Late Holocene air temperature variability reconstructed from the sediments of Laguna Escondida, Patagonia, Chile (45 degrees 30 ' S)

Climate and environmental reconstructions from natural archives are important for the interpretation of current climatic change. Few quantitative high-resolution reconstructions exist for South America which is the only land mass extending from the tropics to the southern high latitudes at 56°S. We analyzed sediment cores from two adjacent lakes in Northern Chilean Patagonia, Lago Castor (45°36′S, 71°47′W) and Laguna Escondida (45°31′S, 71°49′W). Radiometric dating (210Pb, 137Cs, 14C-AMS) suggests that the cores reach back to c. 900 BC (Laguna Escondida) and c. 1900 BC (Lago Castor). Both lakes show similarities and reproducibility in sedimentation rate changes and tephra layer deposition. We found eight macroscopic tephras (0.2–5.5 cm thick) dated at 1950 BC, 1700 BC, at 300 BC, 50 BC, 90 AD, 160 AD, 400 AD and at 900 AD. These can be used as regional time-synchronous stratigraphic markers. The two thickest tephras represent known well-dated explosive eruptions of Hudson volcano around 1950 and 300 BC. Biogenic silica flux revealed in both lakes a climate signal and correlation with annual temperature reanalysis data (calibration 1900–2006 AD; Lago Castor r = 0.37; Laguna Escondida r = 0.42, seven years filtered data). We used a linear inverse regression plus scaling model for calibration and leave-one-out cross-validation (RMSEv = 0.56 °C) to reconstruct sub decadal-scale temperature variability for Laguna Escondida back to AD 400. The lower part of the core from Laguna Escondida prior to AD 400 and the core of Lago Castor are strongly influenced by primary and secondary tephras and, therefore, not used for the temperature reconstruction. The temperature reconstruction from Laguna Escondida shows cold conditions in the 5th century (relative to the 20th century mean), warmer temperatures from AD 600 to AD 1150 and colder temperatures from AD 1200 to AD 1450. From AD 1450 to AD 1700 our reconstruction shows a period with stronger variability and on average higher values than the 20th century mean. Until AD 1900 the temperature values decrease but stay slightly above the 20th century mean. Most of the centennial-scale features are reproduced in the few other natural climate archives in the region. The early onset of cool conditions from c. AD 1200 onward seems to be confirmed for this region.

Presence of new mecA and mph(C) variants conferring antibiotic resistance in Staphylococcus spp. isolated from the skin of horses before and after clinic admission

Because of the frequency of multiple antibiotic resistance, Staphylococcus species often represent a challenge in incisional infections of horses undergoing colic surgery. To investigate the evolution of antibiotic resistance patterns before and after preventative peri- and postoperative penicillin treatment, staphylococci were isolated from skin and wound samples at different times during hospitalization. Most staphylococci were normal skin commensals and belonged to the common coagulase-negative group. In some cases they turned out to be opportunistic pathogens present in wound infections. MICs were determined for 12 antibiotics, and antibiotic resistance genes were detected by microarray. At hospital admission, horses harbored staphylococci that were susceptible to antibiotics or resistant to one group of drugs, mainly due to the presence of new variants of the methicillin and macrolide resistance genes mecA and mph(C), respectively. After 3 days, the percentage of Staphylococcus isolates displaying antibiotic resistance, as well as the number of resistance genes per isolate, increased moderately in hospitalized horses without surgery or penicillin treatment but dramatically in hospitalized horses after colic surgery as well as penicillin treatment. Staphylococcus species displaying multiple resistance were found to harbor mainly genes conferring resistance to beta-lactams (mecA and blaZ), aminoglycosides [str and aac(6')-Ie-aph(2')-Ia], and trimethoprim [dfr(A) and dfr(D)]. Additional genes conferring resistance to macrolides [mph(C), erm(C), and erm(B)], tetracycline [tet(K) and tet(M)], chloramphenicol [cat(pC221) and cat(pC223)], and streptothricin (sat4) appeared in several strains. Hospitalization and preventive penicillin use were shown to act as selection agents for multidrug-resistant commensal staphylococcal flora.

Benefits from the use of a pimecrolimus-based treatment in the management of atopic dermatitis in clinical practice. Analysis of a Swiss cohort

BACKGROUND: Controlled studies established the efficacy and good tolerability of pimecrolimus cream 1% for the treatment of atopic dermatitis but they may not reflect real-life use. OBJECTIVE: To evaluate the efficacy, tolerability and cosmetic acceptance of a pimecrolimus-based regimen in daily practice in Switzerland. METHODS: This was a 6-month, open-label, multicentre study in 109 patients (55% > or = 18 years) with atopic dermatitis. Pimecrolimus cream 1% was incorporated into patients' standard treatment protocols. RESULTS: The pimecrolimus-based treatment was well tolerated and produced disease improvement in 65.7% of patients. It was particularly effective on the face (improvement rate: 75.0%). Mean pimecrolimus consumption decreased from 6.4 g/day (months 1-3) to 4.0 g/day (months 3-6) as disease improved. Most patients (74.1%) rated their disease control as 'complete' or 'good' and 90% were highly satisfied with the cream formulation. CONCLUSION: The use of a pimecrolimus-based regimen in everyday practice was effective, well tolerated and well accepted by patients.

Response to Innes and Mattsson: Neospora caninum emerges from the shadow of Toxoplasma gondii

It is tempting to extrapolate research findings regarding the intensively studied Toxoplasma gondii to Neospora caninum. This is based on morphological and ultrastructural studies, the molecular phylogeny of both parasites, their wide host ranges in nature, their ability to invade many different cell types in vitro and the occurrence of homologous proteins in both species. However, as Innes and Mattsson point out, T. gondii is the most successful parasite worldwide, whereas N. caninum has a more limited host range. Thus, some of the most challenging questions are: (i) what is T. gondii doing that N. caninum is not doing, or is doing differently, that renders the former so much more successful? And (ii) can some of these features be exploited for the development of interventional tools to limit infection and pathology caused by N. caninum?

Amino acid sequence of the alpha subunit and computer modelling of the alpha and beta subunits of echicetin from the venom of Echis carinatus (saw-scaled viper)

Echicetin, a heterodimeric protein from the venom of Echis carinatus, binds to platelet glycoprotein Ib (GPIb) and so inhibits platelet aggregation or agglutination induced by various platelet agonists acting via GPIb. The amino acid sequence of the beta subunit of echicetin has been reported and found to belong to the recently identified snake venom subclass of the C-type lectin protein family. Echicetin alpha and beta subunits were purified. N-terminal sequence analysis provided direct evidence that the protein purified was echicetin. The paper presents the complete amino acid sequence of the alpha subunit and computer models of the alpha and beta subunits. The sequence of alpha echicetin is highly similar to the alpha and beta chains of various heterodimeric and homodimeric C-type lectins. Neither of the fully reduced and alkylated alpha or beta subunits of echicetin inhibited the platelet agglutination induced by von Willebrand factor-ristocetin or alpha-thrombin. Earlier reports about the inhibitory activity of reduced and alkylated echicetin beta subunit might have been due to partial reduction of the protein.

CSTX-1, a toxin from the venom of the hunting spider Cupiennius salei, is a selective blocker of L-type calcium channels in mammalian neurons

The inhibitor cystine-knot motif identified in the structure of CSTX-1 from Cupiennius salei venom suggests that this toxin may act as a blocker of ion channels. Whole-cell patch-clamp experiments performed on cockroach neurons revealed that CSTX-1 produced a slow voltage-independent block of both mid/low- (M-LVA) and high-voltage-activated (HVA) insect Ca(v) channels. Since C. salei venom affects both insect as well as rodent species, we investigated whether Ca(v) channel currents of rat neurons are also inhibited by CSTX-1. CSTX-1 blocked rat neuronal L-type, but no other types of HVA Ca(v) channels, and failed to modulate LVA Ca(v) channel currents. Using neuroendocrine GH3 and GH4 cells, CSTX-1 produced a rapid voltage-independent block of L-type Ca(v) channel currents. The concentration-response curve was biphasic in GH4 neurons and the subnanomolar IC(50) values were at least 1000-fold lower than in GH3 cells. L-type Ca(v) channel currents of skeletal muscle myoballs and other voltage-gated ion currents of rat neurons, such as I(Na(v)) or I(K(v)) were not affected by CSTX-1. The high potency and selectivity of CSTX-1 for a subset of L-type channels in mammalian neurons may enable the toxin to be used as a molecular tool for the investigation of this family of Ca(v) channels.

Cupiennin 1a, an antimicrobial peptide from the venom of the neotropical wandering spider Cupiennius salei, also inhibits the formation of nitric oxide by neuronal nitric oxide synthase

Cupiennin 1a (GFGALFKFLAKKVAKTVAKQAAKQGAKYVVNKQME-NH2) is a potent venom component of the spider Cupiennius salei. Cupiennin 1a shows multifaceted activity. In addition to known antimicrobial and cytolytic properties, cupiennin 1a inhibits the formation of nitric oxide by neuronal nitric oxide synthase at an IC50 concentration of 1.3 +/- 0.3 microM. This is the first report of neuronal nitric oxide synthase inhibition by a component of a spider venom. The mechanism by which cupiennin 1a inhibits neuronal nitric oxide synthase involves complexation with the regulatory protein calcium calmodulin. This is demonstrated by chemical shift changes that occur in the heteronuclear single quantum coherence spectrum of 15N-labelled calcium calmodulin upon addition of cupiennin 1a. The NMR data indicate strong binding within a complex of 1 : 1 stoichiometry.