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The purpose of this study was to investigate the role of skin conductance level reactivity (SCLR) and respiratory sinus arrhythmia reactivity (RSAR) in preschoolers' social dominance, as well as potential gender differences in these associations. Reactivity was assessed in response to viewing videos of social exclusion and a post-aggression discussion. In a community sample of 94 preschool children followed over one calendar year, reactivity to the post-aggression discussion, but not exclusion, video was related to social dominance. Specifically, increased RSAR to the post-aggression discussion video was positively associated with concurrent social dominance for both boys and girls. Longitudinally, for boys only, coactivation (i.e., increases in SCLR accompanied by increases in RSAR) to the post-aggression discussion video, which may reflect dysregulated, emotionally labile reactions to stress, was associated with relatively low levels of social dominance across the course of the year. Overall, findings contribute to a growing literature documenting the role of autonomic reactivity in preschoolers' social adjustment and extend this work to their capacity to achieve and maintain socially dominant positions with peers.

Biofilm-forming Bacillus species are often involved in persistent contamination and spoilage of dairy products. They therefore present a major microbiological challenge in the field of dairy food quality and safety. Due to their substantial physiological versatility, Bacillus species can survive in various parts of dairy manufacturing plants, leading to a high risk of product spoilage and potential dissemination of foodborne diseases. Furthermore, biofilm and heat-resistant spore formation make these bacteria challenging to eliminate. Thus, some strategies have been employed to remove, prevent, or delay the formation of Bacillus biofilms in the dairy industry, but with limited success. Lack of understanding of the Bacillus biofilm structure and behavior in conditions relevant to dairy-associated environments could partially account for this situation. The current paper reviews dairy-associated biofilm formation by Bacillus species, with particular attention to the role of biofilm in Bacillus species adaptation and survival in a dairy processing environment. Relevant model systems are discussed for the development of novel antimicrobial approaches to improve the quality of dairy food. © 2020 Society of Chemical Industry.

Alpha1-antitrypsin (AAT) deficiency predisposes individuals to emphysema and liver diseases such as cirrhosis and hepatocellular carcinoma. The deficiency results from mutations in the SERPIN1A gene encoding AAT molecules that cause hepatotoxic retention within the endoplasmic reticulum. Since the E342K mutation is the basis for destabilization leading to lung and liver pathologies, we used the crystal structure of the mutated AAT as the basis for molecular docking selection of candidate compounds that may bind and stabilize the 342K structural pocket. We identified compounds that inhibited intracellular accumulation of AAT in hepatocytes in vitro. These data suggest that drug binding to a structural site encoded by a mutation associated with AAT deficiency has the potential for clinical utility by modulating conformational transitions.

In March 2018, the President of the International Society for Research on Aggression (ISRA), Mike Potegal, appointed a special commission to prepare a report on youth violence. This commission was “charged with the task of producing a public statement on the known risk factors for youth violence, based on the current state of scientific knowledge. If the Commission finds sufficient evidence of harmful effects, then its public statement may include public policy recommendations.” What follows is the final report of the Youth Violence Commission, delivered in March 2018.This report was written by a group of ISRA researchers with expertise on youth violence. This report is based on a previous youth violence report (Bushman et al., 2016), but it is shorter in length, more accessible in language, contains additional material, and is more up-to-date.

The present short-term longitudinal study examined prospective associations between two forms of peer victimization (i.e., physical, relational) and both externalizing and internalizing problems in early childhood. The study assessed 97 children (42 girls; M age = 45.22 months, SD = 6.99) over the course of one school year with assessments occurring at the end of each semester (approximately 6 months apart). Multiple methods were used to collect data over the course of one school year to test theoretically driven hypotheses. Cross-lagged path analyses were conducted, revealing significant associations between relational victimization and increases in depressive symptoms. On the other hand, relational victimization was also significantly associated with decreases in externalizing problems (e.g., inattention, deception/lying) and increases in prosocial behavior. Physical aggression predicted increases in physical victimization, supporting hypotheses that children displaying physically aggressive behavior are likely to be reactive to negative peer interactions and endure future victimization.

We establish an algorithm that produces an optimal strategy for retirees to withdraw funds between their tax-deferred accounts (TDAs), like traditional IRA/401(k) accounts, and their Roth IRA/401(k) accounts, in the context of a financial model based on American tax law. This optimal strategy follows a geometrically simple, intuitive approach that can be used to maximize the size of a retiree's bequest to an heir or, alternatively, to maximize a retiree's portfolio longevity. We give examples where retirees following the approach currently implemented by major investment firms, like Fidelity and Vanguard, will reduce their bequests by approximately 10% or lose 18 months of portfolio longevity compared to our optimal approach. Further, our strategy and algorithm can be extended to many cases where the retiree has additional, known yearly sources of money, such as income from part-time work, taxable investment accounts, and Social Security.

Recent data suggest alternative mechanisms that promote human leukocyte antigen (HLA)-associated drug syndromes. Hypersensitive responses have been attributed to drug interactions with HLA molecules, peptides presented by HLA molecules and T-cell antigen receptors. Definition of an increasing number of HLA-associated drug syndromes suggests that polymorphism in the antigen-binding cleft residues influence recognition of specific drugs. Recent data demonstrate that small molecule drugs bind within the antigen-binding cleft of HLA in a manner that alters the repertoire of HLA-bound peptide ligands. This drug recognition mechanism permits presentation of self-peptides to which the host has not been tolerized. This altered repertoire mechanism is analogous to massive polyclonal T-cell responses occurring in mismatched HLA organ transplantation in which the drug in effect creates a novel HLA allele. Alteration of the self-peptide repertoire by HLA-binding small molecules may be the mechanistic basis for a diverse set of deleterious T-cell responses since the antigen-binding cleft has structural features that are compatible with binding drug-like small molecules. Small molecule drugs that bind elements of the trimolecular complex (T-cell receptor, peptide, and HLA) may cause short- and long-term adverse effects by a diverse set of mechanisms.

Two studies investigated potential mediators of the association between relational victimization and relational aggression. Self-report measures of aggressive behavior among peers, exclusivity, hostile attribution biases, and borderline personality disorder (BPD) symptoms were collected. In study 1, participants were 180 female emerging adults (M = 18.82, SD = 1.18). Both exclusivity and hostile attribution biases for relational provocations were found to partially mediate the association between relational victimization and relational aggression. In study 2, participants were 54 female emerging adults (M = 19.16, SD = 1.11). Symptoms of BPD were not found to mediate the association between relational victimization and relational aggression, yet unique associations with relational aggression were observed. The results add to recent research guided by a social process model in which links between victimization and aggression are more clearly understood. Copyright © 2011 John Wiley & Sons, Ltd. Language: en

The current study involved a short-term longitudinal study of young children (M = 44.56 months, SD = 11.88, N = 103) to test the prospective associations between peer victimization and aggression subtypes. Path analyses documented that teacher-reported physical victimization was uniquely associated with increases in observed physical aggression over time. The path model also revealed that teacher-reported relational victimization was uniquely associated with statistically significant increases in observed relational aggression over time. Ways in which these findings extend the extant developmental literature are discussed.

In this study, we checked whether HSP70 preparations of different origins are able to protect model animals (rats) from endotoxic shock and modify the response of myeloid cells to lipopolysaccharide (LPS) challenge. It was shown that HSP70 preparations can effectively protect organisms from endotoxic shock by strongly decreasing mortality and restoring both homeostasis and various hemodynamic characteristics. At the cellular level, HSP70 preparations significantly inhibit LPS-induced reactive oxygen species production in various myeloid cells and decrease NO expression in macrophages, which is enhanced after LPS priming. In parallel, HSP70 preconditioning partially normalizes neutrophil apoptosis, which is disturbed as a result of LPS stimulation. These results suggest that the antiseptic actions of HSP70 preparations are probably realized at the level of receptor membrane complexes of myeloid cells, which represent the major target of LPS action. Taken together, our findings show that extracellular mammalian HSP70 may play an important role in innate immunity modulation and stimulation of endogenous protective mechanisms, both at the cellular and organism levels, which make this protein a promising base for the development of efficient antiseptic drugs.

The purpose of this study was to investigate the distinct forms (i.e., physical and relational) and functions (i.e., proactive and reactive) of aggressive behavior during early childhood (n = 101; M age = 45.09 months). Forms, but not functions, of aggressive behavior were stable over time. A number of contributors to aggression were associated with distinct subtypes of aggressive behavior. Females and socially dominant children were more relationally aggressive and older children were less physically aggressive than their peers. Longitudinal analyses indicated that social dominance predicted decreases in physical aggression and peer exclusion predicted increases in relational aggression. Overall, the results provide support for the distinction between subtypes of aggression in early childhood.

The study of social dominance has a long tradition within the peer relationships literature, but rarely has the topic been investigated observationally and longitudinally within other salient close relationships. The present study investigated the role of experiences in social relationships and adjustment indices in childhood in predicting later observed non-verbal social dominance behaviors in the context of romantic relationships in emerging adults. Analyses from a subsample (N = 70) from a 29-year prospective longitudinal study revealed links between early peer behavior and subsequent romantic relationship interactions for men and women. Non-verbal social dominance behaviors were concurrently associated with poor romantic relationship quality, conflict, and physical and verbal aggression within the dyad. Both childhood externalizing and internalizing behaviors significantly predicted non-verbal social dominance behaviors in the romantic partner interactions.

Genes at the centromeric end of the human leukocyte antigen region influence adaptive autoimmune diseases and cancer. In this study, we characterized protein expression of HKE2, a gene located in the centromeric portion of the class II region of the major histocompatibility complex encoding subunit 6 of prefoldin. Immunohistochemical analysis using an anti-HKE2 antibody indicated that HKE2 protein expression is dramatically upregulated as a consequence of activation. In a tissue microarray and in several tumors, HKE2 was overexpressed in certain cancers compared with normal counterparts. The localization of the HKE2 gene to the class II region, its cytoplasmic expression and putative protein-binding domain suggest that HKE2 may function in adaptive immunity and cancer.

We observed 48 children from rural preschools (M=64 months old) in two different social contexts to test hypotheses about the type (relational, physical, verbal, nonverbal), contextual independence, and sociometry of girls’ and boys’ aggressive tactics. We predicted and generally found that (1) girls displayed more relational aggression than boys while boys displayed more physical and verbal aggression than girls, and that children received more physical and verbal aggression from male peers, and tended to receive more relational aggression from female peers, (2) behavioral observations of aggression corresponded with teacher reports of children's aggressive styles, (3) aggression observed during free play predicted children's aggressive styles in a structured setting at both the group and individual levels, and (4) aggressive tactics were associated with projected sociometric characteristics (dominance and peer acceptance).

Methods Peripheral blood mononuclear cells (PBMCs) were isolated from patients with CBZ-SJS/TEN and healthy controls, stimulated with 10ug/mL CBZ (Sigma, cat. no. C4024-5G) and cultured over a 9-14 day period. RNA was isolated at various time points and TCR V subtypes were assessed using digital droplet PCR (Bio-Rad QX100 droplet digital PCR system). Drug specific T-cell INF and granulysin responses were assessed by ELISpot and ICS. In silico modelling was used to examine the interaction between the known specific TCR V and V chains, CBZ and HLA-B*15:02.

Jak2 is a cytoplasmic tyrosine kinase that has been linked to hematological malignancies. Recently, a somatic Jak2 mutation (Jak2-V617F) has been identified in several myeloproliferative disorders such as polycythemia vera, essential thrombocythemia and myeloid metaplasia with myelofibrosis. These myeloproliferative disorders are characterized by unregulated expansion of one or more cells in the blood. The presence of the Jak2-V617F mutation in cells results in uncontrolled cell division and resistance to the negative feedback mechanisms that govern normal cell growth. The availability of a Jak2 tyrosine kinase specific inhibitor would facilitate our understanding of these Jak2-related disorders and perhaps serve a clinical benefit for patients. However, the most widely used Jak2 inhibitor, AG490, suffers from a general lack of specificity. Here, we used a novel approach to identify Jak2-specific inhibitors. We used in silico homology modeling of the Jak2 kinase domain to identify solvent accessible exposed pockets on the surface of the Jak2 protein. We then used a high-throughput program called DOCK to predict the ability of 20,000 small molecules to interact with a structural pocket adjacent to the ATP binding site of murine Jak2. The predicted binding energies of interaction between each compound and the Jak2 kinase domain were calculated and the top six scoring compounds were tested for their ability to inhibit Jak2 tyrosine kinase function in vitro. One of these compounds, 2-methyl-1-phenyl-4-pyridin-2-yl-2-(2-pyridin-2-ylethyl)butan-1-one (Z3) effectively inhibited Jak2-V617F and Jak2-WT autophosphorylation. We were able to show that Z3 inhibits total Jak2 tyrosine phosphorylation as well as Jak2 phosphorylation at the critical tyrosine 1007 residue in both a dose-and time-dependent manner. Z3 is able to reduce growth hormone-dependent Jak2 activation and is a direct inhibitor of Jak2-WT and Jak2-V617F tyrosine kinase autophosphorylation as measured by an in vitro kinase assay. Moreover, we found that Z3 inhibits proliferation of human erythroleukemia (HEL) cells, which express the Jak2-V617F mutation. In summary, this work demonstrates proof-of-principle concept that in silico molecular modeling can be used as a means to identify specific tyrosine kinase inhibitors. Z3 Inhibits Jak2 Tyrosine Autophosphorylation in a Dose-Dependent Manner Z3 Inhibits Jak2 Tyrosine Autophosphorylation in a Dose-Dependent Manner Z3 Inhibits Growth Hormone Mediated Jak2 Phosphorylation at Tyrosine 1007 Z3 Inhibits Growth Hormone Mediated Jak2 Phosphorylation at Tyrosine 1007

Background/Purpose: Camp JRA (Juveniles Reaching Achievement) has been offering a week of fun, education, friendship, independence and support for 17 years to children with arthritis and related diseases. The number of campers has grown from 28 the first year to 120 maximum capacity for the past few years. Experienced Pediatric Rheumatology nurses and physicians provide hands-on care in the “Med Shed” at Camp JRA. Medical information is completed by parents, pediatric rheumatologists and primary care providers. The senior medical staff review and verify the information. Over the past 5 years we identified that coping with environmental allergies consumed a disproportionate amount of time for the staff and we felt unprepared to optimally address these issues. We wish to share our strategy in addressing the growing concern about environmental sensitivities in a residential week long camp for children with rheumatic diseases. Mindfulness of drug allergies is standard of care in any environment where medications are given. Coping with food allergies has assumed a significant position in our hierarchy of medical responsibilities in the Med Shed, as well. We found ourselves struggling to manage the increasing complexity of this issue. We found that some campers had multiple allergies listed that had not been reported, and no details were provided. For many years, we have run a very organized medical camp, however, this issue confounded our care of these complex children. Methods: The emergence of the multiple allergies issue was a barrier to providing a confidently safe camp environment. New approaches were developed and implemented. 1. We developed new allergy history questionaire that triggered progression to further detailed information. 2. We consulted with our Pediatric Allergist to develop an algorithm for assessment of symptoms (Attached to poster). 3. We developed an Allergy Action Plan specific to each camper with allergy issues, approved in advance by parent and signed. 4. We developed a system for Epi-pen storage: over the door holder with multiple clear pockets, with the Epi-pen, the child's photo, the signed Allergy Action Plan. Results: We oriented all medical staff who worked in the Med-Shed to the new system. When implemented at Camp JRA in July 2013 and we experienced no allergy response problems. Increasing allergy sensitivities in patients requires a proactive plan for residential camps. We have developed a model for assessing allergies and reaction preparedness. This plan has improved our confidence that we can provide safe rheumatologic AND allergy response care. Conclusion: The development of increasing allergy sensitivities and concerns by families and patients requires a proactive plan for residential camps of children with rheumatic disease. We hve developed a model for assessing allergies and reaction preparedness.