Dictionary Learning and Sparse Coding-based Denoising for High-Resolution Task Functional Connectivity MRI Analysis

We propose a novel denoising framework for task functional Magnetic Resonance Imaging (tfMRI) data to delineate the high-resolution spatial pattern of the brain functional connectivity via dictionary learning and sparse coding (DLSC). In order to address the limitations of the unsupervised DLSC-based fMRI studies, we utilize the prior knowledge of task paradigm in the learning step to train a data-driven dictionary and to model the sparse representation. We apply the proposed DLSC-based method to Human Connectome Project (HCP) motor tfMRI dataset. Studies on the functional connectivity of cerebrocerebellar circuits in somatomotor networks show that the DLSC-based denoising framework can significantly improve the prominent connectivity patterns, in comparison to the temporal non-local means (tNLM)-based denoising method as well as the case without denoising, which is consistent and neuroscientifically meaningful within motor area. The promising results show that the proposed method can provide an important foundation for the high-resolution functional connectivity analysis, and provide a better approach for fMRI preprocessing.Comment: 8 pages, 3 figures, MLMI201

When Optimal Feedback Control Is Not Enough: Feedforward Strategies Are Required for Optimal Control with Active Sensing

Movement planning is thought to be primarily determined by motor costs such as inaccuracy and effort. Solving for the optimal plan that minimizes these costs typically leads to specifying a time-varying feedback controller which both generates the movement and can optimally correct for errors that arise within a movement. However, the quality of the sensory feedback during a movement can depend substantially on the generated movement. We show that by incorporating such state-dependent sensory feedback, the optimal solution incorporates active sensing and is no longer a pure feedback process but includes a significant feedforward component. To examine whether people take into account such state-dependency in sensory feedback we asked people to make movements in which we controlled the reliability of sensory feedback. We made the visibility of the hand state-dependent, such that the visibility was proportional to the component of hand velocity in a particular direction. Subjects gradually adapted to such a sensory perturbation by making curved hand movements. In particular, they appeared to control the late visibility of the movement matching predictions of the optimal controller with state-dependent sensory noise. Our results show that trajectory planning is not only sensitive to motor costs but takes sensory costs into account and argues for optimal control of movement in which feedforward commands can play a significant role.Wellcome Trust (Grant IDs: WT091547MA, WT097803MA), Royal Society (Noreen Murray Professorship in Neurobiology

Exertional rhabdomyolysis in a 21-year-old, healthy female after performing three sets of the biceps curl exercise to failure with 30% 1RM: A case report

Background: The optimal resistance training program to elicit muscle hypertrophy has been consistently debated and researched. Although 3 sets of 10 repetitions at 70-80% of the 1-repetition maximum (1RM) is widely recommended, recent studies have shown that low-load (~30% 1RM), high-repetition (3 sets of 30-40 repetitions) resistance training can elicit similar muscular hypertrophy. Therefore, this type of resistance training has gained popularity, perhaps because less weight is lifted for a longer duration. In the process of testing this hypothesis in a research study in our laboratory, a subject diagnosed with exertional rhabdomyolysis after completing a single resistance training session that involved 3 sets to failure at 30% 1RM. Exertional rhabdomyolysis is a condition characterized by the excessive breakdown of striated skeletal muscle that releases proteins from the muscle cell, particularly myoglobin, into the blood that can be toxic to the kidneys and is a significant health concern. Case Report: Reviewed were the events leading up to and throughout the diagnosis of exertional rhabdomyolysis in a healthy, recreationally-trained, 21-year-old female that was enrolled in a study that compared the acute effects of the traditional high-load, low-repetition versus low-load, high-repetition resistance training. The subject completed a total of 143 repetitions of the bilateral dumbbell bicep curl exercise. Three days post-exercise she reported excessive muscle soreness and swelling and sought medical attention. She was briefly hospitalized and then discharged with instructions to take acetaminophen for soreness, drink plenty of water, rest, and monitor her creatine kinase (CK) concentrations. Changes in the subject’s CK concentrations, ultrasound-determined muscle thickness and echo intensity were monitored over a 14-day period are reported. Discussion: This case illustrates the potential risk of developing exertional rhabdomyolysis after a low-load, high-repetition resistance training session in healthy, young, recreationally-trained women. The fact that exertional rhabdomyolysis is a possible outcome is enough to warrant caution when prescribing this type of resistance exercise

Effects of oxidized low density lipoprotein, lipid mediators and statins on vascular cell interactions

The integrin heterodimer CD11b/CD18 (alpha M beta 2, Mac-1, CR3) expressed on monocytes or polymorphonuclear leukocytes (PMN) is a receptor for iC3b, fibrinogen, heparin, and for intercellular adhesion molecule (ICAM)-1 on endothelium, crucially contributing to vascular cell interactions in inflammation and atherosclerosis. In this report, we summarize our findings on the effects of lipid mediators and lipid-lowering drugs. Exposure of endothelial cells to oxidized low density lipoprotein (oxLDL) induces upregulation of ICAM-1 and increases adhesion of monocytic cells expressing Mac-1. Inhibition experiments show that monocytes use distinct ligands, i.e. ICAM-1 and heparan sulfate proteoglycans for adhesion to oxLDL-treated endothelium. An albumin-transferable oxLDL activity is inhibited by the antioxidant pyrrolidine dithiocarbamate (PDTC), while 8-epi-prostaglandin F2 alpha (8-epi-PGF2 alpha) or lysophosphatidylcholine had no effect, implicating yet unidentified radicals. Sequential adhesive! and signaling events lead to the firm adhesion of rolling PMN on activated and adherent platelets, which may occupy areas of endothelial denudation. Shear resistant arrest of PMN on thrombin-stimulated platelets in flow conditions requires distinct regions of Mac-1, involving its interactions with fibrinogen bound to platelet alpha llb beta 3, and with other platelet ligands. Both arrest and adhesion strengthening under flow are stimulated by platelet-activating factor and leukotriene B4, but not by the chemokine receptor CXCR2. We tested whether Mac-1-dependent monocyte adhesiveness is affected by inhibitors of hydroxy-methylglutaryl-Coenzyme A reductase (statins) which improve morbidity and survival of patients with coronary heart disease. As compared to controls, adhesion of isolated monocytes to endothelium ex vivo was increased in patients with hypercholesterolemia. Treatment with statins decreased total and low density lipoprotein (LDL) cholesterol plasma levels, surface expression of Mac-1, and resulted in a dramatic reduction of Mac,mediated monocyte adhesion to endothelium. The inhibition of monocyte adhesion was reversed by mevalonate but not LDL in vitro,indicating that isoprenoid precursors are crucial for adhesiveness of Mac-1. Such effects may crucially contribute to the clinical benefit of statins, independent of cholesterol-lowering, and may represent a paradigm for novel, anti-inflammatory mechanisms of action by this class of drugs

Isolation and fine mapping of Rps6: An intermediate host resistance gene in barley to wheat stripe rust

A plant may be considered a nonhost of a pathogen if all known genotypes of a plant species are resistant to all known isolates of a pathogen species. However, if a small number of genotypes are susceptible to some known isolates of a pathogen species this plant maybe considered an intermediate host. Barley (Hordeum vulgare) is an intermediate host for Puccinia striiformis f. sp. tritici (Pst), the causal agent of wheat stripe rust. We wanted to understand the genetic architecture underlying resistance to Pst and to determine whether any overlap exists with resistance to the host pathogen, Puccinia striiformis f. sp. hordei (Psh). We mapped Pst resistance to chromosome 7H and show that host and intermediate host resistance is genetically uncoupled. Therefore, we designate this resistance locus Rps6. We used phenotypic and genotypic selection on F2:3 families to isolate Rps6 and fine mapped the locus to a 0.1 cM region. Anchoring of the Rps6 locus to the barley physical map placed the region on two adjacent fingerprinted contigs. Efforts are now underway to sequence the minimal tiling path and to delimit the physical region harbouring Rps6. This will facilitate additional marker development and permit identification of candidate genes in the region

Cross-Linking Amine-Rich Compounds into High Performing Selective CO2 Absorbents

Amine-based absorbents play a central role in CO2 sequestration and utilization. Amines react selectively with CO2, but a drawback is the unproductive weight of solvent or support in the absorbent. Efforts have focused on metal organic frameworks (MOFs) reaching extremely high CO2 capacity, but limited selectivity to N2 and CH4, and decreased uptake at higher temperatures. A desirable system would have selectivity (cf. amine) and high capacity (cf. MOF), but also increased adsorption at higher temperatures. Here, we demonstrate a proof-of-concept where polyethyleneimine (PEI) is converted to a high capacity and highly selective CO2 absorbent using buckminsterfullerene (C60) as a cross-linker. PEI-C60 (CO2 absorption of 0.14 g/g at 0.1 bar/90°C) is compared to one of the best MOFs, Mg-MOF-74 (0.06 g/g at 0.1 bar/90°C), and does not absorb any measurable amount of CH4 at 50 bar. Thus, PEI-C60 can perform better than MOFs in the sweetening of natural gas

Rare Copy Number Deletions Predict Individual Variation in Intelligence

Phenotypic variation in human intellectual functioning shows substantial heritability, as demonstrated by a long history of behavior genetic studies. Many recent molecular genetic studies have attempted to uncover specific genetic variations responsible for this heritability, but identified effects capture little variance and have proven difficult to replicate. The present study, motivated an interest in “mutation load” emerging from evolutionary perspectives, examined the importance of the number of rare (or infrequent) copy number variations (CNVs), and the total number of base pairs included in such deletions, for psychometric intelligence. Genetic data was collected using the Illumina 1MDuoBeadChip Array from a sample of 202 adult individuals with alcohol dependence, and a subset of these (N = 77) had been administered the Wechsler Abbreviated Scale of Intelligence (WASI). After removing CNV outliers, the impact of rare genetic deletions on psychometric intelligence was investigated in 74 individuals. The total length of the rare deletions significantly and negatively predicted intelligence (r = −.30, p = .01). As prior studies have indicated greater heritability in individuals with relatively higher parental socioeconomic status (SES), we also examined the impact of ethnicity (Anglo/White vs. Other), as a proxy measure of SES; these groups did not differ on any genetic variable. This categorical variable significantly moderated the effect of length of deletions on intelligence, with larger effects being noted in the Anglo/White group. Overall, these results suggest that rare deletions (between 5% and 1% population frequency or less) adversely affect intellectual functioning, and that pleotropic effects might partly account for the association of intelligence with health and mental health status. Significant limitations of this research, including issues of generalizability and CNV measurement, are discussed

Fox-1 family of RNA-binding proteins

The Fox-1 family of RNA-binding proteins are evolutionarily conserved regulators of tissue-specific alternative splicing in metazoans. The Fox-1 family specifically recognizes the (U)GCAUG stretch in regulated exons or in flanking introns, and either promotes or represses target exons. Recent unbiased bioinformatics analyses of alternatively spliced exons and comparison of various vertebrate genomes identified the (U)GCAUG stretch as a highly conserved and widely distributed element enriched in intronic regions surrounding exons with altered inclusion in muscle, heart, and brain, consistent with specific expression of Fox-1 and Fox-2 in these tissues. Global identification of Fox-2 target RNAs in living cells revealed that many of the Fox-2 target genes themselves encode splicing regulators. Further systematic elucidation of target genes of the Fox-1 family and other splicing regulators in various tissues will lead to a comprehensive understanding of splicing regulatory networks