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Several studies suggest poorer episodic memory among adults with overweight (OW) relative to those with healthy weight (HW); however, few have used food stimuli. To understand the salience of food-related items when assessing memory, we adapted an episodic memory task, by replacing some non-food words with snack foods. Participants were 96 weight-loss seeking adults with OW compared to 48 adults with HW from the community matched on age, gender, ethnicity, and education. Overall memory ability was similar, although a trend showed the adults with HW performed better than adults with OW on immediate recall (d = 0.32, p = 0.07). However, there were clear differences in the use of learning strategies. Adults with HW utilized sematic clustering more effectively than adults with OW during all test phases (ds = 0.44-0.62; ps ≤ 0.01). Adults with HW also utilized serial clustering more effectively (d = 0.51; p < 0.01). Adults with HW showed better semantic clustering for both food and non-food words during immediate and short delay recall (ds = 0.42-0.78; ps ≤ 0.01) but semantic clustering was only better for the non-food category at long delay (d = 0.55; p < 0.01). These results show that adults with OW utilized less efficient learning strategies throughout the task and food-related content may impact learning. Clinically, these findings may suggest that weight-loss treatments should consider incorporating the teaching of learning and memory strategies to help increase utilization of new skills., Competing Interests: Declaration of competing interest No conflict of interest was declared., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose of Review: Recent research has highlighted executive function and neurocognitive deficits among individuals with eating and weight disorders, identifying a potential target for treatment. Treatments targeting executive function for eating and weight disorders are emerging. This review aims to summarize the recent literature evaluating neurocognitive/executive function-oriented treatments for eating and weight disorders and highlights additional work needed in this area., Recent Findings: Cognitive remediation therapy (CRT) for anorexia nervosa has been the most extensively studied neurocognitive treatment for eating disorders. Results demonstrate that CRT improves executive function and may aid in the reduction of eating disorder symptomatology. Computer training programs targeting modifying attention and increasing inhibition are targeting reduction of binge eating and weight loss with modest success. Neurocognitive treatments are emerging and show initial promise for eating and weight disorders. Further research is necessary to determine whether these treatments can be used as stand-alone treatments or whether they need to be used as an adjunct to or in conjunction with other evidence-based treatments to improve outcomes.

Background: The Papanicolaou (Pap) screen has been successful in reducing cervical cancer; but exhibits low sensitivity when detecting cervical dysplasia. Use of molecular biomarkers in Pap tests may improve diagnostic accuracy., Design: Monoclonal antibodies to Minichromosome Maintenance Protein 2 (MCM2) and DNA Topoisomerase II α (TOP2A) were selected for use in IHC based on their ability to differentiate normal from diseased cervical tissues in tissue microarrays. Enhanced Green Fluorescent Protein Western blot analysis was used to help identify binding epitopes specific to MCM2 and TOP2A antibody clones. Antibody affinity was determined by solution phase affinity measurement and immunohistochemistry was performed using high affinity MCM2 or TOP2A antibodies on serial histological sections., Results: Antibody clones to MCM2 and TOP2A clones were selected based on their ability to detect over expression in abnormal cervical epithelia. In IHC, MCM2-27C5.6 and MCM2-26H6.19 demonstrated superior staining in abnormal cervical tissue over the MCM2-CRCT2.1 antibody. A combination of MCM2 and TOP2A antibodies showed greater staining when compared to staining with any of the antibodies alone on serial histological sections. Distinct linear epitopes were elucidated for each of the MCM2 and TOP2A clones. Affinity values (Kd) for MCM2 or TOP2A antibodies had a similar range. In a research study, the MCM2 and TOP2A (BD ProEx™ C) antibody cocktail showed increased epithelia staining with increasing dysplasia. The use of BD ProEx™ C in combination with H&E staining enhanced immunohistochemical discrimination of dysplastic and non-dysplastic FFPE cervical tissue specimens., Conclusions: BD ProEx™ C containing MCM2 and TOP2A antibodies showed strong specific nuclear staining that correlated with increased dysplasia and lesion severity. Enhanced performance of the antibodies was linked to their unique topography recognition. BD ProEx™ C incorporates antibodies that enhance detection of CIN2+ cervical disease., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The chromosomal translocation t(8;21) often found in acute myeloid leukemia generates an oncogenic fusion protein AML1-ETO. This chimeric oncoprotein disrupts wild-type AML1 function and dysregulates genes important for normal myelopoiesis. Monoclonal antibodies that can capture and detect the AML1-ETO fusion protein would help with early diagnosis and treatment prognosis of acute myeloid leukemia. We report the development of murine monoclonal antibodies (MAbs) that specifically bind epitopes encoded by either AML1 or ETO. Since alignment to the human ETO protein indicated almost 100% homology to the mouse ortholog, a strategy was needed to instruct humoral immunity in mice to focus and respond to self-epitopes. Our strategy to develop capture/detector reagents involved producing MAbs that would bind to epitopes within the non-fused myelopic protein (i.e., either AML1 or ETO). This included a process to select antibodies for their ability to also recognize the translocated chromosomal AML1-ETO fusion protein and to identify complementary capture/detector antibody pairs. Construction of a peptide hapten-carrier complex and use of a rapid immunization protocol resulted in IgM-IgG ETO specific MAbs. These MAbs bound specifically to a recombinant form of AML1-ETO fusion protein expressed in HEK and to an endogenous AML1-ETO form of the fusion protein expressed in Kasumi-1. We report the development of murine hybridoma MAbs derived from immunizations with a peptide "self-epitope." Our findings provide a potential strategy to instruct humoral immunity in mice to focus and respond to self-epitopes. This strategy has been validated with the oncogenic fusion protein AML1-ETO involved in acute myeloid leukemia.

The Raf/MEK/ERK kinase cascade is pivotal in transmitting signals from membrane receptors to transcription factors that control gene expression culminating in the regulation of cell cycle progression. This cascade can prevent cell death through ERK2 and p90(Rsk) activation and phosphorylation of apoptotic and cell cycle regulatory proteins. The PI3K/Akt kinase cascade also controls apoptosis and can phosphorylate many apoptotic and cell cycle regulatory proteins. These pathways are interwoven as Akt can phosphorylate Raf and result in its inactivation, and Raf can be required for the antiapoptotic effects of Akt. In this study, the effects of activated Raf (Raf-1, A-Raf and B-Raf) and PI3K/Akt proteins on abrogation of cytokine dependence in FL5.12 hematopoietic cells were examined. Activated Raf, PI3K or Akt expression, by themselves, did not readily relieve cytokine dependence. The presence of activated Raf and PI3K/Akt increased the isolation of factor-independent cells from 400- to 2500-fold depending upon the particular combination examined. The individual effects of activated Raf and Akt on proliferation, apoptosis and autocrine growth factor synthesis were further examined with hormone-inducible constructs (Delta Raf-1:AR and Delta Akt:ER*(Myr(+)). Activation of either Raf or Akt hindered cell death; however, both proliferation and maximal synthesis of autocrine cytokines were dependent upon activation of both signaling pathways. The effects of small molecular weight inhibitors on DNA synthesis and cytokine gene expression were also examined. The PI3K inhibitor, LY294002, inhibited growth and cytokine gene expression. This effect could be synergistically increased by addition of the MEK inhibitor UO126. These cells will be useful in elucidating the interactions between Raf/MEK/ERK and PI3K/Akt cascades in proliferation, apoptosis, and leukemogenesis, as well as evaluating the efficacy of signal transduction inhibitors that target these cascades.

This chapter will focus on introduction of various wild type (WT) and mutant genes into cells by DNA transfection. Techniques for analysis of the inheritance, expression, and biological effects of the introduced genes will be described. Various strong and weak points about three different techniques of stable gene transfer, including calcium-phosphate DNA precipitation, transfection via liposomes, and transfection via electroporation, will be discussed.

Elucidation of signal transduction pathways involved in proliferation, cell cycle progression and the regulation of apoptosis has shown great promise in the treatment of various diseases including neoplastic, inflammatory, autoimmune, immunodeficiency, arthritic and neurodegenerative disorders. By understanding how these signal transduction pathways function, chemotherapeutic targets may be identified which will suppress or eliminate the disease. This information may eventually be translated into therapy, which would either eliminate or safely contain the patient's disease. This chapter will focus on basic tissue culture techniques which are used to elucidate signal transduction pathways. Furthermore, this chapter will provide a general background for understanding how gene transfer techniques can be used to elucidate signal transduction pathways as well as various pitfalls commonly encountered with their usage.

This chapter will focus on understanding how various wild type (WT), dominant negative (DN), constitutively active (CA), and conditionally active (COND) oncogenes, as well as antisense (AS) genes contained in retroviral vectors may be used to elucidate signal transduction pathways. We will describe methods to introduce these genes into cells and subsequent analysis of inheritance, expression, and biological effects of the genes introduced. Furthermore, we will discuss various strong points about each of these different types of constructs, how they can be used to elucidate signal transduction, apoptotic, and drug resistance pathways as well as various pitfalls commonly encountered with their usage.