State-Dependent Differences in Functional Connectivity in Young Children With Autism Spectrum Disorder

AbstractBackgroundWhile there is increasing evidence of altered brain connectivity in autism, the degree and direction of these alterations in connectivity and their uniqueness to autism has not been established. The aim of the present study was to compare connectivity in children with autism to that of typically developing controls and children with developmental delay without autism.MethodsWe assessed EEG spectral power, coherence, phase lag, Pearson and partial correlations, and epileptiform activity during the awake, slow wave sleep, and REM sleep states in 137 children aged 2 to 6years with autism (n=87), developmental delay without autism (n=21), or typical development (n=29).FindingsWe found that brain connectivity, as measured by coherence, phase lag, and Pearson and partial correlations distinguished children with autism from both neurotypical and developmentally delayed children. In general, children with autism had increased coherence which was most prominent during slow wave sleep.InterpretationFunctional connectivity is distinctly different in children with autism compared to samples with typical development and developmental delay without autism. Differences in connectivity in autism are state and region related. In this study, children with autism were characterized by a dynamically evolving pattern of altered connectivity

Targeted knock-down of miR21 primary transcripts using snoMEN vectors induces apoptosis in human cancer cell lines

We have previously reported an antisense technology, 'snoMEN vectors', for targeted knock-down of protein coding mRNAs using human snoRNAs manipulated to contain short regions of sequence complementarity with the mRNA target. Here we characterise the use of snoMEN vectors to target the knock-down of micro RNA primary transcripts. We document the specific knock-down of miR21 in HeLa cells using plasmid vectors expressing miR21-targeted snoMEN RNAs and show this induces apoptosis. Knock-down is dependent on the presence of complementary sequences in the snoMEN vector and the induction of apoptosis can be suppressed by over-expression of miR21. Furthermore, we have also developed lentiviral vectors for delivery of snoMEN RNAs and show this increases the efficiency of vector transduction in many human cell lines that are difficult to transfect with plasmid vectors. Transduction of lentiviral vectors expressing snoMEN targeted to pri-miR21 induces apoptosis in human lung adenocarcinoma cells, which express high levels of miR21, but not in human primary cells. We show that snoMEN-mediated suppression of miRNA expression is prevented by siRNA knock-down of Ago2, but not by knock-down of Ago1 or Upf1. snoMEN RNAs colocalise with Ago2 in cell nuclei and nucleoli and can be co-immunoprecipitated from nuclear extracts by antibodies specific for Ago2

Direct cloning of double-stranded RNAs from RNase protection analysis reveals processing patterns of C/D box snoRNAs and provides evidence for widespread antisense transcript expression

We describe a new method that allows cloning of double-stranded RNAs (dsRNAs) that are generated in RNase protection experiments. We demonstrate that the mouse C/D box snoRNA MBII-85 (SNORD116) is processed into at least five shorter RNAs using processing sites near known functional elements of C/D box snoRNAs. Surprisingly, the majority of cloned RNAs from RNase protection experiments were derived from endogenous cellular RNA, indicating widespread antisense expression. The cloned dsRNAs could be mapped to genome areas that show RNA expression on both DNA strands and partially overlapped with experimentally determined argonaute-binding sites. The data suggest a conserved processing pattern for some C/D box snoRNAs and abundant expression of longer, non-coding RNAs in the cell that can potentially form dsRNAs

Nontemplated Nucleotide Additions Distinguish the Small RNA Composition in Cells from Exosomes

Functional biomolecules, including small noncoding RNAs (ncRNAs), are released and transmitted between mammalian cells via extracellular vesicles (EVs), including endosome-derived exosomes. The small RNA composition in cells differs from exosomes, but underlying mechanisms have not been established. We generated small RNA profiles by RNA sequencing (RNA-seq) from a panel of human B cells and their secreted exosomes. A comprehensive bioinformatics and statistical analysis revealed nonrandomly distributed subsets of microRNA (miRNA) species between B cells and exosomes. Unexpectedly, 3′ end adenylated miRNAs are relatively enriched in cells, whereas 3′ end uridylated isoforms appear overrepresented in exosomes, as validated in naturally occurring EVs isolated from human urine samples. Collectively, our findings suggest that posttranscriptional modifications, notably 3′ end adenylation and uridylation, exert opposing effects that may contribute, at least in part, to direct ncRNA sorting into EVs.T.W. is supported by VIDI 91711366. D.M.P. is supported by personal Dutch Cancer Society research award (KWF-5510). This work was funded by AICR grant 11-0157 and NWO-VENI 91696087 awarded to D.M.P

The Blueprint: #BlackInTheArts

The Black Musicians Coalition is pleased to present The Blueprint: #blackinthearts, an interdisciplinary Black History celebration that incorporates new and old aspects of Black art and the impact that it has on current music and art styles. The production features an original arrangement of the Black National Anthem and multiple choreographed dance numbers all by KSU students as well as performances by KSU SOM faculty member Tyrone Jackson. This event is brought together by a collaboration of student leaders from each school in the College of the Arts: Music, Theater, Dance and Visual Arts. The acts highlight the students’ contributions to their disciplinary fields as well as their experiences being Black and in the arts.https://digitalcommons.kennesaw.edu/musicprograms/2373/thumbnail.jp

The immune system as a foundation for immunologic therapy and hematologic malignancies: a historical perspective.

In this review we aim to provide a historical overview of the immunotherapeutic approaches which have been developed for the treatment of hematological malignancies. After briefly summarizing the development of the theory of cancer immune surveillance, we describe how initial studies discovering the efficacy of the immune-mediated graft-versus-tumor effects after allogeneic hematopoietic cell transplantation led to new transplantation approaches (termed non-myeloablative transplantation) relying almost exclusively on graft-versus-tumor effects for tumor eradication. We then summarize important steps in the development of tumor vaccines and autologous adoptive immunotherapy in patients with hematological malignancies. Finally, we describe historical discoveries leading to the recent success with monoclonal antibodies as treatment for lymphomas, chronic lymphocytic leukemia, and acute myeloid leukemia

Physical fitness, fatigue, and quality of life after liver transplantation

Fatigue is often experienced after liver transplantation. The aims of this cross-sectional study were to assess physical fitness (cardiorespiratory fitness, neuromuscular fitness, body composition) in liver transplant recipients and to explore whether physical fitness is related to severity of fatigue. In addition, we explored the relationship between physical fitness and health-related quality of life. Included were 18 patients 1–5 years after transplantation (aged 48.0 ± 11.8 years) with varying severity of fatigue. Peak oxygen uptake during cycle ergometry, 6-min walk distance, isokinetic muscle strength of the knee extensors, body mass index, waist circumference, skinfold thickness, severity of fatigue, and health-related quality of life were measured. Cardiorespiratory fitness in the liver transplant recipients was on average 16–34% lower than normative values (P ≤ 0.05). Furthermore, the prevalence of obesity seemed to be higher than in the general population (17 vs. 10%). We found no deficit in neuromuscular fitness. Cardiorespiratory fitness was the only fitness component that was related with severity of fatigue (rs = −0.61 to rs = -0.50, P ≤ 0.05). Particularly cardiorespiratory fitness was related with several aspects of health-related quality of life (rs = 0.48 to rs = 0.70, P ≤ 0.05). Results of our study imply that cardiorespiratory fitness and body composition are impaired in liver transplant recipients and that fitness is related with severity of fatigue (only cardiorespiratory fitness) and quality of life (particularly cardiorespiratory fitness) in this group. These findings have implications for the development of rehabilitation programs for liver transplant recipients

Researcher identity : exploring the transformatory power of the research experience

In consumer research we frequently focus on the phenomenon of transformation; be that the transformatory effects of a particular consumption community or the great body of work being carried out under the banner of Transformative Consumer Research. However there is a particular transformation which occurs in the field of interpretivist consumer research that, we would argue, is overlooked – that of researcher transformation. We present as data our reflexive considerations on the ways in which our own research with vulnerable consumers has affected and changed us. We consider short term transformations in the field, reflecting on the various ways that researcher identity is carefully managed and negotiated to fit with the social-cultural setting. We also consider longer term transformations and discuss the enduring impact of the research process – the people we have met, the homes we have visited and the stories we have heard. By reflecting on the shaping of identities ‘in the field’ we aim to deepen our appreciation of the interpretive consumer research process and contribute to theoretical understanding of transformative identity research

Effects of temperature on the transmission of Yersinia Pestis by the flea, Xenopsylla Cheopis, in the late phase period

<p>Abstract</p> <p>Background</p> <p>Traditionally, efficient flea-borne transmission of <it>Yersinia pestis</it>, the causative agent of plague, was thought to be dependent on a process referred to as blockage in which biofilm-mediated growth of the bacteria physically blocks the flea gut, leading to the regurgitation of contaminated blood into the host. This process was previously shown to be temperature-regulated, with blockage failing at temperatures approaching 30°C; however, the abilities of fleas to transmit infections at different temperatures had not been adequately assessed. We infected colony-reared fleas of <it>Xenopsylla cheopis </it>with a wild type strain of <it>Y. pestis </it>and maintained them at 10, 23, 27, or 30°C. Naïve mice were exposed to groups of infected fleas beginning on day 7 post-infection (p.i.), and every 3-4 days thereafter until day 14 p.i. for fleas held at 10°C, or 28 days p.i. for fleas held at 23-30°C. Transmission was confirmed using <it>Y. pestis</it>-specific antigen or antibody detection assays on mouse tissues.</p> <p>Results</p> <p>Although no statistically significant differences in per flea transmission efficiencies were detected between 23 and 30°C, efficiencies were highest for fleas maintained at 23°C and they began to decline at 27 and 30°C by day 21 p.i. These declines coincided with declining median bacterial loads in fleas at 27 and 30°C. Survival and feeding rates of fleas also varied by temperature to suggest fleas at 27 and 30°C would be less likely to sustain transmission than fleas maintained at 23°C. Fleas held at 10°C transmitted <it>Y. pestis </it>infections, although flea survival was significantly reduced compared to that of uninfected fleas at this temperature. Median bacterial loads were significantly higher at 10°C than at the other temperatures.</p> <p>Conclusions</p> <p>Our results suggest that temperature does not significantly effect the per flea efficiency of <it>Y. pestis </it>transmission by <it>X. cheopis</it>, but that temperature is likely to influence the dynamics of <it>Y. pestis </it>flea-borne transmission, perhaps by affecting persistence of the bacteria in the flea gut or by influencing flea survival. Whether <it>Y. pestis </it>biofilm production is important for transmission at different temperatures remains unresolved, although our results support the hypothesis that blockage is not necessary for efficient transmission.</p