Rapid parallel adaptive radiations from a single hybridogenic ancestral population

The Alpine lake whitefish (Coregonus lavaretus) species complex is a classic example of a recent radiation, associated with colonization of the Alpine lakes following the glacial retreat (less than 15 kyr BP). They have formed a unique array of endemic lake flocks, each with one to six described sympatric species differing in morphology, diet and reproductive ecology. Here, we present a genomic investigation of the relationships between and within the lake flocks. Comparing the signal between over 1000 AFLP loci and mitochondrial control region sequence data, we use phylogenetic tree-based and population genetic methods to reconstruct the phylogenetic history of the group and to delineate the principal centres of genetic diversity within the radiation. We find significant cytonuclear discordance showing that the genomically monophyletic Alpine whitefish clade arose from a hybrid swarm of at least two glacial refugial lineages. Within this radiation, we find seven extant genetic clusters centred on seven lake systems. Most interestingly, we find evidence of sympatric speciation within and parallel evolution of equivalent phenotypes among these lake systems. However, we also find the genetic signature of human-mediated gene flow and diversity loss within many lakes, highlighting the fragility of recent radiations.

A pyrosequencing assay for the rapid discrimination of mitochondrial lineages in the Salmo trutta species complex

The European trout (Salmo trutta species complex) is genetically very diverse consisting of five distinct mitochondrial lineages that probably originated in the Pleistocene. Here, we describe a novel pyrosequencing protocol to generate two short sequence reads from the mitochondrial control region, which allow the unambiguous identification of all five lineages. The approach was found to be easily transferable between laboratories and should be a valuable tool for the assessment of genetic diversity in trout. Pyrosequencing-based assays for molecular species identification are expected to be generally useful whenever multiple positions in a short DNA sequence need to be assessed.

Rapid exclusion or confirmation of heparin-induced thrombocytopenia: a single-center experience with 1,291 patients

The current gold-standard for diagnosing heparin-induced thrombocytopenia is the detection of platelet-activating antibodies by means of functional assays which, since they are time consuming and not widely available, are not suited to guiding acute treatment decisions. The objective of our study was to assess the ability of more rapid immunoassays to predict the presence of functionally relevant anti-platelet factor 4/heparin-antibodies.

Rapid qualitative urinary tract infection pathogen identification by SeptiFast real-time PCR

Background Urinary tract infections (UTI) are frequent in outpatients. Fast pathogen identification is mandatory for shortening the time of discomfort and preventing serious complications. Urine culture needs up to 48 hours until pathogen identification. Consequently, the initial antibiotic regimen is empirical. Aim To evaluate the feasibility of qualitative urine pathogen identification by a commercially available real-time PCR blood pathogen test (SeptiFast®) and to compare the results with dipslide and microbiological culture. Design of study Pilot study with prospectively collected urine samples. Setting University hospital. Methods 82 prospectively collected urine samples from 81 patients with suspected UTI were included. Dipslide urine culture was followed by microbiological pathogen identification in dipslide positive samples. In parallel, qualitative DNA based pathogen identification (SeptiFast®) was performed in all samples. Results 61 samples were SeptiFast® positive, whereas 67 samples were dipslide culture positive. The inter-methodological concordance of positive and negative findings in the gram+, gram- and fungi sector was 371/410 (90%), 477/492 (97%) and 238/246 (97%), respectively. Sensitivity and specificity of the SeptiFast® test for the detection of an infection was 0.82 and 0.60, respectively. SeptiFast® pathogen identifications were available at least 43 hours prior to culture results. Conclusion The SeptiFast® platform identified bacterial DNA in urine specimens considerably faster compared to conventional culture. For UTI diagnosis sensitivity and specificity is limited by its present qualitative setup which does not allow pathogen quantification. Future quantitative assays may hold promise for PCR based UTI pathogen identification as a supplementation of conventional culture methods.

Rapid synthesis of arylgold compounds using dielectric heating

Dielectric heating has been successfully used in the preparation of a range of arylgold compounds. The approach is tolerant of a number of functional groups and rapidly generates the organometallic complexes in moderate to excellent yields.

Rapid Facilitation of Ultrasound Production and Lordosis in Female Hamsters by Horizontal Cuts Between the Septum and Preoptic Area

Horizontal cuts between the septum and preoptic area (anterior roof deafferentation, or ARD) dramatically affect sexual behavior, and in ways that could explain a variety of differences across behavioral categories (precopulatory, copulatory), species, and the sexes. Yet little is known about how these effects develop. Such information would be useful generally and could be pivotal in clarifying the mechanism for ultrasonic vocalization in female hamsters. Ultrasounds serve these animals as precopulatory signals that can attract males and help initiate mating. Their rates can be increased by either ARD or lesions of the ventromedial hypothalamus (VMN). If these effects are independent, they would require a mechanism that includes multiple structures and pathways within the forebrain and hypothalamus. However, it currently is not clear if they are independent: VMN lesions could affect vocalization by causing incidental damage to the same fibers targeted by ARD. Fortunately, past studies of VMN lesions have described a response with a very distinctive time course. This raises the possibility of assessing the independence of the two lesion effects by describing just the development of the response to ARD. To accomplish this, female hamsters were observed for levels of ultrasound production and lordosis before and after control surgery or ARD. As expected, both behaviors were facilitated by these cuts. Further, these effects began to appear by two days after surgery and were fully developed by six days. These results extend previous descriptions of the ARD effect by describing its development and time course. In turn, the rapid responses to ARD suggest that these cuts trigger disinhibitory changes in pathways that differ from those affected by VMN lesions. 2013

Sensitive and rapid detection of ganciclovir resistance by PCR based MALDI-TOF analysis

Cytomegalovirus (CMV) infection is associated with significant morbidity and mortality in transplant recipients. Resistance against ganciclovir is increasingly observed. According to current guidelines, direct drug resistance testing is not always performed due to high costs and work effort, even when resistance is suspected.

A sensitized RNA interference screen identifies a novel role for the PI3K p110γ isoform in medulloblastoma cell proliferation and chemoresistance

Medulloblastoma is the most common malignant brain tumor in children and is associated with a poor outcome. We were interested in gaining further insight into the potential of targeting the human kinome as a novel approach to sensitize medulloblastoma to chemotherapeutic agents. A library of small interfering RNA (siRNA) was used to downregulate the known human protein and lipid kinases in medulloblastoma cell lines. The analysis of cell proliferation, in the presence or absence of a low dose of cisplatin after siRNA transfection, identified new protein and lipid kinases involved in medulloblastoma chemoresistance. PLK1 (polo-like kinase 1) was identified as a kinase involved in proliferation in medulloblastoma cell lines. Moreover, a set of 6 genes comprising ATR, LYK5, MPP2, PIK3CG, PIK4CA, and WNK4 were identified as contributing to both cell proliferation and resistance to cisplatin treatment in medulloblastoma cells. An analysis of the expression of the 6 target genes in primary medulloblastoma tumor samples and cell lines revealed overexpression of LYK5 and PIK3CG. The results of the siRNA screen were validated by target inhibition with specific pharmacological inhibitors. A pharmacological inhibitor of p110γ (encoded by PIK3CG) impaired cell proliferation in medulloblastoma cell lines and sensitized the cells to cisplatin treatment. Together, our data show that the p110γ phosphoinositide 3-kinase isoform is a novel target for combinatorial therapies in medulloblastoma.

Rapid assessment of cerebral autoregulation by near-infrared spectroscopy and a single dose of phenylephrine

Rapid bedside determination of cerebral blood pressure autoregulation (AR) may improve clinical utility. We tested the hypothesis that cerebral Hb oxygenation (HbDiff) and cerebral Hb volume (HbTotal) measured by near-infrared spectroscopy (NIRS) would correlate with cerebral blood flow (CBF) after single dose phenylephrine (PE). Critically ill patients requiring artificial ventilation and arterial lines were eligible. During rapid blood pressure rise induced by i.v. PE bolus, ΔHbDiff and ΔHbTotal were calculated by subtracting values at baseline (normotension) from values at peak blood pressure elevation (hypertension). With the aid of NIRS and bolus injection of indocyanine green, relative measures of CBF, called blood flow index (BFI), were determined during normotension and during hypertension. BFI during hypertension was expressed as percentage from BFI during normotension (BFI%). Autoregulation indices (ARIs) were calculated by dividing BFI%, ΔHbDiff, and ΔHbTotal by the concomitant change in blood pressure. In 24 patients (11 newborns and 13 children), significant correlations between BFI% and ΔHbDiff (or ΔHbTotal) were found. In addition, the associations between Hb-based ARI and BFI%-based ARI were significant with correlation coefficients of 0.73 (or 0.72). Rapid determination of dynamic AR with the aid of cerebral Hb signals and PE bolus seems to be reliable.

[Should we screen and treat subclinical hypothyroidism?]

Subclinical hypothyroidism, defined as an elevated thyroid stimulating hormone and normal thyroxine level, is common with aging, particularly after 65 years old. This condition is potentially associated with important consequences, such as cardiovascular diseases and cognitive disorders. So far, indications for screening and thyroxine replacement therapy are still controversial. In this review, we examine the data on those risks and the potential benefits of the treatment. We also present a large European randomized clinical trial that should clarify this controversy, in order to improve clinical care of patients with subclinical hypothyroidism and to give reliable data on maintaining good health among the elderly.