmental measure, a survey was carried out in four largely arable regions of Germany. The results of this survey show the attitudes of German farmers regarding set-aside farmland for nature conservation in regions dominated by arable farming, and they demonstrate which factors influence the implementation of conservation set-aside.