Cortical Complexity in Cetacean Brains

Cetaceans (dolphins, whales, and porpoises) have a long, dramatically divergent evolutionary history compared with terrestrial mammals. Throughout their 55–60 million years of evolution, cetaceans acquired a compelling set of characteristics that include echolocation ability (in odontocetes), complex auditory and communicative capacities, and complex social organization. Moreover, although cetaceans have not shared a common ancestor with primates for over 90 million years, they possess a set of cognitive attributes that are strikingly convergent with those of many primates, including great apes and humans. In contrast, cetaceans have evolved a highly unusual combination of neurobiological features different from that of primates. As such, cetacean brains offer a critical opportunity to address questions about how complex behavior can be based on very different neuroanatomical and neurobiological evolutionary products. Cetacean brains and primate brains are arguably most meaningfully conceived as alternative evolutionary routes to neurobiological and cognitive complexity. In this article, we summarize data on brain size and hemisphere surface configuration in several cetacean species and present an overview of the cytoarchitectural complexity of the cerebral cortex of the bottlenose dolphin

Structural genetic variation and dyslipidemia among men in the multicenter aids cohort study

While highly active antiretroviral therapy has resulted in slowing the rate of progression to AIDS among individuals infected with human immunodeficiency virus, it has also resulted in detrimental metabolic lipid changes. As this dyslipidemia is not observed for all individuals receiving antiviral therapy, genetic factors likely influence the increased susceptibility for some. We designed this study to investigate the role of human gene copy number variation (CNV) in therapy associated dyslipidemia and risk assessment as well as investigating mRNA expression levels to identify new genetic variants associated with this lipid dysfunction. A custom multiplex ligation dependent probe amplification assay was developed to analyze CNV of reverse cholesterol transport pathway (RCT) genes within individuals (n=320) enrolled in the Multicenter AIDS Cohort Study (MACS). The resulting analysis demonstrated that CNV was present in extremely low levels within these genes as the only loss identified and verified was observed for CETP in one individual. To further identify lipid metabolism associated genes, blood-derived RNA from 437 MACS participants was analyzed using the Illumina Human HT-12 microarray. Significant transcripts were present only for variation in HDL-C and Triglyceride levels with 4 differentially expressed transcripts (HDC, CPA3, GATA2 & SLC45A3) repeatedly identified. Finally, to determine if CNV can alter the functionality of single nucleotide polymorphism (SNP) genotyping, we analyzed SNPs in regions with/without CNV by Fluorescence Polarization, TaqMan SNP genotyping assays and Sanger Sequencing. SNPs in regions of no CNV were observed to have 3 distinct genotype groups but in the presence of CNV, this distinction was lost resulting in a continuous spread of allele values. These results show that CNV is not a major factor in the development of antiviral therapy-associated dyslipidemia. Other genetic variants, such as HDC, may explain some of the variability. Furthermore, when CNV is present it hinders the ability to SNP genotype when using the standard assumption of three genotype groups. As antiretroviral therapy is becoming more available for the over 35 million living with HIV-1, identification of factors leading to antiviral-associated dyslipidemia is important for Public Health. Here, we have identified genes that could serve as markers for lipid level changes helping physicians custom tailor therapy and care for these individuals

Nutritional status and clinical outcome in postterm neonates undergoing surgery for congenital heart disease.

OBJECTIVE: Poor growth is a common complication in infants with congenital heart disease. There has been much focus on low birth weight as having increased risk of adverse outcomes following neonatal heart surgery. In this study, we examined whether preoperative nutritional status, measured by admission weight-for-age z score, was associated with postoperative clinical outcome. DESIGN: Retrospective case series. SETTING: Pediatric Cardiac ICU at the Royal Brompton Hospital. PATIENTS: Neonates undergoing surgery for congenital heart disease. Those undergoing ductus arteriosus ligation alone were excluded. Children with coexisting noncardiac morbidity were excluded. Outcome variables included prevalence of postoperative complications (including sepsis, delayed chest closure, renal impairment, and necrotizing enterocolitis), duration of ventilation, intensive care stay, postoperative mortality, and mortality at 1 year after surgery. INTERVENTIONS: None. Analysis of patient data only. MEASUREMENTS AND MAIN RESULTS: Two hundred forty-eight neonates fulfilled the entry criteria. Median (interquartile range) age was 7 days (2-15 d), median (interquartile range) weight was 3.3 kg (2.91-3.6 kg), and median weight-for-age z score was -0.77 (-1.44 to 0.01). Twenty-eight children (11%) had a weight-for-age z score of less than -2. There was no evidence that children with lower weight-for-age z score had less severe surgery as measured by the Risk Adjustment for Congenital Heart Surgery 1 score. In multivariable regression analysis, the weight-for-age z at admission had strong correlation with the number of days free of respiratory support (invasive and noninvasive ventilation) at 28 days (p < 0.0001) and with all-cause mortality at 1 year (p = 0.001). CONCLUSIONS: Poor nutritional status as measured by weight-for-age z is associated with adverse short- and long-term outcomes in neonates undergoing surgery for congenital heart disease.This is the accepted manuscript. The final version is available at http://journals.lww.com/pccmjournal/Abstract/2015/06000/Nutritional_Status_and_Clinical_Outcome_in.7.aspx

September 11: Perspectives From the Field of Philanthropy -- Volume Three

Assesses the philanthropic sector's response to September 11 through interviews with leaders in the field. Provides lessons learned in the government-philanthropic relief effort, highlighting unresolved public policy issues. Includes recommendations

The Lantern Vol. 53, No. 2, Spring 1987

• The One • Homecoming-1946 • Puff • Victory • The Prelude • Playtime • There\u27s a Killer in My Heart • Who is Keats? • Relationships • It\u27s OK • Rasping • Wearers of Underwear • Conjecture • Look Her in the Eye • Counterpoint • When the Air is Biting • A Stream of Consciousness • Bach\u27s Concerto in E • Tomorrow Morn • Ruminations on Bob Dylan • Last Night a Dream • Stephen • A Baseball Story • I Am Sorry • And Baby Makes Two • Next on Mr. Steinbeck\u27s Itinerary • Upon Visiting the Nursing Home • Taps for Ralph • Yes, I Believe • The Morning After • Conversation • Dear Man • Autumn Leaveshttps://digitalcommons.ursinus.edu/lantern/1130/thumbnail.jp

Free Fatty Acids Rewire Cancer Metabolism in Obesity-Associated Breast Cancer via Estrogen Receptor and mTOR Signaling

Obesity is a risk factor for postmenopausal estrogen receptor alpha (ERα)-positive (ER+) breast cancer. Molecular mechanisms underlying factors from plasma that contribute to this risk and how these mechanisms affect ERα signaling have yet to be elucidated. To identify such mechanisms, we performed whole metabolite and protein profiling in plasma samples from women at high risk for breast cancer, which led us to focus on factors that were differentially present in plasma of obese versus nonobese postmenopausal women. These studies, combined with in vitro assays, identified free fatty acids (FFA) as circulating plasma factors that correlated with increased proliferation and aggressiveness in ER+ breast cancer cells. FFAs activated both the ERα and mTOR pathways and rewired metabolism in breast cancer cells. Pathway preferential estrogen-1 (PaPE-1), which targets ERα and mTOR signaling, was able to block changes induced by FFA and was more effective in the presence of FFA. Collectively, these data suggest a role for obesity-associated gene and metabolic rewiring in providing new targetable vulnerabilities for ER+ breast cancer in postmenopausal women. Furthermore, they provide a basis for preclinical and clinical trials where the impact of agents that target ERα and mTOR signaling cross-talk would be tested to prevent ER+ breast cancers in obese postmenopausal women

Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report.

We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease

Uso de jogos didáticos como ferramenta de ensino de doenças parasitárias: Use of didactic games as a tool for teaching parasitic diseases

As doenças parasitárias representam um grande problema de saúde pública no Brasil. Acometem principalmente populações com precárias condições de saneamento básico, sendo mais prevalente entre jovens, o que pode acometer o desenvolvimento físico e intelectual dos mesmos. Este trabalho consiste em um estudo transversal aplicado em uma escola do município Betim-MG que propõe intervenções educativas para pré-escolares por meio de jogos didáticos acerca de prevalentes parasitoses e estratégias importantes para preveni-las, atuando na promoção da saúde e desenvolvimento de responsabilidade social. A partir disso, foi desenvolvido um jogo de tabuleiro adaptado às doenças parasitárias para ensinar hábitos de saúde como prevenção de tais doenças. Aplicou-se um questionário pré e pós-teste em 253 alunos do 4º e 5º ano do ensino fundamental, para avaliar a eficácia do jogo quanto à educação em saúde, além de uma aula expositiva no primeiro encontro, com intervalo de uma semana entre as 3 etapas. Os resultados do questionário pós-teste foram significativamente superiores aos do pré-teste, mostrando melhora significativa dos conhecimentos dos alunos acerca das doenças parasitológicas e hábitos saudáveis para preveni-las. O clima competitivo saudável, a interação em equipe, a associação com o cotidiano e as dinâmicas diferentes daquelas propostas em sala de aula contribuíram para que os resultados fossem positivos, demonstrando a eficiência do jogo como ferramenta de ensino para as doenças parasitárias

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts