Large-scale population disappearances and cycling in the white-lipped peccary, a tropical forest mammal.

Many vertebrate species undergo population fluctuations that may be random or regularly cyclic in nature. Vertebrate population cycles in northern latitudes are driven by both endogenous and exogenous factors. Suggested causes of mysterious disappearances documented for populations of the Neotropical, herd-forming, white-lipped peccary (Tayassu pecari, henceforth "WLP") include large-scale movements, overhunting, extreme floods, or disease outbreaks. By analyzing 43 disappearance events across the Neotropics and 88 years of commercial and subsistence harvest data for the Amazon, we show that WLP disappearances are widespread and occur regularly and at large spatiotemporal scales throughout the species' range. We present evidence that the disappearances represent 7-12-year troughs in 20-30-year WLP population cycles occurring synchronously at regional and perhaps continent-wide spatial scales as large as 10,000-5 million km2. This may represent the first documented case of natural population cyclicity in a Neotropical mammal. Because WLP populations often increase dramatically prior to a disappearance, we posit that their population cycles result from over-compensatory, density-dependent mortality. Our data also suggest that the increase phase of a WLP cycle is partly dependent on recolonization from proximal, unfragmented and undisturbed forests. This highlights the importance of very large, continuous natural areas that enable source-sink population dynamics and ensure re-colonization and local population persistence in time and space.

Variability of bovine conceptus-related volumes in early pregnancy measured with transrectal 3-dimensional ultrasonography.

Up until now, bovine fetometry has been entirely based on 2-dimensional ultrasonography. Fetal size is estimated by several linear measurements such as crown-rump length (CRL). However, the advent of 3-dimensional ultrasonography (3D-US) provides in vivo access to the volumes of the fetus and its amniotic sac. The objective of this preliminary observational study was to determine the variability of conceptus-related volumes using transrectal 3D-US in dairy cows and to identify factors affecting them. Furthermore, relationships between the gained measurements and calf birth weight were investigated. In total, 315 Simmental and Holstein-Friesian dairy cows were transrectally examined at d 42 after breeding using a portable ultrasound device (Voluson I, GE Healthcare). Gestational volumes including fetal volume (FV) and amniotic sac volume (ASV) were determined with the software tool VOCAL (Virtual Organ Computer-Aided Analysis, GE Healthcare), whereas amniotic fluid volume (AFV) values were derived from the subtraction of FV from ASV. The CRL was determined by means of 3-dimensional data. The mean values and standard deviations for FV, ASV, AFV, and CRL were 1.47 ± 0.25 cm3, 5.86 ± 1.22 cm3, 4.38 ± 1.02 cm3, and 2.38 ± 0.18 cm, respectively. All gestational volumes and CRL values were affected by breed. In Simmental cattle, larger concepti were observed compared with pregnancies derived from Holstein-Friesian animals. Parity affected only ASV and AFV, with heifers showing greater values than lactating cows. The CRL was positively associated with milk protein content. It was not possible to predict calf weight at birth by using FV, ASV, or AFV; however, tendencies were found for ASV and AFV. The present study was the first to adopt 3D-US volumetry to assess early pregnancy development in dairy cattle. Our results showed that this method could be used successfully to identify minor variations in conceptus growth.

Basement membrane collagen IV deficiency promotes abdominal aortic aneurysm formation.

Abdominal aortic aneurysm (AAA) is a complex disease which is incompletely accounted for. Basement membrane (BM) Collagen IV (COL4A1/A2) is abundant in the artery wall, and several lines of evidence indicate a protective role of baseline COL4A1/A2 in AAA development. Using Col4a1/a2 hemizygous knockout mice (Col4a1/a2+/-, 129Svj background) we show that partial Col4a1/a2 deficiency augmented AAA formation. Although unchallenged aortas were morphometrically and biomechanically unaffected by genotype, explorative proteomic analyses of aortas revealed a clear reduction in BM components and contractile vascular smooth muscle cell (VSMC) proteins, suggesting a central effect of the BM in maintaining VSMCs in the contractile phenotype. These findings were translated to human arteries by showing that COL4A1/A2 correlated to BM proteins and VSMC markers in non-lesioned internal mammary arteries obtained from coronary artery bypass procedures. Moreover, in human AAA tissue, MYH11 (VSMC marker) was depleted in areas of reduced COL4 as assessed by immunohistochemistry. Finally, circulating COL4A1 degradation fragments correlated with AAA progression in the largest Danish AAA cohort, suggesting COL4A1/A2 proteolysis to be an important feature of AAA formation. In sum, we identify COL4A1/A2 as a critical regulator of VSMC phenotype and a protective factor in AAA formation.

Correction to: Induced surface proteins of Staphylococcus epidermidis adhering to titanium implant substrata.

There is a mistake in the original published version of this article. The word 'Streptococcus' in the article title should have been 'Staphylococcus'.

Implications of recent epidemiologic studies for the linear nonthreshold model and radiation protection.

The recently published NCRP Commentary No. 27 evaluated the new information from epidemiologic studies as to their degree of support for applying the linear nonthreshold (LNT) model of carcinogenic effects for radiation protection purposes (NCRP 2018 Implications of Recent Epidemiologic Studies for the Linear Nonthreshold Model and Radiation Protection, Commentary No. 27 (Bethesda, MD: National Council on Radiation Protection and Measurements)). The aim was to determine whether recent epidemiologic studies of low-LET radiation, particularly those at low doses and/or low dose rates (LD/LDR), broadly support the LNT model of carcinogenic risk or, on the contrary, demonstrate sufficient evidence that the LNT model is inappropriate for the purposes of radiation protection. An updated review was needed because a considerable number of reports of radiation epidemiologic studies based on new or updated data have been published since other major reviews were conducted by national and international scientific committees. The Commentary provides a critical review of the LD/LDR studies that are most directly applicable to current occupational, environmental and medical radiation exposure circumstances. This Memorandum summarises several of the more important LD/LDR studies that incorporate radiation dose responses for solid cancer and leukemia that were reviewed in Commentary No. 27. In addition, an overview is provided of radiation studies of breast and thyroid cancers, and cancer after childhood exposures. Non-cancers are briefly touched upon such as ischemic heart disease, cataracts, and heritable genetic effects. To assess the applicability and utility of the LNT model for radiation protection, the Commentary evaluated 29 epidemiologic studies or groups of studies, primarily of total solid cancer, in terms of strengths and weaknesses in their epidemiologic methods, dosimetry approaches, and statistical modelling, and the degree to which they supported a LNT model for continued use in radiation protection. Recommendations for how to make epidemiologic radiation studies more informative are outlined. The NCRP Committee recognises that the risks from LD/LDR exposures are small and uncertain. The Committee judged that the available epidemiologic data were broadly supportive of the LNT model and that at this time no alternative dose-response relationship appears more pragmatic or prudent for radiation protection purposes.

Induced surface proteins of Staphylococcus [corrected] epidermidis adhering to titanium implant substrata.

OBJECTIVE: Staphylococcus epidermidis, as a primary colonizer, is strongly associated with infections of (dental) implants (i.e., peri-implantitis), but little is known about the surface proteome of this bacterium. For the identification of bacterial adhesins, this study investigated the surface proteome of S. epidermidis adhering directly to titanium implant substrata. MATERIALS AND METHODS: S. epidermidis strain ATTC 35984 was cultured either planktonically or on titanium implant specimens. The surface proteomes were isolated by mutanolysin digestion, and proteins were separated by 2D gel electrophoreses to reveal highly expressed proteins only. Protein spots were visualized by silver staining and proteins were identified by mass spectrometry. RESULTS: Surface proteome analyses of S. epidermidis on titanium identified six expressed proteins. Three proteins were highly expressed on the titanium implants including accumulation-associated protein Q8CQD9. These specific proteins could be potential pathogenicity factors of bacteria in peri-implant biofilms. CONCLUSION: For the first time, our study identified S. epidermidis surface proteins, which are expressed after adhesion to titanium implant materials. CLINICAL RELEVANCE: Our study reveals possible candidates for a newly protein-based vaccine against peri-implantitis.

Selective Probing of Hidden Spin-Polarized States in Inversion-Symmetric Bulk MoS_{2}.

Spin- and angle-resolved photoemission spectroscopy is used to reveal that a large spin polarization is observable in the bulk centrosymmetric transition metal dichalcogenide MoS_{2}. It is found that the measured spin polarization can be reversed by changing the handedness of incident circularly polarized light. Calculations based on a three-step model of photoemission show that the valley and layer-locked spin-polarized electronic states can be selectively addressed by circularly polarized light, therefore providing a novel route to probe these hidden spin-polarized states in inversion-symmetric systems as predicted by Zhang et al. [Nat. Phys. 10, 387 (2014).NPAHAX1745-247310.1038/nphys2933].

The hedgehog-signaling pathway is repressed during the osteogenic differentiation of dental follicle cells.

Dental follicle stem cells (DFCs) are precursor cells of alveolar osteoblasts, and previous studies have shown that the growth factor bone morphogenetic protein (BMP)2 induces the osteogenic differentiation of DFCs. However, the molecular mechanism down-stream of the induction of the osteogenic differentiation by BMP2 remains elusive. We investigated therefore the phosphoproteome of DFCs after the induction of the osteogenic differentiation with BMP2. In this study, phosphoproteins of the hedgehog "off" state were differentially expressed. Further analyses revealed that BMP2 induced the expression of repressors of the hedgehog-signaling pathway such as Patched 1 (PTCH1), Suppressor of Fused (SUFU), and Parathyroid Hormone-Related Peptide (PTHrP). Previous studies suggested that hedgehog proteins induce the osteogenic differentiation of mesenchymal stem cells via a paracrine pathway. Indian hedgehog (IHH) induced the expression of the osteogenic transcription factor RUNX2. However, a supplementation of the BMP2-based osteogenic differentiation medium with IHH did not induce the expression of RUNX2. Moreover, IHH inhibited slightly the ALP activity and the mineralization of osteogenic-differentiated DFCs. In conclusion, our results suggest that BMP2 inhibits the hedgehog signaling after the induction of the osteogenic differentiation in DFCs.

Feasibility of an exercise programme in elderly patients undergoing allogeneic stem cell transplantation - a pilot study.

It has been demonstrated that physical exercise benefits younger patients undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT). We designed a prospective pilot study investigating whether elderly patients (>60 years) would also be able to participate in such a programme. It consisted of physiotherapist-supervised alternating endurance and resistance workouts on 6 of 7 days a week. Sixteen consecutive patients undergoing allo-HSCT were enrolled into the study. The median age was 64.5 years. Twelve patients participated in the programme until the time of discharge (75%) from the transplant unit. Therefore, the predefined criteria regarding feasibility were met. The reason for drop out was transplantation associated mortality in all patients (n = 4). Adherence was very good with a median of 85% attended training sessions. No adverse events were recorded. The endurance capacity dropped by 7% and lower extremity strength improved by 2% over time. Quality of life decreased during the study period, with global health being significantly worse at the time of discharge. In conclusion, a combined and intensified strength and endurance exercise programme is feasible and safe in a population of elderly patients undergoing allo-HSCT. Further research should focus on exploring effect sizes of such an intervention by conducting randomised controlled trials.

Outcomes for split-thickness skin transplantation in high-risk patients using octenidine.

Skin transplantation is a commonly used surgical technique; however, the complication rate, including postoperative infection and delayed wound healing due to inefficient perfusion, is significantly higher in patients suffering from comorbidities. Hence, a subsequent repeat procedure is often necessary. In this report, two case studies are presented in which an octenidine-based antiseptic is used with a tie-over dressing (TOD) instead of povidone iodine (PVP-iodine), following a split-thickness skin graft. The two patients selected were deemed to be at high risk of impaired wound healing due to comorbidities. The first patient, a confirmed smoker with diabetes, presented with a nodular melanoma that was resected and covered with a split-thickness skin graft. After 5 days of negative pressure wound therapy as a TOD, in combination with PVP-iodine, the graft became necrotic. A second split-thickness skin graft was performed and an antiseptic regimen with octenidine in combination with the same TOD resulted in a completely healed transplant. The second patient, also a confirmed smoker with diabetes and receiving oral corticosteroid treatment, was diagnosed with a skin necrosis on her leg. Following the split-thickness skin graft, octenidine and TOD were applied. The patient's skin graft completely healed without any adverse events. These two case studies indicate that the combination of octenidine and TOD following split-thickness skin transplantation is safe, well-tolerated and appears to have positive benefits in the reconstruction of defects in patients with impaired wound healing.

Impact of electron-hole correlations on the 1T-TiSe_{2} electronic structure.

Several experiments have been performed on 1T-TiSe_{2} in order to identify whether the electronic structure is semimetallic or semiconducting without reaching a consensus. In this Letter, we theoretically study the impact of electron-hole and electron-phonon correlations on the bare semimetallic and semiconducting electronic structure. The resulting electron spectral functions provide a direct comparison of both cases and demonstrate that 1T-TiSe_{2} is of predominant semiconducting character with some spectral weight crossing the Fermi level.

Development and validation of a novel SPR-based assay principle for bispecific molecules.

Surface plasmon resonance (SPR) is increasingly applied in drug discovery, early development and production. However, there are remarkably few reports describing the application of SPR in a regulated environment. Here, we describe a novel SPR-based assay, which enables us to assess the binding activity of a bivalent-bispecific anti-Ang-2/anti-VEGF antibody to both targets in a single setup. Validation of the assay revealed a high level of precision, accuracy, linearity and specificity. Upon analysis of temperature stressed samples it could be shown that firstly, the assay is able to indicate function-loss and secondly, it allows the parallel analysis of an additional interaction. Therefore, the described assay is highly suitable for quality assessment of the Ang-2/VEGF CrossMab. Additionally, the use of SPR in the context of assay development and routine use in a GMP environment is discussed.

Comparative study of elbow disorders in young high-performance gymnasts.

The study aimed to investigate the prognosis of osteochondral affection (e.g., osteochondritis dissecans (OCD), cartilage lesions, fractures and bone edema in the elbows of high-performance gymnasts (n=30) compared to prognosis results with athletes not undergoing excessive stress on the upper extremity (n=29). The study also tested a novel isotropic 3D-FSE-sequence (CUBE) technique as an early diagnostic modality. Standard protocol was used to conduct the MRI examinations, which were then compared to results from the CUBE - sequence. The gymnast group (p=0.012) presented a significantly higher prevalence of complaints in the elbow joint compared to the other athlete group. Furthermore, osteochondral lesions in MRIs appeared more frequently in the group of gymnasts (n=10, 33%, p=0.033), including 7 cases (23%) of OCD. In the control athlete group 2 asymptomatic cases of OCD and one case of bone edema were detected. The MRI investigation with the CUBE - sequence showed similar results as the standard MRI protocol in terms of the diagnosis sensitivity. The current study indicates that juvenile gymnasts are at a higher risk for osteochondral lesions of the elbow than athletes without excessive stress on the upper extremities.

The nature and source of irregular discharges to stormwater entering Sydney estuary, Australia.

Irregular discharges of polluted stormwater into drainage systems during base flow (no rainfall) result in acute ecological impacts within fluvial and estuarine environments. In this study, metal and TSS concentrations were significantly more variable during business hours of weekdays (i.e. high-business activity) than weekends/public holidays (i.e. low-business activity) within three highly-urbanised catchments of Sydney estuary (Australia), as determined by analysing multivariate dispersion (PERMDISP). Concentrations of TSS and all metals analysed (Al, Ca, Cu, Fe, Mg, Pb and Zn) were also significantly greater during high- than low-business periods within at least one of the three catchments. In no case were concentrations significantly higher during low- than high-business periods. This pattern of contamination supports the hypothesis that commercial and industrial sources are major contributors of irregular discharges of contamination to Sydney estuary. Irregular discharges and consequential ecological impacts may be effectively reduced in this environment by focussing management efforts on these activities.

Smad-interacting protein 1 affects acute and tonic, but not chronic pain.

BACKGROUND: Smad-interacting protein 1 (also named Zeb2 and Zfhx1b) is a transcription factor that plays an important role in neuronal development and, when mutated, causes Mowat-Wilson syndrome (MWS). A corresponding mouse model carrying a heterozygous Zeb2 deletion was comprehensively analysed in the German Mouse Clinic. The most prominent phenotype was the reduced pain sensitivity. In this study, we investigated the role of Zeb2 in inflammatory and neuropathic pain. METHODS: For this, we tested mutant Zeb2 animals in different models of inflammatory pain like abdominal constriction, formalin and carrageenan test. Furthermore, we studied the pain reactivity of the mice after peripheral nerve ligation. To examine the nociceptive transmission of primary sensory dorsal root ganglia (DRG) neurons, we determined the neuronal activity in the spinal dorsal horn after the formalin test using staining of c-Fos. Next, we characterized the neuronal cell population in the DRGs and in the sciatic nerve to study the effect of the Zeb2 mutation on peripheral nerve morphology. RESULTS: The present data show that Zeb2 is involved in the development of primary sensory DRG neurons, especially of C- and Aδ fibres. These alterations contribute to a hypoalgesic phenotype in inflammatory but not in neuropathic pain in these Zeb2(+/-) mice. CONCLUSION: Our data suggest that the under-reaction to pain observed in MWS patients results from a reduced responsivity to nociceptive stimulation rather than an inability to communicate discomfort.

Clinical and dermoscopic characteristics of Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy with a high mortality rate. Diagnosis is often delayed. OBJECTIVES: To characterize the dermoscopic features of MCC. METHODS: Clinical and dermoscopic images of 12 biopsy-proven MCCs were analysed in a retrospective manner, with existing dermoscopic criteria being scored independently by three dermatologists. RESULTS: The four most frequent clinical features were cherry red colour, shiny surface, sharp circumscription and nodular morphology. Significant dermoscopic features included linear irregular and polymorphous vessels, poorly focused vessels, milky pink areas, white areas, structureless areas and architectural disorder. Pigmented structures were absent from all lesions. CONCLUSIONS: The dermoscopic features described herein help the clinician to distinguish MCC from other benign and malignant red nodules. Increasing recognition of the presenting features will facilitate earlier diagnosis of MCC and reduced mortality.

Enzyme replacement therapy for alpha-mannosidosis: 12 months follow-up of a single centre, randomised, multiple dose study.

BACKGROUND: Alpha-mannosidosis (OMIM 248500) is a rare lysosomal storage disease (LSD) caused by alpha-mannosidase deficiency. Manifestations include intellectual disabilities, facial characteristics and hearing impairment. A recombinant human alpha-mannosidase (rhLAMAN) has been developed for weekly intravenous enzyme replacement therapy (ERT). We present the preliminary data after 12 months of treatment. METHODS: This is a phase I-II study to evaluate safety and efficacy of rhLAMAN. Ten patients (7-17 y) were treated. We investigated efficacy by testing motor function (6-minutes-Walk-Test (6-MWT), 3-min-Stair-Climb-Test (3-MSCT), The Bruininks-Oseretsky Test of Motor Proficiency (BOT2), cognitive function (Leiter-R), oligosaccharides in serum, urine and CSF and Tau- and GFA-protein in CSF. RESULTS: Oligosaccharides: S-, U- and CSF-oligosaccharides decreased 88.6% (CI -92.0 -85.2, p < 0.001), 54.1% (CI -69.5- -38.7, p < 0,001), and 25.7% (CI -44.3- -7.1, p < 0.05), respectively. Biomarkers: CSF-Tau- and GFA-protein decreased 15%, p < 0.009) and 32.5, p < 0.001 respectively. Motor function: Improvements in 3MSCT (31 steps (CI 6.8-40.5, p < 0.01) and in 6MWT (60.4 m (CI -8.9 -51.1, NS) were achieved. Cognitive function: Improvement in the total Equivalence Age of 4 months (0.34) was achieved in the Leiter R test (CI -0.2-0.8, NS). CONCLUSIONS: These data suggest that rhLAMAN may be an encouraging new treatment for patients with alpha-mannosidosis.The study is designed to continue for a total of 18 months. Longer-term follow-up of patients in this study and the future placebo-controlled phase 3 trial are needed to provide greater support for the findings in this study.

The magnitude of variability produced by methods used to estimate annual stormwater contaminant loads for highly urbanised catchments.

Stormwater contaminant loading estimates using event mean concentration (EMC), rainfall/runoff relationship calculations and computer modelling (Model of Urban Stormwater Infrastructure Conceptualisation--MUSIC) demonstrated high variability in common methods of water quality assessment. Predictions of metal, nutrient and total suspended solid loadings for three highly urbanised catchments in Sydney estuary, Australia, varied greatly within and amongst methods tested. EMC and rainfall/runoff relationship calculations produced similar estimates (within 1 SD) in a statistically significant number of trials; however, considerable variability within estimates (∼50 and ∼25 % relative standard deviation, respectively) questions the reliability of these methods. Likewise, upper and lower default inputs in a commonly used loading model (MUSIC) produced an extensive range of loading estimates (3.8-8.3 times above and 2.6-4.1 times below typical default inputs, respectively). Default and calibrated MUSIC simulations produced loading estimates that agreed with EMC and rainfall/runoff calculations in some trials (4-10 from 18); however, they were not frequent enough to statistically infer that these methods produced the same results. Great variance within and amongst mean annual loads estimated by common methods of water quality assessment has important ramifications for water quality managers requiring accurate estimates of the quantities and nature of contaminants requiring treatment.

Mapping of electron-hole excitations in the charge-density-wave system 1T-TiSe2 using resonant inelastic x-ray scattering.

In high-resolution resonant inelastic x-ray scattering at the Ti L edge of the charge-density-wave system 1T-TiSe(2), we observe sharp low energy loss peaks from electron-hole pair excitations developing at low temperature. These excitations are strongly dispersing as a function of the transferred momentum of light. We show that the unoccupied bands close to the Fermi level can effectively be probed in this broadband material. Furthermore, we extract the order parameter of the charge-density-wave phase from temperature-dependent measurements.