Ataxia due to vertebral hemangiosarcoma with evidence of disseminated disease in a 20-year old Swiss Warmblood mare

A 20-year old Swiss Warmblood mare was referred to the Swiss Institute of Equine Medicine with a history of poor performance, coughing and ataxia and hindlimb weakness which progressed to recumbency. Lung auscultation revealed pronounced wheezing, blood work showed signs of chronic inflammation and increased bone turnover and thoracic ultrasound indicated patchy pulmonary consolidation. Cerebrospinal fluid revealed only mild, unspecific changes allowing exclusion of meningoencephalomyelitis and clinically relevant bleeding. Despite medical treatment and support in a sling the mare did not improve and was euthanized. Necropsy revealed a poorly demarcated, non-encapsulated and invasively growing mass dorsally in the musculature at the level of the forth cervical vertebra (C4) infiltrating the vertebral body and the spinal canal at the level of C1–C2. Multiple nodular, firm masses were present in all lobes of the lung and appeared to be mainly located in vessels. Histologically the masses were composed of spindle cells with marked anisocytosis, anisocaryosis, a high mitotic activity and showed invasive growth. These neoplastic cells stained positive for CD31, an endothelial cell marker, which confirmed diagnosis of a hemangiosarcoma. Definite ante mortem diagnosis of hemangiosarcoma, which is rare in horses, is challenging. Besides the vertebral localization, disseminated, locally invasive and cutaneous forms of hemangiosarcoma exist and can be either acquired or congenital. Prognosis for equine hemangiosarcoma and response to treatment are usually poor and progression of clinical signs is rapid. Vertebral hemangiosarcoma is an uncommon cause of spinal ataxia in horses.

A reconstruction of radiocarbon production and total solar irradiance from the Holocene ¹⁴C and CO₂ records: implications of data and model uncertainties

Radiocarbon production, solar activity, total solar irradiance (TSI) and solar-induced climate change are reconstructed for the Holocene (10 to 0 kyr BP), and TSI is predicted for the next centuries. The IntCal09/SHCal04 radiocarbon and ice core CO2 records, reconstructions of the geomagnetic dipole, and instrumental data of solar activity are applied in the Bern3D-LPJ, a fully featured Earth system model of intermediate complexity including a 3-D dynamic ocean, ocean sediments, and a dynamic vegetation model, and in formulations linking radiocarbon production, the solar modulation potential, and TSI. Uncertainties are assessed using Monte Carlo simulations and bounding scenarios. Transient climate simulations span the past 21 thousand years, thereby considering the time lags and uncertainties associated with the last glacial termination. Our carbon-cycle-based modern estimate of radiocarbon production of 1.7 atoms cm−2 s−1 is lower than previously reported for the cosmogenic nuclide production model by Masarik and Beer (2009) and is more in-line with Kovaltsov et al. (2012). In contrast to earlier studies, periods of high solar activity were quite common not only in recent millennia, but throughout the Holocene. Notable deviations compared to earlier reconstructions are also found on decadal to centennial timescales. We show that earlier Holocene reconstructions, not accounting for the interhemispheric gradients in radiocarbon, are biased low. Solar activity is during 28% of the time higher than the modern average (650 MeV), but the absolute values remain weakly constrained due to uncertainties in the normalisation of the solar modulation to instrumental data. A recently published solar activity–TSI relationship yields small changes in Holocene TSI of the order of 1 W m−2 with a Maunder Minimum irradiance reduction of 0.85 ± 0.16 W m−2. Related solar-induced variations in global mean surface air temperature are simulated to be within 0.1 K. Autoregressive modelling suggests a declining trend of solar activity in the 21st century towards average Holocene conditions.

Long-lasting hyperexcitability induced by depolarization in the absence of detectable Ca2+ signals.

Learning and memory depend on neuronal alterations induced by electrical activity. Most examples of activity-dependent plasticity, as well as adaptive responses to neuronal injury, have been linked explicitly or implicitly to induction by Ca(2+) signals produced by depolarization. Indeed, transient Ca(2+) signals are commonly assumed to be the only effective transducers of depolarization into adaptive neuronal responses. Nevertheless, Ca(2+)-independent depolarization-induced signals might also trigger plastic changes. Establishing the existence of such signals is a challenge because procedures that eliminate Ca(2+) transients also impair neuronal viability and tolerance to cellular stress. We have taken advantage of nociceptive sensory neurons in the marine snail Aplysia, which exhibit unusual tolerance to extreme reduction of extracellular and intracellular free Ca(2+) levels. The axons of these neurons exhibit a depolarization-induced memory-like hyperexcitability that lasts a day or longer and depends on local protein synthesis for induction. Here we show that transient localized depolarization of these axons in an excised nerve-ganglion preparation or in dissociated cell culture can induce short- and intermediate-term axonal hyperexcitability as well as long-term protein synthesis-dependent hyperexcitability under conditions in which Ca(2+) entry is prevented (by bathing in nominally Ca(2+) -free solutions containing EGTA) and detectable Ca(2+) transients are eliminated (by adding BAPTA-AM). Disruption of Ca(2+) release from intracellular stores by pretreatment with thapsigargin also failed to affect induction of axonal hyperexcitability. These findings suggest that unrecognized Ca(2+)-independent signals exist that can transduce intense depolarization into adaptive cellular responses during neuronal injury, prolonged high-frequency activity, or other sustained depolarizing events.

Characterization of the human tissue transglutaminase gene promoter

Transglutaminases are a family of calcium-dependent enzymes, that catalyze the covalent cross-linking of proteins by forming $\varepsilon(\gamma$-glutamyl)lysine isopeptide bonds. In order to investigate the molecular mechanisms regulating the expression of the tissue transglutaminase gene and to determine its biological functions, the goal of this research has been to clone and characterize the human tissue transglutaminase promoter. Thirteen clones of the tissue transglutaminase gene were obtained from the screening of a human placental genomic DNA library. A 1.74 Kb fragment derived from DNA located immediately upstream of the translation start site was subcloned and sequenced. Sequence analysis of this DNA fragment revealed that it contains a TATA box (TATAA), a CAAT box (GGACAAT), and a series of potential transcription factor binding sites and hormone response elements. Four regions of significant homology, a GC-rich region, a TG-rich region, an AG-rich region, and HR1, were identified by aligning 1.8 Kb of DNA flanking the human, mouse, and guinea pig tissue transglutaminase genes.^ To measure promoter activity, we subcloned the 1.74 Kb fragment of the tissue transglutaminase gene into a luciferase reporter vector to generate transglutaminase promoter/luciferase reporter constructs. Transfection experiments showed that this DNA segment includes a functional promoter with high constitutive activity. Deletion analysis revealed that the SP1 sites or corresponding sequences contribute to this activity. We investigated the role of DNA methylation in regulating the activity of the promoter and found that in vitro methylation of tissue transglutaminase promoter/luciferase reporter constructs suppressed their basal activity. Methylation of the promoter is inversely correlated with the expression of the tissue transglutaminase gene in vivo. These results suggest that DNA methylation may be one of the mechanisms regulating the expression of the gene. The tumor suppressor gene product p53 was also shown to inhibit the activity of the promoter, suggesting that induction of the tissue transglutaminase gene is not involved in the p53-dependent programmed cell death pathway. Although retinoids regulate the expression of the tissue transglutaminase gene in vivo, retinoid-inducible activity can not be identified in 3.7 Kb of DNA 5$\sp\prime$ to the tissue transglutaminase gene.^ The structure of the 5$\sp\prime$ end of the tissue transglutaminase gene was mapped. Alignment analysis of the human tissue transglutaminase gene with other human transglutaminases showed that tissue transglutaminase is the simplest member of transglutaminase superfamily. Transglutaminase genes show a conserved core of exons and introns but diverse N-terminuses and promoters. These observations suggest that key regulatory sequences and promoter elements have been appended upstream of the core transglutaminase gene to generate the diversity of regulated expression and regulated activity characteristic of the transglutaminase gene family. ^

Genetic Relatedness, Antimicrobial and Biocide Susceptibility Comparative Analysis of Methicillin-Resistant and -Susceptible Staphylococcus pseudintermedius from Portugal

Forty methicillin-resistant and -susceptible Staphylococcus pseudintermedius (MRSP and MSSP, respectively) from colonization and infection in dogs and cats were characterized for clonality, antimicrobial, and biocide susceptibility. MSSP were genetically more diverse than MRSP by multi-locus sequence typing and pulsed-field gel electrophoresis. Three different spa types (t06, t02, t05) and two SCCmec types (II-III and V) were detected in the MRSP isolates. All MRSP and two MSSP strains were multidrug-resistant. Several antibiotic resistance genes (mecA, blaZ, tet(M), tet(K), aac(6')-Ie-aph(2')-Ia, aph(3')-III, ant(6)-Ia, sat4, erm(B), lnu(A), dfr(G), and catpC221) were identified by microarray and double mutations in the gyrA and grlA genes and a single mutation in the rpoB gene were detected by sequence analysis. No differences were detected between MSSP and MRSP in the chlorhexidine acetate (CHA) minimum inhibitory concentrations (MICs). However, two MSSP had elevated MIC to triclosan (TCL) and one to benzalkonium chloride and ethidium bromide. One MSSP isolate harboured a qacA gene, while in another a qacB gene was detected. None of the isolates harboured the sh-fabI gene. Three of the biocide products studied had high bactericidal activity (Otodine(®), Clorexyderm Spot Gel(®), Dermocanis Piocure-M(®)), while Skingel(®) failed to achieve a five log reduction in the bacterial counting. S. pseudintermedius have become a serious therapeutic challenge in particular if methicillin- resistance and/or multidrug-resistance are involved. Biocides, like CHA and TCL, seem to be clinically effective and safe topical therapeutic options.

Periodontitis and Gingivitis in Inflammatory Bowel Disease

BACKGROUND: The oral cavity is frequently affected in patients with inflammatory bowel disease (IBD), especially in patients with Crohn's disease (CD). Periodontitis is thought to influence systemic autoimmune or inflammatory diseases. We aimed to analyze the relationship of periodontitis and gingivitis markers with specific disease characteristics in patients with IBD and to compare these data with healthy controls. METHODS: In a prospective 8-month study, systematic oral examinations were performed in 113 patients with IBD, including 69 patients with CD and 44 patients with ulcerative colitis. For all patients, a structured personal history was taken. One hundred thirteen healthy volunteers served as a control group. Oral examination focussed on established oral health markers for periodontitis (bleeding on probing, loss of attachment, and periodontal pocket depth) and gingivitis (papilla bleeding index). Additionally, visible oral lesions were documented. RESULTS: Both gingivitis and periodontitis markers were higher in patients with IBD than in healthy control. In univariate analysis and logistic regression analysis, perianal disease was a risk factor for periodontitis. Nonsmoking decreased the risk of having periodontitis. No clear association was found between clinical activity and periodontitis in IBD. In only the CD subgroup, high clinical activity (Harvey-Bradshaw index > 10) was associated with 1 periodontitis marker, the loss of attachment at sites of maximal periodontal pocket depth. Oral lesions besides periodontitis and gingivitis were not common, but nevertheless observed in about 10% of patients with IBD. CONCLUSIONS: IBD, and especially perianal disease in CD, is associated with periodontitis. Optimal therapeutic strategies should probably focus on treating both local oral and systemic inflammation.

Long-term perspective on wildfires in the western USA

Understanding the causes and consequences of wildfires in forests of the western United States requires integrated information about fire, climate changes, and human activity on multiple temporal scales. We use sedimentary charcoal accumulation rates to construct long-term variations in fire during the past 3,000 y in the American West and compare this record to independent fire-history data from historical records and fire scars. There has been a slight decline in burning over the past 3,000 y, with the lowest levels attained during the 20th century and during the Little Ice Age (LIA, ca. 1400-1700 CE Common Era]). Prominent peaks in forest fires occurred during the Medieval Climate Anomaly (ca. 950-1250 CE) and during the 1800s. Analysis of climate reconstructions beginning from 500 CE and population data show that temperature and drought predict changes in biomass burning up to the late 1800s CE. Since the late 1800s, human activities and the ecological effects of recent high fire activity caused a large, abrupt decline in burning similar to the LIA fire decline. Consequently, there is now a forest ``fire deficit'' in the western United States attributable to the combined effects of human activities, ecological, and climate changes. Large fires in the late 20th and 21st century fires have begun to address the fire deficit, but it is continuing to grow.

A 13,600-year diatom oxygen isotope record from the South Carpathians (Romania): Reflection of winter conditions and possible links with North Atlantic circulation changes

This study provides a continuous lateglacial and Holocene record of diatom silica oxygen isotope changes (delta O-18(DIAT)) in a subalpine lake sediment sequence obtained from the Retezat Mts (Taul dintre Brazi, 1740 m a.s.l.). This through-flow, shallow, high-altitude lake with a surface area of only 0.4 ha has short water residence time and is predominantly fed by snowmelt and rainwater. Its delta O-18(DIAT) record principally reflects the oxygen isotope composition of the winter and spring precipitation, as diatom blooms occur mainly in the spring and early summer. Hence, changes in delta O-18(DIAT) are interpreted as seasonal scale changes: in the amount of winter precipitation. Low oxygen isotope values (27-28.5 parts per thousand) occurred during the lateglacial until 12,300 cal BP, followed by a sharp increase thereafter. In the Holocene delta O-18(DIAT) values ranged from 29 to 31 parts per thousand until 3200 cal BP, followed by generally lower values during the late Holocene (27-30 parts per thousand). Short-term decreases in the isotopic values were found between 10,140-9570, 9000-8500, 7800-7300, 6300-5800, 5500-5000 and at 8015, 4400, 4000 cal BP. After 3200 cal BP a decreasing trend was visible with the lowest values between 3100-2500 and after 2100 cal BP The general trend in the record suggests that contribution of winter precipitation was generally lower between 11,680 and 3200 cal BP, followed by increased contribution during the last millennia. The late Holocene decrease in delta O-18(DIAT) shows good agreement with the speleothem delta O-18, lake level and testate amoebae records from the Carpathian Mountains that also display gradual delta O-18 decrease and lake level/mire water table level rise after 3200 cal BR Strong positive correlation with North Atlantic circulation and solar activity proxies, such as the Austrian and Hungarian speleothem records, furthermore suggested that short-term increases in the isotopic ratios in the early and mid Holocene are likely connectable to high solar activity phases and high frequency of positive North Atlantic Oscillation indexes that may have resulted in decreased winter precipitation in this region.

Combining charcoal sediment and molecular markers to infer a Holocene fire history in the Maya Lowlands of Petén, Guatemala

Vegetation changes in the Maya Lowlands during the Holocene are a result of changing climate conditions, solely anthropogenic activities, or interactions of both factors. As a consequence, it is difficult to assess how tropical ecosystems will cope with projected changes in precipitation and land-use intensification over the next decades. We investigated the role offire during the Holocene by combining macroscopic charcoal and the molecular fire proxies levoglucosan, mannosan and galactosan. Combining these two different fire proxies allows a more robust understanding of the complex history of fire re- gimes at different spatial scales during the Holocene. In order to infer changes in past biomass burning, we analysed a lake sediment core from Lake Peten Itza, Guatemala, and compared our results with millennial-scale vegetation and climate change available in the area. We detected three periods of high fire activity during the Holocene: 9500 e 6000 cal yr BP, 3700 cal yr BP and 2700 cal yr BP. We attribute the first maximum mostly to climate conditions and the last maximum to human activities. The rapid change between burned vegetation types at the 3700 cal yr BP fire maximum may result from human activity.

Modern solar maximum forced late twentieth century Greenland cooling

The abrupt Northern Hemispheric warming at the end of the twentieth century has been attributed to an enhanced greenhouse effect. Yet Greenland and surrounding subpolar North Atlantic remained anomalously cold in 1970s to early 1990s. Here we reconstructed robust Greenland temperature records (North Greenland Ice Core Project and Greenland Ice Sheet Project 2) over the past 2100 years using argon and nitrogen isotopes in air trapped within ice cores and show that this cold anomaly was part of a recursive pattern of antiphase Greenland temperature responses to solar variability with a possible multidecadal lag. We hypothesize that high solar activity during the modern solar maximum (approximately 1950s–1980s) resulted in a cooling over Greenland and surrounding subpolar North Atlantic through the slowdown of Atlantic Meridional Overturning Circulation with atmospheric feedback processes.

Holocene vegetation development in the catchment of Sagistalsee (1935 m asl), a small lake in the Swiss Alps

Pollen and plant macrofossils were analysed at Sägistalsee (1935 m asl), a small lake near timber-line in the Swiss Northern Alps. Open forests with Pinus cembra and Abies alba covered the catchment during the early Holocene (9000–6300 cal. BP), suggesting subcontinental climate conditions. After the expansion of Picea abies between 6300 and 6000 cal. BP the subalpine forest became denser and the tree-line reached its maximum elevation at around 2260 m asl. Charcoal fragments in the macrofossil record indicate the beginning of Late-Neolithic human impact at ca. 4400 cal. BP, followed by a extensive deforestation and lowering of the forest-limit in the catchment of Sägistalsee at 3700 cal. BP (Bronze Age). Continuous human activity, combined with a more oceanic climate during the later Holocene, led to the local extinction of Pinus cembra and Abies alba and favoured the mass expansion of Picea and Alnus viridis in the subalpine area of the Northern Alps. The periods before 6300 and after 3700 cal. BP are characterised by high erosion activity in the lake's catchment, whereas during the phase of dense Picea-Pinus cembra-Abies forests (6300–3700 cal. BP) soils were stable and sediment-accumulation rates in the lake were low. Due to decreasing land-use at higher altitudes during the Roman occupation and the Migration period, forests spread beween ca. 2000 and 1500 cal. BP, before human impact increased again in the early Middle Ages. Recent reforestation due to land-use changes in the 20th century is recorded in the top sediments. Pollen-inferred July temperature and annual precipitation suggest a trend to cooler and more oceanic climate starting at about 5500 cal. BP.

Vegetation and fire history of coastal north-eastern Sardinia (Italy) under changing Holocene climates and land use

Little is known about the vegetation and fire history of Sardinia, and especially the long-term history of the thermo-Mediterranean belt that encompasses its entire coastal lowlands. A new sedimentary record from a coastal lake based on pollen, spores, macrofossils and microscopic charcoal analysis is used to reconstruct the vegetation and fire history in north-eastern Sardinia. During the mid-Holocene (c. 8,100–5,300 cal bp), the vegetation around Stagno di Sa Curcurica was characterised by dense Erica scoparia and E. arborea stands, which were favoured by high fire activity. Fire incidence declined and evergreen broadleaved forests of Quercus ilex expanded at the beginning of the late Holocene. We relate the observed vegetation and fire dynamics to climatic change, specifically moister and cooler summers and drier and milder winters after 5,300 cal bp. Agricultural activities occurred since the Neolithic and intensified after c. 7,000 cal bp. Around 2,750 cal bp, a further decline of fire incidence and Erica communities occurred, while Quercus ilex expanded and open-land communities became more abundant. This vegetation shift coincided with the historically documented beginning of Phoenician period, which was followed by Punic and Roman civilizations in Sardinia. The vegetational change at around 2,750 cal bp was possibly advantaged by a further shift to moister and cooler summers and drier and milder winters. Triggers for climate changes at 5,300 and 2,750 cal bp may have been gradual, orbitally-induced changes in summer and winter insolation, as well as centennial-scale atmospheric reorganizations. Open evergreen broadleaved forests persisted until the twentieth century, when they were partly substituted by widespread artificial pine plantations. Our results imply that highly flammable Erica vegetation, as reconstructed for the mid-Holocene, could re-emerge as a dominant vegetation type due to increasing drought and fire, as anticipated under global change conditions.

Mass accumulation rates, age, sedimentation rate and bulk density at the East Pacific Rise

The rate at which hydrothermal precipitates accumulate, as measured by the accumulation rate of manganese, can be used to identify periods of anomalous hydrothermal activity in the past. From a preliminary study of Sites 597 and 598, four periods prior to 6 Ma of anomalously high hydrothermal activity have been identified: 8.5 to 10.5 Ma, 12 to 16 Ma, 17 to 18 Ma, and 23-to-27 Ma. The 18-Ma anomaly is the largest and is associated with the jump in spreading from the fossil Mendoza Ridge to the East Pacific Rise, whereas the 23-to-27-Ma anomaly is correlated with the birth of the Galapagos Spreading Center and resultant ridge reorganization. The 12-to-16-Ma and 8.5-to-10.5-Ma anomalies are correlated with periods of anomalously high volcanism around the rim of the Pacific Basin and may be related to other periods of ridge reorganization along the East Pacific Rise. There is no apparent correlation between periods of fast spreading at 19°S and periods of high hydrothermal activity. We thus suggest that periods when hydrothermal activity and crustal alteration at mid-ocean ridges are the most pronounced may be periods of large-scale ridge reorganization.

Major and minor elements in hydrothermal and pelagic sediments at DSDP Leg 70 Holes

Interaction between young basaltic crust and seawater near the oceanic speading centers is one of the important processes affecting the chemical composition of the oceanic layer. The formation of metalliferous hydrothermal sediments results from this interaction. The importance of the interaction between seawater and basalt in determining the chemical composition of pore waters from sediments is well known. The influence of mineral solutions derived from this interaction on ocean water composition and the significant flux of some elements (e.g., Mn) are reported by Lyle (1976), Bogdanov et al. (1979), and others. Metal-rich sediments found in active zones of the ocean basins illustrate the influence of seawater-basalt interaction and its effect on the sedimentary cover in such areas. The role of hydrothermal activity and seawater circulation in basalts with regard to global geochemistry cycles has recently been demonstrated by Edmond, Measures, McDuff, McDuff et al. (1979), and Edmond, Measures, Mangum (1979). In the area of the Galapagos Spreading Center the interaction of sediments and solutions derived from interaction of seawater and basalt has resulted in the formation of hydrothermal mounds. The mounds are composed of manganese crusts and green clay interbedded and mixed with pelagic nannofossil ooze. These mounds are observed only in areas characterized by high heat flow (Honnorez, et al., 1981) and high hydrothermal activity.

(Table 1) Results of geothermal measurements in the Black Sea 2000 and 2001 expeditions

According to the World Ocean Program in the northeastern part of the continental slope of the Black Sea geothermal, seismologic and seismic studies were carried out. An analysis of heat flow distribution allowed to distinguish a negative geothermal anomaly near the Dzhubga area, where the Russia-Turkey pipeline was being constructed. During seismological observations (August-September 1999, September 2001) more than 1200 seismic events were recorded. They proved high tectonic activity of the region under study, which stimulates gravitational sediment transport on the continental slope. The seismo-acoustic survey carried out in the area of the geothermal anomaly revealed no reflecting horizons within the sedimentary cover. This may be related to turbidite-landsliding processes. Results of modeling of the heat flow anomaly showed that it had originated approximately 1000 years ago due to a powerful landslide. This also suggests a possibility of an avalanche displacement of sedimentary masses in the area of the pipeline at present.