Combined loss of proapoptotic genes Bak or Bax with Bim synergizes to cause defects in hematopoiesis and in thymocyte apoptosis

The proapoptotic members of the Bcl-2 family can be subdivided into members that contain several Bcl-2 homology (BH) domains and those that contain only the BH3 domain. Although it is known that BH3-only proteins and the multi-BH domain proteins, Bak and Bax, are essential for programmed cell death, the overlapping role of these two subgroups has not been examined in vivo. To investigate this, we generated Bak/Bim and Bax/Bim double deficient mice. We found that although Bax−/−Bim−/−, but not Bak−/−Bim−/−, mice display webbed hind and front paws and malocclusion of the incisors, both groups of mice present with dysregulated hematopoiesis. Combined loss of Bak and Bim or Bax and Bim causes defects in myeloid and B-lymphoid development that are more severe than those found in the single knock-out mice. Bak−/−Bim−/− mice have a complement of thymocytes that resembles those in control mice, whereas Bax−/−Bim−/− mice are more similar to Bim−/− mice. However, thymocytes isolated from Bak−/−Bim−/− or Bax−/−Bim−/− mice are markedly more resistant to apoptotic stimuli mediated by the intrinsic pathway as compared with thymocytes from single-knockout mice. These data suggest an essential overlapping role for Bak or Bax and Bim in the intrinsic apoptotic pathway

Screening and Assessment in Trauma-Informed Care: An Evidence-Based Practice Project

This Evidence-Based Practice (EBP) project examined the following question: What interprofessional and occupational therapy screening and assessment measures are used in trauma-informed care and what are their psychometric characteristics

Flotillin microdomains interact with the cortical cytoskeleton to control uropod formation and neutrophil recruitment

The association between flotillin microdomains and the cortical cytoskeleton controls myosin IIa activation and neutrophil chemotaxis

Pro-apoptotic Bid is required for the resolution of the effector phase of inflammatory arthritis

Rheumatoid arthritis is an autoimmune disease characterized by hyperplasia of the synovial lining and destruction of cartilage and bone. Recent studies have suggested that a lack of apoptosis contributes to the hyperplasia of the synovial lining and to the failure in eliminating autoreactive cells. Mice lacking Fas or Bim, two pro-apoptotic proteins that mediate the extrinsic and intrinsic death cascades, respectively, develop enhanced K/BxN serum transfer-induced arthritis. Since the pro-apoptotic protein Bid functions as an intermediate between the extrinsic and intrinsic apoptotic pathways, we examined the role that it plays in inflammatory arthritis. Mice deficient in Bid (Bid-/-) show a delay in the resolution of K/BxN serum transfer-induced arthritis. Bid-/- mice display increased inflammation, bone destruction, and pannus formation compared to wild-type mice. Furthermore, Bid-/- mice have elevated levels of CXC chemokine and IL-1β in serum, which are associated with more inflammatory cells throughout the arthritic joint. In addition, there are fewer apoptotic cells in the synovium of Bid-/- compared to Wt mice. These data suggest that extrinsic and intrinsic apoptotic pathways cooperate through Bid to limit development of inflammatory arthritis

Deriving a lexicon for a precision grammar from language documentation resources: a case study of Chintang

Language documentation projects typically invest a lot of effort in creating digitized lexical resources, which are used in the creation of dictionaries and in the glossing of collected texts. We present and evaluate a methodology for repurposing such a lexical resource developed for Chintang (ISO639-3: ctn), a language of Nepal, for use with a precision implemented grammar developed in the DELPH-IN formalism. The target lexicon, when combined with a set of morphological rules, achieves 57% type-level coverage and 50% token-level coverage of held-out texts, while maintaining a feature-level accuracy F-measure of 70%. As lexicon development is typically one of the most expensive aspects of creating a precision grammar, this represents a significant savings of effort

Mechanism Description - Mindd 1: Prediabetes, Delay Discounting and Executive Function (Epstein/Bickel)

Impulsivity will be measured using the following discounting tasks: a) Adjusting Amount Discounting Task b) Adjusting Delay Discounting Tas

Expected Association with Behavior - Mindd 1: Prediabetes, Delay Discounting and Executive Function (Epstein/Bickel)

The prevention of Type 2 diabetes (T2D) for someone with prediabetes requires making behavior changes to prevent future disease progression. The rational approach for someone with prediabetes would be to eat healthier, be more active, lose weight, and manage comorbidities (e.g., hypertension and dyslipidemia). The Diabetes Prevention Program and other lifestyle change programs have shown that diabetes can be prevented with sustained behavior change (Group, 2003). Many individuals with Type 2 diabetes discount the future, and make choices that maximize current pleasure and short-term gain. Not surprisingly, the majority of patients with chronic disease do not adhere to their medication regimens. Discounting of the future may cause an individual with prediabetes not to make choices needed to improve their future health. Delay discounting (DD) describes the choice of smaller immediate versus larger delayed rewards, a behavioral process related to a wide variety of health behaviors. Study researchers believe that DD also functions as a proximal marker related to self-regulation for those with prediabetes, and modifying DD may contribute to prevention of T2D

Hypothesis - Mindd 1: Prediabetes, Delay Discounting and Executive Function (Epstein/Bickel)

Relative to the less adherent prediabetics, those with prediabetes who are more adherent to behavioral and medical prescriptions will discount less and exhibit greater activation in two regions, lateral prefrontal cortex (LPC), and anterior cingulate cortex (AC) related to the ability to delay gratification

Experimental Methods - Mindd 1: Prediabetes, Delay Discounting and Executive Function (Epstein/Bickel)

This section describes the study related procedures participants will be asked to undergo