EBV-positive Hodgkin lymphoma is associated with suppression of p21cip1/waf1 and a worse prognosis

<p>Abstract</p> <p>Background</p> <p>About 30-50% of Hodgkin lymphomas (HLs) harbor the Epstein-Barr virus (EBV), but the impact of EBV infection on clinical outcomes has been unclear. EBV-encoded small RNAs (<it>EBER</it>s) are presented in all EBV-infected cells, but their functions are still less understood.</p> <p>Results</p> <p><it>EBER1 </it>was transfected into two HL cell lines, KMH2 and L428, and microarrays were used to screen for <it>EBER1</it>-induced changes. We found that <it>EBER1 </it>suppressed <it>p21</it>^cip1/waf1transcription in HL cell lines. In addition, positive regulators of <it>p21</it>^cip1/waf1transcription, such as p53, EGR1, and STAT1, were decreased. Suppression of <it>p21</it>^cip1/waf1in the <it>EBER1</it>⁺HL cell lines was associated with increased resistance to histone deacetylase inhibitors or proteasome inhibitors, drugs known to cause apoptosis by increasing p21^cip1/waf1levels. On biopsy specimens, EBV⁺HLs had weaker expression of both p21^cip1/waf1and active caspase 3. Clinically, suppression of p21^cip1/waf1in EBV⁺HLs was associated with a worse 2-year disease-free survival rate (45% for EBV⁺HLs <it>vs</it>. 77% for EBV^-HLs, <it>p </it>= 0.002).</p> <p>Conclusion</p> <p>Although the underlying mechanisms are still relatively unclear, <it>EBER1 </it>inhibits <it>p21</it>^cip1/waf1transcription and prevents apoptosis through down-regulation of p53, EGR1, and STAT1. The anti-apoptotic activity of <it>EBER1 </it>may be important in the rescue of Reed-Sternberg cells from drug-induced apoptosis and in the clinical behaviors of EBV⁺HLs.</p

Urbane Dörfer: räumliche Entgrenzungsprozesse und parzellierte Gemeinschaftsformen

A-Dorf liegt im Einzugsgebiet von zwei Großstädten und besteht seit dem Jahr 953. Ursprünglich und für den größten Teil seiner Geschichte war das Dorf eine bäuerliche Siedlung, hat aber seit den 1950er-Jahren einen deutlichen sozialstrukturellen Wandel durchgemacht. Die Einwohnerschaft hat sich seit den 1970er-Jahren durch Neubaugebiete nahezu verdoppelt. Insbesondere die Zugezogenen weisen eine eher pragmatische, zweckrationale Ortsbindung auf und sind überlokal orientiert. Ihr Lebens- und Aktionsraum geht weit über die Grenzen des Dorfes hinaus. Dies hat auch Konsequenzen für dörfliche Formen der Gemeinschaftsbildung, die inzwischen weit stärker Ergebnisse von individuellen Selektionen sind und nicht mehr durch Strukturen des Kontextes erzwungen werden. Sehr deutlich wurde dies z. B. bei den Beziehungen zu Nachbarn/ innen oder dörflichen Vereinen und Interessengruppen. »Die« Dorfgemeinschaft im Singular wird ersetzt durch interessenspezifische Teilgemeinschaften.»A-Village« is located in the catchment area of two major cities and exists since 1953. Originally, and for the most part of its history, it was a rural village, but since the 1950s it went through a major change concerning its social structure. The number of inhabitants has almost doubled since the 1970s, due to housing estates. Especially the recent settlers have a more pragmatic and function-guided binding to the village and are globally orientated. Their space of living and action exceeds the narrow boundaries of the village to a greater extent. These facts have consequences for the way of forming communities, and are less the implications of contextual structures, but reflect more results of selections by individuals. This is evident, for example, in the case of relations with neighbours or associations and interest groups. The »village-community« in the singular is being replaced by segmented communities, which are being formed to serve special interests

Interoceptive awareness: MBSR training alters information processing of salience network

Mindfulness refers to a mental state of awareness of internal experience without judgment. Studies have suggested that each mindfulness practice may involve a unique mental state, but the underlying neurophysiological mechanisms remain unknown. Here we examined how distinct mindfulness practices after mindfulness-based intervention alter brain functionality. Specifically, we investigated the functional alterations of the salience network (SN) using functional magnetic resonance imaging (fMRI) among the two interoceptive mindfulness practices—breathing and body scan—associated with interoceptive awareness in fixed attention and shifted attention, respectively. Long-distance functional connectivity (FC) and regional homogeneity (ReHo) approaches were applied to measure distant and local neural information processing across various mental states. We hypothesized that mindful breathing and body scan would yield a unique information processing pattern in terms of long-range and local functional connectivity (FC). A total of 18 meditation-naïve participants were enrolled in an 8-week mindfulness-based stress reduction (MBSR) program alongside a waitlist control group (n = 14), with both groups undergoing multiple fMRI sessions during breathing, body scan and resting state for comparison. We demonstrated that two mindfulness practices affect both the long-distance FCSN and the local ReHo, only apparent after the MBSR program. Three functional distinctions between the mindfulness practices and the resting state are noted: (1) distant SN connectivity to occipital regions increased during the breathing practice (fixed attention), whereas the SN increased connection with the frontal/central gyri during the body scan (shifting attention); (2) local ReHo increased only in the parietal lobe during the body scan (shifting attention); (3) distant and local connections turned into a positive correlation only during the mindfulness practices after the MBSR training, indicating a global enhancement of the SN information processing during mindfulness practices. Though with limited sample size, the functional specificity of mindfulness practices offers a potential research direction on neuroimaging of mindfulness, awaiting further studies for verification

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities

Graphene-Based Nanocomposites for Energy Storage

Since the first report of using micromechanical cleavage method to produce graphene sheets in 2004, graphene/graphene-based nanocomposites have attracted wide attention both for fundamental aspects as well as applications in advanced energy storage and conversion systems. In comparison to other materials, graphene-based nanostructured materials have unique 2D structure, high electronic mobility, exceptional electronic and thermal conductivities, excellent optical transmittance, good mechanical strength, and ultrahigh surface area. Therefore, they are considered as attractive materials for hydrogen (H2) storage and high-performance electrochemical energy storage devices, such as supercapacitors, rechargeable lithium (Li)-ion batteries, Li–sulfur batteries, Li–air batteries, sodium (Na)-ion batteries, Na–air batteries, zinc (Zn)–air batteries, and vanadium redox flow batteries (VRFB), etc., as they can improve the efficiency, capacity, gravimetric energy/power densities, and cycle life of these energy storage devices. In this article, recent progress reported on the synthesis and fabrication of graphene nanocomposite materials for applications in these aforementioned various energy storage systems is reviewed. Importantly, the prospects and future challenges in both scalable manufacturing and more energy storage-related applications are discussed

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead