Constitutive surface expression of the thromboxane A2 receptor is Pim kinase-dependent.

Background: The thromboxane A2 receptor (TPαR) plays an important role in the amplification of platelet responses during thrombosis. Receptor activity is regulated by internalization and receptor desensitization. The mechanism by which constitutive surface expression of the TPαR is regulated is unknown.

Cultural and co-designed principles for developing a Māori kaumātua housing village to address health and social wellbeing.

Background: The current study is a case study of a Māori (Indigenous people of New Zealand) organisation and their developmental processes in creating a kaumātua (older people) housing village for health and social wellbeing. This study identifies how a set of established co-design and culturally-centred principles were enacted when creating and developing the village.

Method: A mixed-method concurrent design was used in creating the case with interviews (n = 4), focus groups (N = 4 with 16 total participants) and survey questionnaires (n = 56) involving kaumātua and organisation members.

Tuakana-teina peer education programme to help Māori elders enhance wellbeing and social connectedness.

Background: There are significant inequities between Māori (Indigenous people) and non-Māori in ageing outcomes. This study used a strengths-based approach based on the key cultural concept of mana motuhake (autonomy and self-actualisation) to develop a tuakana-teina (literally older sibling-younger sibling) peer education programme to assist kaumātua (elders) in addressing health and social needs. The purpose of this study was to test the impact on those receiving the programme.

Enhancing health outcomes for Māori elders through an intergenerational cultural exchange and physical activity programme: a cross-sectional baseline study.

Background: The study offers baseline data for a strengths-based approach emphasizing intergenerational cultural knowledge exchange and physical activity developed through a partnership with kaumātua (Māori elders) and kaumātua service providers. The study aims to identify the baseline characteristics, along with correlates of five key outcomes.

Methods: The study design is a cross-sectional survey.

Adaptation and implementation processes of a culture-centred community-based peer-education programme for older Māori.

Background: Health inequities experienced by kaumātua (older Māori) in Aotearoa, New Zealand, are well documented. Examples of translating and adapting research into practice that identifies ways to help address such inequities are less evident. The study used the He Pikinga Waiora (HPW) implementation framework and the Consolidated Framework for Implementation Research (CFIR) to explore promising co-design and implementation practices in translating an evidence-based peer-education programme for older Māori to new communities.

Condensin I and condensin II proteins form a LINE-1 dependent super condensin complex and cooperate to repress LINE-1.

Condensin I and condensin II are multi-subunit complexes that are known for their individual roles in genome organization and preventing genomic instability. However, interactions between condensin I and condensin II subunits and cooperative roles for condensin I and condensin II, outside of their genome organizing functions, have not been reported. We previously discovered that condensin II cooperates with Gamma Interferon Activated Inhibitor of Translation (GAIT) proteins to associate with Long INterspersed Element-1 (LINE-1 or L1) RNA and repress L1 protein expression and the retrotransposition of engineered L1 retrotransposition in cultured human cells.

Codesigning a Culture-Centered Age-Friendly Community for Māori Kaumātua: Cultural Principles and Practices.

Objectives: This study examined a Māori (Indigenous people of Aotearoa New Zealand) age-friendly housing development. Two Māori community groups worked with multiple stakeholders to codesign a culture-centered, kaumātua (older adults) urban housing community. The purpose was to identify codesign and culture-centered principles in the development.

Enhancing Well-Being and Social Connectedness for Māori Elders Through a Peer Education (Tuakana-Teina) Programme: A Cross-Sectional Baseline Study.

Māori kaumātua (elders) face stark health and social inequities compared to non-Māori New Zealanders. The tuakana-teina (older sibling-younger sibling) peer education programme is a strengths-based approach to enhance well-being and social connectedness. The purpose of this study is to present the baseline data from this programme and identify correlates of well-being outcomes.

Identifying the Facilitators and Barriers in Disseminating and Adopting a Health Intervention Developed by a Community-Academic Partnership.

The literature regarding implementation science of evidence-based health interventions in Māori communities is limited, and there is a push for new and innovative delivery methods of health interventions in New Zealand. The purpose of the study was to identify the facilitators and barriers in implementing a health intervention designed by others and was framed by the Consolidated Framework for Implementation Research (CFIR). This study explored general perceptions of the implementation process and also included a case study, the Kaumātua Mana Motuhake (older people's autonomy and self-actualization) project; a codesigned peer education intervention for older Māori.

An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enters host cells via an interaction between its Spike protein and the host cell receptor angiotensin-converting enzyme 2 (ACE2). By screening a yeast surface-displayed library of synthetic nanobody sequences, we developed nanobodies that disrupt the interaction between Spike and ACE2. Cryo-electron microscopy (cryo-EM) revealed that one nanobody, Nb6, binds Spike in a fully inactive conformation with its receptor binding domains locked into their inaccessible down state, incapable of binding ACE2.

Zafirlukast is a broad-spectrum thiol isomerase inhibitor that inhibits thrombosis without altering bleeding times.

Background And Purpose: Multiple members of the thiol isomerase (TI) family of enzymes are present in and released by platelets. Inhibition of these enzymes results in diminished platelet responses, aggregation, adhesion and thrombus formation. Recently, the therapeutic potential of TI inhibition has been recognised and drug-development technologies were used to identify selective small molecule inhibitors.

Kaumātua Mana Motuhake Pōi: a study protocol for enhancing wellbeing, social connectedness and cultural identity for Māori elders.

Background: The Aotearoa New Zealand population is ageing accompanied by health and social challenges including significant inequities that exist between Māori and non-Māori around poor ageing and health. Although historically kaumātua (elder Māori) faced a dominant society that failed to realise their full potential as they age, Māori culture has remained steadfast in upholding elders as cultural/community anchors. Yet, many of today's kaumātua have experienced 'cultural dissonance' as the result of a hegemonic dominant culture subjugating an Indigenous culture, leading to generations of Indigenous peoples compelled or forced to dissociate with their culture.

An ultra-potent synthetic nanobody neutralizes SARS-CoV-2 by locking Spike into an inactive conformation.

Without an effective prophylactic solution, infections from SARS-CoV-2 continue to rise worldwide with devastating health and economic costs. SARS-CoV-2 gains entry into host cells via an interaction between its Spike protein and the host cell receptor angiotensin converting enzyme 2 (ACE2). Disruption of this interaction confers potent neutralization of viral entry, providing an avenue for vaccine design and for therapeutic antibodies.

Inhibition of post-termination ribosome recycling at premature termination codons in UPF1 ATPase mutants.

Recognition and rapid degradation of mRNA harboring premature translation termination codons (PTCs) serves to protect cells from accumulating non-functional and potentially toxic truncated polypeptides. Targeting of PTC-containing transcripts is mediated by the nonsense-mediated mRNA decay (NMD) pathway and requires a conserved set of proteins including UPF1, an RNA helicase whose ATPase activity is essential for NMD. Previously, we identified a functional interaction between the NMD machinery and terminating ribosomes based on 3' RNA decay fragments that accrue in UPF1 ATPase mutants.

Māori Becoming Peer Educators in Later Life: Impacts on Identity, Well-being, and Social Connectedness.

Objective: The aim of this study was to examine ways that older Māori (New Zealand's Indigenous people) enhanced their ability to be peer educators and how this role impacted on their sense of purpose and well-being in later life.

Method: Kaupapa Māori and community-based participatory research principles guided the peer intervention involving 26 Māori kaumātua (older people 55 years and older) as peer educators (tuakana) for 121 other kaumātua (teina) facing transitions in later life. Each pair held up to 3 conversations; independent coders rated tuakana communication skills.

Kaumātua Mana Motuhake: peer education intervention to help Māori elders during later-stage life transitions.

Background: Aotearoa/New Zealand has a population that is ageing and there are challenges to health and social outcomes related to related to key life transitions (e.g., retirement, change in health conditions, loss of spouse).

Low-dose Btk inhibitors selectively block platelet activation by CLEC-2.

Inhibitors of the tyrosine kinase Btk have been proposed as novel antiplatelet agents. In this study we show that low concentrations of the Btk inhibitor ibrutinib block CLEC-2-mediated activation and tyrosine phosphorylation including Syk and PLCγ2 in human platelets. Activation is also blocked in patients with X-linked agammaglobulinemia (XLA) caused by a deficiency or absence of Btk.

Physicochemical and Biological Examination of Two Glatiramer Acetate Products.

Herein we compared 40 mg/mL lots of the active ingredient, glatiramer acetate, manufactured by Mylan/Natco to the active ingredient, glatiramer acetate in Copaxone (Teva Pharmaceuticals, Ltd., Netanya Israel) using physicochemical (PCC) methods and biological assays. No differences were seen between the Mylan/Natco and Teva lots with some low resolution release PCC assays (amino acid analysis, molecular weight distribution, interaction with Coomassie Brilliant Blue G-250).