Does time equal vision in the acute treatment of a cohort of AQP4 and MOG optic neuritis?

Objective To investigate whether visual disability which is known to accumulate by poor recovery from optic neuritis (ON) attacks can be lessened by early treatment, we investigated whether the time from symptom onset to high-dose IV methylprednisolone (IVMP) affected visual recovery. Methods: A retrospective study was performed in a consecutive cohort of patients following their first aquaporin-4 (AQP4)-IgG or myelin oligodendrocyte glycoprotein (MOG)-IgG-ON. Best-corrected visual acuity (BCVA) in ON eyes at 3 months (BCVA3mo) was correlated with time to IVMP (days). In cases of bilateral ON, 1 eye was randomly selected. Results: A total of 29 of 37 patients had ON (27 AQP4-seropositive neuromyelitis optica spectrum disorder [NMOSD] and 9 MOG-IgG-ON), 2 of whom refused treatment. Of the 27 patients included, 10 presented later than 7 days from onset. The median BCVA3mo of patients treated >7 days was 20/100 (interquartile range 20/100–20/200). Patients treated >7 days had an OR of 5.50 (95% CI 0.88–34.46, p = 0.051) of failure to regain 0.0 logMAR vision (20/20) and an OR of 10.0 (95% CI 1.39–71.9) of failure to regain 0.2 logMAR vision (20/30) (p = 0.01) compared with patients treated within 7 days. ROC analysis revealed that the optimal criterion of delay in IVMP initiation was ≤4 days, with a sensitivity and specificity of 71.4% and 76.9%, respectively. Conclusions: In this retrospective study of ON with AQP4 and MOG-IgG, even a 7-day delay in IVMP initiation was detrimental to vision. These results highlight the importance of early treatment for the long-term visual recovery in this group of patients. A prospective, multicenter study of the effects of timing of IVMP is currently underway. Classification of evidence: This study provides Class IV evidence that hyperacute treatment of AQP4 and MOG-ON with IVMP increases the chance for good visual recovery (20/20 vision) and that even a greater than 7-day delay in treatment is associated with a higher risk for poor visual recovery

The transcription factor Hey and nuclear lamins specify and maintain cell identity

The inability of differentiated cells to maintain their identity is a hallmark of age-related diseases. We found that the transcription factor Hey supervises the identity of differentiated enterocytes (ECs) in the adult Drosophila midgut. Lineage tracing established that Hey-deficient ECs are unable to maintain their unique nuclear organization and identity. To supervise cell identity, Hey determines the expression of nuclear lamins, switching from a stem-cell lamin configuration to a differentiated lamin configuration. Moreover, continued Hey expression is required to conserve large-scale nuclear organization. During aging, Hey levels decline, and EC identity and gut homeostasis are impaired, including pathological reprograming and compromised gut integrity. These phenotypes are highly similar to those observed upon acute targeting of Hey or perturbation of lamin expression in ECs in young adults. Indeed, aging phenotypes were suppressed by continued expression of Hey in ECs, suggesting that a Hey-lamin network safeguards nuclear organization and differentiated cell identity

Does \u2018bigger\u2019mean \u2018better\u2019? Pitfalls and shortcuts associated with big data for social research

\u2018Big data is here to stay.\u2019 This key statement has a double value: is an assumption as well as the reason why a theoretical reflection is needed. Furthermore, Big data is something that is gaining visibility and success in social sciences even, overcoming the division between humanities and computer sciences. In this contribution some considerations on the presence and the certain persistence of Big data as a socio-technical assemblage will be outlined. Therefore, the intriguing opportunities for social research linked to such interaction between practices and technological development will be developed. However, despite a promissory rhetoric, fostered by several scholars since the birth of Big data as a labelled concept, some risks are just around the corner. The claims for the methodological power of bigger and bigger datasets, as well as increasing speed in analysis and data collection, are creating a real hype in social research. Peculiar attention is needed in order to avoid some pitfalls. These risks will be analysed for what concerns the validity of the research results \u2018obtained through Big data. After a pars distruens, this contribution will conclude with a pars construens; assuming the previous critiques, a mixed methods research design approach will be described as a general proposal with the objective of stimulating a debate on the integration of Big data in complex research projecting

Low-dose retinoic acid enhances in vitro invasiveness of human oral squamous-cell-carcinoma cell lines

Retinoids inhibit the proliferation of several types of tumour cells, and are used for patients with several malignant tumours. In this study, we examined the effect of retinoic acids (RAs) on the invasive potentials of the oral squamous cell carcinoma (SCC) cells, BHY and HNt. BHY cells expressed all of retinoid nuclear receptors (RARα, β, γ, and RXRα) and cytoplasmic retinoic acid binding proteins (CRABP1 and CRABP2). HNt cells lacked the expression of RARβ, but expressed other nuclear receptors and CRABPs. All-trans retinoic acid (ATRA) and 13-cis retinoic acid (13-cisRA) (10−6and 10−7M) inhibited the growth of the cells, but low-dose ATRA and 13-cisRA (10−8M) marginally affected the growth of the cells. Surprisingly, low-dose RAs enhanced the activity of tissue-type plasminogen activator (tPA), and activated pro-matrix metalloproteinases (proMMP2 and proMMP9). Activation of proMMP2 and proMMP9 was inhibited by aprotinin, a serine-proteinase, tPA inhibitor. Furthermore, low-dose RAs enhanced the in vitro invasiveness of BHY cells. These results indicate that low-dose RAs enhances the in vitro invasiveness of oral SCC cells via an activation of proMMP2 and proMMP9 probably mediated by the induction of tPA. © 2001 Cancer Research Campaign http://www.bjcancer.co

Performance of Survivin mRNA as a Biomarker for Bladder Cancer in the Prospective Study UroScreen

BACKGROUND: Urinary biomarkers have the potential to improve the early detection of bladder cancer. Most of the various known markers, however, have only been evaluated in studies with cross-sectional design. For proper validation a longitudinal design would be preferable. We used the prospective study UroScreen to evaluate survivin, a potential biomarker that has multiple functions in carcinogenesis. METHODS/RESULTS: Survivin was analyzed in 5,716 urine samples from 1,540 chemical workers previously exposed to aromatic amines. The workers participated in a surveillance program with yearly examinations between 2003 and 2010. RNA was extracted from urinary cells and survivin was determined by Real-Time PCR. During the study, 19 bladder tumors were detected. Multivariate generalized estimation equation (GEE) models showed that β-actin, representing RNA yield and quality, had the strongest influence on survivin positivity. Inflammation, hematuria and smoking did not confound the results. Survivin had a sensitivity of 21.1% for all and 36.4% for high-grade tumors. Specificity was 97.5%, the positive predictive value (PPV) 9.5%, and the negative predictive value (NPV) 99.0%. CONCLUSIONS: In this prospective and so far largest study on survivin, the marker showed a good NPV and specificity but a low PPV and sensitivity. This was partly due to the low number of cases, which limits the validity of the results. Compliance, urine quality, problems with the assay, and mRNA stability influenced the performance of survivin. However, most issues could be addressed with a more reliable assay in the future. One important finding is that survivin was not influenced by confounders like inflammation and exhibited a relatively low number of false-positives. Therefore, despite the low sensitivity, survivin may still be considered as a component of a multimarker panel

Transcriptome Kinetics Is Governed by a Genome-Wide Coupling of mRNA Production and Degradation: A Role for RNA Pol II

Transcriptome dynamics is governed by two opposing processes, mRNA production and degradation. Recent studies found that changes in these processes are frequently coordinated and that the relationship between them shapes transcriptome kinetics. Specifically, when transcription changes are counter-acted with changes in mRNA stability, transient fast-relaxing transcriptome kinetics is observed. A possible molecular mechanism underlying such coordinated regulation might lay in two RNA polymerase (Pol II) subunits, Rpb4 and Rpb7, which are recruited to mRNAs during transcription and later affect their degradation in the cytoplasm. Here we used a yeast strain carrying a mutant Pol II which poorly recruits these subunits. We show that this mutant strain is impaired in its ability to modulate mRNA stability in response to stress. The normal negative coordinated regulation is lost in the mutant, resulting in abnormal transcriptome profiles both with respect to magnitude and kinetics of responses. These results reveal an important role for Pol II, in regulation of both mRNA synthesis and degradation, and also in coordinating between them. We propose a simple model for production-degradation coupling that accounts for our observations. The model shows how a simple manipulation of the rates of co-transcriptional mRNA imprinting by Pol II may govern genome-wide transcriptome kinetics in response to environmental changes

New Insights into Metabolic Properties of Marine Bacteria Encoding Proteorhodopsins

Proteorhodopsin phototrophy was recently discovered in oceanic surface waters. In an effort to characterize uncultured proteorhodopsin-exploiting bacteria, large-insert bacterial artificial chromosome (BAC) libraries from the Mediterranean Sea and Red Sea were analyzed. Fifty-five BACs carried diverse proteorhodopsin genes, and we confirmed the function of five. We calculate that proteorhodopsin-exploiting bacteria account for 13% of microorganisms in the photic zone. We further show that some proteorhodopsin-containing bacteria possess a retinal biosynthetic pathway and a reverse sulfite reductase operon, employed by prokaryotes oxidizing sulfur compounds. Thus, these novel phototrophs are an unexpectedly large and metabolically diverse component of the marine microbial surface water

A Modified View on Octocorals: Heteroxenia fuscescens Nematocysts Are Diverse, Featuring Both an Ancestral and a Novel Type

Cnidarians are characterized by the presence of stinging cells containing nematocysts, a sophisticated injection system targeted mainly at prey-capture and defense. In the anthozoan subclass Octocorallia nematocytes have been considered to exist only in low numbers, to be small, and all of the ancestral atrichous-isorhiza type. This study, in contrast, revealed numerous nematocytes in the octocoral Heteroxenia fuscescens. The study demonstrates the applicability of cresyl-violet dye for differential staining and stimulating discharge of the nematocysts. In addition to the atrichous isorhiza-type of nematocysts, a novel type of macrobasic-mastigophore nematocysts was found, featuring a shaft, uniquely comprised of three loops and densely packed arrow-like spines. In contrast to the view that octocorals possess a single type of nematocyst, Heteroxenia fuscescens features two distinct types, indicating for the first time the diversification and complexity of nematocysts for Octocorallia

Democracy, protest and public sphere in Russia after the 2011–2012 anti-government protests: digital media at stake

The 2011–2012 Russian protest mobilisations were largely enabled by the rise of social networks. Social and technological advancements paired to pave the way for the ‘biggest protests since the fall of USSR’. Ubiquitous and uncensored social media facilitated the networking and mobilisation for this protest activity: Liberal masses were able to share and discuss their grievances, unite and coordinate online for the offline protest. The digitally savvy protest public developed to confront the government, which appeared to be astonished by the scale of protest. Those mobilisations marked an important gap between the government’s conception of the society and the real state of resistance. This article studies three main hypotheses regarding the potential of the protest movement in Russia. The hypotheses were drawn from recent sociological, political and media studies on Russian resistance. Current research aims to contribute to the debate from the digital media perspective. It therefore evaluates three main assumptions: Digital media have the potential to empower, dependent upon the relevant political, social and economic factors; digital media isolates protest publics and therefore may be more useful for the government than the resistance; and recent censorship of digital media communication signals a tightening of both formal and informal restrictions against opposition and protest politics. This article uses theoretical and factual evidence on the limitations of democracy and the public sphere and conceptualises the government’s management of resistance in Russia during and after the 2011–2012 protests. It studies how the hybrid political regime in Russia balances restrictions on freedom of speech with strengthened state propaganda and how it mediates media oppression and invites self-censorship. Finally, it examines how the state communication watchdog has recently focused its attention at the digital realm. This move confirms the importance of the online protest communication for the Russian political environment. Yet the state’s acknowledgement of digital political resistance may lead to further oppression and curbing of this emerging component of Russian politics