CAR-NK Cells Effectively Target SARS-CoV-2-Spike-Expressing Cell Lines .

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is highly contagious and presents a significant public health issue. Current therapies used to treat coronavirus disease 2019 (COVID-19) include monoclonal antibody cocktail, convalescent plasma, antivirals, immunomodulators, and anticoagulants. The vaccines from Pfizer and Moderna have recently been authorized for emergency use, which are invaluable for the prevention of SARS-CoV-2 infection.

Comparing the Effectiveness of Education Versus Digital Cognitive Behavioral Therapy for Adults With Sickle Cell Disease: Protocol for the Cognitive Behavioral Therapy and Real-time Pain Management Intervention for Sickle Cell via Mobile Applications (CaRISMA) Study.

Background: Patients with sickle cell disease (SCD) experience significant medical and psychological stressors that affect their mental health, well-being, and disease outcomes. Digital cognitive behavioral therapy (CBT) has been used in other patient populations and has demonstrated clinical benefits. Although evidence-based, nonpharmacological interventions for pain management are widely used in other populations, these treatments have not been well studied in SCD.

Iterative tyrosine phosphorylation controls non-canonical domain utilization in Crk.

Crk, the prototypical member of a class of Src homology-2 (SH2) and Src homology-3 (SH3) domain containing proteins that controls the coordinated assembly of signaling complexes, is regulated by phosphorylation of Y221 in the linker region, which forms an intramolecular SH2-pY221 auto-clamp to interrupt SH2-N-terminal SH3 domain (SH3N) signaling. Here, we show using LC-MS/MS and by generating phospho-specific antibodies that, iteratively with Y221, the Crk C-terminal SH3 domain (SH3C) is routinely phosphorylated on Y239 and/or Y251 by several extracellular stimuli known to engage Crk. Although phosphorylation at Y221 auto-inhibits the Crk SH2, phosphorylation of the SH3C generates an unconventional phosphoSH3C-SH3N unit in which the SH3N is fully functional to bind polyproline type II ligands and the phosphoSH3C binds de novo to other SH2 domains.

Vaccine-induced IgG antibodies to V1V2 regions of multiple HIV-1 subtypes correlate with decreased risk of HIV-1 infection.

Unlabelled: In the RV144 HIV-1 vaccine efficacy trial, IgG antibody (Ab) binding levels to variable regions 1 and 2 (V1V2) of the HIV-1 envelope glycoprotein gp120 were an inverse correlate of risk of HIV-1 infection. To determine if V1V2-specific Abs cross-react with V1V2 from different HIV-1 subtypes, if the nature of the V1V2 antigen used to asses cross-reactivity influenced infection risk, and to identify immune assays for upcoming HIV-1 vaccine efficacy trials, new V1V2-scaffold antigens were designed and tested. Protein scaffold antigens carrying the V1V2 regions from HIV-1 subtypes A, B, C, D or CRF01_AE were assayed in pilot studies, and six were selected to assess cross-reactive Abs in the plasma from the original RV144 case-control cohort (41 infected vaccinees, 205 frequency-matched uninfected vaccinees, and 40 placebo recipients) using ELISA and a binding Ab multiplex assay.

Phosphorylation of Crk on tyrosine 251 in the RT loop of the SH3C domain promotes Abl kinase transactivation.

Here, we report the identification and characterization of a novel tyrosine phosphorylation site in the carboxy-terminal Src Homology 3 (SH3) (SH3C) domain of the Crk adaptor protein. Y251 is located in the highly conserved RT loop structure of the SH3C, a region of Crk involved in the allosteric regulation of the Abl kinase. Exploiting kinase assays to show that Y251 is phosphorylated by Abl in vitro, we generated affinity-purified antisera against phosphorylated Y251 in Crk and showed that Abl induces phosphorylation at Y251 in vivo, and that the kinetics of phosphorylation at Y251 and the negative regulatory Y221 site in vitro are similar.

The course of eating disorders in patients with borderline personality disorder: a 10-year follow-up study.

Objective: The purpose of this study was to describe the longitudinal course of eating disorders in patients with borderline personality disorder.

Method: The SCID I was administered to 290 borderline inpatients and 72 participants with other axis II disorders during their index admission and at five contiguous 2-year follow-up periods.

Results: The prevalence of anorexia, bulimia, and eating disorder not otherwise specified (EDNOS) declined significantly over time for those in both study groups but the prevalence of EDNOS remained significantly higher among borderline patients.

Proapoptotic function of the nuclear Crk II adaptor protein.

Crk II and Crk L have both cytosolic and nuclear functions. While Crk L is a bona fide nuclear signaling protein because of its ability to bind tyrosine-phosphorylated STAT5 and act as a transcriptional coactivator, the function of nuclear Crk II is less well understood. The present study was undertaken to investigate whether Crk II is in the nucleus, how Crk II translocates into the nucleus, whether it possesses a functional NES, and to determine if nuclear Crk II affects cell cycle checkpoints and promotes apoptosis.

Proline cis-trans isomerization controls autoinhibition of a signaling protein.

Autoinhibition is being widely used in nature to repress otherwise constitutive protein activities and is typically regulated by extrinsic factors. Here we show that autoinhibition can be controlled by an intrinsic intramolecular switch afforded by prolyl cis-trans isomerization. We find that a proline on the linker tethering the two SH3 domains of the Crk adaptor protein interconverts between the cis and trans conformation.

Transactivation of Abl by the Crk II adapter protein requires a PNAY sequence in the Crk C-terminal SH3 domain.

To gain a better understanding of how Crk II regulates the function of the Abl tyrosine kinase, we explored the function of the C-terminal linker and SH3 domain, a region of Crk II that is still poorly understood. Molecular modeling, tryptophan fluorescence, and covariation sequence alignment indicate that the Crk-SH3-C has a unique binding groove and RT loop not observed in typical SH3 domains. Based on these models, we made a series of mutations in the linker and in residues predicted to destabilize the putative binding pocket and RT loop.

C-terminal SH3 domain of CrkII regulates the assembly and function of the DOCK180/ELMO Rac-GEF.

Genetic studies in Caenorhabditis elegans identified an evolutionarily conserved CED-2 (CrkII), CED-5 (DOCK180), CED-12 (ELMO), CED-10 (Rac1) module important for cell migration and phagocytosis of apoptotic cells. Previous studies have shown that DOCK180 and ELMO comprise an unconventional bipartite Dbl homology domain-independent Rac guanine nucleotide exchange factor (Rac-GEF); but it is still unclear how CrkII functions in Rac-GEF activity. In this study, we have characterized a unique function of CrkII in phagocytosis and Rac activation mediated by the C-terminal SH3 domain, a region of CrkII that has no clear cellular or biochemical function.

Centile reference charts for total energy expenditure in infants from 1 to 12 months.

Background: A knowledge of energy expenditure in infancy is required for the estimation of recommended daily amounts of food energy, for designing artificial infant feeds, and as a reference standard for studies of energy metabolism in disease states.

Objectives: The objectives of this study were to construct centile reference charts for total energy expenditure (TEE) in infants across the first year of life.

Methods: Repeated measures of TEE using the doubly labeled water technique were made in 162 infants at 1.

Comparison of measured sleeping metabolic rate and predicted basal metabolic rate during the first year of life: evidence of a bias changing with increasing metabolic rate.

Objective: To compare measurements of sleeping metabolic rate (SMR) in infancy with predicted basal metabolic rate (BMR) estimated by the equations of Schofield.

Methods: Some 104 serial measurements of SMR by indirect calorimetry were performed in 43 healthy infants at 1.5, 3, 6, 9 and 12 months of age.

Fast-track office-based anesthesia: a comparison of propofol versus desflurane with antiemetic prophylaxis in spontaneously breathing patients.

Compared to propofol, maintenance of anesthesia with desflurane provided significantly better intraoperative conditions during office-based surgery. In addition, desflurane with routine antiemetic prophylaxis was associated with a faster early recovery and similar incidence of postoperative side effects.

Delay in serum stimulation of Erk activity caused by oncogenic transformation.

Mitogenic growth factor stimulation activates several signal transduction pathways, including the well-characterized Ras-Erk pathway, resulting in transient activation of Erk1 and Erk2. Oncogenic transformation, however, causes constitutive activation of growth signalling pathways, resulting in an accelerated rate of cell division. We investigated the effects of transformation on serum and growth factor stimulation of Erk1 and Erk2, and show that stimulation of these MAP kinases, as well as the Erk activator Mek, is delayed in oncogene transformed cells.

Relative contributions of voluntary apnoea, exposure to cold and face immersion in water to diving bradycardia in humans.

1. Diving or face immersion bradycardia is a well recognized but incompletely understood reflux which occurs in man and other mammals. 2.

Identification and characterization of a high-affinity interaction between v-Crk and tyrosine-phosphorylated paxillin in CT10-transformed fibroblasts.

The genome of avian sarcoma virus CT10 encodes a fusion protein in which viral Gag sequences are fused to cellular Crk sequences containing primarily Src homology 2 (SH2) and Src homology 3 (SH3) domains. Transformation of chicken embryo fibroblasts (CEF) with the Gag-Crk fusion protein results in the elevation of tyrosine phosphorylation on specific cellular proteins with molecular weights of 130,000, 110,000, and 70,000 (p130, p110, and p70, respectively), an event which has been correlated with cell transformation. In this study, we have identified the 70-kDa tyrosine-phosphorylated protein in CT10-transformed CEF (CT10-CEF) as paxillin, a cytoskeletal protein suggested to be important for organizing the focal adhesion.

The product of the cellular crk gene consists primarily of SH2 and SH3 regions.

We have cloned and sequenced a complementary DNA encoding the cellular homologue of the transforming oncogene v-crk of avian sarcoma virus CT10. This complementary DNA contains an open reading frame of 915 base pairs that encodes a polypeptide of 305 amino acids. The first 205 amino acids of this c-Crk protein were identical to those of the CT10 encoded v-Crk protein, with the exception of 5 amino acids.

Biological and biochemical activity of v-Crk chimeras containing the SH2/SH3 regions of phosphatidylinositol-specific phospholipase C-gamma and Src.

The chicken CT10 virus oncogene product, P47gag-crk, contains SH2/SH3 domains that have been identified as conserved domains among proteins involved in signal transduction. We studied the functional similarity of the SH2/SH3 domains by replacing those of v-Crk with those of phosphatidylinositol-specific phospholipase C-gamma, v-Src, or c-Src. The transforming activity of v-Crk was partially retained in a mutant with a v-Src SH3 domain but not in the other mutants with heterologous SH2/SH3 domains.

Generation of Met-enkephalin Arg6Phe7 immunoreactivity by proteolytic cleavage of mammalian plasma precursors by pepsin.

A region-specific antiserum raised against the C-terminal heptapeptide of proenkephalin A (Met-enk Arg6Phe7) was used in RIA studies to show that rat, human, and ovine plasma contain substrates (mol wt, 68K) that yield nanomolar amounts of Met-enk Arg6Phe7 (ME-RF) after treatment with pepsin under acid conditions. This ovine plasma-derived immunoreactivity diluted in parallel to the ME-RF standard in RIA and chromatographed as two low mol wt species (approximately 1K) which were less hydrophobic than the standard on size exclusion and reverse phase chromatography. The pepsin-generated material displaced [3H]naloxone from rat brain binding sites; its potency was about 1000-fold that of ME-RF, assuming near 100% cross-reactivity with the antiserum.

Beta endorphin and dynorphin levels in rat pituitary and hypothalamus: age studies.

The content of immunoreactive (ir)-beta-endorphin, ir-dynorphin 1-17, and ir-dynorphin 1-8 was determined in hypothalamus, anterior pituitary, and neurointermediate lobe of rats 3-24 months of age. In the anterior pituitary ir-beta-endorphin showed a progressive rise with age (0.5 +/- 0.