Role of Ras signaling in hematological malignancies and the potential role of inhibitors of the Ras signaling cascade as anti-cancer agents

[no abstract

Facing Facts: Facial Injuries from Stand-up Electric Scooters

Background Stand-up electric scooters (SES) are a popular public transportation method. Numerous safety concerns have arisen since their recent introduction. Methods A retrospective chart review was performed to identify patients presenting to the emergency departments in Indianapolis, who sustained SES-related injuries. Results A total of 89 patients were included in our study. The average patient age was 29 ± 12.9 years in a predominantly male cohort (65.2%). No patient was documented as wearing a helmet during the event of injury. Alcohol intoxication was noted in 14.6% of accidents. Falling constituted the leading trauma mechanism (46.1%). Injuries were most common on Saturday (24.7%) from 14h00 to 21h59 (55.1%). Injury types included: abrasions/contusions (33.7%), fractures (31.5%), lacerations (27.0%), or joint injuries (18.0%). The head and neck region (H&N) was the most frequently affected site (42.7%). Operative management under general anesthesia was necessary for 13.5% of injuries. Nonoperative management primarily included conservative orthopedic care (34.8%), pain management with nonsteroidal anti-inflammatory drugs (NSAIDs) (34.8%) and/or opioids (4.5%), bedside laceration repairs (27.0%), and wound dressing (10.1%). Individuals sustaining head and neck injuries were more likely to be older (33.8 vs. 25.7 years, p=0.003), intoxicated by alcohol (29.0% vs. 3.9%, p=0.002), and requiring CT imaging (60.5% vs. 9.8%, p <0.001). Conclusion Although SESs provide a convenient transportation modality, unregulated use raises significant safety concerns. More data need to be collected to guide future safety regulations

3D chemical characterization of frozen hydrated hydrogels using ToF-SIMS with argon cluster sputter depth profiling

Hydrogels have been used extensively in bioengineering as artificial cell culture supports. Investigation of the interrelationship between cellular response to the hydrogel and its chemistry ideally requires methods that allow characterization without labels and can map species in three dimensional to follow biomolecules adsorbed to, and absorbed into, the open structure before and during culture. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) has the potential to be utilized for through thickness characterization of hydrogels. The authors have established a simple sample preparation procedure to successfully achieve analysis of frozen hydrated hydrogels using ToF-SIMS without the need for dry glove box entry equipment. They demonstrate this on a poly(2-hydroxyethyl methacrylate) (pHEMA) film where a model protein (lysozyme) is incorporated using two methods to demonstrate how protein distribution can be determined. A comparison of lysozyme incorporation is made between the situation where the protein is present in a polymer dip coating solution and where lysozyme is in an aqueous medium in which the film is incubated. It is shown that protonated water clusters H(H2O)nþ where n ¼ 5–11 that are indicative of ice are detected through the entire thickness of the pHEMA. The lysozyme distribution through the pHEMA hydrogel films can be determined using the intensity of a characteristic amino acid secondary ion fragment

Neuronal Modulation of Brown Adipose Activity Through Perturbation of White Adipocyte Lipogenesis [preprint]

White adipose tissue (WAT) secretes factors to communicate with other metabolic organs to maintain energy homeostasis. We previously reported that perturbation of adipocyte de novo lipogenesis (DNL) by deletion of fatty acid synthase (FASN) causes expansion of sympathetic neurons within white adipose tissue (WAT) and the appearance of beige adipocytes. Here we report evidence that white adipocyte DNL activity is also coupled to neuronal regulation and thermogenesis in brown adipose tissue (BAT). Induced deletion of FASN in all adipocytes in mature mice (iAdFASNKO) enhanced sympathetic innervation and neuronal activity as well as UCP1 expression in both WAT and BAT. In contrast, selective ablation of FASN in brown adipocytes of mice (iUCP1FASNKO) failed to modulate sympathetic innervation and the thermogenic program in BAT. Surprisingly, DNL in brown adipocytes was also dispensable in maintaining euthermia when UCP1FASNKO mice were cold-exposed. These results indicate that DNL in white adipocytes influences long distance signaling to BAT, which can modify BAT sympathetic innervation and expression of genes involved in thermogenesis

Addressing data integration challenges to link ecological processes across scales

Data integration is a statistical modeling approach that incorporates multiple data sources within a unified analytical framework. Macrosystems ecology – the study of ecological phenomena at broad scales, including interactions across scales – increasingly employs data integration techniques to expand the spatiotemporal scope of research and inferences, increase the precision of parameter estimates, and account for multiple sources of uncertainty in estimates of multiscale processes. We highlight four common analytical challenges to data integration in macrosystems ecology research: data scale mismatches, unbalanced data, sampling biases, and model development and assessment. We explain each problem, discuss current approaches to address the issue, and describe potential areas of research to overcome these hurdles. Use of data integration techniques has increased rapidly in recent years, and given the inferential value of such approaches, we expect continued development and wider application across ecological disciplines, especially in macrosystems ecology

Bibliometric Analysis of Gender Authorship Trends and Collaboration Dynamics over 30 Years of Spine 1985 to 2015

Study Design. A bibliometric analysis. Objective. The aim of this article was to study bibliometric changes over the last 30 years of Spine. These trends are important regarding academic publication productivity. Summary of Background Data. Inflation in authorship number and other bibliometric variables has been described in the scientific literature. The issue of author gender is taking on increasing importance, as efforts are being made to close the gender gap. Methods. From 1985 to 2015, 10-year incremental data for several bibliometric variables were collected, including author gender. Standard bivariate statistical analyses were performed. Trends over time were assessed by the Cochran linear trend. A P < 0.05 was considered statistically significant. Results. Inclusion criteria were met for 1566 manuscripts. The majority of the manuscripts were from North America (51.2%), Europe (25.2%), and Asia (20.8%). The number of manuscripts, authors, countries, pages, and references all increased from 1985 to 2015. There was a slight increase in female first authors over time (17.5% to 18.4%, P = 0.048). There was no gender change over time for corresponding authors (14.3% to 14.0%, P = 0.29). There was an 88% increase in the percentage of female first authors having male corresponding authors (P = 0.00004), and a 123% increase in male first authors having female corresponding authors (P = 0.0002). The 14% to 18% of female authors in Spine is higher than the ∼5% female membership of the Scoliosis Research Society and North American Spine Society. Conclusion. Manuscripts in Spine over the past 30 years have shown a significant increase in the number of authors, collaborating institutions and countries, printed pages, references, and number of times each manuscript was cited. There has been a mild increase in female first authorship, but none in corresponding authorship. Increases in female authorship will likely require recruitment of more females into the discipline rather than providing females in the discipline with authorship opportunities. Level of Evidence: N/

Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques.

Broadly neutralizing monoclonal antibodies protect against infection with HIV-1 in animal models, suggesting that a vaccine that elicits these antibodies would be protective in humans. However, it has not yet been possible to induce adequate serological responses by vaccination. Here, to activate B cells that express precursors of broadly neutralizing antibodies within polyclonal repertoires, we developed an immunogen, RC1, that facilitates the recognition of the variable loop 3 (V3)-glycan patch on the envelope protein of HIV-1. RC1 conceals non-conserved immunodominant regions by the addition of glycans and/or multimerization on virus-like particles. Immunization of mice, rabbits and rhesus macaques with RC1 elicited serological responses that targeted the V3-glycan patch. Antibody cloning and cryo-electron microscopy structures of antibody-envelope complexes confirmed that immunization with RC1 expands clones of B cells that carry the anti-V3-glycan patch antibodies, which resemble precursors of human broadly neutralizing antibodies. Thus, RC1 may be a suitable priming immunogen for sequential vaccination strategies in the context of polyclonal repertoires