Enhancer SINEs Link Pol III to Pol II Transcription in Neurons

Spatiotemporal regulation of gene expression depends on the cooperation of multiple mechanisms, including the functional interaction of promoters with distally located enhancers. Here, we show that, in cortical neurons, a subset of short interspersed nuclear elements (SINEs) located in the proximity of activity-regulated genes bears features of enhancers. Enhancer SINEs (eSINEs) recruit the Pol III cofactor complex TFIIIC in a stimulus-dependent manner and are transcribed by Pol III in response to neuronal depolarization. Characterization of an eSINE located in proximity to the Fos gene (FosRSINE1) indicated that the FosRSINE1-encoded transcript interacts with Pol II at the Fos promoter and mediates Fos relocation to Pol II factories, providing an unprecedented molecular link between Pol III and Pol II transcription. Strikingly, knockdown of the FosRSINE1 transcript induces defects of both cortical radial migration in vivo and activity-dependent dendritogenesis in vitro, demonstrating that FosRSINE1 acts as a strong enhancer of Fos expression in diverse physiological contexts

Is there any gender difference in epidemiology, clinical presentation and co-morbidities of non-functioning pituitary adenomas? A prospective survey of a National Referral Center and review of the literature

Purpose: Gender differences in patients diagnosed with non-functioning Pituitary Adenomas (NFPA) in a National Referral Center for Pituitary Tumors at the Federico II University of Naples, Italy. Methods: Patients newly diagnosed with non-functioning sellar masses found on pituitary Magnetic Resonance Imaging from January 1st 2016 to December 31th 2018 underwent anthropometric measurements, basal evaluation of pituitary function, and metabolic assessment. Fatty live index (FLI) and visceral adiposity index (VAI) were calculated. Results: Seventy-three patients (35 males, 51.1 ± 17.0 years; 38 females, 41.8 ± 18.1 years) presented with NFPA. Lesions > 1 cm (85.7% vs. 47.3%; χ2 = 10.26, p = 0.001) and hypopituitarism (77.1% vs. 7.9%; χ2 = 33.29, p = 0.001) were more frequent in males than females. The highest sizes of pituitary adenomas were significantly associated with male gender (OR = 1.05, p = 0.049; R2 = 0.060; IC 1.00–1.10). Headache (62.8% vs. 31.6%; χ2 = 5.96, p = 0.015) and visual field deficits (57.1% vs. 26.3%; χ2 = 5.93, p = 0.015) were significantly more frequent in males than in females. There was no sex difference in obesity prevalence, but the metabolic syndrome was more common among males than females (60.6% vs. 26.3%; χ2 = 7.14, p = 0.001). FLI was also higher in males (69.6 ± 27.3 vs. 49.2 ± 31.3; p < 0.001), while there were no differences in VAI. Conclusions: Apart from the possible delay in the diagnosis induced by the gender differences in symptom presentation, the higher prevalence of macroadenomas amongst NFPA in males compared with females let to hypothesize a key role of the sex hormone profile as predictive factors of their biological behavior and metabolic profile. Further studies are, however, mandatory to better support the influence of gender differences on onset, progression, and metabolic consequences of NFPA

Failure by congestion of pedicled and free flaps for reconstruction of lower limbs after trauma: the role of negative-pressure wound therapy

Lower limb reconstruction with pedicled or free flaps can be commonly compromised by venous insufficiency. This complication often leads to partial/complete flap necrosis and increases the risk of superinfection. Negative-pressure wound therapy (NPWT) is known to increase local blood flow, decrease edema, promote tissue granulation, and reduce the likelihood of soft tissue infection. This study aims to evaluate the effectiveness of NPWT in the treatment of congested pedicled and free flaps of the lower limb after reconstructions in lower limb traumas. A retrospective analysis was performed on four congested (pedicled and free) flaps on the lower limbs. NPWT was applied in all cases after partial flap debridement. NPWT was able to improve and resolve tissue edema and venous insufficiency, avoid further flap necrosis, and promote granulation. On NPWT removal, a split-thickness skin graft was applied on the wound, achieving complete and uneventful healing. NPWT is a useful instrument in managing flaps affected by venous insufficiency in lower limb reconstruction, although larger studies are necessary to better define the effectiveness and indications of NPWT in this setting

Stepwise shortening of agalsidase beta infusion duration in Fabry disease: Clinical experience with infusion rate escalation protocol

Background: Although enzyme replacement therapy with agalsidase beta resulted in a variety of clinical benefits, life-long biweekly intravenous infusion may impact on patients’ quality of life. Moreover, regular infusions are time-consuming: although a stepwise shortening of infusion duration is allowed up to a minimum of 1.5 hr, in most centers it remains ≥3 hr, and no data exists about the safety and tolerability of agalsidase beta administration at maximum tolerated infusion rate. Methods: In this study, we reported our experience with a stepwise infusion rate escalation protocol developed in our center in a cohort of 53 Fabry patients (both already receiving and treatment-naΪve), and explored factors predictive for the infusion rate increase tolerability. Results: Fifty-two patients (98%) reduced infusion duration ≤3 hr; of these, 38 (72%) even reached a duration ≤2 hr. We found a significant difference between the mean duration reached by already treated and naΪve patients (p <.01). More severely affected patients (male patients and those with lower enzyme activity) received longer infusions for higher risk of infusion-associated reactions (IARs). A significant correlation between anti-agalsidase antibodies and IARs was found. Conclusion: Our infusion rate escalation protocol is safe and could improve patient compliance, satisfaction and quality of life

Indeterminacy of Spatiotemporal Cardiac Alternans

Cardiac alternans, a beat-to-beat alternation in action potential duration (at the cellular level) or in ECG morphology (at the whole heart level), is a marker of ventricular fibrillation, a fatal heart rhythm that kills hundreds of thousands of people in the US each year. Investigating cardiac alternans may lead to a better understanding of the mechanisms of cardiac arrhythmias and eventually better algorithms for the prediction and prevention of such dreadful diseases. In paced cardiac tissue, alternans develops under increasingly shorter pacing period. Existing experimental and theoretical studies adopt the assumption that alternans in homogeneous cardiac tissue is exclusively determined by the pacing period. In contrast, we find that, when calcium-driven alternans develops in cardiac fibers, it may take different spatiotemporal patterns depending on the pacing history. Because there coexist multiple alternans solutions for a given pacing period, the alternans pattern on a fiber becomes unpredictable. Using numerical simulation and theoretical analysis, we show that the coexistence of multiple alternans patterns is induced by the interaction between electrotonic coupling and an instability in calcium cycling.Comment: 20 pages, 10 figures, to be published in Phys. Rev.

Characterization of Evidence for Human System Risk Assessment

Understanding the kinds of evidence available and using the best evidence to answer a question is critical to evidenced-based decision-making, and it requires synthesis of evidence from a variety of sources. Categorization of human system risks in spaceflight, in particular, focuses on how well the integration and interpretation of all available evidence informs the risk statement that describes the relationship between spaceflight hazards and an outcome of interest. A mature understanding and categorization of these risks requires: 1) sufficient characterization of risk, 2) sufficient knowledge to determine an acceptable level of risk (i.e., a standard), 3) development of mitigations to meet the acceptable level of risk, and 4) identification of factors affecting generalizability of the evidence to different design reference missions. In the medical research community, evidence is often ranked by increasing confidence in findings gleaned from observational and experimental research (e.g., "levels of evidence"). However, an approach based solely on aspects of experimental design is problematic in assessing human system risks for spaceflight. For spaceflight, the unique challenges and opportunities include: (1) The independent variables in most evidence are the hazards of spaceflight, such as space radiation or low gravity, which cannot be entirely duplicated in terrestrial (Earth-based) analogs, (2) Evidence is drawn from multiple sources including medical and mission operations, Lifetime Surveillance of Astronaut Health (LSAH), spaceflight research (LSDA), and relevant environmental & terrestrial databases, (3) Risk metrics based primarily on LSAH data are typically derived from available prevalence or incidence data, which may limit rigorous interpretation, (4) The timeframe for obtaining adequate spaceflight sample size (n) is very long, given the small population, (5) Randomized controlled trials are unattainable in spaceflight, (6) Collection of personal and environmental data on the astronaut population may create opportunities for advanced analytics and human-environment modeling that goes beyond that achieved in isolated experimental designs; and (7) Translation of relevant research to operations is a complex, transdisciplinary enterprise in which the approach must apply across the physical, biological, behavioral, and social sciences. The approach to synthesizing evidence must address both source and fidelity of data, and reflect the most general attributes of quality of evidence in science and engineering: reliability and validity. The authors are developing a two-factor approach which includes the various kinds of evidence required to understand risks and for the integrated interpretation of all evidence that is essential to develop standards and countermeasures. A unified framework for aggregating and assessing different kinds of evidence provides a consistent, traceable, evidence-based decision-making process to translate research to operations in an environment where engineers, scientists, physicians, and managers all engage in analyzing the trade space of vehicle design, standards, requirements and solutions for spaceflight

Subject preferences of fifth-grade children.

Thesis (Ed.M.)--Boston University N.B.:Pages 155 and 309 are missing from original thesis

Ptilomycalin A, crambescidin 800 and related new highly cytotoxic guanidine alkaloids from the starfishes Fromia monilis and Celerina heffernani

Two novel pentacyclic guanidine alkaloids, celeromycalin 3 and fromiamycalin 4, have been isolated from the New Caledonian starfishes Celerina heffernani and Fromia monilis, respectively. The new compounds exhibited an high cytotoxic activity like the previous crambescidins. These complex pentacyclic guanidines are typical sponges metabolites and their occurence in starfishes is noteworthy. Fromia monilis also contained the less active component 5, made up from an hydroxyspermidine residue linked to a long chain omega-hydroxyacid

Workload measurement in a communication application operated through a P300-based brain-computer interface

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