Evaluation of peak-picking algorithms for protein mass spectrometry

Peak picking is an early key step in MS data analysis. We compare three commonly used approaches to peak picking and discuss their merits by means of statistical analysis. Methods investigated encompass signal-to-noise ratio, continuous wavelet transform, and a correlation-based approach using a Gaussian template. Functionality of the three methods is illustrated and discussed in a practical context using a mass spectral data set created with MALDI-TOF technology. Sensitivity and specificity are investigated using a manually defined reference set of peaks. As an additional criterion, the robustness of the three methods is assessed by a perturbation analysis and illustrated using ROC curves

Age-dependent modulation of motor network connectivity for skill acquisition, consolidation and interlimb transfer after motor practice

Objective: Age-related differences in neural strategies for motor learning are not fully understood. We determined the effects of age on the relationship between motor network connectivity and motor skill acquisition, consolidation, and interlimb transfer using dynamic imaging of coherent sources. Methods: Healthy younger (n = 24, 18-24 y) and older (n = 24, 65-87 y) adults unilaterally practiced a visuomotor task and resting-state electroencephalographic data was acquired before and after practice as well as at retention. Results: The results showed that right-hand skill acquisition and consolidation did not differ between age groups. However, age affected the ability to transfer the newly acquired motor skill to the non-practiced limb. Moreover, strengthened left- and right-primary motor cortex-related beta conectivity was negatively and positively associated with right-hand skill acquisition and left-hand skill consolidation in older adults, respectively. Conclusion: Age-dependent modulations of bilateral resting-state motor network connectivity indicate age-specific strategies for the acquisition, consolidation, and interlimb transfer of novel motor tasks. Significance: The present results provide insights into the mechanisms underlying motor learning that are important for the development of interventions for patients with unilateral injuries. (C) 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved

Development and distribution of the non-indigenous Pacific oyster (Crassostrea gigas) in the Dutch Wadden Sea

Pacific oysters (Crassostrea gigas) were first observed in the Dutch Wadden Sea near Texel in 1983. The population increased slowly in the beginning but grew exponentially from the mid-1990s onwards, although now some stabilisation seems to be occurring. They occur on a variety of substrates such as mussel beds (Mytilus edulis), shell banks, dikes and poles. After initial settlement spat may fall on older individuals and congregate to dense clumps and subsequently form reefs. Individual Pacific oysters grow 3–4 cm long in their first year and 2–3 cm in their second year. Many mussel beds (Mytilus edulis) are slowly taken over by Pacific oysters, but there are also several reports of mussel spat settling on Pacific oyster reefs. This might in the end result in combined reefs. Successful Pacific oyster spat fall seems to be related to high summer temperatures, but also after mild summers much spat can be found on old (Pacific oyster) shells. Predation is of limited importance. Mortality factors are unknown, but every now and then unexplained mass mortality occurs. The gradual spread of the Pacific oyster in the Dutch Wadden Sea is documented in the first instance based on historical and anecdotal information. At the start of the more in-depth investigation in 2002, Pacific oysters of all size classes were already present near Texel. Near Ameland the development could be followed from the first observed settlement. On dense reefs each square metre may contain more than 500 adult Pacific oysters, weighing more than 100 kg per m² fresh weigh

Aberrant brain network connectivity in pre-symptomatic and manifest Huntington's disease: a systematic review

Resting-state functional magnetic resonance imaging (rs-fMRI) has the potential to shed light on the pathophysiological mechanisms of Huntington's disease (HD), paving the way to new therapeutic interventions. A systematic review of the literature was conducted in three online databases according to PRISMA guidelines, using keywords for HD, functional connectivity, and rs-fMRI. We included studies investigating connectivity in pre-symptomatic (pre-HD) and manifest HD gene carriers compared to healthy controls, implementing seed-based connectivity, independent component analysis, regional property and graph analysis approaches. Visual network showed reduced connectivity in manifest HD, while network/areas underpinning motor functions were consistently altered in both manifest HD and pre-HD, showing disease stage-dependent changes. Cognitive networks underlying executive and attentional functions showed divergent anterior-posterior alterations, reflecting possible compensatory mechanisms. The involvement of these networks in pre-HD is still unclear. In conclusion, aberrant connectivity of the sensory-motor network is observed in the early stage of HD while, as pathology spreads, other networks might be affected, such as the visual and executive/attentional networks. Moreover, sensory-motor and executive networks exhibit hyper- and hypo-connectivity patterns following different spatiotemporal trajectories. These findings could help to implement future huntingtin-lowering interventions

Generalizing post-stroke prognoses from research data to clinical data

Around a third of stroke survivors suffer from acquired language disorders (aphasia), but current medicine cannot predict whether or when they might recover. Prognostic research in this area increasingly draws on datasets associating structural brain imaging data with outcome scores for ever-larger samples of stroke patients. The aim is to learn brain-behaviour trends from these data, and generalize those trends to predict outcomes for new patients. The practical significance of this work depends on the expected breadth of that generalization. Here, we show that these models can generalize across countries and native languages (from British patients tested in English to Chilean patients tested in Spanish), across neuroimaging technology (from MRI to CT), and from scans collected months or years after stroke for research purposes, to scans collected days or weeks after stroke for clinical purposes

“Open Sesame?”: biomarker status of the human equilibrative nucleoside transporter-1 and molecular mechanisms influencing its expression and activity in the uptake and cytotoxicity of gemcitabine in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive tumor characterized by early invasiveness, rapid progression and resistance to treatment. Gemcitabine has been for more than twenty years the main therapy for PDAC both in the palliative and adjuvant setting. After the introduction of FOLFIRINOX as upfront treatment for metastatic disease, gemcitabine is still commonly used in combination with nab-paclitaxel as an alternative first-line regimen, as well as a monotherapy in elderly patients unfit for combination chemotherapy. As a hydrophilic nucleoside analogue, gemcitabine requires nucleoside transporters to permeate the plasma membrane, and a major role in the uptake of this drug is played by human equilibrative nucleoside transporter 1 (hENT-1). Several studies have proposed hENT-1 as a biomarker for gemcitabine efficacy in PDAC. A recent comprehensive multimodal analysis of hENT-1 status evaluated its predictive role by both immunohistochemistry (with five different antibodies), and quantitative-PCR, supporting the use of the 10D7G2 antibody. High hENT-1 levels observed with this antibody were associated with prolonged disease-free and overall-survival in patients receiving gemcitabine adjuvant chemotherapy. We discuss this analysis and lists molecular factors influencing hENT-1. Improved knowledge on these factors should help in the identification of subgroups of patients who may benefit from specific therapies and overcome the limitations of traditional biomarker studies

FMRI resting slow fluctuations correlate with the activity of fast cortico-cortical physiological connections

Recording of slow spontaneous fluctuations at rest using functional magnetic resonance imaging (fMRI) allows distinct long-range cortical networks to be identified. The neuronal basis of connectivity as assessed by resting-state fMRI still needs to be fully clarified, considering that these signals are an indirect measure of neuronal activity, reflecting slow local variations in de-oxyhaemoglobin concentration. Here, we combined fMRI with multifocal transcranial magnetic stimulation (TMS), a technique that allows the investigation of the causal neurophysiological interactions occurring in specific cortico-cortical connections. We investigated whether the physiological properties of parieto-frontal circuits mapped with short-latency multifocal TMS at rest may have some relationship with the resting-state fMRI measures of specific resting-state functional networks (RSNs). Results showed that the activity of fast cortico-cortical physiological interactions occurring in the millisecond range correlated selectively with the coupling of fMRI slow oscillations within the same cortical areas that form part of the dorsal attention network, i.e., the attention system believed to be involved in reorientation of attention. We conclude that resting-state fMRI ongoing slow fluctuations likely reflect the interaction of underlying physiological cortico-cortical connections