Are Neuronal Mechanisms of Attentional Modulation Universal Across Human Sensory and Motor Brain Maps?

One\u27s experience of shifting attention from the color to the smell to the act of picking a flower seems like a unitary process applied, at will, to one modality after another. Yet, the unique experience of sight vs smell vs movement might suggest that the neural mechanisms of attention have been selectively optimized to employ each modality to greatest advantage. Relevant experimental data can be difficult to compare across modalities due to design and methodological heterogeneity. Here we outline some of the issues related to this problem and suggest how experimental data can be obtained across modalities using more uniform methods and measurements. The ultimate goal is to spur efforts across disciplines to provide a large and varied database of empirical observations that will either support the notion of a universal neural substrate for attention or more clearly identify to what degree attentional mechanisms are specialized for each modality

Overlapping regions of visuospatial and motor attention maps maintain spatial congruency in human posterior parietal cortex

Organization of Data: Separate files are included that provide: the demographic information for each participant the stimulus timing information for each run All data for individual participants are compressed into a single file All participant files include an anatomical image All participant files are in AFNI format with *.BRIK and *.HEAD extensions Raw data for individual runs are included for each participant Runs are labeled 1-5 to correspond to the stimulus timing file Multiple repetitions of the same stimulus timing are indicated by a letter subscript at the end. For example, a participant who performed run 1 twice would have a file with the run1A extension and another file with the run1B extension. Participants for the first experiment are number consecutively 1-9. Participants for the second set of experiments are lettered consecutively A-J All runs related to the attention task have ‘attn’ in the run title All runs related to the intention task have ‘intn’ in the run title If data were collected on multiple days, skull-stripped anatomical images are provided for both days.https://dc.uwm.edu/kinesiology_facdata/1000/thumbnail.jp

Remote concussion history does not affect visually-guided reaching in young adult females

Aim: We examined the long-term effects of concussions in young adult females on visuomotor behavior during a visually-guided reaching task of various complexities. Materials & methods: 20 females with a history of longer than 6 months since a concussion and 20 healthy females quickly and accurately performed a delayed reach to a previously cued target. Results: As both cognitive and motor load increased, task performance decreased for both groups (p \u3c 0.05). However, contrary to our primary hypothesis, no differences in task performance were found between the two experimental groups (p \u3e 0.05). Conclusion: The young adult females with a remote history of concussion demonstrated no deficits in visuomotor behavior on an attention-mediated reaching task as compared with control participants. Lay abstract: Current literature is inconclusive regarding the long-term effects of concussion. Some have argued that the differing results are due to many uncontrolled factors in study design. In this study, 20 females with a history of concussion more than 6 months ago and 20 healthy females performed a reaching task under different levels of difficulty. As the reaching task got harder, both groups had greater difficulty doing the task quickly and accurately (p \u3c 0.05). Surprisingly, however, no differences in reaching performance existed between the two groups (p \u3e 0.05). Young adult females with a remote history of concussion demonstrated no greater problems with complicated reaching tasks when compared with control participants when experimental conditions are tightly controlled

Molecular Study of Preterm Birth: Genomic Ancestry, Race, and Ethnicity

BACKGROUND: Inova Translational Medicine Institute (ITMI) initiated a study to identify genomic markers predictive of preterm birth (PTB). Molecular Study of Preterm Birth evaluated ancestral reference genomes, self-reported country of birth, race and ethnicity, as well as data from the electronic medical records (EMR). Family and racial predispositions to PTB suggest genomic characterizations may confer increased risk. OBJECTIVE: To investigate genomic ancestry utilizing the electronic medical record, self-reported race/ethnicity, and principle component analysis to determine the molecular characterization of genomics and preterm birth

Effects of Thresholding on Voxel-Wise Correspondence of Breath-Hold and Resting-State Maps of Cerebrovascular Reactivity

Functional magnetic resonance imaging for presurgical brain mapping enables neurosurgeons to identify viable tissue near a site of operable pathology which might be at risk of surgery-induced damage. However, focal brain pathology (e.g., tumors) may selectively disrupt neurovascular coupling while leaving the underlying neurons functionally intact. Such neurovascular uncoupling can result in false negatives on brain activation maps thereby compromising their use for surgical planning. One way to detect potential neurovascular uncoupling is to map cerebrovascular reactivity using either an active breath-hold challenge or a passive resting-state scan. The equivalence of these two methods has yet to be fully established, especially at a voxel level of resolution. To quantitatively compare breath-hold and resting-state maps of cerebrovascular reactivity, we first identified threshold settings that optimized coverage of gray matter while minimizing false responses in white matter. When so optimized, the resting-state metric had moderately better gray matter coverage and specificity. We then assessed the spatial correspondence between the two metrics within cortical gray matter, again, across a wide range of thresholds. Optimal spatial correspondence was strongly dependent on threshold settings which if improperly set tended to produce statistically biased maps. When optimized, the two CVR maps did have moderately good correspondence with each other (mean accuracy of 73.6%). Our results show that while the breath-hold and resting-state maps may appear qualitatively similar they are not quantitatively identical at a voxel level of resolution

Photobiomodulation preserves mitochondrial redox state and is retinoprotective in a rodent model of retinitis pigmentosa

Photobiomodulation (PBM) by far-red (FR) to near-infrared (NIR) light has been demonstrated to restore the function of damaged mitochondria, increase the production of cytoprotective factors and prevent cell death. Our laboratory has shown that FR PBM improves functional and structural outcomes in animal models of retinal injury and retinal degenerative disease. The current study tested the hypothesis that a brief course of NIR (830 nm) PBM would preserve mitochondrial metabolic state and attenuate photoreceptor loss in a model of retinitis pigmentosa, the P23H transgenic rat. P23H rat pups were treated with 830 nm light (180 s; 25 mW/cm2; 4.5 J/cm2) using a light-emitting diode array (Quantum Devices, Barneveld, WI) from postnatal day (p) 10 to p25. Sham-treated rats were restrained, but not treated with 830 nm light. Retinal metabolic state, function and morphology were assessed at p30 by measurement of mitochondrial redox (NADH/FAD) state by 3D optical cryo-imaging, electroretinography (ERG), spectral-domain optical coherence tomography (SD-OCT), and histomorphometry. PBM preserved retinal metabolic state, retinal function, and retinal morphology in PBM-treated animals compared to the sham-treated group. PBM protected against the disruption of the oxidation state of the mitochondrial respiratory chain observed in sham-treated animals. Scotopic ERG responses over a range of flash intensities were significantly greater in PBM-treated rats compared to sham controls. SD-OCT studies and histological assessment showed that PBM preserved the structural integrity of the retina. These findings demonstrate for the first time a direct effect of NIR PBM on retinal mitochondrial redox status in a well-established model of retinal disease. They show that chronic proteotoxic stress disrupts retinal bioenergetics resulting in mitochondrial dysfunction, and retinal degeneration and that therapies normalizing mitochondrial metabolism have considerable potential for the treatment of retinal degenerative disease

Follicular fluid high density lipoprotein-associated micronutrient levels are associated with embryo fragmentation during IVF

To investigate whether follicular fluid lipid-soluble micronutrients are associated with embryo morphology parameters during IVF. Follicle fluid and oocytes were obtained prospectively from 81 women. Embryo morphology parameters were used as surrogate markers of oocyte health. HDL lipids and lipid-soluble micronutrients were analyzed by high-pressure liquid chromatography. Non-parametric bi-variate analysis and multivariable ordinal logistic regression models were employed to examine associations between biochemical and embryo morphology parameters. Follicular fluid HDL cholesterol (r = −0.47, p < 0.01), α-tocopherol (r = −0.41, p < 0.01), δ-tocopherol (r = −0.38, p < 0.05) and β-cryptoxanthine (r = −0.42, p < 0.01) are negatively correlated with embryo fragmentation. Ordinal logistic regression models indicate that a 0.1 μmol/L increase in β-cryptoxanthine, adjusted for γ-tocopherol, is associated with a 75% decrease in the cumulative odds of higher embryo fragmentation (p = 0.010). Follicular fluid HDL micronutrients may play an important role in the development of the human oocyte as evident by embryo fragmentation during IVF

Genomic and molecular characterization of preterm birth.

Preterm birth (PTB) complications are the leading cause of long-term morbidity and mortality in children. By using whole blood samples, we integrated whole-genome sequencing (WGS), RNA sequencing (RNA-seq), and DNA methylation data for 270 PTB and 521 control families. We analyzed this combined dataset to identify genomic variants associated with PTB and secondary analyses to identify variants associated with very early PTB (VEPTB) as well as other subcategories of disease that may contribute to PTB. We identified differentially expressed genes (DEGs) and methylated genomic loci and performed expression and methylation quantitative trait loci analyses to link genomic variants to these expression and methylation changes. We performed enrichment tests to identify overlaps between new and known PTB candidate gene systems. We identified 160 significant genomic variants associated with PTB-related phenotypes. The most significant variants, DEGs, and differentially methylated loci were associated with VEPTB. Integration of all data types identified a set of 72 candidate biomarker genes for VEPTB, encompassing genes and those previously associated with PTB. Notably, PTB-associated genes RAB31 and RBPJ were identified by all three data types (WGS, RNA-seq, and methylation). Pathways associated with VEPTB include EGFR and prolactin signaling pathways, inflammation- and immunity-related pathways, chemokine signaling, IFN-γ signaling, and Notch1 signaling. Progress in identifying molecular components of a complex disease is aided by integrated analyses of multiple molecular data types and clinical data. With these data, and by stratifying PTB by subphenotype, we have identified associations between VEPTB and the underlying biology

Cohesin is required for higher-order chromatin conformation at the imprinted IGF2-H19 locus

Cohesin is a chromatin-associated protein complex that mediates sister chromatid cohesion by connecting replicated DNA molecules. Cohesin also has important roles in gene regulation, but the mechanistic basis of this function is poorly understood. In mammalian genomes, cohesin co-localizes with CCCTC binding factor (CTCF), a zinc finger protein implicated in multiple gene regulatory events. At the imprinted IGF2-H19 locus, CTCF plays an important role in organizing allele-specific higher-order chromatin conformation and functions as an enhancer blocking transcriptional insulator. Here we have used chromosome conformation capture (3C) assays and RNAi-mediated depletion of cohesin to address whether cohesin affects higher order chromatin conformation at the IGF2-H19 locus in human cells. Our data show that cohesin has a critical role in maintaining CTCF-mediated chromatin conformation at the locus and that disruption of this conformation coincides with changes in IGF2 expression. We show that the cohesin-dependent, higher-order chromatin conformation of the locus exists in both G1 and G2 phases of the cell cycle and is therefore independent of cohesin's function in sister chromatid cohesion. We propose that cohesin can mediate interactions between DNA molecules in cis to insulate genes through the formation of chromatin loops, analogous to the cohesin mediated interaction with sister chromatids in trans to establish cohesion

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century