Naupliar and Metanaupliar development of Thysanoessa raschii (Malacostraca, Euphausiacea) from Godthåbsfjord, Greenland, with a reinstatement of the ancestral status of the free-living Nauplius in Malacostracan evolution

The presence of a characteristic crustacean larval type, the nauplius, in many crustacean taxa has often been considered one of the few uniting characters of the Crustacea. Within Malacostraca, the largest crustacean group, nauplii are only present in two taxa, Euphauciacea (krill) and Decapoda Dendrobranchiata. The presence of nauplii in these two taxa has traditionally been considered a retained primitive characteristic, but free-living nauplii have also been suggested to have reappeared a couple of times from direct developing ancestors during malacostracan evolution. Based on a re-study of Thysanoessa raschii (Euphausiacea) using preserved material collected in Greenland, we readdress this important controversy in crustacean evolution, and, in the process, redescribe the naupliar and metanaupliar development of T. raschii. In contrast to most previous studies of euphausiid development, we recognize three (not two) naupliar (= ortho-naupliar) stages (N1-N3) followed by a metanauplius (MN). While there are many morphological changes between nauplius 1 and 2 (e.g., appearance of long caudal setae), the changes between nauplius 2 and 3 are few but distinct. They involve the size of some caudal spines (largest in N3) and the setation of the antennal endopod (an extra seta in N3). A wider comparison between free-living nauplii of both Malacostraca and non-Malacostraca revealed similarities between nauplii in many taxa both at the general level (e.g., the gradual development and number of appendages) and at the more detailed level (e.g., unclear segmentation of naupliar appendages, caudal setation, presence of frontal filaments). We recognize these similarities as homologies and therefore suggest that free-living nauplii were part of the ancestral malacostracan type of development. The derived morphology (e.g., lack of feeding structures, no fully formed gut, high content of yolk) of both euphausiid and dendrobranchiate nauplii is evidently related to their non-feeding (lecithotrophic) status

Translation of experimental cardioprotective capability of P2Y(12) inhibitors into clinical outcome in patients with ST-elevation myocardial infarction

We studied the translational cardioprotective potential of P2Y12 inhibitors against acute myocardial ischemia/reperfusion injury (IRI) in an animal model of acute myocardial infarction and in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). P2Y12 inhibitors may have pleiotropic effects to induce cardioprotection against acute myocardial IRI beyond their inhibitory effects on platelet aggregation. We compared the cardioprotective effects of clopidogrel, prasugrel, and ticagrelor on infarct size in an in vivo rat model of acute myocardial IRI, and investigated the effects of the P2Y12 inhibitors on enzymatic infarct size (48-h area-under-the-curve (AUC) troponin T release) and clinical outcomes in a retrospective study of STEMI patients from the CONDI-2/ERIC-PPCI trial using propensity score analyses. Loading with ticagrelor in rats reduced infarct size after acute myocardial IRI compared to controls (37 ± 11% vs 52 ± 8%, p  0.99 and 49 ± 9%, p > 0.99, respectively). Correspondingly, troponin release was reduced in STEMI patients treated with ticagrelor compared to clopidogrel (adjusted 48-h AUC ratio: 0.67, 95% CI 0.47–0.94). Compared to clopidogrel, the composite endpoint of cardiac death or hospitalization for heart failure within 12 months was reduced in STEMI patients loaded with ticagrelor (HR 0.63; 95% CI 0.42–0.94) but not prasugrel (HR 0.84, 95% CI 0.43–1.63), prior to PPCI. Major adverse cardiovascular events did not differ between clopidogrel, ticagrelor, or prasugrel. The cardioprotective effects of ticagrelor in reducing infarct size may contribute to the clinical benefit observed in STEMI patients undergoing PPCI

Whole-genome amplified DNA from stored dried blood spots is reliable in high resolution melting curve and sequencing analysis

<p>Abstract</p> <p>Background</p> <p>The use of dried blood spots (DBS) samples in genomic workup has been limited by the relative low amounts of genomic DNA (gDNA) they contain. It remains to be proven that whole genome amplified DNA (wgaDNA) from stored DBS samples, constitutes a reliable alternative to gDNA.</p> <p>We wanted to compare melting curves and sequencing results from wgaDNA derived from DBS samples with gDNA derived from whole blood.</p> <p>Methods</p> <p>gDNA was extracted from whole blood obtained from 10 patients with lone atrial fibrillation (mean age 22.3 years). From their newborn DBS samples, stored at -24°C, genomic DNA was extracted and whole-genome amplified in triplicates. Using high resolution melting curve analysis and direct sequencing in both wgaDNA and gDNA samples, all coding regions and adjacent intron regions of the genes <it>SCN5A </it>and <it>KCNA5 </it>were investigated.</p> <p>Results</p> <p>Altered melting curves was present in 85 of wgaDNA samples and 81 of gDNA samples. Sequence analysis identified a total of 31 variants in the 10 wgaDNA samples. The same 31 variants were found in the exact same pattern of samples in the gDNA group. There was no false positive or negative sequence variation in the wgaDNA group.</p> <p>Conclusions</p> <p>The use of DNA amplified in triplicates from DBS samples is reliable and can be used both for high resolution curve melting analysis as well as direct sequence analysis. DBS samples therefore can serve as an alternative to whole blood in sequence analysis.</p

Stroke genetics: prospects for personalized medicine.

Epidemiologic evidence supports a genetic predisposition to stroke. Recent advances, primarily using the genome-wide association study approach, are transforming what we know about the genetics of multifactorial stroke, and are identifying novel stroke genes. The current findings are consistent with different stroke subtypes having different genetic architecture. These discoveries may identify novel pathways involved in stroke pathogenesis, and suggest new treatment approaches. However, the already identified genetic variants explain only a small proportion of overall stroke risk, and therefore are not currently useful in predicting risk for the individual patient. Such risk prediction may become a reality as identification of a greater number of stroke risk variants that explain the majority of genetic risk proceeds, and perhaps when information on rare variants, identified by whole-genome sequencing, is also incorporated into risk algorithms. Pharmacogenomics may offer the potential for earlier implementation of 'personalized genetic' medicine. Genetic variants affecting clopidogrel and warfarin metabolism may identify non-responders and reduce side-effects, but these approaches have not yet been widely adopted in clinical practice

Relative Stability of Core Groups in Pollination Networks in a Biodiversity Hotspot over Four Years

Plants and their pollinators form pollination networks integral to the evolution and persistence of species in communities. Previous studies suggest that pollination network structure remains nested while network composition is highly dynamic. However, little is known about temporal variation in the structure and function of plant-pollinator networks, especially in species-rich communities where the strength of pollinator competition is predicted to be high. Here we quantify temporal variation of pollination networks over four consecutive years in an alpine meadow in the Hengduan Mountains biodiversity hotspot in China. We found that ranked positions and idiosyncratic temperatures of both plants and pollinators were more conservative between consecutive years than in non-consecutive years. Although network compositions exhibited high turnover, generalized core groups – decomposed by a k-core algorithm – were much more stable than peripheral groups. Given the high rate of turnover observed, we suggest that identical plants and pollinators that persist for at least two successive years sustain pollination services at the community level. Our data do not support theoretical predictions of a high proportion of specialized links within species-rich communities. Plants were relatively specialized, exhibiting less variability in pollinator composition at pollinator functional group level than at the species level. Both specialized and generalized plants experienced narrow variation in functional pollinator groups. The dynamic nature of pollination networks in the alpine meadow demonstrates the potential for networks to mitigate the effects of fluctuations in species composition in a high biodiversity area

Whole genome sequencing reveals high clonal diversity of Escherichia coli isolated from patients in a tertiary care hospital in Moshi, Tanzania

Abstract Background Limited information regarding the clonality of circulating E. coli strains in tertiary care hospitals in low and middle-income countries is available. The purpose of this study was to determine the serotypes, antimicrobial resistance and virulence genes. Further, we carried out a phylogenetic tree reconstruction to determine relatedness of E. coli isolated from patients in a tertiary care hospital in Tanzania. Methods E. coli isolates from inpatients admitted at Kilimanjaro Christian Medical Centre between August 2013 and August 2015 were fully genome-sequenced at KCMC hospital. Sequence analysis was done for identification of resistance genes, Multi-Locus Sequence Typing, serotyping, and virulence genes. Phylogeny reconstruction using CSI Phylogeny was done to ascertain E. coli relatedness. Stata 13 (College Station, Texas 77,845 USA) was used to determine Cohen’s kappa coefficient of agreement between the phenotypically tested and whole genome sequence predicted antimicrobial resistance. Results Out of 38 E. coli isolates, 21 different sequence types (ST) were observed. Eight (21.1%) isolates belonged to ST131; of which 7 (87.5.%) were serotype O25:H4. Ten (18.4%) isolates belonged to ST10 clonal complex; of these, four (40.0%) were ST617 with serotype O89:H10. Twenty-eight (73.7%) isolates carried genes encoding beta-lactam resistance enzymes. On average, agreement across all drugs tested was 83.9%. Trimethoprim/sulphamethoxazole (co-trimoxazole) showed moderate agreement: 45.8%, kappa =15% and p = 0.08. Amoxicillin-clavulanate showed strongest agreement: 87.5%, kappa = 74% and p = 0.0001. Twenty-two (57.9%) isolates carried virulence factors for host cells adherence and 25 (65.7%) for factors that promote E. coli immune evasion by increasing survival in serum. The phylogeny analysis showed that ST131 clustering close together whereas ST10 clonal complex had a very clear segregation of the ST617 and a mix of the rest STs. Conclusion There is a high diversity of E. coli isolated from patients admitted to a tertiary care hospital in Tanzania. This underscores the necessity to routinely screen all bacterial isolates of clinical importance in tertiary health care facilities. WGS use for laboratory-based surveillance can be an effective early warning system for emerging pathogens and resistance mechanisms in LMICs

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Cutaneous nociception and neurogenic inflammation evoked by PACAP38 and VIP

Pituitary adenylate cyclase-activating peptide-38 (PACAP38) and vasoactive intestinal peptide (VIP) belong to the same secretin–glucagon superfamily and are present in nerve fibers in dura and skin. Using a model of acute cutaneous pain we explored differences in pain perception and vasomotor responses between PACAP38 and VIP in 16 healthy volunteers in a double-blind, placebo-controlled, crossover study. All participants received intradermal injections of 200 pmol PACAP38, 200 pmol VIP and placebo into the volar forearm. Measurements included pain intensity on a visual analog scale (VAS), blood flow by laser Doppler flowmetry, visual flare and wheal. Pain intensities after PACAP38 and VIP were mild and limited to a short time of about 100 s after injection. The area under the VAS-time curve was larger following PACAP38 (P = 0.004) and VIP (P = 0.01) compared to placebo. We found no statistical difference in pain perception between PACAP38 and VIP. Skin blood flow increase, flare and wheal were larger after both PACAP38 (P = 0.011) and VIP (P = 0.001) compared to placebo. VIP induced a considerably larger increase in skin blood flow, flare and wheal than PACAP38 (P = 0.002). In conclusion, we found that peripheral nociceptive cutaneous responses elicited by PACAP38 and VIP are similar in healthy volunteers. This suggests that acute pain and vasomotor responses following intradermal injections of PACAP38 and VIP are primarily mediated by VPAC receptors

Generalization of auditory sensory and cognitive learning in typically developing children

Despite the well-established involvement of both sensory (“bottom-up”) and cognitive (“top-down”) processes in literacy, the extent to which auditory or cognitive (memory or attention) learning transfers to phonological and reading skills remains unclear. Most research has demonstrated learning of the trained task or even learning transfer to a closely related task. However, few studies have reported “far-transfer” to a different domain, such as the improvement of phonological and reading skills following auditory or cognitive training. This study assessed the effectiveness of auditory, memory or attention training on far-transfer measures involving phonological and reading skills in typically developing children. Mid-transfer was also assessed through untrained auditory, attention and memory tasks. Sixty 5- to 8-year-old children with normal hearing were quasi-randomly assigned to one of five training groups: attention group (AG), memory group (MG), auditory sensory group (SG), placebo group (PG; drawing, painting), and a control, untrained group (CG). Compliance, mid-transfer and far-transfer measures were evaluated before and after training. All trained groups received 12 x 45-min training sessions over 12 weeks. The CG did not receive any intervention. All trained groups, especially older children, exhibited significant learning of the trained task. On pre- to post-training measures (test-retest), most groups exhibited improvements on most tasks. There was significant mid-transfer for a visual digit span task, with highest span in the MG, relative to other groups. These results show that both sensory and cognitive (memory or attention) training can lead to learning in the trained task and to mid-transfer learning on a task (visual digit span) within the same domain as the trained tasks. However, learning did not transfer to measures of language (reading and phonological awareness), as the PG and CG improved as much as the other trained groups. Further research is required to investigate the effects of various stimuli and lengths of training on the generalization of sensory and cognitive learning to literacy skills