Aerobic fitness is associated with greater white matter integrity in children

Aerobic fitness has been found to play a positive role in brain and cognitive health of children. Yet, many of the neural biomarkers related to aerobic fitness remain unknown. Here, using diffusion tensor imaging, we demonstrated that higher aerobic fitness was related to greater estimates of white matter microstructure in children. Higher fit 9- and 10-year-old children showed greater fractional anisotropy (FA) in sections of the corpus callosum, corona radiata, and superior longitudinal fasciculus, compared to lower fit children. The FA effects were primarily characterized by aerobic fitness differences in radial diffusivity, thereby raising the possibility that estimates of myelination may vary as a function of individual differences in fitness during childhood. White matter structure may be another potential neural mechanism of aerobic fitness that assists in efficient communication between gray matter regions as well as the integration of regions into networks. © 2014 Chaddock-Heyman, Erickson, Holtrop, Voss, Pontifex, Raine, Hillman and Kramer

Adjunct primer for the use of national comprehensive cancer network guidelines for the surgical management of cutaneous malignant melanoma patients

Recently, a Surveillance Epidemiology and End Results (SEER) survey of melanoma patterns of care by the Mayo Clinic, Scottsdale showed remarkable deviations from best practice patterns throughout the country. The study, which analyzed the SEER records of 35,126 stage I to III cutaneous malignant melanoma patients treated from 2004 to 2006, showed that adherence to National Comprehensive Cancer Network (NCCN) therapeutic resection margins occurred in less than 36% of patients. Similarly, considerable variation in the quality of melanoma care in the United States when assessed using 26 quality indicators drawn by a panel of melanoma experts was independently reported. These observations underscore the significant lack of adherence to published best practice patterns reflected by the NCCN guidelines. The untoward effects of these variations in practice pattern can have an inordinate impact on the survival of melanoma patients in whom long term outcomes are affected by the adequacy of surgical management. Thin malignant melanoma is curable; however, thick or node positive melanoma is often incurable. This outcome is determined not only by the stage at presentation but by the use of best practice patterns as reflected in current NCCN cutaneous melanoma practice guidelines

Transkingdom Networks: A Systems Biology Approach to Identify Causal Members of Host-Microbiota Interactions

Improvements in sequencing technologies and reduced experimental costs have resulted in a vast number of studies generating high-throughput data. Although the number of methods to analyze these "omics" data has also increased, computational complexity and lack of documentation hinder researchers from analyzing their high-throughput data to its true potential. In this chapter we detail our data-driven, transkingdom network (TransNet) analysis protocol to integrate and interrogate multi-omics data. This systems biology approach has allowed us to successfully identify important causal relationships between different taxonomic kingdoms (e.g. mammals and microbes) using diverse types of data

Early and Middle Holocene Hunter-Gatherer Occupations in Western Amazonia: The Hidden Shell Middens

We report on previously unknown early archaeological sites in the Bolivian lowlands, demonstrating for the first time early and middle Holocene human presence in western Amazonia. Multidisciplinary research in forest islands situated in seasonally-inundated savannahs has revealed stratified shell middens produced by human foragers as early as 10,000 years ago, making them the oldest archaeological sites in the region. The absence of stone resources and partial burial by recent alluvial sediments has meant that these kinds of deposits have, until now, remained unidentified. We conducted core sampling, archaeological excavations and an interdisciplinary study of the stratigraphy and recovered materials from three shell midden mounds. Based on multiple lines of evidence, including radiocarbon dating, sedimentary proxies (elements, steroids and black carbon), micromorphology and faunal analysis, we demonstrate the anthropogenic origin and antiquity of these sites. In a tropical and geomorphologically active landscape often considered challenging both for early human occupation and for the preservation of hunter-gatherer sites, the newly discovered shell middens provide evidence for early to middle Holocene occupation and illustrate the potential for identifying and interpreting early open-air archaeological sites in western Amazonia. The existence of early hunter-gatherer sites in the Bolivian lowlands sheds new light on the region's past and offers a new context within which the late Holocene "Earthmovers" of the Llanos de Moxos could have emerged. © 2013 Lombardo et al

Hepatitis C virus infects and perturbs liver stem cells

Hepatitis C virus (HCV) is the leading cause of death from liver disease. How HCV infection causes lasting liver damage and increases cancer risk remains unclear. Here, we identify bipotent liver stem cells as novel targets for HCV infection, and their erroneous differentiation as the potential cause of impaired liver regeneration and cancer development. We show 3D organoids generated from liver stem cells from actively HCV-infected individuals carry replicating virus and maintain low-grade infection over months. Organoids can be infected with a primary HCV isolate. Virus-inclusive single-cell RNA sequencing uncovered transcriptional reprogramming in HCV+ cells supporting hepatocytic differentiation, cancer stem cell development, and viral replication while stem cell proliferation and interferon signaling are disrupted. Our data add a new pathogenesis mechanism—infection of liver stem cells—to the biology of HCV infection that may explain progressive liver damage and enhanced cancer risk through an altered stem cell state

Readability estimates for commonly used health-related quality of life surveys

To estimate readability of seven commonly used health-related quality of life instruments: SF-36, HUI, EQ-5D, QWB-SA, HALex, Minnesota Living with Heart Failure Questionnaire (MLHFQ), and the NEI-VFQ-25. The Flesch–Kincaid (F–K) and Flesch Reading Ease (FRE) formulae were used to estimate readability for every item in each measure. The percentage of items that require more than 5 years of formal schooling according to F–K was 50 for the EQ-5D, 53 for the SF-36, 80 for the VFQ-25, 85 for the QWB-SA, 100 for the HUI, HALex, and the MLHFQ. The percentage of items deemed harder than “easy” according to FRE was 50 for the SF-36, 67 for the EQ-5D, 79 for the QWB-SA, 80 for the VFQ-25, 100 for the HUI, HALex, and the MLHFQ. All seven surveys have a substantial number of items with high readability levels that may not be appropriate for the general population

Teaching energy conservation as a unifying principle in physics

In this work we present the design and assessment of a teaching sequence aimed at introducing the principle of energy conservation at post-compulsory secondary school level (16-18 year olds). The proposal is based on the result of research into teaching-learning difficulties and on the analysis of the physics framework. Evidence is shown that this teaching sequence, together with the methodology used in the classroom, may result in students having a better grasp of the principle of energy conservation. Keywords Physics education · Energy conceptions · Teaching activitie

Comparison of Whole Blood and Peripheral Blood Mononuclear Cell Gene Expression for Evaluation of the Perioperative Inflammatory Response in Patients with Advanced Heart Failure

Background: Heart failure (HF) prevalence is increasing in the United States. Mechanical Circulatory Support (MCS) therapy is an option for Advanced HF (AdHF) patients. Perioperatively, multiorgan dysfunction (MOD) is linked to the effects of device implantation, augmented by preexisting HF. Early recognition of MOD allows for better diagnosis, treatment, and risk prediction. Gene expression profiling (GEP) was used to evaluate clinical phenotypes of peripheral blood mononuclear cells (PBMC) transcriptomes obtained from patients’ blood samples. Whole blood (WB) samples are clinically more feasible, but their performance in comparison to PBMC samples has not been determined. Methods: We collected blood samples from 31 HF patients (57¡15 years old) undergoing cardiothoracic surgery and 7 healthy age-matched controls, between 2010 and 2011, at a single institution. WB and PBMC samples were collected at a single timepoint postoperatively (median day 8 postoperatively) (25–75% IQR 7–14 days) and subjected to Illumina single color Human BeadChip HT12 v4 whole genome expression array analysis. The Sequential Organ Failure Assessment (SOFA) score was used to characterize the severity of MOD into low (# 4 points), intermediate (5–11), and high ($ 12) risk categories correlating with GEP. Results: Results indicate that the direction of change in GEP of individuals with MOD as compared to controls is similar when determined from PBMC versus WB. The main enriched terms by Gene Ontology (GO) analysis included those involved in the inflammatory response, apoptosis, and other stress response related pathways. The data revealed 35 significant GO categories and 26 pathways overlapping between PBMC and WB. Additionally, class prediction using machine learning tools demonstrated that the subset of significant genes shared by PBMC and WB are sufficient to train as a predictor separating the SOFA groups. Conclusion: GEP analysis of WB has the potential to become a clinical tool for immune-monitoring in patients with MO

The Effects of Biting and Pulling on the Forces Generated during Feeding in the Komodo Dragon (Varanus komodoensis)

In addition to biting, it has been speculated that the forces resulting from pulling on food items may also contribute to feeding success in carnivorous vertebrates. We present an in vivo analysis of both bite and pulling forces in Varanus komodoensis, the Komodo dragon, to determine how they contribute to feeding behavior. Observations of cranial modeling and behavior suggest that V. komodoensis feeds using bite force supplemented by pulling in the caudal/ventrocaudal direction. We tested these observations using force gauges/transducers to measure biting and pulling forces. Maximum bite force correlates with both body mass and total body length, likely due to increased muscle mass. Individuals showed consistent behaviors when biting, including the typical medial-caudal head rotation. Pull force correlates best with total body length, longer limbs and larger postcranial motions. None of these forces correlated well with head dimensions. When pulling, V. komodoensis use neck and limb movements that are associated with increased caudal and ventral oriented force. Measured bite force in Varanus komodoensis is similar to several previous estimations based on 3D models, but is low for its body mass relative to other vertebrates. Pull force, especially in the ventrocaudal direction, would allow individuals to hunt and deflesh with high success without the need of strong jaw adductors. In future studies, pull forces need to be considered for a complete understanding of vertebrate carnivore feeding dynamics

From L-Dopa to Dihydroxyphenylacetaldehyde: A Toxic Biochemical Pathway Plays a Vital Physiological Function in Insects

One protein in Aedes aegypti, classified into the aromatic amino acid decarboxylase (AAAD) family based on extremely high sequence homology (∼70%) with dopa decarboxylase (Ddc), was biochemically investigated. Our data revealed that this predicted AAAD protein use L-dopa as a substrate, as does Ddc, but it catalyzes the production of 3,4-dihydroxylphenylacetaldehyde (DHPAA) directly from L-dopa and apparently has nothing to do with the production of any aromatic amine. The protein is therefore named DHPAA synthase. This subsequently led to the identification of the same enzyme in Drosophila melanogaster, Anopheles gambiae and Culex quinquefasciatus by an initial prediction of putative DHPAA synthase based on sequence homology and subsequent verification of DHPAA synthase identity through protein expression and activity assays. DHPAA is highly toxic because its aldehyde group readily reacts with the primary amino groups of proteins, leading to protein crosslinking and inactivation. It has previously been demonstrated by several research groups that Drosophila DHPAA synthase was expressed in tissues that produce cuticle materials and apparent defects in regions of colorless, flexible cuticular structures have been observed in its gene mutants. The presence of free amino groups in proteins, the high reactivity of DHPAA with the free amino groups, and the genetically ascertained function of the Drosophila DHPAA synthase in the formation of colorless, flexible cuticle, when taken together, suggest that mosquito and Drosophila DHPAA synthases are involved in the formation of flexible cuticle through their reactive DHPAA-mediated protein crosslinking reactions. Our data illustrate how a seemingly highly toxic pathway can serve for an important physiological function in insects