Mutant mice lacking alternatively spliced p53 isoforms unveil as a male-specific prognostic factor in Myc-driven B-cell lymphomas.

The gene encodes several isoforms of elusive biological significance. Here, we show that mice lacking the alternatively spliced (AS) exon, thereby expressing the canonical p53 protein but not isoforms with the AS C-terminus, have unexpectedly lost a male-specific protection against Myc-induced B-cell lymphomas. Lymphomagenesis was delayed in males compared to males, but also compared to and females.

Tuning Co-Operative Energy Transfer in Copper(I) Complexes Using Two-Photon Absorbing Diimine-Based Ligand Sensitizers.

Photocatalysis mediated by low energy light wavelengths has potential to enable safer, sustainable synthetic methods. A phenanthroline-derived ligand bathocupSani, with a large two-photon absorption (TPA) cross section was used to construct a heteroleptic complex [Cu(bathocupSani)(DPEPhos)]BF and a homoleptic complex [Cu(bathocupSani)]BF. The ligand and the respective homoleptic complex with copper exhibit two-photon upconversion with an anti-Stokes shift of 1.

Self-Reported Sobriety Labels: Perspectives from Alumni of Inpatient Addiction Treatment.

Background: There is a lack of consensus in the addiction field as to how to refer to alumni of residential treatment who no longer use substances or who reduce their use. In the literature, this label and broader identity are typically discussed in technical (amount and frequency of use) or social terms (environment and social network changes).

Objective: The current paper seeks to simplify the discussion by focusing on personal labels without complex technical or social considerations.

Rethinking telepresence: post- and pre-COVID-19.

Following the marked increase in the use of digital technologies during the recent pandemic, the article reconsiders the concept of social , in the sense of interpersonal connection at a distance, locating it in the and within media studies. It reminds the reader that, for centuries, when people were separated from one another by the force of various circumstances, including pandemics, they resorted to technologies at their disposal to experience telepresence, long before the term itself was coined by scholars. Foremost among these has been the epistolary, a vitally important interpersonal media largely overlooked by media and telepresence researchers.

An Implementation Approach to Translating Assessment Data into Treatment for Disorders of Addiction.

Effective translation of data to inform real-time patient care is lacking in addiction inpatient settings. The current study presents the optimization of an assessment report that is used by clinicians to individualize treatment. A multi-aim, iterative approach was taken, utilizing an implementation science perspective to arrive at a final version of the assessment report.

Conceptions of sexual health by gay men living with HIV in serodifferent couples in Montreal, Canada: results from a qualitative analysis.

Background: Gay, bisexual, and other men (GBM) who have sex with men living with HIV in serodifferent couples (one partner living with HIV, the other HIV-negative) may encounter unique sexual health challenges. This study aimed to explore their definition of sexual health that could improve service provision.

Methods: We interviewed 10 gay-identified men living with HIV from 2017 to 2019 as part of CTNPT013, a study on the sexual health of HIV serodifferent GBM couples conducted at two HIV-specialised clinics in Montreal, Canada.

Adapting, Implementing, and Maintaining a Group Cognitive Behavioral Therapy Program at an Inpatient Addiction Treatment Facility.

Background: Quality training is an oft-cited barrier to effective implementation and ongoing delivery of high-quality evidence-based practice (EBP) across fields. This is especially true in the addiction field, but there is little cited evidence for optimal methods to improve EBP in inpatient addiction facilities with minimal resources.

Objective: The current paper focuses on evaluating the state of our facility's group CBT manual and clinical training on the manual in a "realistic" (ie, non-RCT, non-grant-funded) inpatient addiction treatment setting.

It is not all about the alpha: elevated expression of p53β variants is associated with lower probability of survival in a retrospective melanoma cohort.

Background: Melanoma is the deadliest type of skin cancer and despite improvements in treatment outcomes, melanoma claimed 57,043 lives in 2020. In most malignancies, p53 mutation rates are above 50% and provide prognostic indications. However, in melanoma where less than a quarter of cases harbour a p53 mutation, the significance of the tumour suppressor may be questioned.

Predicting weighted unobserved nodes in a regulatory network using answer set programming.

Background: The impact of a perturbation, over-expression, or repression of a key node on an organism, can be modelled based on a regulatory and/or metabolic network. Integration of these two networks could improve our global understanding of biological mechanisms triggered by a perturbation. This study focuses on improving the modelling of the regulatory network to facilitate a possible integration with the metabolic network.

Urinary bladder recurrences following ureteroscopic biopsies of upper tract urothelial cancers: a multi-centre observational study with genomic assessment for clonality.

Background And Aims: Urinary bladder recurrences (UBRs) after radical nephroureterectomy (RNUx) are a known challenge in patients with upper-tract urothelial cancers (UTUCs). We aim to assess factors associated with UBR and clonal-relatedness with resected UTUC.

Methods: Patients who underwent RNUx for UTUC between 1998 and 2015 in five institutions were identified.

Alterations in the p53 isoform ratio govern breast cancer cell fate in response to DNA damage.

Our previous studies have shown that p53 isoform expression is altered in breast cancer and related to prognosis. In particular, a high ∆40p53:p53α ratio is associated with worse disease-free survival. In this manuscript, the influence of altered Δ40p53 and p53α levels on the response to standard of care DNA-damaging agents used in breast cancer treatment was investigated in vitro.

A pilot study comparing in-person and remote outpatient substance use treatment services on quality-of-life outcomes.

Background: The widespread shift from in-person to Telehealth services during the Covid-19 pandemic irreversibly shifted the landscape of outpatient substance use treatment. This shift was necessitated by health, rather than data-driven, reasons. As we reflect on whether to continue providing Telehealth services moving forward, we require empirical support on the effectiveness of Telehealth services (compared to in-person services) in terms of patient outcomes, such as Quality of Life (QOL), to support this decision.

Δ133p53 coordinates ECM-driven morphogenesis and gene expression in three-dimensional mammary epithelial acini.

Growing evidence indicates that p53 (encoded by TP53) has a crucial role in normal tissue development. The role of the canonical p53 (p53α) and its 12 isoforms in development and homeostasis of healthy tissue remains poorly understood. Here, we demonstrate that the Δ133p53 isoforms, the three short isoforms of p53, respond specifically to laminin-111 and play an important regulatory role in formation of mammary organoids in concert with p53α.

A Novel Role of SMG1 in Cholesterol Homeostasis That Depends Partially on p53 Alternative Splicing.

SMG1, a phosphatidylinositol 3-kinase-related kinase (PIKK), essential in nonsense-mediated RNA decay (NMD), also regulates p53, including the alternative splicing of p53 isoforms reported to retain p53 functions. We confirm that SMG1 inhibition in MCF7 tumor cells induces p53β and show p53γ increase. Inhibiting SMG1, but not UPF1 (a core factor in NMD), upregulated several cholesterol pathway genes.

Cytoplasmic p53β Isoforms Are Associated with Worse Disease-Free Survival in Breast Cancer.

mutations are associated with tumour progression, resistance to therapy and poor prognosis. However, in breast cancer, 's overall mutation frequency is lower than expected (~25%), suggesting that other mechanisms may be responsible for the disruption of this critical tumour suppressor. p53 isoforms are known to enhance or disrupt p53 pathway activity in cell- and context-specific manners.

Low level of Fibrillarin, a ribosome biogenesis factor, is a new independent marker of poor outcome in breast cancer.

Background: A current critical need remains in the identification of prognostic and predictive markers in early breast cancer. It appears that a distinctive trait of cancer cells is their addiction to hyperactivation of ribosome biogenesis. Thus, ribosome biogenesis might be an innovative source of biomarkers that remains to be evaluated.

Deriving a Measure of Social Recovery Capital From the Important People and Activities Instrument: Construction and Psychometric Properties.

Aim: This study presents a measure of Social Recovery Capital (SRC) derived from the Important People and Activities instrument (IPA).

Methods: The sample comprised young adults who participated in the Collaborative Study on the Genetics of Alcoholism, a high-risk family study of alcohol use disorder (N = 2472). Exploratory and confirmatory factor analysis identified influential items and factor structure, adjusting for family relatedness.

Adaptive homeostasis and the p53 isoform network.

All living organisms have developed processes to sense and address environmental changes to maintain a stable internal state (homeostasis). When activated, the p53 tumour suppressor maintains cell and organ integrity and functions in response to homeostasis disruptors (stresses) such as infection, metabolic alterations and cellular damage. Thus, p53 plays a fundamental physiological role in maintaining organismal homeostasis.

Effect of p53 and its N-terminally truncated isoform, Δ40p53, on breast cancer migration and invasion.

Breast cancer is the most diagnosed malignancy in women, with over half a million women dying from this disease each year. In our previous studies, ∆40p53, an N-terminally truncated p53 isoform, was found to be upregulated in breast cancers, and a high ∆40p53 : p53α ratio was linked with worse disease-free survival. Although p53α inhibits cancer migration and invasion, little is known about the role of ∆40p53 in regulating these metastasis-related processes and its role in contributing to worse prognosis.

p53 isoforms differentially impact on the POLι dependent DNA damage tolerance pathway.

The recently discovered p53-dependent DNA damage tolerance (DDT) pathway relies on its biochemical activities in DNA-binding, oligomerization, as well as complex formation with the translesion synthesis (TLS) polymerase iota (POLι). These p53-POLι complexes slow down nascent DNA synthesis for safe, homology-directed bypass of DNA replication barriers. In this study, we demonstrate that the alternative p53-isoforms p53β, p53γ, Δ40p53α, Δ133p53α, and Δ160p53α differentially affect this p53-POLι-dependent DDT pathway originally described for canonical p53α.

Δ133p53β isoform pro-invasive activity is regulated through an aggregation-dependent mechanism in cancer cells.

The p53 isoform, Δ133p53β, is critical in promoting cancer. Here we report that Δ133p53β activity is regulated through an aggregation-dependent mechanism. Δ133p53β aggregates were observed in cancer cells and tumour biopsies.