What are the Effects of Maternal Obesity on Synaptic Function in the Maternal and Offspring Hippocampus?

Obesity is a global epidemic that is associated with several adverse health consequences. In addition, there is also a growing prevalence of obesity in pregnancy. Maternal obesity places the fetus in an abnormal in utero condition that can produce alterations in development leading to permanent programming of physiological systems. Obesity is also associated with cognitive dysfunction, which calls for investigations into its effects on the hippocampus, a brain area involved in learning and memory. Long-term potentiation (LTP), a neurophysiological correlate for learning and memory, can be examined in hippocampal slices. This study aimed to fill in the gap in literature regarding the effect of obesity on hippocampal synaptic plasticity in female rats, and maternal obesity effects on offspring hippocampal synaptic plasticity. Female Sprague-Dawley rats were fed either a control diet (CD), or a high-fat diet (HFD; 40% of calories from saturated fat) for 16 weeks. Impaired glucose tolerance and greater retroperitoneal fat pad weight indicated an obese phenotype in HFD rats; as well, the modified diet led to impaired LTP: CD rats had 10% more potentiation in amplitude, and 11% more potentiation in slope than HFD rats. Offspring were weaned onto control diet at post-natal day 21. Reduced success rates for achieving LTP, and lowered magnitudes of mean LTP in the offspring, strongly suggest that maternal obesity may have compromised hippocampal synaptic plasticity, and warrants further study

Genetische und biochemische Charakterisierung von Nup192p - ein essentielles zentrales Nukleoporin des Kernporenkomplexes

Ein Hauptmerkmal eukaryotischer Zellen ist der von einer Kernmembran umschlossene Zellkern. Der regulierte Molekülaustausch zwischen Zellkern und Zytoplasma wird durch die in der Kernhülle liegenden Kernporenkomplexe (NPCs) ermöglicht. In der Hefe S. cerevisiae sind zwar alle am Aufbau des NPCs beteiligten Nukleoporine identifiziert, aber nur teilweise charakterisiert. Die vorliegende Arbeit beschäftigt sich mit Nup192p, einem der größten und eines der wenigen essentiellen Nukleoporine der Hefe S. cerevisiae ist. Um mehr über Funktion, Lage und Struktur von Nup192p zu erfahren, wurden genetische und biochemische Analysen durchgeführt. Die Ergebnisse dieser Arbeit zeigen, dass Nup192p auf genetischer Ebene spezifisch mit dem essentiellen Nsp1p-Nup49p-Nup57p-Nic96p-Komplex, dem essentiellen Nup84p-Komplex sowie mit Nup188p interagiert. Mittels Affinitätschromatographie und Western Blot Analyse konnte gezeigt werden, dass die genetischen Interaktionen zwischen Nup192p und Nup188p bzw. zwischen Nup192p und Nsp1p, Nup49p sowie Nic96p auf biochemischer Ebene direkten Interaktionen entsprechen. Dagegen sind die biochemischen Interaktionen zwischen Nup192p und dem Nup84p-Komplex schwächer ausgeprägt. Dies könnte bedeuten, dass Nup192p und der Nup84p-Komplexes aufeinander folgende oder überlappende Funktion in der NPC-Biogenese besitzen könnten. Die Ergebnisse unterstützen das Modell, dass Nup192p ein zentraler und essentieller struktureller Bestandteil der Speichen-Ring-Struktur ist. In dieser Umgebung könnte Nup192p Bestandteile des zentralen Transportkanals, z.B. den Nsp1p-Komplex, über Nic96p und Nup188p mit transmembranen Kernporenproteinen, wie Pom152p verbinden. Als möglicher Bestandteil des Speichen-Ring-Komplexes könnte Nup192p eine stabilisierende Funktion besitzen. Während der NPC-Biogenese könnte Nup192p als ein Gerüst fungieren und das Einfügen der mit Nup192p interagierenden Nukleoporine am richtigen Ort ermöglichen oder erleichtern

Fact Sheet: Conducting effective skill building workshops

Workshops that build both research and clinical skills are popular learning events in primary health care. They are cost effective compared with individual training activities and provide a means of connecting the material to be learned to the leaders' context, as well as providing opportunities for group interaction

Occurrence of Aceria tosichella in Brazil

O objetivo deste trabalho foi avaliar a ocorrência de Aceria tosichella Keifer (Prostigmata: Eriophyidae), ácaro-do-enrolamento-do-trigo, no Rio Grande do Sul. Amostras para detectar espécimes de A. tosichella foram coletadas em lavouras de trigo, milho e aveia e em potenciais gramíneas hospedeiras em 46 localidades, em outubro de 2006 e em agosto e outubro de 2007. Amostras de trigo tambÚm foram coletadas em casas de vegetaþÒo na Embrapa Trigo, Passo Fundo, RS. EspÚcimes de A. tosichella foram encontradas em amostras de trigo de Passo Fundo, Palmeira das Missões, São Luís Gonzaga e Santo Antonio das Missões. Sintomas de infestação de A. tosichella foram observados somente em condições de casa de vegetação. Este é o primeiro registro de A. tosichella no Brasil e o segundo na América do Sul.The objective of this work was to evaluate the occurrence of Aceria tosichella Keifer (Prostigmata: Eriophyidae), the wheat curl mite, in Rio Grande do Sul, Brazil. Samples to detect A. tosichella specimens were collected in wheat, corn, oat crops and potential host grasses in 46 localities, in October 2006, August and October 2007. Samples of wheat were also collected in experimental greenhouses at Embrapa Trigo, Passo Fundo, RS, Brazil. A. tosichella specimens were found in wheat samples from Passo Fundo, Palmeira das Missões, São Luís Gonzaga, and Santo Antônio das Missões, RS, Brazil. Symptoms due to A. tosichella infestations were observed only in greenhouse conditions. This is the first report of A. tosichella in Brazil and the second in South America

A personalized platform identifies trametinib plus zoledronate for a patient with KRAS-mutant metastatic colorectal cancer

Colorectal cancer remains a leading source of cancer mortality worldwide. Initial response is often followed by emergent resistance that is poorly responsive to targeted therapies, reflecting currently undruggable cancer drivers such as KRAS and overall genomic complexity. Here, we report a novel approach to developing a personalized therapy for a patient with treatment-resistant metastatic KRAS-mutant colorectal cancer. An extensive genomic analysis of the tumor's genomic landscape identified nine key drivers. A transgenic model that altered orthologs of these nine genes in the Drosophila hindgut was developed; a robotics-based screen using this platform identified trametinib plus zoledronate as a candidate treatment combination. Treating the patient led to a significant response: Target and nontarget lesions displayed a strong partial response and remained stable for 11 months. By addressing a disease's genomic complexity, this personalized approach may provide an alternative treatment option for recalcitrant disease such as KRAS-mutant colorectal cancer

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

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin