Vertebrate DNA in Fecal Samples from Bonobos and Gorillas: Evidence for Meat Consumption or Artefact?

Background: Deciphering the behavioral repertoire of great apes is a challenge for several reasons. First, due to their elusive behavior in dense forest environments, great ape populations are often difficult to observe. Second, members of the genus Pan are known to display a great variety in their behavioral repertoire; thus, observations from one population are not necessarily representative for other populations. For example, bonobos (Pan paniscus) are generally believed to consume almost no vertebrate prey. However, recent observations show that at least some bonobo populations may consume vertebrate prey more commonly than previously believed. We investigated the extent of their meat consumption using PCR amplification of vertebrate mitochondrial DNA (mtDNA) segments from DNA extracted from bonobo feces. As a control we also attempted PCR amplifications from gorilla feces, a species assumed to be strictly herbivorous. Principal Findings: We found evidence for consumption of a variety of mammalian species in about 16% of the samples investigated. Moreover, 40% of the positive DNA amplifications originated from arboreal monkeys. However, we also found duiker and monkey mtDNA in the gorilla feces, albeit in somewhat lower percentages. Notably, the DNA sequences isolated from the two ape species fit best to the species living in the respective regions. This result suggests that the sequences are of regional origin and do not represent laboratory contaminants. Conclusions: Our results allow at least three possible and mutually not exclusive conclusions. First, all results may represent contamination of the feces by vertebrate DNA from the local environment. Thus, studies investigating a species' diet from feces DNA may be unreliable due to the low copy number of DNA originating from diet items. Second, there is some inherent difference between the bonobo and gorilla feces, with only the later ones being contaminated. Third, similar to bonobos, for which the consumption of monkeys has only recently been documented, the gorilla population investigated (for which very little observational data are as yet available) may occasionally consume small vertebrates. Although the last explanation is speculative, it should not be discarded a-priori given that observational studies continue to unravel new behaviors in great ape species

Double coherence resonance in neuron models driven by discrete correlated noise

We study the influence of correlations among discrete stochastic excitatory or inhibitory inputs on the response of the FitzHugh-Nagumo neuron model. For any level of correlation the emitted signal exhibits at some finite noise intensity a maximal degree of regularity, i.e., a coherence resonance. Furthermore, for either inhibitory or excitatory correlated stimuli a {\it Double Coherence Resonance} (DCR) is observable. DCR refers to a (absolute) maximum coherence in the output occurring for an optimal combination of noise variance and correlation. All these effects can be explained by taking advantage of the discrete nature of the correlated inputs.Comment: 4 pages, 3 figures in eps, to appear in Physical Review Letter

Measurement of the Neutrino Asymmetry Parameter B in Neutron Decay

A new measurement of the neutrino asymmetry parameter B in neutron decay, the angular correlation between neutron spin and anti-neutrino momentum, is presented. The result, B=0.9802(50), agrees with the Standard Model expectation and earlier measurements, and permits improved tests on ``new physics'' in neutron decay.Comment: 4 pages, 2 figures; v2: revised PRL versio

Time and phenotype-dependent transcriptome analysis in AAV-TGFβ1 and Bleomycin-induced lung fibrosis models

We have previously established a novel mouse model of lung fibrosis based on Adeno-associated virus (AAV)-mediated pulmonary overexpression of TGFβ1. Here, we provide an in-depth characterization of phenotypic and transcriptomic changes (mRNA and miRNA) in a head-to-head comparison with Bleomycin-induced lung injury over a 4-week disease course. The analyses delineate the temporal state of model-specific and commonly altered pathways, thereby providing detailed insights into the processes underlying disease development. They further guide appropriate model selection as well as interventional study design. Overall, Bleomycin-induced fibrosis resembles a biphasic process of acute inflammation and subsequent transition into fibrosis (with partial resolution), whereas the TGFβ1-driven model is characterized by pronounced and persistent fibrosis with concomitant inflammation and an equally complex disease phenotype as observed upon Bleomycin instillation. Finally, based on an integrative approach combining lung function data, mRNA/miRNA profiles, their correlation and miRNA target predictions, we identify putative drug targets and miRNAs to be explored as therapeutic candidates for fibrotic diseases. Taken together, we provide a comprehensive analysis and rich data resource based on RNA-sequencing, along with a strategy for transcriptome-phenotype coupling. The results will be of value for TGFβ research, drug discovery and biomarker identification in progressive fibrosing interstitial lung diseases

Dynamical response of the Hodgkin-Huxley model in the high-input regime

The response of the Hodgkin-Huxley neuronal model subjected to stochastic uncorrelated spike trains originating from a large number of inhibitory and excitatory post-synaptic potentials is analyzed in detail. The model is examined in its three fundamental dynamical regimes: silence, bistability and repetitive firing. Its response is characterized in terms of statistical indicators (interspike-interval distributions and their first moments) as well as of dynamical indicators (autocorrelation functions and conditional entropies). In the silent regime, the coexistence of two different coherence resonances is revealed: one occurs at quite low noise and is related to the stimulation of subthreshold oscillations around the rest state; the second one (at intermediate noise variance) is associated with the regularization of the sequence of spikes emitted by the neuron. Bistability in the low noise limit can be interpreted in terms of jumping processes across barriers activated by stochastic fluctuations. In the repetitive firing regime a maximization of incoherence is observed at finite noise variance. Finally, the mechanisms responsible for spike triggering in the various regimes are clearly identified.Comment: 14 pages, 24 figures in eps, submitted to Physical Review

Humour interventions for patients in palliative care-a randomized controlled trial.

PURPOSE: The effect of humour on end-of-life patients could be beneficial and is worth investigating. However, data on humour interventions for patients in palliative care are scarce. This study evaluated the effects of a humour intervention in a palliative care setting. METHODS: A two-step intervention was developed based on the humour habits programme by McGhee. Patients were assisted to remember funny episodes from their past and recognize humorous aspects of the present and encouraged to produce humour. The intervention and control group completed questionnaires on life satisfaction, cheerfulness, symptom burden, and perceived stress and if possible gave saliva samples to investigate oxytocin levels. The study was a randomized controlled monocentre study on patients treated in a palliative care ward. Participants had to be conscious and alert enough to complete data collection. Overall, 55 patients were included and randomized to the intervention or control group. RESULTS: Parameters in the control group did not change significantly. In the intervention group, seriousness, bad mood, and stress were reduced. Cheerfulness increased significantly after the intervention. However, the methodologically complex intervention setting was too exhausting for the majority of patients. CONCLUSION: Patients who were able to participate benefited from the effects of the intervention on multiple levels. For future research simple interventions, biomarkers for well-being and assessments by staff or proxies are needed to include patients with reduced cognitive and physical performance status at the end of their lives. TRIAL REGISTRATION: DRKS00028978 German Registry of Clinical Studies

Identification and Characterization of Post-activated B Cells in Systemic Autoimmune Diseases

Autoimmune diseases (AID) such as systemic lupus erythematosus (SLE), primary Sjögren's syndrome (pSS), and rheumatoid arthritis (RA) are chronic inflammatory diseases in which abnormalities of B cell function play a central role. Although it is widely accepted that autoimmune B cells are hyperactive in vivo, a full understanding of their functional status in AID has not been delineated. Here, we present a detailed analysis of the functional capabilities of AID B cells and dissect the mechanisms underlying altered B cell function. Upon BCR activation, decreased spleen tyrosine kinase (Syk) and Bruton's tyrosine kinase (Btk) phosphorylation was noted in AID memory B cells combined with constitutive co-localization of CD22 and protein tyrosine phosphatase (PTP) non-receptor type 6 (SHP-1) along with hyporesponsiveness to TLR9 signaling, a Syk-dependent response. Similar BCR hyporesponsiveness was also noted specifically in SLE CD27- B cells together with increased PTP activities and increased transcripts for PTPN2, PTPN11, PTPN22, PTPRC, and PTPRO in SLE B cells. Additional studies revealed that repetitive BCR stimulation of normal B cells can induce BCR hyporesponsiveness and that tissue-resident memory B cells from AID patients also exhibited decreased responsiveness immediately ex vivo, suggesting that the hyporesponsive status can be acquired by repeated exposure to autoantigen(s) in vivo. Functional studies to overcome B cell hyporesponsiveness revealed that CD40 co-stimulation increased BCR signaling, induced proliferation, and downregulated PTP expression (PTPN2, PTPN22, and receptor-type PTPs). The data support the conclusion that hyporesponsiveness of AID and especially SLE B cells results from chronic in vivo stimulation through the BCR without T cell help mediated by CD40-CD154 interaction and is manifested by decreased phosphorylation of BCR-related proximal signaling molecules and increased PTPs. The hyporesponsiveness of AID B cells is similar to a form of functional anergy

Autologous chondrocyte implantation versus ACI using 3D-bioresorbable graft for the treatment of large full-thickness cartilage lesions of the knee

BACKGROUND: In autologous chondrocyte implantation (ACI), the periosteum patch which is sutured over the cartilage defect has been identified as a major source of complications such as periosteal hypertrophy. In the present retrospective study, we compared midterm results of first-generation ACI with a periosteal patch to second generation ACI using a biodegradable collagen fleece (BioSeed-C) in 82 patients suffering from chronic posttraumatic and degenerative cartilage lesions of the knee. METHODS: Clinical outcome was assessed in 42 patients of group 1 and in 40 patients of group 2 before implantation of the autologous chondrocytes and at a minimum follow-up of 2 years using the ICRS score, the modified Cincinnati score and the Lysholm score. RESULTS: Although patients treated with BioSeed-C had more previous surgical procedures on their respective knees, highly significant improvements (P < 0.001) were assessed in both groups at comparable outcome levels: the ICRS score improved from grade D (poor) preoperatively to grade C (fair); the modified Cincinnati knee score from 3.26 to 6.4 (group 1) and 3.3 and 6.88 (group 2). Lysholm score improved from 33 to 70 points (group 1) and from 47 to 78 points (group 2), respectively. Revision surgery was due to symptomatic periosteal hypertrophy (n = 4), graft failure (n = 3), plica syndrome (n = 2) synovectomy (n = 1) (group 1); and graft failure (n = 2), debridement (n = 1), synovectomy (n = 2) (group 2). CONCLUSION: These results suggest that BioSeed-C is an equally effective treatment option for focal degenerative chondral lesions of the knee in this challenging and complex patient profile