Autoreactive T cells target peripheral nerves in Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is a rare heterogenous disorder of the peripheral nervous system, which is usually triggered by a preceding infection, and causes a potentially life-threatening progressive muscle weakness1. Although GBS is considered an autoimmune disease, the mechanisms that underlie its distinct clinical subtypes remain largely unknown. Here, by combining in vitro T cell screening, single-cell RNA sequencing and T cell receptor (TCR) sequencing, we identify autoreactive memory CD4+ cells, that show a cytotoxic T helper 1 (TH1)-like phenotype, and rare CD8+ T cells that target myelin antigens of the peripheral nerves in patients with the demyelinating disease variant. We characterized more than 1,000 autoreactive single T cell clones, which revealed a polyclonal TCR repertoire, short CDR3ß lengths, preferential HLA-DR restrictions and recognition of immunodominant epitopes. We found that autoreactive TCRß clonotypes were expanded in the blood of the same patient at distinct disease stages and, notably, that they were shared in the blood and the cerebrospinal fluid across different patients with GBS, but not in control individuals. Finally, we identified myelin-reactive T cells in the nerve biopsy from one patient, which indicates that these cells contribute directly to disease pathophysiology. Collectively, our data provide clear evidence of autoreactive T cell immunity in a subset of patients with GBS, and open new perspectives in the field of inflammatory peripheral neuropathies, with potential impact for biomedical applications.

A glacial lake outburst floods hazard assessment in the Patagonian Andes combining inventory data and case-studies.

We present a glacial-related lake inventory for a region spanning 41.5° - 47° S in Patagonian Andes, where information on past glacier lake outburst floods (GLOF's) has hitherto remained significantly underreported. Analyzing remotely sensed images, we obtained data on 702 glacial-related lakes. Through detailed geomorphic assessments and manual supervision, we revised current inventories and added 35 GLOFs triggered from moraine/bedrock dammed lakes failures. The regional GLOF inventory presented contains information on 71 historical failures of moraine/bedrock dammed glacial lakes. From this database we analyzed outburst timing and managed to constrain 37 events occurrences within a period of 1 year. Around 40 % of them have occurred since the early 2000's, most of them originating from lakes probably formed as a delayed response to the glacial retreat imposed by the end of the Little Ice Age. On the other hand, we analyzed meteorological conditions for a sub-set of 10 events constrained within a 10-days period, finding a strong link between atmospheric rivers, cut-off lows impacting the southern Andes, and GLOFs. Only one case is likely to have been triggered by a Mw 4.9 earthquake. Based on topographic potential for avalanching, we estimated GLOF hazard potential, recognizing at least 3 subregions with high hazard, which moreover can be highly susceptible to climate conditions that regionally affect GLOF occurrence.

Histo-morphological effects on equine synovium after arthroscopic synovectomy using two different motorized synovial resectors and two different intensities.

The purpose of the study was to determine the histo-morphological effects on villous synovium after synovectomy using two different motorized synovial resectors and two different intensities ex-vivo. Thirty-three (n = 33) equine metacarpophalangeal/metatarsophalangeal joints were used. Synovectomy was performed along the dorsomedial/dorsolateral synovium (n = 66) using two motorized synovial resectors (aggressive full radius resector, AFRR, used at two intensities: single treatment, n = 24 vs. triple treatment, n = 21 vs. aggressive meniscus side cutter, AMSC, n = 21). Arthroscopic images were evaluated blindly for resector type and intensity. Histological images were evaluated descriptive for synovial morphology and the extent of tissue loss using a microscopic scale. Scanning electron microscopy described the synovial morphology. The synovectomized areas were specific for each resector used and distinguishable from arthroscopic images. The AFRR demonstrated a clear demarcation between treated and non-treated areas and removed the stratum synoviale completely including parts of the underlying stratum fibrosum. In contrast, the AMSC showed less clear demarcation, villous scaffolds and no involvement of the stratum fibrosum. Triple intense treated AFFR samples resulted in significantly deeper lesions compared to single treatments (p = 0.037) but could not be distinguished on arthroscopic images. The morphological effects on villous synovium differ according to the resector type used. The extent of synovial tissue loss cannot be estimated from arthroscopic images but histologically. The type and use of motorized synovial resector determines the morphological alterations of the treated synovium. Arthroscopic control is considered unsuitable to control synovectomy depth.

Combining conventional tree-ring measurements with wood anatomy and strontium isotope analyses enables dendroprovenancing at the local scale.

Dendroprovenancing provides critical information regarding the origin of wood, allowing further insights into economic exploitation strategies and source regions of timber products. Traditionally, dendroprovenancing relies on pattern-matching of tree rings, but its spatial resolution is limited by the geographical coverage of species-specific chronologies available for crossdating and, in the case of short-distance trades, by scarce environmental variability. Here, we present an approach to provenance timber with high spatial resolution from forested areas that have been exploited intensively throughout history, with the aim to understand the sustainability of the various woodland management practices used to supply timber products. To this end, we combined tree-ring width (TRW), wood anatomical and geochemical analyses in addition to multivariate statistical validation procedures to trace the origin of living oak trees (Quercus robur) sampled in four stands located within a 30-km radius around the city of Limoges (Haute-Vienne, France). We demonstrate that TRW and wood anatomical variables (and in particular cell density) robustly discriminate the eastern from the western site, while failing to trace the origin of trees from the northern and southern sites. Here, strontium isotopic ratios (87Sr/86Sr) and Ca concentrations identify clusters of trees which could not be identified with TRW or wood anatomy. Ultimately, our study demonstrates that the coupling of wood anatomy with geochemical signatures allows to correctly pinpoint the origin of trees. Given the small geographic scale of our study and the limited differences in elevation and climate between study sites, our results are particularly promising for future dendroprovenancing studies. We thus conclude that the combination of multiple approaches will not only increase the accuracy of dendroprovenancing studies at local scales, but could also be implemented at much larger scales to identify trends in historic timber supply throughout Europe.

Genetic architecture and lifetime dynamics of inbreeding depression in a wild mammal.

Inbreeding depression is ubiquitous, but we still know little about its genetic architecture and precise effects in wild populations. Here, we combine long-term life-history data with 417 K imputed SNP genotypes for 5952 wild Soay sheep to explore inbreeding depression on a key fitness component, annual survival. Inbreeding manifests in long runs of homozygosity (ROH), which make up nearly half of the genome in the most inbred individuals. The ROH landscape varies widely across the genome, with islands where up to 87% and deserts where only 4% of individuals have ROH. The fitness consequences of inbreeding are severe; a 10% increase in individual inbreeding FROH is associated with a 60% reduction in the odds of survival in lambs, though inbreeding depression decreases with age. Finally, a genome-wide association scan on ROH shows that many loci with small effects and five loci with larger effects contribute to inbreeding depression in survival.

Recent atmospheric drying in Siberia is not unprecedented over the last 1,500 years.

Newly developed millennial δ13C larch tree-ring chronology from Siberia allows reconstruction of summer (July) vapor pressure deficit (VPD) changes in a temperature-limited environment. VPD increased recently, but does not yet exceed the maximum values reconstructed during the Medieval Warm Anomaly. The most humid conditions in the Siberian North were recorded in the Early Medieval Period and during the Little Ice Age. Increasing VPD under elevated air temperature affects the hydrology of these sensitive ecosystems by greater evapotranspiration rates. Further VPD increases will significantly affect Siberian forests most likely leading to drought and forest mortality even under additional access of thawed permafrost water. Adaptation strategies are needed for Siberian forest ecosystems to protect them in a warming world.

Economic valuation of ecosystem-based rockfall risk reduction considering disturbances and comparison to structural measures.

Forests provide a series of ecosystem services, including the protection from natural hazards. Thanks to these forests, structural protection measures can be avoided in many places. A realistic long-term valuation of this ecosystem-based risk reduction provided by the forest is essential. The aim of this study is to assess the Net Present Value (NPV) of a protection forest using a risk-based approach and compare it to the NPV of rockfall nets. Costs to be included in the NPV calculation are forest management interventions, net construction, and benefits are the risk reduction and wood sales. The risk reduction is monetised as avoided costs, i.e. the difference between the yearly rockfall risk with and without measure. Uncertainties in the protection effect due to possible forest fires were simulated over a period of 100years using a Monte-Carlo approach. Both the protection forest and the nets effectively reduce rockfall risk at the study site. The NPV of the nets is highly negative (-124,100 CHF/ha), indicating that they are economically not worthwhile at the study site. The NPV of the protection forest is highly positive (162,400 CHF/ha). The variation of the NPV due to fires is very low and the influence of this disturbance on the long-term efficiency of the protection forest is small. Building temporary nets in case of a large fire can restore the protective effect. Their NPV is, however, lower compared to the situation without net. By calculating the NPV of a forest considering its risk reducing effect, we provide a methodology for a realistic valuation of its protective effect. It is based on a case study, which, however, can be applied in a broader context. The presented approach can serve as basis to find optimal combinations of investment in natural hazard prevention, be this ecosystem-based or structural measures.

Assessment of potential neuropathic changes in cattle after cautery disbudding.

Disbudding of calves is a standard husbandry procedure to reduce the risk of injuries to other cattle and to workers. Whereas acute pain resulting from disbudding has been studied extensively, little is known about chronic pain as a potential long-term consequence. The goal of the present study was to investigate possible morphological changes in the cornual nerve as a function of disbudding. Samples were collected from 17 randomly selected bulls and from 21 calves from a prospective clinical study. Among the calves, 13 were disbudded and 8 were sham-disbudded. Out of the disbudded calves, 4 showed signs of chronic pain. In all the animals, the infraorbital nerve was used as a methodological check. Morphological analysis included measuring minimal diameters of the axons present in both the cornual and infraorbital nerves. Sympathetic fibers were identified as based on the presence of Tyroxine hydroxylase (TH). TH-negative fibers were considered afferents. Trigeminal ganglia from the calves were immunostained for glial fibrillary acidic protein (GFAP) and Activating transcription factor 3 (ATF3). R. cornualis and N. infraorbitalis differed in terms of axon diameters and proportion of TH-positive fibers. Weak evidence (p > .091) of a difference in axon diameters between control and disbudded calves was found in R. cornualis, but the proportion of TH-positive fibers was alike in both groups. Average glial envelope and the percentages of ATF3-positive neurons revealed no difference between calves with and without signs of pain. Thus, available evidence is insufficient to support neuropathic changes as a result of disbudding in calves.

Tree-ring correlations suggest links between moderate earthquakes and distant rockfalls in the Patagonian Cordillera.

Earthquakes with magnitudes M > 7 can trigger large landslides and rockfalls at epicenter distances of up to 400 km, whereas moderate shaking (M = 5-7) is generally thought to result in abundant co-seismic mass movements in the vicinity of the epicenter. Although one might anticipate that large magnitude earthquakes off the Chilean coast would result in abundant rockfall in the Patagonian Cordillera, only limited research has explored this hypothesis. Here, we use tree-ring records from 63 cross-sections of century-old (103.9 ± 40.1 yr) Nothofagus pumilio trees to develop a calendar-dated record of small rockfall events (101-102 m3) on a talus slope located next to Monte Fitz Roy (El Chaltén, Argentina; 49°4'S, 72°57'W). The resulting rockfall record is used to infer that subduction zone seismicity at the Triple Junction and intraplate shaking around Lago Argentino almost systematically caused rockfall activity at this site, even if seismicity occurred at large distances (up to 300 km away) and with moderate intensity (M = 5-7). About one third of the rockfalls are triggered by factors other than earthquakes, predominantly in spring when freeze-thaw cycles occur frequently at the site. Despite the fact that seismicity is not the only trigger of rockfall activity at Cerro Crestón, at the foot of Monte Vespignani, we conclude that, in regions where topographic amplification plays a role, small rockfalls can be triggered by earthquakes of moderate intensity at large distances from the epicenter.

Tree-ring reconstruction of snow avalanche activity: Does avalanche path selection matter?

In the current context of anthropogenic global warming, one of the purposes of dendrogeomorphic analyses is to provide long and continuous chronologies of mass movements, so as to detect potential trends or shift related to increasing temperatures. However, on documented slopes, the comparison between historical archives and tree-ring records suggests that dendrogeomorphic reconstructions systematically underestimate the natural activity of the process under investigation. In the specific case of snow avalanches, underestimation generally amounts to 50% and the main causes generally given for this difference are related to the magnitude of past events. In this study, we hypothesize that the morphometric characteristics of avalanche paths and their forest cover could have significant impacts on the length and reliability of tree-ring reconstructions. In order to test this hypothesis, we selected four adjacent, albeit differently structured, avalanche paths from the Queyras massif (French Alps), with the aim to compare their potential for a continuous reconstruction of past avalanche activity. On the most active avalanche paths characterized by high-altitude release areas (covered only by shrubby vegetation), tree-ring reconstructions do not exceed one century in length, with recurrence intervals of high magnitude events >25 years. By contrast, on forested couloirs where lower slopes and forest coverage up to the release areas limits the intensity of events, the frequency of reconstructed snow avalanches is 2.5 times higher, the reconstructions span longer periods and the convergence rate with historical archives attest to the reliability of the dendrogeomorphic approach. These results suggest that a careful selection of couloirs is essential and that priority should be given to forested sites as (i) they allow for exhaustive and (ii) reliable reconstructions over (iii) long periods of time.

Climate-growth relationships in a Larix decidua Mill. network in the French Alps.

A better understanding of the respective role of key climatic variables on tree growth is crucial for an accurate assessment of how ongoing global changes may affect both dynamics and distribution of forest tree species in the future. The aim of this study was (i) to explore growth patterns of European larch (Larix decidua Mill.) through a network of tree-ring chronologies developed for the French Alps and (ii) to identify the main climatic drivers explaining radial growth. Climate-growth relationships were coupled with a hierarchical analysis. This relationship revealed significant variability expressed spatially by the existence of five clusters, initially discriminated by an elevational contrast related to (i) a negative correlation between summer temperatures and larch growth at lower elevations and (ii) a stronger response of low-elevation larch stands to winter precipitation. In the high-elevation clusters, tree growth depends on previous autumn and current summer temperatures and water supply in July. The differentiation, that portrays a strong geographical coherence, is mainly related to the latitudinal gradient; (i) the northwestern stands are mostly sensitive to high temperatures in summer; (ii) the growth of the southernmost clusters is equally driven by temperatures during autumn, winter, and summers; (iii) the populations of a cluster located in a transitional zone of the inner French Alps, subject to both Mediterranean and Continental influences, exhibit negative correlations to late winter and early spring precipitation. This significant spatial heterogeneity of climate-tree ring relationships in L. decidua clearly underlines the high plasticity of the species to adapt its growth to local climate conditions.

Demographic histories and genetic diversity across pinnipeds are shaped by human exploitation, ecology and life-history.

A central paradigm in conservation biology is that population bottlenecks reduce genetic diversity and population viability. In an era of biodiversity loss and climate change, understanding the determinants and consequences of bottlenecks is therefore an important challenge. However, as most studies focus on single species, the multitude of potential drivers and the consequences of bottlenecks remain elusive. Here, we combined genetic data from over 11,000 individuals of 30 pinniped species with demographic, ecological and life history data to evaluate the consequences of commercial exploitation by 18th and 19th century sealers. We show that around one third of these species exhibit strong signatures of recent population declines. Bottleneck strength is associated with breeding habitat and mating system variation, and together with global abundance explains much of the variation in genetic diversity across species. Overall, bottleneck intensity is unrelated to IUCN status, although the three most heavily bottlenecked species are endangered. Our study reveals an unforeseen interplay between human exploitation, animal biology, demographic declines and genetic diversity.

[Surgical treatment of adult spinal deformities]. / Operative Behandlung adulter spinaler Deformitäten.

BACKGROUND: Adult spinal deformity (ASD) is mostly a progressive disease which usually leads to chronic pain. Due to increased prevalence in older people many patients suffer from comorbidities, which make conservative and surgical treatment even more complex. OBJECTIVE: This article provides an overview on the current conservative and surgical treatment options. MATERIAL AND METHODS: An extensive literature search was carried out via Medline plus an additional evaluation of the authors' personal experiences was performed. RESULTS: The current conservative and surgical treatments are outlined and potential risk factors and predictors which may lead to inferior clinical outcome are discussed. CONCLUSION: Patients for whom even conservative treatment leads to success should be identified earlier and better. The surgical treatment ranges from minimally invasive decompression to multilevel fusions. Complications in large corrective interventions can be substantial but if the indications are correctly assessed, such complex surgical treatment has excellent clinical results in terms of pain and quality of life.

[Operative treatment of degenerative diseases of the lumbar spine]. / Operative Versorgung degenerativer Erkrankungen der Lendenwirbelsäule.

BACKGROUND: Degenerative diseases of the lumbar spine and associated lower back pain represent a major epidemiological and health-related economic challenge. A distinction is made between specific and unspecific lower back pain. In specific lower back pain lumbar disc herniation and spinal canal stenosis with or without associated segment instability are among the most frequent pathologies. Diverse conservative and operative strategies for treatment of these diseases are available. OBJECTIVES: The aim of this article is to present an overview of current data and an evidence-based assessment of the possible forms of treatment. MATERIAL AND METHODS: An extensive literature search was carried out via Medline plus an additional evaluation of the authors' personal experiences. RESULTS: Conservative and surgical treatment represent efficient treatment options for degenerative diseases of the lumbar spine. Surgical treatment of lumbar disc herniation shows slight advantages compared to conservative treatment consisting of faster recovery of neurological deficits and a faster restitution of pain control. Surgical decompression is superior to conservative measures for the treatment of spinal canal stenosis and degenerative spondylolisthesis. In this scenario conservative treatment represents an important supporting measure for surgical treatment in order to improve the mobility of patients and the outcome of surgical treatment. CONCLUSION: The treatment of specific lower back pain due to degenerative lumbar pathologies represents an interdisciplinary challenge, requiring both conservative and surgical treatment strategies in a synergistic treatment concept in order to achieve the best results for patients.

[Operative treatment of the degenerative cervical spine]. / Operative Versorgung der degenerativen Halswirbelsäule.

BACKGROUND: Degenerative alterations of the cervical spine often entail disc herniations and stenoses of the spinal canal and/or neural foramen. Mediolateral or lateral compression of nerve roots causes cervical radiculopathy, which is an indication for surgery in cases of significant motor deficits or refractory pain. Median canal encroachment may result in compression of the spinal cord and cervical myelopathy. Its natural history is typically characterized by episodic deterioration, so that surgical decompression is indicated in cases of clear myelopathic signs. OBJECTIVE: The aim of the present article is to outline the operative options for patients with cervical radiculopathy and myelopathy. Furthermore, we describe the operative complications and the outcome in these patients. MATERIAL AND METHODS: For this manuscript a systematic PubMed search was carried out, the papers were systematically analyzed for the best evidence and this was combined with the authors' experience. RESULTS AND CONCLUSION: Depending on the cervical pathology, the most prevalent surgical options for radiculopathy include anterior cervical discectomy and fusion (ACDF), cervical arthroplasty or posterior cervical foraminotomy. Cervical myelopathy may be decompressed by ACDF, corpectomy or posterior approaches like laminectomy plus instrumented fusion or laminoplasty. The outcome depends on the cervical pathology and the type of operation. Overall, in long-term follow-up studies the results of all surgical techniques on the cervical spine are generally considered to be very good, although specific patient characteristics are more suited for a particular approach.

Climate warming enhances snow avalanche risk in the Western Himalayas.

Ongoing climate warming has been demonstrated to impact the cryosphere in the Indian Himalayas, with substantial consequences for the risk of disasters, human well-being, and terrestrial ecosystems. Here, we present evidence that the warming observed in recent decades has been accompanied by increased snow avalanche frequency in the Western Indian Himalayas. Using dendrogeomorphic techniques, we reconstruct the longest time series (150 y) of the occurrence and runout distances of snow avalanches that is currently available for the Himalayas. We apply a generalized linear autoregressive moving average model to demonstrate linkages between climate warming and the observed increase in the incidence of snow avalanches. Warming air temperatures in winter and early spring have indeed favored the wetting of snow and the formation of wet snow avalanches, which are now able to reach down to subalpine slopes, where they have high potential to cause damage. These findings contradict the intuitive notion that warming results in less snow, and thus lower avalanche activity, and have major implications for the Western Himalayan region, an area where human pressure is constantly increasing. Specifically, increasing traffic on a steadily expanding road network is calling for an immediate design of risk mitigation strategies and disaster risk policies to enhance climate change adaption in the wider study region.

A study of the damage behaviour of porcine intervertebral discs in a bioreactor environment.

The intervertebral discs are cartilaginous, articulating structures that lie between vertebral bodies, allowing flexibility, transmission, modification, and also distribution of the forces to the spinal column. Disc degeneration is characterised by progressive loss of disc height and exaggerated radial bulging. Therefore, the spine becomes shorter, stiffer, and less mobile. In the last several decades, there is a strong need for a tissue engineering strategy that alleviates pain and restores spine function by directly addressing the underlying biological causes of disc degeneration. Numerous studies that are currently showing potential have been conducted on developing regenerative and reparative strategies for treating this condition. In this study, to numerically describe the anisotropic mechanical damage behaviour of discs, the pseudo-elastic damage model was applied. To experimentally picture the biomechanical response of discs and to study the damage mechanisms as well as the spinal disc herniation, a special bioreactor was evolved. The specimens were obtained from pigs aged six months. A total of eight functional spine units were taken from porcine lumbar spines (L1-L2). Firstly, the experiments were performed by using long-term cyclic uniaxial compression tests. Secondly, the mean value of experimental results with consideration of the different shapes and sizes of the samples was calculated. Afterwards, the experimental results were compared with outcomes of numerical simulations.

Ranid Herpesvirus 3 and Proliferative Dermatitis in Free-Ranging Wild Common Frogs (Rana Temporaria).

Amphibian pathogens are of current interest as contributors to the global decline of amphibians. However, compared with chytrid fungi and ranaviruses, herpesviruses have received relatively little attention. Two ranid herpesviruses have been described: namely, Ranid herpesvirus 1 (RHV1) and Ranid herpesvirus 2 (RHV2). This article describes the discovery and partial characterization of a novel virus tentatively named Ranid herpesvirus 3 (RHV3), a candidate member of the genus Batrachovirus in the family Alloherpesviridae. RHV3 infection in wild common frogs (Rana temporaria) was associated with severe multifocal epidermal hyperplasia, dermal edema, a minor inflammatory response, and variable mucous gland degeneration. Intranuclear inclusions were numerous in the affected epidermis together with unique extracellular aggregates of herpesvirus-like particles. The RHV3-associated skin disease has features similar to those of a condition recognized in European frogs for the last 20 years and whose cause has remained elusive. The genome of RHV3 shares most of the features of the Alloherpesviruses. The characterization of this presumptive pathogen may be of value for amphibian conservation and for a better understanding of the biology of Alloherpesviruses.

Gully evolution and geomorphic adjustments of badlands to reforestation.

Badlands and gullied areas are among those geomorphic environments with the highest erosion rates worldwide. Nevertheless, records of their evolution and their relations with anthropogenic land transformation are scarcer. Here we combine historical data with aerial photographs and tree-ring records to reconstruct the evolution of a badland in a Mediterranean environment of Central Spain. Historical sources suggest an anthropogenic origin of this badland landscape, caused by intense quarrying activities during the 18th century. Aerial photographs allowed detection of dramatic geomorphic changes and the evolution of an emerging vegetation cover since the 1960s, due to widespread reforestation. Finally, tree-ring analyses of exposed roots allowed quantification of recent channel incision of the main gully, and sheet erosion processes. Our results suggest that reforestation practices have influenced the initiation of an episode of incision in the main channel in the 1980s, through the hypothesized creation of disequilibrium in water-sediment balance following decoupling of hillslopes from channel processes. These findings imply an asymmetry in the geomorphic response of badlands to erosion such that in the early evolution stages, vegetation removal results in gullying, but that reforestation alone does not necessarily stabilize the landforms and may even promote renewed incision.