Community composition of epibenthic megafauna on the West Greenland Shelf

Epibenthic organisms are a critical component of the marine environment, functioning as ecosystem engineers, habitat and food for other organisms. Our knowledge of the diversity, complexity and sensitivities of these habitats is limited, particularly at higher latitudes and greater depths. The West Coast of Greenland is the site of a commercially important shrimp trawl fishery, but there are few published records describing the benthic community structure of the region. Here we report results from benthic camera surveys conducted at 119 sites, over 3 years, spanning 1400 km of the West Greenland continental shelf (61–725 m depth). A total of 29 classes of epibenthic taxa were identified from the images. There are significant differences of composition and diversity in sites with hard and soft substrate. Hard-substrate communities are relatively diverse with higher abundances and are characterised by sessile, attached groups such as Hydrozoa, Anthozoa, Bryozoa and Porifera. Soft-sediment sites are less diverse and dominated by Polychaeta and have specialist Malacostraca such as the commercially exploited shrimp, Pandalus borealis. Distribution patterns and variation in epibenthic megafauna are related to substrate and the environmental parameters depth, temperature and current speed. This study represents the first quantitative characterisation of epibenthic megafaunal assemblages on the West Greenland continental shelf. These data constitute an important baseline, albeit in a region heavily impacted by trawl fisheries, and demonstrate the utility of benthic photography for examining and monitoring seabed diversity and change

Dynamic Rearrangement of Cell States Detected by Systematic Screening of Sequential Anticancer Treatments

Signaling networks are nonlinear and complex, involving a large ensemble of dynamic interaction states that fluctuate in space and time. However, therapeutic strategies, such as combination chemotherapy, rarely consider the timing of drug perturbations. If we are to advance drug discovery for complex diseases, it will be essential to develop methods capable of identifying dynamic cellular responses to clinically relevant perturbations. Here, we present a Bayesian dose-response framework and the screening of an oncological drug matrix, comprising 10,000 drug combinations in melanoma and pancreatic cancer cell lines, from which we predict sequentially effective drug combinations. Approximately 23% of the tested combinations showed high-confidence sequential effects (either synergistic or antagonistic), demonstrating that cellular perturbations of many drug combinations have temporal aspects, which are currently both underutilized and poorly understood

Lactate saturation limits bicarbonate detection in hyperpolarized 13 C-pyruvate MRI of the brain

PURPOSE: To investigate the potential effects of [1‐(13)C]lactate RF saturation pulses on [(13)C]bicarbonate detection in hyperpolarized [1‐(13)C]pyruvate MRI of the brain. METHODS: Thirteen healthy rats underwent MRI with hyperpolarized [1‐(13)C]pyruvate of either the brain (n = 8) or the kidneys, heart, and liver (n = 5). Dynamic, metabolite‐selective imaging was used in a cross‐over experiment in which [1‐(13)C]lactate was excited with either 0° or 90° flip angles. The [(13)C]bicarbonate SNR and apparent [1‐(13)C]pyruvate‐to‐[(13)C]bicarbonate conversion (k (PB)) were determined. Furthermore, simulations were performed to identify the SNR optimal flip‐angle scheme for detection of [1‐(13)C]lactate and [(13)C]bicarbonate. RESULTS: In the brain, the [(13)C]bicarbonate SNR was 64% higher when [1‐(13)C]lactate was not excited (5.8 ± 1.5 vs 3.6 ± 1.3; 1.2 to 3.3–point increase; p = 0.0027). The apparent k (PB) decreased 25% with [1‐(13)C]lactate saturation (0.0047 ± 0.0008 s(−1) vs 0.0034 ± 0.0006 s(−1); 95% confidence interval, 0.0006–0.0019 s(−1) increase; p = 0.0049). These effects were not present in the kidneys, heart, or liver. Simulations suggest that the optimal [(13)C]bicarbonate SNR with a TR of 1 s in the brain is obtained with [(13)C]bicarbonate, [1‐(13)C]lactate, and [1‐(13)C]pyruvate flip angles of 60°, 15°, and 10°, respectively. CONCLUSIONS: Radiofrequency saturation pulses on [1‐(13)C]lactate limit [(13)C]bicarbonate detection in the brain specifically, which could be due to shuttling of lactate from astrocytes to neurons. Our results have important implications for experimental design in studies in which [(13)C]bicarbonate detection is warranted

Phase transitions in biological membranes

Native membranes of biological cells display melting transitions of their lipids at a temperature of 10-20 degrees below body temperature. Such transitions can be observed in various bacterial cells, in nerves, in cancer cells, but also in lung surfactant. It seems as if the presence of transitions slightly below physiological temperature is a generic property of most cells. They are important because they influence many physical properties of the membranes. At the transition temperature, membranes display a larger permeability that is accompanied by ion-channel-like phenomena even in the complete absence of proteins. Membranes are softer, which implies that phenomena such as endocytosis and exocytosis are facilitated. Mechanical signal propagation phenomena related to nerve pulses are strongly enhanced. The position of transitions can be affected by changes in temperature, pressure, pH and salt concentration or by the presence of anesthetics. Thus, even at physiological temperature, these transitions are of relevance. There position and thereby the physical properties of the membrane can be controlled by changes in the intensive thermodynamic variables. Here, we review some of the experimental findings and the thermodynamics that describes the control of the membrane function.Comment: 23 pages, 15 figure

Early diagnosis of amyotrophic lateral sclerosis by threshold tracking and conventional transcranial magnetic stimulation

© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.Background and purpose: Short-interval intracortical inhibition by threshold tracking (T-SICI) has been proposed as a diagnostic tool for amyotrophic lateral sclerosis (ALS) but has not been compared directly with conventional amplitude measurements (A-SICI). This study compared A-SICI and T-SICI for sensitivity and clinical usefulness as biomarkers for ALS. Methods: In all, 104 consecutive patients referred with suspicion of ALS were prospectively included and were subsequently divided into 62 patients with motor neuron disease (MND) and 42 patient controls (ALS mimics) by clinical follow-up. T-SICI and A-SICI recorded in the first dorsal interosseus muscle (index test) were compared with recordings from 53 age-matched healthy controls. The reference standard was the Awaji criteria. Clinical scorings, conventional nerve conduction studies and electromyography were also performed on the patients. Results: Motor neuron disease patients had significantly reduced T-SICI and A-SICI compared with the healthy and patient control groups, which were similar. Sensitivity and specificity for discriminating MND patients from patient controls were high (areas under the receiver operating characteristic curves 0.762 and 0.810 for T-SICI and A-SICI respectively at 1-3.5 ms). Paradoxically, T-SICI was most reduced in MND patients with the fewest upper motor neuron (UMN) signs (Spearman ρ = 0.565, p = 4.3 × 10-6 ). Conclusions: Amplitude-based measure of cortical inhibition and T-SICI are both sensitive measures for the detection of cortical involvement in MND patients and may help early diagnosis of ALS, with T-SICI most abnormal before UMN signs have developed. The gradation in T-SICI from pathological facilitation in patients with minimal UMN signs to inhibition in those with the most UMN signs may be due to progressive degeneration of the subset of UMNs experiencing facilitation.info:eu-repo/semantics/publishedVersio

Training American listeners to perceive Mandarin tones

This is the publisher's version, also available electronically from http://scitation.aip.org/content/asa/journal/jasa/106/6/10.1121/1.428217.Auditory training has been shown to be effective in the identification of non-native segmental distinctions. In this study, it was investigated whether such training is applicable to the acquisition of non-native suprasegmentalcontrasts, i.e., Mandarin tones. Using the high-variability paradigm, eight American learners of Mandarin were trained in eight sessions during the course of two weeks to identify the four tones in natural words produced by native Mandarin talkers. The trainees’ identification accuracy revealed an average 21% increase from the pretest to the post-test, and the improvement gained in training was generalized to new stimuli (18% increase) and to new talkers and stimuli (25% increase). Moreover, the six-month retention test showed that the improvement was retained long after training by an average 21% increase from the pretest. The results are discussed in terms of non-native suprasegmental perceptual modification, and the analogies between L2 acquisition processes at the segmental and suprasegmental levels

Acoustic and perceptual evaluation of Mandarin tone productions before and after perceptual training

This is the publisher's version, also available electronically from http://scitation.aip.org/content/asa/journal/jasa/113/2/10.1121/1.1531176.Training American listeners to perceive Mandarin tones has been shown to be effective, with trainees’ identification improving by 21%. Improvement also generalized to new stimuli and new talkers, and was retained when tested six months after training [Y. Wang et al., J. Acoust. Soc. Am. 106, 3649–3658 (1999)]. The present study investigates whether the tonecontrasts gained perceptually transferred to production. Before their perception pretest and after their post-test, the trainees were recorded producing a list of Mandarin words. Their productions were first judged by native Mandarin listeners in an identification task. Identification of trainees’ post-test tone productions improved by 18% relative to their pretest productions, indicating significant tone production improvement after perceptual training. Acoustic analyses of the pre- and post-training productions further reveal the nature of the improvement, showing that post-training tone contours approximate native norms to a greater degree than pretraining tone contours. Furthermore, pitch height and pitch contour are not mastered in parallel, with the former being more resistant to improvement than the latter. These results are discussed in terms of the relationship between non-native tone perception and production as well as learning at the suprasegmental level

Phase state dependent current fluctuations in pure lipid membranes

Current fluctuations in pure lipid membranes have been shown to occur under the influence of transmembrane electric fields (electroporation) as well as a result from structural rearrangements of the lipid bilayer during phase transition (soft perforation). We demonstrate that the ion permeability during lipid phase transition exhibits the same qualitative temperature dependence as the macroscopic heat capacity of a D15PC/DOPC vesicle suspension. Microscopic current fluctuations show distinct characteristics for each individual phase state. While current fluctuations in the fluid phase show spike-like behaviour of short time scales (~ 2ms) with a narrow amplitude distribution, the current fluctuations during lipid phase transition appear in distinct steps with time scales in the order of ~ 20ms. 1 We propose a theoretical explanation for the origin of time scales and permeability based on a linear relationship between lipid membrane susceptibilities and relaxation times in the vicinity of the phase transition.Comment: 22 pages including 6 figure

Mesenchymal stromal cell activation by breast cancer secretomes in bioengineered 3D microenvironments

Mesenchymal stromal cells (MSCs) are key contributors of the tumour microenvironment and are known to promote cancer progression through reciprocal communication with cancer cells, but how they become activated is not fully understood. Here, we investigate how breast cancer cells from different stages of the metastatic cascade convert MSCs into tumour-associated MSCs (TA-MSCs) using unbiased, global approaches. Using mass spectrometry, we compared the secretomes of MCF-7 cells, invasive MDA-MB-231 cells, and sublines isolated from bone, lung, and brain metastases and identified ECM and exosome components associated with invasion and organ-specific metastasis. Next, we used synthetic hydrogels to investigate how these different secretomes activate MSCs in bioengineered 3D microenvironments. Using kinase activity profiling and RNA sequencing, we found that only MDA-MB-231 breast cancer secretomes convert MSCs into TA-MSCs, resulting in an immunomodulatory phenotype that was particularly prominent in response to bone-tropic cancer cells. We have investigated paracrine signalling from breast cancer cells to TA-MSCs in 3D, which may highlight new potential targets for anticancer therapy approaches aimed at targeting tumour stroma

Effect of intonation on Cantonese lexical tones

In tonal languages, there are potential conflicts between the F0-based changes due to the coexistence of intonation and lexical tones. In the present study, the interaction of tone and intonation in Cantonese was examined using acoustic and perceptual analyses. The acoustic patterns of tones at the initial, medial, and final positions of questions and statements were measured. Results showed that intonation affects both the F0 level and contour, while the duration of the six tones varied as a function of positions within intonation contexts. All six tones at the final position of questions showed rising F0 contour, regardless of their canonical form. Listeners were overall more accurate in the identification of tones presented within the original carrier than of the same tones in isolation. However, a large proportion of tones 33, 21, 23, and 22 at the final position of questions were misperceived as tone 25 both within the original carrier and as isolated words. These results suggest that although the intonation context provided cues for correct tone identification, the intonation-induced changes in F0 contour cannot always be perceptually compensated for, resulting in some erroneous perception of the identity of Cantonese tone. © 2006 Acoustical Society of America.published_or_final_versio