Healthy grocery delivery in the usual care for adults recovering from an acute coronary event: protocol for a three-arm randomised controlled trial.

Introduction: Coronary heart disease is a major contributor to the global burden of disease. Appropriate nutrition is a cornerstone of the prevention and treatment of coronary heart disease; however, barriers including cost and access to recommended foods limits long-term adherence for many. We are conducting, in adults with coronary heart disease, a randomised controlled trial comparing usual care with two dietary interventions in which usual care is augmented by 12 weeks free delivered groceries.

Reducing the burden of knee osteoarthritis through community pharmacy: Protocol for a randomised controlled trial of the Knee Care for Arthritis through Pharmacy Service.

Introduction: Knee osteoarthritis (OA) negatively impacts the health outcomes and equity, social and employment participation, and socio-economic wellbeing of those affected. Little community-based support is offered to people with knee OA in Aotearoa New Zealand. Identifying Māori and non-Māori with knee OA in community pharmacy and providing co-ordinated, evidence- and community-based care may be a scalable, sustainable, equitable, effective and cost-effective approach to improve health and wellbeing.

Ras protein abundance correlates with Ras isoform mutation patterns in cancer.

Activating mutations of Ras genes are often observed in cancer. The protein products of the three Ras genes are almost identical. However, for reasons that remain unclear, KRAS is far more frequently mutated than the other Ras isoforms in cancer and RASopathies.

Uncertainty and certainty: perceptions and experiences of prediabetes in New Zealand primary care – a qualitative study.

Introduction Prediabetes is the asymptomatic precursor to type two diabetes mellitus, a significant and growing public health problem in New Zealand (NZ). Little is known about how general practitioners (GPs) and nurses view prediabetes care, and similarly little is known about how people with prediabetes view their condition and care. Aim This study aimed to investigate the views of NZ GPs and nurses, and people with prediabetes about prediabetes and its management.

A randomised controlled trial of a probiotic and a prebiotic examining metabolic and mental health outcomes in adults with pre-diabetes.

Aims: To evaluate the effect of the probiotic HN001 and/or cereal enriched with oat-derived beta-glucan (OBG) on metabolic and mental health outcomes when administered to adults with pre-diabetes.

Design: 2×2 factorial design randomised, parallel-groups placebo-controlled; double-blinded for probiotic, single-blinded for cereals.

Participants: Community-dwelling adults aged 18-80 years with pre-diabetes: glycated haemoglobin (HbA) 41-49 mmol/mol.

The Impact of COVID-19 on diet and lifestyle behaviours for pregnant women with diabetes.

Background/aims: A self-reported online survey was performed to investigate the immediate effect of COVID-19 lockdown restrictions in New Zealand on dietary intake, and lifestyle behaviours among pregnant women with diabetes.

Participants/methods: The survey was sent to 82 pregnant women who had Type 1, Type 2 Diabetes, or Gestational Diabetes and attended the Diabetes in Pregnancy Clinic in Wellington, New Zealand in May 2020, while the most restrictive COVID-19 lockdown measures were in place. All women received standard pregnancy nutrition advice provided by a dietitian, were monitoring blood glucose levels with nursing support, and seeing specialist endocrinologists and obstetricians for their pregnancy care.

Absolute Quantitation of GTPase Protein Abundance.

Ras proteins and other small molecular weight GTPases are molecular switches controlling a wide range of cellular functions. High homology and functional redundancy between closely related family members are commonly observed. Antibody-based methods are commonly used to characterize their protein expression.

The Frequency of Ras Mutations in Cancer.

Ras is frequently mutated in cancer, however, there is a lack of consensus in the literature regarding the cancer mutation frequency of Ras, with quoted values varying from 10%-30%. This variability is at least in part due to the selective aggregation of data from different databases and the dominant influence of particular cancer types and particular Ras isoforms within these datasets. To provide a more definitive figure for Ras mutation frequency in cancer, we cross-referenced the data in all major publicly accessible cancer mutation databases to determine reliable mutation frequency values for each Ras isoform in all major cancer types.

Food 4 Health - He Oranga Kai: Assessing the efficacy, acceptability and economic implications of Lactobacillus rhamnosus HN001 and β-glucan to improve glycated haemoglobin, metabolic health, and general well-being in adults with pre-diabetes: study protocol for a 2 × 2 factorial design, parallel group, placebo-controlled randomized controlled trial, with embedded qualitative study and economic analysis.

Background: The rates of pre-diabetes and type 2 diabetes mellitus are increasing worldwide, producing significant burdens for individuals, families, and healthcare systems. In New Zealand, type 2 diabetes mellitus and pre-diabetes disproportionally affect Māori, Pacific, and South Asian peoples. This research evaluates the efficacy, acceptability, and economic impact of a probiotic capsule and a prebiotic cereal intervention in adults with pre-diabetes on metabolic and mental health and well-being outcomes.

Isoform-specific Ras signaling is growth factor dependent.

HRAS, NRAS, and KRAS isoforms are almost identical proteins that are ubiquitously expressed and activate a common set of effectors. In vivo studies have revealed that they are not biologically redundant; however, the isoform specificity of Ras signaling remains poorly understood. Using a novel panel of isogenic SW48 cell lines endogenously expressing wild-type or G12V-mutated activated Ras isoforms, we have performed a detailed characterization of endogenous isoform-specific mutant Ras signaling.

Maternal supplementation alone with Lactobacillus rhamnosus HN001 during pregnancy and breastfeeding does not reduce infant eczema.

Background: In a randomized placebo-controlled trial, we previously found that the probiotic Lactobacillus rhamnosus HN001 (HN001) taken by mothers from 35 weeks of gestation until 6 months post-partum if breastfeeding and their child from birth to age 2 years halved the risk of eczema during the first 2 years of life. We aimed to test whether maternal supplementation alone is sufficient to reduce eczema and compare this to our previous study when both the mother and their child were supplemented.

Methods: In this 2-centre, parallel double-blind, randomized placebo-controlled trial, the same probiotic as in our previous study (HN001, 6 × 10 colony-forming units) was taken daily by mothers from 14-16 weeks of gestation till 6 months post-partum if breastfeeding, but was not given directly to the child.

New Perspectives, Opportunities, and Challenges in Exploring the Human Protein Kinome.

The human protein kinome comprises 535 proteins that, with the exception of approximately 50 pseudokinases, control intracellular signaling networks by catalyzing the phosphorylation of multiple protein substrates. While a major research focus of the last 30 years has been cancer-associated Tyr and Ser/Thr kinases, over 85% of the kinome has been identified to be dysregulated in at least one disease or developmental disorder. Despite this remarkable statistic, for the majority of protein kinases and pseudokinases, there are currently no inhibitors progressing toward the clinic, and in most cases, details of their physiologic and pathologic mechanisms remain at least partially obscure.

Modulating Protein-Protein Interactions of the Mitotic Polo-like Kinases to Target Mutant KRAS.

Mutations activating KRAS underlie many forms of cancer, but are refractory to therapeutic targeting. Here, we develop Poloppin, an inhibitor of protein-protein interactions via the Polo-box domain (PBD) of the mitotic Polo-like kinases (PLKs), in monotherapeutic and combination strategies to target mutant KRAS. Poloppin engages its targets in biochemical and cellular assays, triggering mitotic arrest with defective chromosome congression.

Early pregnancy probiotic supplementation with Lactobacillus rhamnosus HN001 may reduce the prevalence of gestational diabetes mellitus: a randomised controlled trial.

The study aims to assess whether supplementation with the probiotic Lactobacillus rhamnosus HN001 (HN001) can reduce the prevalence of gestational diabetes mellitus (GDM). A double-blind, randomised, placebo-controlled parallel trial was conducted in New Zealand (NZ) (Wellington and Auckland). Pregnant women with a personal or partner history of atopic disease were randomised at 14-16 weeks' gestation to receive HN001 (6×109 colony-forming units) (n 212) or placebo (n 211) daily.

The Probiotics in Pregnancy Study (PiP Study): rationale and design of a double-blind randomised controlled trial to improve maternal health during pregnancy and prevent infant eczema and allergy.

Background: Worldwide there is increasing interest in the manipulation of human gut microbiota by the use of probiotic supplements to modify or prevent a range of communicable and non-communicable diseases. Probiotic interventions administered during pregnancy and breastfeeding offer a unique opportunity to influence a range of important maternal and infant outcomes. The aim of the Probiotics in Pregnancy Study (PiP Study) is to assess if supplementation by the probiotic Lactobacillus rhamnosus HN001 administered to women from early pregnancy and while breastfeeding can reduce the rates of infant eczema and atopic sensitisation at 1 year, and maternal gestational diabetes mellitus, bacterial vaginosis and Group B Streptococcal vaginal colonisation before birth, and depression and anxiety postpartum.

The mesh is a network of microtubule connectors that stabilizes individual kinetochore fibers of the mitotic spindle.

Kinetochore fibers (K-fibers) of the mitotic spindle are force-generating units that power chromosome movement during mitosis. K-fibers are composed of many microtubules that are held together throughout their length. Here, we show, using 3D electron microscopy, that K-fiber microtubules (MTs) are connected by a network of MT connectors.

Hsp72 is targeted to the mitotic spindle by Nek6 to promote K-fiber assembly and mitotic progression.

Hsp70 proteins represent a family of chaperones that regulate cellular homeostasis and are required for cancer cell survival. However, their function and regulation in mitosis remain unknown. In this paper, we show that the major inducible cytoplasmic Hsp70 isoform, Hsp72, is required for assembly of a robust bipolar spindle capable of efficient chromosome congression.

Decoding RAS isoform and codon-specific signalling.

RAS proteins are key signalling hubs that are oncogenically mutated in 30% of all cancer cases. Three genes encode almost identical isoforms that are ubiquitously expressed, but are not functionally redundant. The network responses associated with each isoform and individual oncogenic mutations remain to be fully characterized.

Coordination of adjacent domains mediates TACC3-ch-TOG-clathrin assembly and mitotic spindle binding.

A complex of transforming acidic coiled-coil protein 3 (TACC3), colonic and hepatic tumor overexpressed gene (ch-TOG), and clathrin has been implicated in mitotic spindle assembly and in the stabilization of kinetochore fibers by cross-linking microtubules. It is unclear how this complex binds microtubules and how the proteins in the complex interact with one another. TACC3 and clathrin have each been proposed to be the spindle recruitment factor.

Aurora A kinase activity is required for localization of TACC3/ch-TOG/clathrin inter-microtubule bridges.

Accurate chromosome segregation during mitosis is achieved by the kinetochore fibers (K-fibers) of the spindle apparatus. These fibers are bundles of microtubules (MTs) connected by non-motor bridges. We recently identified a TACC3/ch-TOG/clathrin complex that constitutes the shortest class of inter-MT bridge in K-fibers.

Pulling it together: The mitotic function of TACC3.

Transforming acidic coiled coil 3 (TACC3) is a non-motor microtubule-associated protein (MAP) that is important for mitotic spindle stability and organization. The exact mechanism by which TACC3 acts at microtubules to stabilize the spindle has been unclear. However, several recent studies identified that the TACC3 complex at microtubules contains clathrin in addition to its previously identified binding partner, colonic and hepatic tumor overexpressed gene (ch-TOG).

A TACC3/ch-TOG/clathrin complex stabilises kinetochore fibres by inter-microtubule bridging.

Kinetochore fibres (K-fibres) of the spindle apparatus move chromosomes during mitosis. These fibres are discrete bundles of parallel microtubules (MTs) that are crosslinked by inter-MT 'bridges' that are thought to improve fibre stability during chromosomal movement. The identity of these bridges is unknown.

The methylated N-terminal tail of RCC1 is required for stabilisation of its interaction with chromatin by Ran in live cells.

Background: Regulator of chromosome condensation 1 (RCC1) is the guanine nucleotide exchange factor for Ran GTPase. Localised generation of Ran-GTP by RCC1 on chromatin is critical for nucleocytoplasmic transport, mitotic spindle assembly and nuclear envelope formation. Both the N-terminal tail of RCC1 and its association with Ran are important for its interaction with chromatin in cells.

Functional equivalence of the clathrin heavy chains CHC17 and CHC22 in endocytosis and mitosis.

Clathrin is crucial for endocytosis and plays a recently described role in mitosis. Two clathrin heavy chains (CHCs) are found in humans: the ubiquitous CHC17, and CHC22, a CHC that is enriched in skeletal muscle. Functional differences have been proposed for these clathrins despite high sequence similarity.

RCC1 isoforms differ in their affinity for chromatin, molecular interactions and regulation by phosphorylation.

RCC1 is the guanine nucleotide exchange factor for Ran GTPase. Generation of Ran-GTP by RCC1 on chromatin provides a spatial signal that directs nucleocytoplasmic transport, mitotic spindle assembly and nuclear envelope formation. We show that RCC1 is expressed in human cells as at least three isoforms, named RCC1alpha, RCC1beta and RCC1gamma, which are expressed at different levels in specific tissues.