Basin-scale study of CO2 storage in stacked sequence of geological formations.

Commercial scale decarbonization through carbon capture and storage may likely involve many CO2 storage projects located in close proximity. The close proximity could raise concerns over caprock integrity associated with reservoir pressure buildup and interference among adjacent projects. Commercial-scale injection will also require large prospective CO2 storage resource and high injectivity in the targeted storage formations. To accommodate the need for both large resource and high injectivity, project operators could consider injecting CO2 into a stacked sequence of formations. This analysis investigates the benefits of injecting CO2 into a vertically stacked sequence of saline formations, over injecting the same amount of CO2 into a single saline formation, in addressing these challenges. Our analysis shows that injecting into the stacked sequence mitigates the extent of pressure buildup among the stacked formations, while still achieving the same or greater target CO2 storage volumes. Among cases modeled, the resulting pressure buildup front is most reduced when each storage site distributes injection volumes over several wells, each of which injects a portion of the total CO2 mass across the stacked sequence. This favorable case not only results in the smallest CO2 aerial footprint, but also shows the largest reduction in the pressure buildup at the top of perforation at the injection wells (upwards of approximately 46% compared to the single-formation storage), the result of which is crucial to maintain caprock integrity. This analysis provides insights into required decision-making when considering multi-project deployment in a shared basin.

Generating luminescent Graphene quantum Dots from Tryptophan: Fluorosensors for hydrogen peroxide in cancer cells.

Herein, we report a single step synthesis of highly fluorescent Graphene Quantum Dots (GQDs) using tryptophan and glycerol as precursors via pyrolysis. The morphological and functional characterization of the prepared GQDs was performed using PXRD, FTIR, TEM, XPS and zeta potential measurements. The prepared GQDs found their practical application in ultrasensitive detection of an emerging potential cancer biomarker, H2O2, by exploiting the fluorescence quenching behaviour of H2O2. To evaluate the detection sensitivity, a series of various concentrations of H2O2 was spiked to biomatrices like, serum and MCF-7 (human breast cancer cell line) cell lysate medium. A remarkably low limit of detection (LOD) was found in serum medium (139.5 pM) which further improved in MCF-7 cell lysate medium (LOD 61.43 pM). Moreover, the sensing capacity of the GQDs was further validated in presence of various physiological variables such as glucose, cholesterol, insulin and nitrite. Sensing assay was also carried out in HaCaT (human keratinocyte cell line) cell lysate medium to compare the performance of our prepared sensor but the non-linearity of the F0/F versus H2O2 concentration plot pointed towards the conduciveness of the MCF-7 cell lysate medium for sensitive detection of H2O2.The mechanism behind the sensing was also explored using spectroscopic methods.

Rural-Urban mild cognitive impairment comparison in West Michigan through EHR.

INTRODUCTION: Mild cognitive impairment (MCI) is a significant public health concern and a potential precursor to Alzheimer's disease (AD). This study leverages electronic health record (EHR) data to explore rural-urban differences in MCI incidence, risk factors, and healthcare navigation in West Michigan. METHODS: Analysis was conducted on 1,528,464 patients from Corewell Health West, using face-to-face encounters between 1/1/2015 and 7/31/2022. MCI cases were identified using International Classification of Diseases (ICD) codes, focusing on patients aged 45+ without prior MCI, dementia, or AD diagnoses. Incidence rates, cumulative incidences, primary care physicians (PCPs), and neuropsychology referral outcomes were examined across rural and urban areas. Risk factors were evaluated through univariate and multivariate Cox regression analyses. The geographic distribution of patient counts, hospital locations, and neurology department referrals were examined. RESULTS: Among 423,592 patients, a higher MCI incidence rate was observed in urban settings compared to rural settings (3.83 vs. 3.22 per 1,000 person-years). However, sensitivity analysis revealed higher incidence rates in rural areas when including patients who progressed directly to dementia. Urban patients demonstrated higher rates of referrals to and completion of neurological services. While the risk factors for MCI were largely similar across urban and rural populations, urban-specific factors for incident MCI are hearing loss, inflammatory bowel disease, obstructive sleep apnea, insomnia, being African American, and being underweight. Common risk factors include diabetes, intracranial injury, cerebrovascular disease, coronary artery disease, stroke, Parkinson's disease, epilepsy, chronic obstructive pulmonary disease, depression, and increased age. Lower risk was associated with being female, having a higher body mass index, and having a higher diastolic blood pressure. DISCUSSION: This study highlights rural-urban differences in MCI incidence and access to care, suggesting potential underdiagnosis in rural areas likely due to reduced access to specialists. Future research should explore socioeconomic, environmental, and lifestyle determinants of MCI to refine prevention and management strategies across geographic settings. Highlights: Leveraged EHRs to explore rural-urban differences in MCI in West Michigan.Revealed a significant underdiagnosis of MCI, especially in rural areas.Observed lower rates of neurological referrals and completions for rural patients.Identified risk factors specific to rural and urban populations.

Interface Engineering of Water-Dispersible Near-Infrared-Emitting CuInZnS/ZnSe/ZnS Quantum Dots.

We report the synthesis of near-infrared (IR)-emitting core/shell/shell quantum dots of CuInZnS/ZnSe/ZnS and their phase transfer to water. The intermediate ZnSe shell was added to inhibit the migration of ions from the standard ZnS shell into the emitting core, which often leads to a blue shift in the emission profile. By engineering the interface between the core and terminal shell layer, the optical properties can be controlled, and emission was maintained in the near-IR region, making the materials attractive for biological applications. In addition, the hydrodynamic diameter of the particle was controlled using amphiphilic polymers.

Insights into the nucleation and growth of BiOCl nanoparticles by in situ X-ray pair distribution function analysis and in situ liquid cell TEM.

The synthesis of bismuth oxyhalides as defined nanostructures is hindered by their fast nucleation and growth in aqueous solutions. Using our recently developed single-source precursor, the formation of bismuth oxychloride in such solutions can be slowed significantly. As reported herein, this advance enables BiOCl formation to be investigated by in situ X-ray total scattering and in situ liquid cell transmission electron microscopy. In situ pair distribution function analysis of X-ray total scattering data reveals the local order of atomic structures throughout the synthesis, while in situ liquid cell transmission electron microscopy allows for tracking the growth of individual nanoparticles. Through this work, the precursor complex is shown to give rise to BiOCl upon heating in solution without the observation of structurally distinct intermediates. The emerging nanoparticles have a widened interlayer spacing, which moderately decreases as the particles grow. Mechanistic insights into the formation of bismuth oxyhalide nanoparticles, including the absence of distinct intermediates within the available time resolution, will help facilitate future design of controlled BiOX nanostructures.

Blended e-learning and certification for medicines development professionals: results of a 7-year collaboration between King's College, London and the GMDP Academy, New York.

Introduction: The field of Medicines Development faces a continuous need for educational evolution to match the interdisciplinary and global nature of the pharmaceutical industry. This paper discusses the outcomes of a 7-year collaboration between King's College London and the Global Medicines Development Professionals (GMDP) Academy, which aimed to address this need through a blended e-learning program. Methods: The collaboration developed a comprehensive curriculum based on the PharmaTrain syllabus, delivered through a combination of asynchronous and synchronous e-learning methods. The program targeted a diverse range of professionals serving in areas related to Medical Affairs. Results: Over seven annual cohorts, 682 participants from eighty-six countries were enrolled in the program. The program's effectiveness was assessed using Kirkpatrick's model, showing elevated levels of satisfaction (over 4.0 on a five-point scale), suggesting significant gains in competence at the cognitive level and leveraged performance. Notably, 70% of responding alumni reported significant improvement in their functions, corroborated by 30% of their supervisors. The further long-term impact of the program on their respective organization has not been established. Discussion: The GMDP Academy's program has significantly contributed to life-long learning in Medicines Development, addressing educational gaps and fostering interdisciplinary collaboration. Its success highlights the importance of continuous education in keeping pace with the industry's evolving demands and underscores the potential of blended learning in achieving educational objectives in pharmaceutical medicine.

Developing the Open Psychedelic Evaluation Nexus consensus measures for assessment of supervised psilocybin services: An e-Delphi study.

BACKGROUND: Voter initiatives in Oregon and Colorado authorize legal frameworks for supervised psilocybin services, but no measures monitor safety or outcomes. AIMS: To develop core measures of best practices. METHODS: A three-phase e-Delphi process recruited 36 experts with 5 or more years' experience facilitating psilocybin experiences in various contexts (e.g., ceremonial settings, indigenous practices, clinical trials), or other pertinent psilocybin expertise. Phase I, an on-line survey with qualitative, open-ended text responses, generated potential measures to assess processes, outcomes, and structure reflecting high quality psilocybin services. In Phase II, experts used seven-point Likert scales to rate the importance and feasibility of the Phase I measures. Measures were priority ranked. Qualitative interviews and analysis in Phase III refined top-rated measures. RESULTS: Experts (n = 36; 53% female; 71% white; 56% heterosexual) reported currently providing psilocybin services (64%) for a mean of 15.2 [SD 13.1] years, experience with indigenous psychedelic practices (67%), and/or conducting clinical trials (36%). Thematic analysis of Phase I responses yielded 55 candidate process measures (e.g., preparatory hours with client, total dose of psilocybin administered, documentation of touch/sexual boundaries), outcome measures (e.g., adverse events, well-being, anxiety/depression symptoms), and structure measures (e.g., facilitator training in trauma informed care, referral capacity for medical/psychiatric issues). In Phase II and III, experts prioritized a core set of 11 process, 11 outcome, and 17 structure measures that balanced importance and feasibility. CONCLUSION: Service providers and policy makers should consider standardizing core measures developed in this study to monitor the safety, quality, and outcomes of community-based psilocybin services.

Long-term climatic stability drives accumulation and maintenance of divergent freshwater fish lineages in a temperate biodiversity hotspot.

Anthropogenic climate change is forecast to drive regional climate disruption and instability across the globe. These impacts are likely to be exacerbated within biodiversity hotspots, both due to the greater potential for species loss but also to the possibility that endemic lineages might not have experienced significant climatic variation in the past, limiting their evolutionary potential to respond to rapid climate change. We assessed the role of climatic stability on the accumulation and persistence of lineages in an obligate freshwater fish group endemic to the southwest Western Australia (SWWA) biodiversity hotspot. Using 19,426 genomic (ddRAD-seq) markers and species distribution modelling, we explored the phylogeographic history of western (Nannoperca vittata) and little (Nannoperca pygmaea) pygmy perches, assessing population divergence and phylogenetic relationships, delimiting species and estimating changes in species distributions from the Pliocene to 2100. We identified two deep phylogroups comprising three divergent clusters, which showed no historical connectivity since the Pliocene. We conservatively suggest these represent three isolated species with additional intraspecific structure within one widespread species. All lineages showed long-term patterns of isolation and persistence owing to climatic stability but with significant range contractions likely under future climate change. Our results highlighted the role of climatic stability in allowing the persistence of isolated lineages in the SWWA. This biodiversity hotspot is under compounding threat from ongoing climate change and habitat modification, which may further threaten previously undetected cryptic diversity across the region.

α-Adrenergic regulation of skeletal muscle blood flow during exercise in patients with heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) has been characterized by lower blood flow to exercising limbs and lower peak oxygen utilization ( V ̇ O 2 ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ ), possibly associated with disease-related changes in sympathetic (α-adrenergic) signaling. Thus, in seven patients with HFpEF (70 ± 6 years, 3 female/4 male) and seven controls (CON) (66 ± 3 years, 3 female/4 male), we examined changes (%Δ) in leg blood flow (LBF, Doppler ultrasound) and leg V ̇ O 2 ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ to intra-arterial infusion of phentolamine (PHEN, α-adrenergic antagonist) or phenylephrine (PE, α1-adrenergic agonist) at rest and during single-leg knee-extension exercise (0, 5 and 10 W). At rest, the PHEN-induced increase in LBF was not different between groups, but PE-induced reductions in LBF were lower in HFpEF (-16% ± 4% vs. -26% ± 5%, HFpEF vs. CON; P < 0.05). During exercise, the PHEN-induced increase in LBF was greater in HFpEF at 10 W (16% ± 8% vs. 8% ± 5%; P < 0.05). PHEN increased leg V ̇ O 2 ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ in HFpEF (10% ± 3%, 11% ± 6%, 15% ± 7% at 0, 5 and 10 W; P < 0.05) but not in controls (-1% ± 9%, -4% ± 2%, -1% ± 5%; P = 0.24). The 'magnitude of sympatholysis' (PE-induced %Δ LBF at rest - PE-induced %Δ LBF during exercise) was lower in patients with HFpEF (-6% ± 4%, -6% ± 6%, -7% ± 5% vs. -13% ± 6%, -17% ± 5%, -20% ± 5% at 0, 5 and 10 W; P < 0.05) and was positively related to LBF, leg oxygen delivery, leg V ̇ O 2 ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ , and the PHEN-induced increase in LBF (P < 0.05). Together, these data indicate that excessive α-adrenergic vasoconstriction restrains blood flow and limits V ̇ O 2 ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ of the exercising leg in patients with HFpEF, and is related to impaired functional sympatholysis in this patient group. KEY POINTS: Sympathetic (α-adrenergic)-mediated vasoconstriction is exaggerated during exercise in patients with heart failure with preserved ejection fraction (HFpEF), which may contribute to limitations of blood flow, oxygen delivery and oxygen utilization in the exercising muscle. The ability to adequately attenuate α1-adrenergic vasoconstriction (i.e. functional sympatholysis) within the vasculature of the exercising muscle is impaired in patients with HFpEF. These observations extend our current understanding of HFpEF pathophysiology by implicating excessive α-adrenergic restraint and impaired functional sympatholysis as important contributors to disease-related impairments in exercising muscle blood flow and oxygen utilization in these patients.

Induction of tauopathy in a mouse model of amyloidosis using intravenous administration of adeno-associated virus vectors expressing human P301L tau.

INTRODUCTION: Alzheimer's disease (AD) is a progressive neurodegenerative disease in which extracellular aggregates of the amyloid beta (Aß) peptide precede widespread intracellular inclusions of the microtubule-associated protein tau. The autosomal dominant form of AD requires mutations that increase production or aggregation of the Aß peptide. This has led to the hypothesis that amyloid deposition initiates downstream responses that lead to the hyperphosphorylation and aggregation of tau. METHODS: Here we use a novel approach, somatic gene transfer via intravenous adeno-associated virus (AAV), to further explore the effects of pre-existing amyloid deposits on tauopathy. APP+PS1 mice, which develop amyloid deposits at 3 to 6 months of age, and non-transgenic littermates were injected at 8 months of age intravenously with AAV-PHP.eB encoding P301L human tau. Tissue was collected at 13 months and tauopathy was assessed. RESULTS: Total human tau expression was observed to be relatively uniform throughout the brain, reflecting the vascular route of AAV administration. Phospho-tau deposition was not equal across brain regions and significantly increased in APP+PS1 mice compared to non-transgenic controls. Interestingly, the rank order of phospho-tau deposition of affected brain regions in both genotypes paralleled the rank order of amyloid plaque deposits in APP+PS1 mice. We also observed significantly increased MAPT RNA expression in APP+PS1 mice compared to non-transgenic despite equal AAV transduction efficiency between groups. DISCUSSION: This model has advantages over prior approaches with widespread uniform human tau expression throughout the brain and the ability to specify the stage of amyloidosis when the tau pathology is initiated. These data add further support to the amyloid cascade hypothesis and suggest RNA metabolism as a potential mechanism for amyloid-induced tauopathy.

Ectoparasites of the Critically Endangered green sawfish Pristis zijsron and sympatric elasmobranchs in Western Australia.

This study reports the metazoan ectoparasite fauna of juvenile Critically Endangered green sawfish, Pristis zijsron, and sympatric elasmobranchs in Western Australia. Five parasite taxa were found on 76 screened P. zijsron: Caligus furcisetifer (Copepoda: Caligidae), Dermopristis pterophila (Monogenea: Microbothriidae), Branchellion plicobranchus and Stibarobdella macrothela (Hirudinea: Piscicolidae), and praniza larvae of an unidentified gnathiid isopod. Only C. furcisetifer and D. pterophila were common, exhibiting discrepant site-specificity, with C. furcisetifer occurring mostly on the head and rostrum, and D. pterophila around the pectoral and pelvic fins. Intensity of infection for C. furcisetifer and D. pterophila increased with host total length and was influenced by host sex, but in opposite directions; intensity of C. furcisetifer was greater on female P. zijsron, whereas intensity of D. pterophila was greater on males. In the Ashburton River, likelihood of infection for C. furcisetifer and D. pterophila on P. zijsron increased with time since substantial freshwater discharge events, suggesting decreased salinity impacts both taxa. In addition to P. zijsron, five other sympatric elasmobranch species were opportunistically screened for ectoparasites in the study area: the giant shovelnose ray, Glaucostegus typus, the eyebrow wedgefish, Rhynchobatus palpebratus, the nervous shark, Carcharhinus cautus, the lemon shark, Negaprion acutidens, and the graceful shark, Carcharhinus amblyrhynchoides. Caligus furcisetifer was found on R. palpebratus; no other parasites of P. zijsron were found on other sympatric elasmobranch species. Conversely, Perissopus dentatus (Copepoda: Pandaridae) was found on all three carcharhinids but not on batoid rays (P. zijsron, G. typus or R. palpebratus).

Cryptic diversity within two widespread diadromous freshwater fishes (Teleostei: Galaxiidae).

Identification of taxonomically cryptic species is essential for the effective conservation of biodiversity. Freshwater-limited organisms tend to be genetically isolated by drainage boundaries, and thus may be expected to show substantial cryptic phylogenetic and taxonomic diversity. By comparison, populations of diadromous taxa, that migrate between freshwater and marine environments, are expected to show less genetic differentiation. Here we test for cryptic diversity in Australasian populations (both diadromous and non-diadromous) of two widespread Southern Hemisphere fish species, Galaxias brevipinnis and Galaxias maculatus. Both mtDNA and nuclear markers reveal putative cryptic species within these taxa. The substantial diversity detected within G. brevipinnis may be explained by its strong climbing ability which allows it to form isolated inland populations. In island populations, G. brevipinnis similarly show deeper genetic divergence than those of G. maculatus, which may be explained by the greater abundance of G. maculatus larvae in the sea allowing more ongoing dispersal. Our study highlights that even widespread, 'high-dispersal' species can harbour substantial cryptic diversity and therefore warrant increased taxonomic and conservation attention.

Quantification of Vitamin A in Edible Oils: Comparison of Portable Device iCheck Chroma3 to High-Performance Liquid Chromatography.

Fortification of edible oil with vitamin A is a widely adopted intervention to minimize the effects of vitamin A deficiency in vulnerable groups and mitigate some of its deleterious consequences. Regulatory monitoring is an important prerequisite to ensure that the fortification program is implemented effectively. Standard laboratory analysis methods for vitamin A in oils to assess adequate addition levels remain expensive and time-consuming. Portable testing devices are relatively less expensive in terms of capital investment and cost per test. However, the reliability of results needs to be assured to ensure acceptability and confidence. This study compared a portable device to high-performance liquid chromatography (HPLC) in terms of quantification of vitamin A in both spiked and commercially fortified oils. Nine oils (soybean, palm, cottonseed, rapeseed, corn, peanut, coconut, sunflower, and rice bran oils) were selected and spiked with retinyl palmitate at six different concentrations, and 112 commercially fortified oils were quantified for their vitamin A content using both methods. A good indicator of intra-day and inter-day repeatability (< 10% CV) was obtained for the measurement of vitamin A in the spiked oils for both methods, which denotes a high agreement between them. Vitamin A recoveries were 97-132% for HPLC and 74-127% for the portable device. A strong positive correlation, r = 0.88, is observed between the two methods for the quantification of vitamin A in the commercially fortified oils. The portable device provides a relatively low-cost, quick, and user-friendly alternative to HPLC.

Comparative Analysis of Response to Cardiac Resynchronisation Therapy Upgrades in Patients with Implantable Cardioverter-Defibrillators and Pacemakers.

Introduction: The efficacy of de novo cardiac resynchronisation therapy (CRT) in patients with heart failure (HF), left ventricular systolic dysfunction (LVSD), and a broad QRS morphology is well established. However, the optimal stage for upgrading patients with existing pacemakers (PPMs) or implantable cardioverter-defibrillators (ICDs) and HF with high-burden right ventricular (RV) pacing remains uncertain. Thus, this multicentre retrospective analysis compared patients with pre-existing PPMs or ICDs who underwent CRT upgrades to investigate the appropriate stage for CRT implantation in these patients and to assess the validity of treating both PPM and ICD recipients under the same recommendation level in the current guidelines. Materials and Methods: A total of 151 participants underwent analysis in this study, comprising 93 upgrades to cardiac resynchronisation therapy with pacemaker (CRT-P) and 58 upgrades to cardiac resynchronisation therapy with defibrillator (CRT-D) across three centres in the UK. The aim of the study was to investigate the safety and efficacy of upgrading to CRT from an existing conventional pacemaker or an ICD in the context of high-burden RV pacing. The analysis was conducted separately for each group, assessing changes in echocardiographic parameters, functional New York Heart Association (NYHA) class, and procedure-related complications. Results: The PPM group had a higher percentage RVP burden compared to the ICD group. Post-upgrade, NYHA functional class and EF and LV volumes improved in both groups; however, the response to an upgrade from a pacemaker was greater compared to an upgrade from an ICD. Post-procedural complication risks were similar across the two subgroups but significantly higher compared to de novo implantation. Conclusions: Within the CRT-P subgroup, participants exhibited better responses than their CRT-D counterparts, evident both in echocardiographic improvements and clinical outcomes. Furthermore, patients with non-ischemic cardiomyopathy (NICM) were better responders than those with ischaemic cardiomyopathy. These findings suggest that international guidelines should consider approaching each subgroup separately in the future.

A pilot study of the Moving On In My Recovery program for people in recovery from substance use.

Background: This study pilot tested Moving On In My Recovery (MOIMR), a 12-session, acceptance-based, cognitive-behavioral, manual-guided group program for individuals in recovery from substance use. MOIMR aims to bridge the gap between formal treatment and sustained recovery. Method: Participants were 61 people in recovery from substance use and in the catchment area of the Betsi Cadwaladr Health Board, North Wales, United Kingdom. Using a variety of questionnaires, participants' psychological flexibility and wellbeing were assessed at baseline, post-treatment, and a three-month follow-up. Participants who dropped out were contacted at the follow-up and interviewed about their experience. Results: The study successfully recruited participants from real-world treatment services. During the study, significant improvements were observed in participants' social functioning, experiential avoidance, recovery capital, low mood, and anxiety. The proportion of participants who achieved abstinence also improved. Qualitative feedback confirmed the benefits that participants derived from attending the MOIMR groups. Conclusion: The program offered significant benefits for the participants despite many of them having apprehensions about undertaking a group-based approach. The gains established by quantitative analysis appeared to be supported by the qualitative findings. These findings suggest that a full randomized controlled trial of MOIMR would be feasible.

Effects of coastal development on sawfish movements and the need for marine animal crossing solutions.

Although human-made barriers to animal movement are ubiquitous across many types of ecosystems, the science behind these barriers and how to ameliorate their effects lags far behind in marine environments compared with terrestrial and freshwater realms. Using juvenile sawfish in an Australian nursery habitat as a model system, we aimed to assess the effects of a major anthropogenic development on the movement behavior of coastal species. We compared catch rates and movement behavior (via acoustic telemetry) of juvenile green sawfish (Pristis zijsron) before and after a major coastal structure was built in an important nursery habitat. Acoustic tracking and catch data showed that the development did not affect levels of sawfish recruitment in the nursery, but it did constrain movements of juveniles moving throughout the nursery, demonstrating the reluctance of shoreline-associated species to travel around large or unfamiliar coastal structures. Given the current lack of information on human-made movement barriers in the marine environment, these findings highlight the need for further research in this area, and we propose the development of and experimentation with marine animal crossings as an important area of emerging research.

Efectos del desarrollo costero sobre los movimientos del pez sierra y la necesidad de soluciones para el cruce de animales marinos Resumen Mientras que las barreras construidas por humanos que limitan el movimiento de animales son ubicuas en muchos tipos de ecosistemas, la ciencia que sustenta estas barreras y la reducción de sus impactos está muy retrasada en ambientes marinos en comparación con medios terrestres y dulceacuícolas. Utilizando peces sierra juveniles en un hábitat de vivero australiano como sistema modelo, intentamos evaluar los efectos de un importante desarrollo antropogénico sobre el comportamiento de especies costeras. Comparamos las tasas de captura y el comportamiento de movimiento (mediante telemetría acústica) de peces sierra verdes juveniles (Pristis zijsron) antes y después de que se construyera infraestructura costera en un importante hábitat de vivero. El seguimiento acústico y los datos de captura mostraron que el desarrollo no afectó los niveles de reclutamiento de pez sierra en el vivero, pero sí restringió los movimientos de los juveniles desplazándose por el vivero, lo cual demuestra la renuencia de las especies asociadas a la costa a viajar alrededor de estructuras costeras grandes o desconocidas. Dada la actual falta de información sobre las barreras de movimiento creadas por el hombre en el medio marino, estos hallazgos destacan la necesidad de realizar más investigaciones en esta campo, y proponemos el desarrollo y la experimentación con cruces para animales marinos como un área importante de investigación emergente.

Phosphate-binding pocket on cyclin B governs CDK substrate phosphorylation and mitotic timing.

Cell cycle progression is governed by complexes of the cyclin-dependent kinases (CDKs) and their regulatory subunits cyclin and Cks1. CDKs phosphorylate hundreds of substrates, often at multiple sites. Multisite phosphorylation depends on Cks1, which binds initial priming phosphorylation sites to promote secondary phosphorylation at other sites. Here, we describe a similar role for a recently discovered phosphate-binding pocket (PP) on B-type cyclins. Mutation of the PP in Clb2, the major mitotic cyclin of budding yeast, alters bud morphology and delays the onset of anaphase. Using phosphoproteomics in vivo and kinase reactions in vitro, we find that mutation of the PP reduces phosphorylation of several CDK substrates, including the Bud6 subunit of the polarisome and the Cdc16 and Cdc27 subunits of the anaphase-promoting complex/cyclosome. We conclude that the cyclin PP, like Cks1, controls the timing of multisite phosphorylation on CDK substrates, thereby helping to establish the robust timing of cell-cycle events.

Transgenic amyloid precursor protein mouse models of amyloidosis. Incomplete models for Alzheimer's disease but effective predictors of anti-amyloid therapies.

INTRODUCTION: Amyloid precursor protein (APP) transgenic mice are models of Alzheimer's disease (AD) amyloidosis, not all of AD. Diffuse, compacted, and vascular deposits in APP mice mimic those found in AD cases. METHODS: Most interventional studies in APP mice start treatment early in the process of amyloid deposition, consistent with a prevention treatment regimen. Most clinical trials treat patients with established amyloid deposits in a therapeutic treatment regimen. RESULTS: The first treatment to reduce amyloid and cognitive impairment in mice was immunotherapy. The APP mouse models not only predicted efficacy, but presaged the vascular leakage called ARIA. The recent immunotherapy clinical trials that removed amyloid and slowed cognitive decline confirms the utility of these early APP models when used in therapeutic designs. DISCUSSION: New mouse models of AD pathologies will add to the research armamentarium, but the early models have accurately predicted responses to amyloid therapies in humans.

Monsoonal wet season influences the migration tendency of a catadromous fish (barramundi Lates calcarifer).

Many animals exhibit partial migration, which occurs when populations contain coexisting contingents of migratory and resident individuals. This individual-level variation in migration behaviour may drive differences in growth, age at maturity and survival. Therefore, partial migration is widely considered to play a key role in shaping population demography. Otolith chemistry and microstructural analysis were used to identify the environmental- and individual-specific factors that influence migratory behaviour in the facultatively catadromous barramundi (Lates calcarifer) at two distinct life history stages: firstly, as juveniles migrating upstream into fresh water; and secondly, as adults or sub-adults returning to the estuarine/marine spawning habitat. Monsoonal climate played an important role in determining the migration propensity of juveniles: individuals born in the driest year examined (weak monsoon) were more than twice as likely to undergo migration to freshwater than those born in the wettest (strong monsoon) year. In contrast, the ontogenetic timing of return migrations to the estuary by adults and sub-adults was highly variable and not strongly associated with the environmental parameters examined. We propose that scarce resources within saline natal habitats during lower rainfall years may provide an ecological incentive for juveniles to migrate upstream, whereas more abundant resources in higher rainfall years may promote resident life histories within estuaries. We conclude that inter-annual climatic variation, here evidenced by monsoonal strength, likely plays an important role in driving the persistence of diversified life histories within wild barramundi populations.