Type 2 diabetes mellitus (T2DM) is a major disease worldwide, causing significant mortality and morbidity. Currently, in Aotearoa, New Zealand, there is a high prevalence of T2DM, with a disproportionate impact on Māori and Pacific populations(1). Moreover, it has been predicted that the prevalence will continually increase. Research has shown that insulin resistance (IR) has been reported to play a critical role in the development of T2DM and other related cardiometabolic diseases(2). Therefore, managing IR is crucial to reducing the development of T2DM. Notably, bioactive compounds in various diets are known to modify the risk of T2DM by regulating IR. Among such dietary compounds include kawakawa (Piper excelsum), an indigenous species used by Māori in traditional medicine (Rongoā). Kawakawa is shown to contain several bioactive compounds that are shown to have insulin-sensitising effects. Research by our group has recently shown kawakawa to have potential anti-diabetic and anti-inflammatory effects in healthy human volunteers(3,4). However, how Kawakawa exerts these effects on insulin signalling and glucose uptake remains unknown. We hypothesise that kawakawa will enhance the glucose uptake in the treated cells and will differentially regulate key genes involved in insulin signalling pathways, including GLUT2, IRS-1, PPAR-γ, and PI3K/Akt, across various tissues. To test our hypothesis, we aim to investigate the mechanistic action of kawakawa extract on insulin signalling pathways in different cell models from metabolically active organs. We will use the same kawakawa powder sample shown to improve postprandial insulin in a healthy population. Cell models representing different insulin-responsive organs: liver (HepG2), skeletal muscle (L6-GLUT4myc), pancreas (MIN6), and adipose (3T3-L1) will be used. The cells will be treated with different doses of kawakawa extract, and glucose uptake will be measured. Key signalling pathways, including GLUT2, IRS-1, PPAR-γ, and PI3K/Akt, will be monitored using western blot and quantitative polymerase chain reaction (qPCR) analysis. The findings of this study have the potential to identify key targets of kawakawa action on insulin signalling in metabolically active organs. These outcomes will inform future research with kawakawa in clinical settings in people with cardiometabolic diseases such as T2DM and can form the basis for developing a dietary intervention for individuals at risk of these diseases. Additionally, Rongoā is an acceptable intervention by Māori, integrating this knowledge with evidence-based scientific interventions would aid in creating a holistic health paradigm that resonates within Māori communities.

Astrobiology is a scientific field that is very interdisciplinary and developing very fast, with many new discoveries generating a high level of attention in both the scientific community and the public. A central goal of astrobiology is to discover life beyond Earth which is, with our current instrumentation and knowledge, arguably within our reach. However, knowledge exchange crossing disciplinary boundaries is becoming increasingly challenging due to different usage of nomenclature and scientific controversies often limited to subdisciplines. There have been some efforts to compile organized databases of terms, concepts and other relevant material within some of the subfields contributing to astrobiology, for example through manually curated online portals designed to benefit students, teachers and practitioners of astrobiology-related research. However, the developments within the subfields and the potentially premature communication of research findings are too fast for objective research portals to remain reliable and up-to-date enough to enable well-informed scientific discussions. We suggest here a novel strategy for developing an online tracers portal as a self-maintaining and self-updating information platform, that would allow not only for a relatively unbiased selection of research results, but also provide fast access to latest scientific discoveries together with potential controversies, such that users of the tracers portal can form their own opinion on all available data rather than obtaining an already filtered and potentially biased selection of information.

Objectives/Goals: The never in mitosis kinase (NEK) family regulates vital processes, namely cell cycle progression, but their potential as therapeutic targets in TNBC has not been fully explored. Our studies aim to develop a toolkit to investigate the functional roles of NEKs in pathologies including carcinogenesis. Methods/Study Population: To assess differential NEK expression in normal and tumor tissues and correlation of gene expression with patient survival, we used Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan–Meier Plotter (KMPlot) pan-cancer analysis, respectively. Basal NEK protein levels were determined by immunoblot across a panel of cell lines, including breast cancer, osteosarcoma, hepatocellular carcinoma, and non-cancerous cells, to identify appropriate systems for evaluation of NEK function. Doxycycline-inducible cell lines were generated by transduction with lentiviral stocks of NEK shRNA and overexpression constructs and antibiotic selection. Expression was analyzed by qPCR and immunoblot. Results/Anticipated Results: Expression of NEK2, 4, 5, 6, 8, and 11 was higher in breast tumors compared to normal tissue by GEPIA analysis. Further examination using KMPlot showed a correlation between elevated NEK6 expression and decreased overall survival in patients with aggressive cancers. As an initial proof-of-concept study, we analyzed NEK6 protein expression in breast cancer cells. Levels of NEK6 were elevated in TNBC cells (MDA-MB-231) compared to hormone receptor positive (HR+) breast cancer cells (MCF7). Using complementary approaches to investigate the functional role of NEK6 in breast cancer, we depleted NEK6 expression using shRNAs in TNBC cells and expressed NEK6 in HR+ cells Discussion/Significance of Impact: Because kinase dysregulation promotes oncogenesis and metastasis, targeting kinases is a key strategy in therapeutic development. A NEK-specific molecular toolkit allows researchers to elucidate NEK functions and contributions to carcinogenesis, promoting advancement of novel therapies.

North Carolina growers have long struggled to control Italian ryegrass, and recent research has confirmed that some Italian ryegrass biotypes have become resistant to nicosulfuron, glyphosate, clethodim, and paraquat. Integrating alternative management strategies is crucial to effectively control such biotypes. The objectives of this study were to evaluate Italian ryegrass control with cover crops and fall-applied residual herbicides and investigate cover crop injury from residual herbicides. This study was conducted during the fall/winter of 2021–22 in Salisbury, NC, and fall/winter of 2021–22 and 2022–23 in Clayton, NC. The study was designed as a 3 × 5 split-plot in which the main plot consisted of three cover crop treatments (no-cover, cereal rye at 80 kg ha−1, and crimson clover at 18 kg ha−1), and the subplots consisted of five residual herbicide treatments (S-metolachlor, flumioxazin, metribuzin, pyroxasulfone, and nontreated). In the 2021–22 season at Clayton, metribuzin injured cereal rye and crimson clover 65% and 55%, respectively. However, metribuzin injured both cover crops ≤6% in 2022–23. Flumioxazin resulted in unacceptable crimson clover injury of 50% and 38% in 2021–22 and 2022–23 in Clayton and 40% in Salisbury, respectively. Without preemergence herbicides, cereal rye controlled Italian ryegrass by 85% and 61% at 24 wk after planting in 2021–22 and 2022–23 in Clayton and 82% in Salisbury, respectively. In 2021–22, Italian ryegrass seed production was lowest in cereal rye plots at both locations, except when it was treated with metribuzin. For example, in Salisbury, cereal rye plus metribuzin resulted in 39,324 seeds m–2, compared to ≤4,386 seeds m–2 from all other cereal rye treatments. In 2022–23, Italian ryegrass seed production in cereal rye was lower when either metribuzin or pyroxasulfone were used preemergence (2,670 and 1,299 seeds m–2, respectively) compared with cereal rye that did not receive an herbicide treatment (5,600 seeds m–2). cereal rye (Secale cereale L.) and crimson clover (Trifolium incarnatum L.)

Two studies were conducted in 2022 and 2023 near Rocky Mount and Clayton, NC, to determine the optimal granular ammonium sulfate (AMS) rate and application timing for pyroxasulfone-coated AMS. In the rate study, AMS rates included 161, 214, 267, 321, 374, 428, and 481 kg ha−1, equivalent to 34, 45, 56, 67, 79, 90, and 101 kg N ha−1, respectively. All rates were coated with pyroxasulfone at 118 g ai ha−1 and topdressed onto 5- to 7-leaf cotton. In the timing study, pyroxasulfone (118 g ai ha−1) was coated on AMS and topdressed at 321 kg ha−1 (67 kg N ha−1) onto 5- to 7-leaf, 9- to 11-leaf, and first bloom cotton. In both studies, weed control and cotton tolerance to pyroxasulfone-coated AMS were compared to pyroxasulfone applied POST and POST-directed. The check in both studies received non-herbicide-treated AMS (321 kg ha−1). Before treatment applications, all plots (including the check) were maintained weed-free with glyphosate and glufosinate. In both studies, pyroxasulfone applied POST was most injurious (8% to 16%), while pyroxasulfone-coated AMS resulted in ≤4% injury. Additionally, no differences in cotton lint yield were observed in either study. With the exception of the lowest rate of AMS (161 kg ha−1; 79%), all AMS rates coated with pyroxasulfone controlled Palmer amaranth ≥83%, comparably to pyroxasulfone applied POST (92%) and POST-directed (89%). In the timing study, the application method did not affect Palmer amaranth control; however, applications made at the mid- and late timings outperformed early applications. These results indicate that pyroxasulfone-coated AMS can control Palmer amaranth comparably to pyroxasulfone applied POST and POST-directed, with minimal risk of cotton injury. However, the application timing could warrant additional treatment to achieve adequate late-season weed control.

An experiment was conducted in 2022 and 2023 near Rocky Mount and Clayton, NC, to evaluate residual herbicide-coated fertilizer for cotton tolerance and Palmer amaranth control. Treatments included acetochlor, atrazine, dimethenamid-P, diuron, flumioxazin, fluometuron, fluridone, fomesafen, linuron, metribuzin, pendimethalin, pyroxasulfone, pyroxasulfone + carfentrazone, S-metolachlor, and sulfentrazone. Each herbicide was individually coated on granular ammonium sulfate (AMS) and top-dressed at 321 kg ha−1 (67 kg N ha−1) onto 5- to 7-leaf cotton. The check plots received the equivalent rate of nonherbicide-treated AMS. Before top-dress, all plots (including the check) were treated with glyphosate and glufosinate to control previously emerged weeds. All herbicides except metribuzin resulted in transient cotton injury. Cotton response to metribuzin varied by year and location. In 2022, metribuzin caused 11% to 39% and 8% to 17% injury at the Clayton and Rocky Mount locations, respectively. In 2023, metribuzin caused 13% to 32% injury at Clayton and 73% to 84% injury at Rocky Mount. Pyroxasulfone (91%), pyroxasulfone + carfentrazone (89%), fomesafen (87%), fluridone (86%), flumioxazin (86%), and atrazine (85%) controlled Palmer amaranth ≥85%. Pendimethalin and fluometuron were the least effective treatments, resulting in 58% and 62% control, respectively. As anticipated, early season metribuzin injury translated into yield loss; plots treated with metribuzin yielded 640 kg ha−1 and were comparable to yields after linuron (790 kg ha−1) was used. These findings suggest that with the exception of metribuzin, residual herbicides coated onto AMS may be suitable and effective in cotton production, providing growers with additional modes of action for late-season control of multiple herbicide–resistant Palmer amaranth.

We present the Pilot Survey Phase 2 data release for the Wide-field ASKAP L-band Legacy All-sky Blind surveY (WALLABY), carried-out using the Australian SKA Pathfinder (ASKAP). We present 1760 H i detections (with a default spatial resolution of 30′′) from three pilot fields including the NGC 5044 and NGC 4808 groups as well as the Vela field, covering a total of $\sim 180$ deg$^2$ of the sky and spanning a redshift up to $z \simeq 0.09$. This release also includes kinematic models for over 126 spatially resolved galaxies. The observed median rms noise in the image cubes is 1.7 mJy per 30′′ beam and 18.5 kHz channel. This corresponds to a 5$\sigma$ H i column density sensitivity of $\sim 9.1\times10^{19}(1 + z)^4$ cm$^{-2}$ per 30′′ beam and $\sim 20$ km s$^{-1}$ channel and a 5$\sigma$ H i mass sensitivity of $\sim 5.5\times10^8 (D/100$ Mpc)$^{2}$ M$_{\odot}$ for point sources. Furthermore, we also present for the first time 12′′ high-resolution images (“cut-outs”) and catalogues for a sub-sample of 80 sources from the Pilot Survey Phase 2 fields. While we are able to recover sources with lower signal-to-noise ratio compared to sources in the Public Data Release 1, we do note that some data quality issues still persist, notably, flux discrepancies that are linked to the impact of side lobes associated with the dirty beams due to inadequate deconvolution. However, in spite of these limitations, the WALLABY Pilot Survey Phase 2 has already produced roughly a third of the number of HIPASS sources, making this the largest spatially resolved H i sample from a single survey to date.

Background: Hyperacute stroke care demands rapid, coordinated care. Traditional metrics like Door-to-Needle time are pivotal but insufficient for capturing the complexity of endovascular stroke interventions. The SMILES collaboration aims to standardize and optimize protocols for door-to-intervention times, incorporating Crew Resource Management (CRM). Methods: The multidisciplinary initiative integrates both hospitals, ED, neurology, and QI teams. We employed a comprehensive approach: stakeholder engagement, simulation-based learning, process mapping, and literature review. Emphasis was placed on enhancing situational awareness, triage and prioritization, cognitive load management, role clarity, effective communication, and debriefing. Results: The collaboration led to PDSA cycles and development of refined stroke protocols. Interventions included: 1) A ’zero point survey’ for team pre-arrival briefings, enhancing situational awareness and role clarity; 2) Streamlined patient registration to reduce cognitive load and improve triage efficiency; 3) Direct transfer of patients to imaging. Additionally, digital tools were implemented to facilitate communication. Simulation sessions reinforced CRM principles, leading to improved team cohesion and operational performance. Conclusions: The SMILES initiative is grounded in CRM principles by standardizing protocols and emphasizing non-technical skills crucial for high-stakes environments. This improves outcomes but also fosters a culture of safety and efficiency. Future directions include an evaluation of these protocols’ impact on patient factors.

Background: Frontotemporal dementia (FTD) often presents with varying neuropsychiatric symptoms (NPS), which may differ based on genetic mutations. We hypothesized distinct NPS trajectories in FTD progression among carriers of chromosome 9 open reading frame 72 (C9orf72), progranulin (GRN), and microtubule-associated protein tau (MAPT) mutations. Methods: We analyzed 1662 participants from ALLFTD, including 342 C9orf72, 148 GRN, 168 MAPT mutation carriers, and 1004 noncarriers. We categorized participants into four stages based on CDR plus NACC FTLD global scores: 1) Presymptomatic (consistent CDR=0), 2) Early conversion (CDR increasing from 0 to 0.5), 3) Advanced conversion (CDR increasing from 0.5 to ≥1.0), and 4) Symptomatic (CDR>1.0). The Neuropsychiatric Inventory-Questionnaire (NPI-Q) assessed NPS changes, analyzed using a mixed-effects model, accounting for age and baseline scores. Results: Our results indicated similar NPS trajectories in the presymptomatic stage for all groups. Notably, during early conversion, C9orf72 and GRN carriers exhibited significantly higher NPI-Q score increases than MAPT carriers, primarily in psychosis and hyperactivity domains. In later stages, increases in NPS were similar across groups. Conclusions: This study suggests familial FTD progression, particularly in TDP-43 pathology, may involve more severe NPS like psychosis or hyperactivity, differing from tau pathology or sporadic FTD. Further research is needed to explore these distinct trajectories.

Plant growth requires the integration of internal and external cues, perceived and transduced into a developmental programme of cell division, elongation and wall thickening. Mechanical forces contribute to this regulation, and thigmomorphogenesis typically includes reducing stem height, increasing stem diameter, and a canonical transcriptomic response. We present data on a bZIP transcription factor involved in this process in grasses. Brachypodium distachyon SECONDARY WALL INTERACTING bZIP (SWIZ) protein translocated into the nucleus following mechanostimulation. Classical touch-responsive genes were upregulated in B. distachyon roots following touch, including significant induction of the glycoside hydrolase 17 family, which may be unique to grass thigmomorphogenesis. SWIZ protein binding to an E-box variant in exons and introns was associated with immediate activation followed by repression of gene expression. SWIZ overexpression resulted in plants with reduced stem and root elongation. These data further define plant touch-responsive transcriptomics and physiology, offering insights into grass mechanotranduction dynamics.

Clinical outcomes of repetitive transcranial magnetic stimulation (rTMS) for treatment of treatment-resistant depression (TRD) vary widely and there is no mood rating scale that is standard for assessing rTMS outcome. It remains unclear whether TMS is as efficacious in older adults with late-life depression (LLD) compared to younger adults with major depressive disorder (MDD). This study examined the effect of age on outcomes of rTMS treatment of adults with TRD. Self-report and observer mood ratings were measured weekly in 687 subjects ages 16–100 years undergoing rTMS treatment using the Inventory of Depressive Symptomatology 30-item Self-Report (IDS-SR), Patient Health Questionnaire 9-item (PHQ), Profile of Mood States 30-item, and Hamilton Depression Rating Scale 17-item (HDRS). All rating scales detected significant improvement with treatment; response and remission rates varied by scale but not by age (response/remission ≥ 60: 38%–57%/25%–33%; <60: 32%–49%/18%–25%). Proportional hazards models showed early improvement predicted later improvement across ages, though early improvements in PHQ and HDRS were more predictive of remission in those < 60 years (relative to those ≥ 60) and greater baseline IDS burden was more predictive of non-remission in those ≥ 60 years (relative to those < 60). These results indicate there is no significant effect of age on treatment outcomes in rTMS for TRD, though rating instruments may differ in assessment of symptom burden between younger and older adults during treatment.