Bridging Employees' Perceptions of Corporate Social Responsibility, Sense-Making for Meaningfulness, and Work Engagement for Successful Self-Regulation.

In response to calls for research on the psychological mechanisms, such as perceptions and attitudes toward corporate citizenship, in promoting positive outcomes at work, this research presents a novel approach by empirically testing a calling conditioned path model from P perception of corporate CSR (P-CSR) to work engagement via meaningfulness under the theoretical framework of self-determination theory. Survey data collected from 224 corporate employees in the US were tested using the PROCESS plugin (version 4.3) in SPSS.

The Natural History of Trisomy 21: Outcome Data from a Large Tertiary Referral Centre.

Objective: The aim of the study was to prospectively gather data on pregnancy outcomes of prenatally diagnosed trisomy 21 (T21) in a large tertiary referral centre.

Methods: Data were gathered prospectively in a large tertiary referral centre over 5 years from 2013 to 2017 inclusively. Baseline demographic and pregnancy outcome data were recorded on an anonymized computerized database.

Generation of SARS-CoV-2 reporter replicon for high-throughput antiviral screening and testing.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) research and antiviral discovery are hampered by the lack of a cell-based virus replication system that can be readily adopted without biosafety level 3 (BSL-3) restrictions. Here, the construction of a noninfectious SARS-CoV-2 reporter replicon and its application in deciphering viral replication mechanisms and evaluating SARS-CoV-2 inhibitors are presented. The replicon genome is replication competent but does not produce progeny virions.

Discovery of an Anion-Dependent Farnesyltransferase Inhibitor from a Phenotypic Screen.

By employing a phenotypic screen, a set of compounds, exemplified by , were identified which potentiate the ability of histone deacetylase inhibitor vorinostat to reverse HIV latency. Proteome enrichment followed by quantitative mass spectrometric analysis employing a modified analogue of as affinity bait identified farnesyl transferase (FTase) as the primary interacting protein in cell lysates. This ligand-FTase binding interaction was confirmed via X-ray crystallography and temperature dependent fluorescence studies, despite lacking structural and binding similarity to known FTase inhibitors.

Discovery of Highly Selective and Potent HDAC3 Inhibitors Based on a 2-Substituted Benzamide Zinc Binding Group.

The selectivity of histone deacetylase inhibitors (HDACis) is greatly impacted by the zinc binding groups. In an effort to search for novel zinc binding groups, we applied a parallel medicinal chemistry (PMC) strategy to quickly synthesize substituted benzamide libraries. We discovered a series containing 2-substituted benzamides as the zinc binding group which afforded highly selective and potent HDAC3 inhibitors, exemplified by compound with a 2-methylthiobenzamide.

Identification of potent inhibitors of the sortilin-progranulin interaction.

High-throughput screening methods have been used to identify two novel series of inhibitors that disrupt progranulin binding to sortilin. Exploration of structure-activity relationships (SAR) resulted in compounds with sufficient potency and physicochemical properties to enable co-crystallization with sortilin. These co-crystal structures supported observed SAR trends and provided guidance for additional avenues for designing compounds with additional interactions within the binding site.

Selective Class I HDAC Inhibitors Based on Aryl Ketone Zinc Binding Induce HIV-1 Protein for Clearance.

HIV persistence in latently infected, resting CD4 T cells is broadly considered a barrier to eradicate HIV. Activation of the provirus using latency-reversing agents (LRAs) followed by immune-mediated clearance to purge reservoirs has been touted as a promising therapeutic approach. Histone deacetylases (HDACs) and histone acetyltransferases (HATs) control the acetylation level of lysine residues in histones to regulate the gene transcription.

Discovery of MK-8718, an HIV Protease Inhibitor Containing a Novel Morpholine Aspartate Binding Group.

A novel HIV protease inhibitor was designed using a morpholine core as the aspartate binding group. Analysis of the crystal structure of the initial lead bound to HIV protease enabled optimization of enzyme potency and antiviral activity. This afforded a series of potent orally bioavailable inhibitors of which MK-8718 was identified as a compound with a favorable overall profile.

Development of a sensitive amplified luminescent proximity homogeneous assay to monitor the interactions between pTEFb and Tat.

The viral transactivator protein (Tat) plays an essential role in the replication of human immunodeficiency type 1 virus (HIV-1) by recruiting the host positive transcription elongation factor (pTEFb) to the RNA polymerase II transcription machinery to enable an efficient HIV-1 RNA elongation process. Blockade of the interaction between Tat and pTEFb represents a novel strategy for developing a new class of antiviral agents. In this study, we developed a homogeneous assay in AlphaLISA (amplified luminescent proximity homogeneous assay) format using His-tagged pTEFb and biotinylated Tat to monitor the interaction between Tat and pTEFb.

Chondroitin sulfate promotes activation of cathepsin K.

Cathepsin K (CatK), a major lysosomal collagenase produced by osteoclasts, plays an important role in bone resorption. Evidence exists that the collagenase activity of CatK is promoted by chondroitin sulfate (CS), a sulfated glycosaminoglycan. This study examines the role of CS in facilitating CatK activation.

Does the addition of integrated cognitive behaviour therapy and motivational interviewing improve the outcomes of standard care for young people with comorbid depression and substance misuse?

Objective: To determine whether the addition of cognitive behaviour therapy and motivational interviewing (CBT/MI) to standard alcohol and other drug (AOD) care improves outcomes for young people with comorbid depression and substance misuse.

Participants And Setting: Participants were young people with comorbid depression (Kessler Psychological Distress Scale score ≥ 17) and substance misuse (mainly alcohol and/or cannabis) seeking treatment at two youth AOD services in Melbourne, Australia. The study was conducted between September 2006 and September 2008.

Identification and biological evaluation of a series of 1H-benzo[de]isoquinoline-1,3(2H)-diones as hepatitis C virus NS5B polymerase inhibitors.

The hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase (RdRp) plays a central role in virus replication. NS5B has no functional equivalent in mammalian cells and, as a consequence, is an attractive target for inhibition. Herein, we present 1H-benzo[de]isoquinoline-1,3(2H)-diones as a new series of selective inhibitors of HCV NS5B polymerase.

Outcomes of an integrated cognitive behaviour therapy (CBT) treatment program for co-occurring depression and substance misuse in young people.

Background: There are high rates of co-occurring depression among young people with substance use disorders. While there is preliminary evidence for the effectiveness of integrated cognitive behaviour therapy (CBT) in combination with antidepressants among alcohol and substance dependent adolescents and adults with co-existing depression, no studies have examined the effectiveness of integrated CBT interventions in the absence of pharmacotherapy. The aim of the current study was to determine the outcomes of an integrated CBT intervention for co-occurring depression and substance misuse in young people presenting to a mental health setting.

Integrated cognitive behaviour therapy for co-occurring substance misuse and major depression: lessons from a youth mental health service.

Objective: The aim of this paper is to describe a 20-week integrated cognitive behavioural therapy (CBT) program addressing co-occurring substance misuse and major depression in young people.

Method: Participants were aged between 15 and 25 years, met DSM-IV criteria for major depressive disorder and had at least weekly illicit drug use and/or weekly alcohol use exceeding the Australian national guidelines on alcohol.

Results: Between December 2004 and January 2007, an integrated CBT program was offered to 60 young people with co-occurring depression and substance misuse who presented to a youth-specific mental health service.