Archaeological Discoveries on Schnidejoch and at Other Ice Sites in the European Alps

Only a few sites in the Alps have produced archaeological finds from melting ice. To date, prehistoric finds from four sites dating from the Neolithic period, the Bronze Age, and the Iron Age have been recovered from small ice patches (Schnidejoch, Lötschenpass, Tisenjoch, and Gemsbichl/Rieserferner). Glaciers, on the other hand, have yielded historic finds and frozen human remains that are not more than a few hundred years old (three glacier mummies from the 16th to the 19th century and military finds from World Wars I and II). Between 2003 and 2010, numerous archaeological finds were recovered from a melting ice patch on the Schnidejoch in the Bernese Alps (Cantons of Berne and Valais, Switzerland). These finds date from the Neolithic period, the Early Bronze Age, the Iron Age, Roman times, and the Middle Ages, spanning a period of 6000 years. The Schnidejoch, at an altitude of 2756 m asl, is a pass in the Wildhorn region of the western Bernese Alps. It has yielded some of the earliest evidence of Neolithic human activity at high altitude in the Alps. The abundant assemblage of finds contains a number of unique artifacts, mainly from organic materials like leather, wood, bark, and fibers. The site clearly proves access to high-mountain areas as early as the 5th millennium BC, and the chronological distribution of the finds indicates that the Schnidejoch pass was used mainly during periods when glaciers were retreating.

New data on the Lateglacial period of SW Europe: a high resolution multiproxy record from Laguna de la Roya (NW Iberia)

High-resolution multiproxy analyses were performed on a 128 cm section of organic sediments accumulated in a small mountain lake in NW Iberia (Laguna de la Roya, 1608 m asl). The pollen stratigraphy together with radiocarbon dating provided the basis for a chronology ranging from 15,600 to 10,500 cal yr BP. Chironomid-inferred July air temperatures suggest a temperature range from 7 to 13 degrees C, also evidencing two well-established cold periods which may be equivalent to the INTIMATE stages GS-2a and GS-1. Furthermore, a number of short cold events (with summer temperatures dropping about 0.5-1 degrees C) appear intercalated within the Lateglacial Interstadial (possibly equivalent to the INTIMATE cold events GI-1d, GI-1c2 and GI-1b) and the early Holocene (possibly equivalent to the 11.2 k event). The temperature variations predicted by our reconstruction allow explaining the changes in local conditions and productivity of the lake inferred from the biological record of the same sediment core. Furthermore, they also agree with the local and regional vegetation dynamics, and the main oscillations deduced for the vegetation belts. Based on its chronology our multiproxy record indicates a similar temperature development in NW Iberia as inferred by the Greenland delta O-18 record, the marine deep-sea records off the Atlantic Iberian Margin, and other chironomid-based Lateglacial temperature reconstructions from Europe. Nevertheless, the impact of most of the less intense Lateglacial/early Holocene cold events in NW Iberia was most probably limited to very sensitive sites that were very close to ecotonal situations. Particularly, our new pollen record indicates that they were represented as three minor environmental crises occurring during the Lateglacial Interestadial in this area. The Older Dryas event (in our usage corresponding to the Aegelsee Oscillation in Central Europe and event GI-1d in central Greenland) has previously been described in this region, but its age and duration (ca 14,250-14050 cal yr BP) is now better constrained. The two subsequent stages, La Roya I (ca 13,600-13,400 cal yr BP) and La Roya II (ca 13,300-12,900 cal yr BP) have been described for first time in NW Iberia. (C) 2013 Elsevier Ltd. All rights reserved.

Understanding the role of argininosuccinate lyase transcript variants in the clinical and biochemical variability of the urea cycle disorder argininosuccinic aciduria

Argininosuccinic aciduria (ASA) is an autosomal recessive urea cycle disorder caused by deficiency of argininosuccinate lyase (ASL) with a wide clinical spectrum from asymptomatic to severe hyperammonemic neonatal onset life-threatening courses. We investigated the role of ASL transcript variants in the clinical and biochemical variability of ASA. Recombinant proteins for ASL wild type, mutant p.E189G, and the frequently occurring transcript variants with exon 2 or 7 deletions were (co-)expressed in human embryonic kidney 293T cells. We found that exon 2-deleted ASL forms a stable truncated protein with no relevant activity but a dose-dependent dominant negative effect on enzymatic activity after co-expression with wild type or mutant ASL, whereas exon 7-deleted ASL is unstable but seems to have, nevertheless, a dominant negative effect on mutant ASL. These findings were supported by structural modeling predictions for ASL heterotetramer/homotetramer formation. Illustrating the physiological relevance, the predominant occurrence of exon 7-deleted ASL was found in two patients who were both heterozygous for the ASL mutant p.E189G. Our results suggest that ASL transcripts can contribute to the highly variable phenotype in ASA patients if expressed at high levels. Especially, the exon 2-deleted ASL variant may form a heterotetramer with wild type or mutant ASL, causing markedly reduced ASL activity.

Repeated measurements of cerebral blood flow in the left superior temporal gyrus reveal tonic hyperactivity in patients with auditory verbal hallucinations: a possible trait marker

Background: The left superior temporal gyrus (STG) has been suggested to play a key role in auditory verbal hallucinations (AVH) in patients with schizophrenia. Methods: Eleven medicated subjects with schizophrenia and medication-resistant AVH and 19 healthy controls underwent perfusion magnetic resonance (MR) imaging with arterial spin labeling (ASL). Three additional repeated measurements were conducted in the patients. Patients underwent a treatment with transcranial magnetic stimulation (TMS) between the first 2 measurements. The main outcome measure was the pooled cerebral blood flow (CBF), which consisted of the regional CBF measurement in the left STG and the global CBF measurement in the whole brain. Results: Regional CBF in the left STG in patients was significantly higher compared to controls (p < 0.0001) and to the global CBF in patients (p < 0.004) at baseline. Regional CBF in the left STG remained significantly increased compared to the global CBF in patients across time (p < 0.0007), and it remained increased in patients after TMS compared to the baseline CBF in controls (p < 0.0001). After TMS, PANSS (p = 0.003) and PSYRATS (p = 0.01) scores decreased significantly in patients. Conclusions: This study demonstrated tonically increased regional CBF in the left STG in patients with schizophrenia and auditory hallucinations despite a decrease in symptoms after TMS. These findings were consistent with what has previously been termed a trait marker of AVH in schizophrenia.

The onset of Neoglaciation 6000 years ago in western Mongolia revealed by an ice core from the Tsambagarav mountain range

Glacier highstands since the Last Glacial Maximum are well documented for many regions, but little is known about glacier fluctuations and lowstands during the Holocene. This is because the traces of minimum extents are difficult to identify and at many places are still ice covered, limiting the access to sample material. Here we report a new approach to assess minimal glacier extent, using a 72-m long surface-to-bedrock ice core drilled on Khukh Nuru Uul, a glacier in the Tsambagarav mountain range of the Mongolian Altai (4130 m asl, 48°39.338′N, 90°50.826′E). The small ice cap has low ice temperatures and flat bedrock topography at the drill site. This indicates minimal lateral glacier flow and thereby preserved climate signals. The upper two-thirds of the ice core contain 200 years of climate information with annual resolution, whereas the lower third is subject to strong thinning of the annual layers with a basal ice age of approximately 6000 years before present (BP). We interpret the basal ice age as indicative of ice-free conditions in the Tsambagarav mountain range at 4100 m asl prior to 6000 years BP. This age marks the onset of the Neoglaciation and the end of the Holocene Climate Optimum. The ice-free conditions allow for adjusting the Equilibrium Line Altitude (ELA) and derive the glacier extent in the Mongolian Altai during the Holocene Climate Optimum. Based on the ELA-shift, we conclude that most of the glaciers are not remnants of the Last Glacial Maximum but were formed during the second part of the Holocene. The ice core derived accumulation reconstruction suggests important changes in the precipitation pattern over the last 6000 years. During formation of the glacier, more humid conditions than presently prevailed followed by a long dry period from 5000 years BP until 250 years ago. Present conditions are more humid than during the past millennia. This is consistent with precipitation evolution derived from lake sediment studies in the Altai.

Static and dynamic characteristics of cerebral blood flow during the resting state in schizophrenia

Background: The cerebral network that is active during rest and is deactivated during goal-oriented activity is called the default mode network (DMN). It appears to be involved in self-referential mental activity. Atypical functional connectivity in the DMN has been observed in schizophrenia. One hypothesis suggests that pathologically increased DMN connectivity in schizophrenia is linked with a main symptom of psychosis, namely, misattribution of thoughts. Methods: A resting-state pseudocontinuous arterial spin labeling (ASL) study was conducted to measure absolute cerebral blood flow (CBF) in 34 schizophrenia patients and 27 healthy controls. Using independent component analysis (ICA), the DMN was extracted from ASL data. Mean CBF and DMN connectivity were compared between groups using a 2-sample t test. Results: Schizophrenia patients showed decreased mean CBF in the frontal and temporal regions (P < .001). ICA demonstrated significantly increased DMN connectivity in the precuneus (x/y/z = -16/-64/38) in patients than in controls (P < .001). CBF was not elevated in the respective regions. DMN connectivity in the precuneus was significantly correlated with the Positive and Negative Syndrome Scale scores (P < .01). Conclusions: In schizophrenia patients, the posterior hub-which is considered the strongest part of the DMN-showed increased DMN connectivity. We hypothesize that this increase hinders the deactivation of the DMN and, thus, the translation of cognitive processes from an internal to an external focus. This might explain symptoms related to defective self-monitoring, such as auditory verbal hallucinations or ego disturbances.

Functional connectivity in BOLD and CBF data: similarity and reliability of resting brain networks

Resting-state functional connectivity (FC) fMRI (rs-fcMRI) offers an appealing approach to mapping the brain's intrinsic functional organization. Blood oxygen level dependent (BOLD) and arterial spin labeling (ASL) are the two main rs-fcMRI approaches to assess alterations in brain networks associated with individual differences, behavior and psychopathology. While the BOLD signal is stronger with a higher temporal resolution, ASL provides quantitative, direct measures of the physiology and metabolism of specific networks. This study systematically investigated the similarity and reliability of resting brain networks (RBNs) in BOLD and ASL. A 2×2×2 factorial design was employed where each subject underwent repeated BOLD and ASL rs-fcMRI scans on two occasions on two MRI scanners respectively. Both independent and joint FC analyses revealed common RBNs in ASL and BOLD rs-fcMRI with a moderate to high level of spatial overlap, verified by Dice Similarity Coefficients. Test-retest analyses indicated more reliable spatial network patterns in BOLD (average modal Intraclass Correlation Coefficients: 0.905±0.033 between-sessions; 0.885±0.052 between-scanners) than ASL (0.545±0.048; 0.575±0.059). Nevertheless, ASL provided highly reproducible (0.955±0.021; 0.970±0.011) network-specific CBF measurements. Moreover, we observed positive correlations between regional CBF and FC in core areas of all RBNs indicating a relationship between network connectivity and its baseline metabolism. Taken together, the combination of ASL and BOLD rs-fcMRI provides a powerful tool for characterizing the spatiotemporal and quantitative properties of RBNs. These findings pave the way for future BOLD and ASL rs-fcMRI studies in clinical populations that are carried out across time and scanners.

Interhemispheric cerebral blood flow balance during recovery of motor hand function after ischemic stroke - a longitudinal MRI study using arterial spin labeling perfusion

BACKGROUND Unilateral ischemic stroke disrupts the well balanced interactions within bilateral cortical networks. Restitution of interhemispheric balance is thought to contribute to post-stroke recovery. Longitudinal measurements of cerebral blood flow (CBF) changes might act as surrogate marker for this process. OBJECTIVE To quantify longitudinal CBF changes using arterial spin labeling MRI (ASL) and interhemispheric balance within the cortical sensorimotor network and to assess their relationship with motor hand function recovery. METHODS Longitudinal CBF data were acquired in 23 patients at 3 and 9 months after cortical sensorimotor stroke and in 20 healthy controls using pulsed ASL. Recovery of grip force and manual dexterity was assessed with tasks requiring power and precision grips. Voxel-based analysis was performed to identify areas of significant CBF change. Region-of-interest analyses were used to quantify the interhemispheric balance across nodes of the cortical sensorimotor network. RESULTS Dexterity was more affected, and recovered at a slower pace than grip force. In patients with successful recovery of dexterous hand function, CBF decreased over time in the contralesional supplementary motor area, paralimbic anterior cingulate cortex and superior precuneus, and interhemispheric balance returned to healthy control levels. In contrast, patients with poor recovery presented with sustained hypoperfusion in the sensorimotor cortices encompassing the ischemic tissue, and CBF remained lateralized to the contralesional hemisphere. CONCLUSIONS Sustained perfusion imbalance within the cortical sensorimotor network, as measured with task-unrelated ASL, is associated with poor recovery of dexterous hand function after stroke. CBF at rest might be used to monitor recovery and gain prognostic information.

Assignment of the porcine tumour necrosis factor alpha and beta genes to the chromosome region 7p11-q11 by in situ hybridization

The loci of the porcine tumour necrosis factor genes, alpha (TNFA) and beta (TNFB), have been chromosomally assigned by radioactive in situ hybridization. The genomic probes for TNFA and TNFB yielded signals above 7p11-q11, a region that has been shown earlier to carry the porcine major histocompatibility locus (SLA). These mapping data along with preliminary molecular studies suggest a genomic organization of the SLA that is similar to that of human and murine major histocompatibility complexes.

Relationships between functional traits and inorganic nitrogen acquisition among eight contrasting European grass species

Backgrounds and Aims Leaf functional traits have been used as a basis to categoize plants across a range of resource-use specialization, from those that conserve available resources to those that exploit them. However, the extent to which the leaf functional traits used to define the resource-use strategies are related to root traits and are good indicators of the ability of the roots to take up nitrogen (N) are poorly known. This is an important question because interspecific differences in N uptake have been proposed as one mechanism by which species coexistence may be determined. This study therefore investigated the relationships between functional traits and N uptake ability for grass species across a range of conservative to exploitative resource-use strategies.Methods Root uptake of NH4+ and NO3-, and leaf and root functional traits were measured for eight grass species sampled at three grassland sites across Europe, in France, Austria and the UK. Species were grown in hydroponics to determine functional traits and kinetic uptake parameters (Imax and Km) under standardized conditions.Key Results Species with high specific leaf area (SLA) and shoot N content, and low leaf and root dry matter content (LDMC and RDMC, respectively), which are traits associated with the exploitative syndrome, had higher uptake and affinity for both N forms. No trade-off was observed in uptake between the two forms of N, and all species expressed a higher preference for NH4+.Conclusions The results support the use of leaf traits, and especially SLA and LDMC, as indicators of the N uptake ability across a broad range of grass species. The difficulties associated with assessing root properties are also highlighted, as root traits were only weakly correlated with leaf traits, and only RDMC and, to a lesser extent, root N content were related to leaf traits.

The impact of neural invasion severity in gastrointestinal malignancies: a clinicopathological study.

OBJECTIVES Because neural invasion (NI) is still inconsistently reported and not well characterized within gastrointestinal malignancies (GIMs), our aim was to determine the exact prevalence and severity of NI and to elucidate the true impact of NI on patient's prognosis. BACKGROUND The union internationale contre le cancer (UICC) recently added NI as a novel parameter in the current TNM classification. However, there are only a few existing studies with specific focus on NI, so that the distinct role of NI in GIMs is still uncertain. MATERIALS AND METHODS NI was characterized in approximately 16,000 hematoxylin and eosin tissue sections from 2050 patients with adenocarcinoma of the esophagogastric junction (AEG)-I-III, squamous cell carcinoma (SCC) of the esophagus, gastric cancer (GC), colon cancer (CC), rectal cancer (RC), cholangiocellular cancer (CCC), hepatocellular cancer (HCC), and pancreatic cancer (PC). NI prevalence and severity was determined and related to patient's prognosis and survival. RESULTS NI prevalence largely varied between HCC/6%, CC/28%, RC/34%, AEG-I/36% and AEG-II/36%, SCC/37%, GC/38%, CCC/58%, and AEG-III/65% to PC/100%. NI severity score was uppermost in PC (24.9±1.9) and lowest in AEG-I (0.8±0.3). Multivariable analyses including age, sex, TNM stage, and grading revealed that the prevalence of NI was significantly associated with diminished survival in AEG-II/III, GC, and RC. However, increasing NI severity impaired survival in AEG-II/III and PC only. CONCLUSIONS NI prevalence and NI severity strongly vary within GIMs. Determination of NI severity in GIMs is a more precise tool than solely recording the presence of NI and revealed dismal prognostic impact on patients with AEG-II/III and PC. Evidently, NI is not a concomitant side feature in GIMs and, therefore, deserves special attention for improved patient stratification and individualized therapy after surgery.