Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 702
Filter
1.
J Physiol ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38843407

ABSTRACT

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.

2.
J Addict Dis ; : 1-9, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38715246

ABSTRACT

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.

3.
Food Anal Methods ; 17(6): 847-854, 2024.
Article in English | MEDLINE | ID: mdl-38765762

ABSTRACT

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.

4.
Alzheimers Dement (N Y) ; 10(2): e12470, 2024.
Article in English | MEDLINE | ID: mdl-38689599

ABSTRACT

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.

5.
Parasitol Int ; 101: 102900, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38701942

ABSTRACT

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).


Subject(s)
Ectoparasitic Infestations , Endangered Species , Fish Diseases , Animals , Western Australia , Fish Diseases/parasitology , Fish Diseases/epidemiology , Ectoparasitic Infestations/veterinary , Ectoparasitic Infestations/parasitology , Ectoparasitic Infestations/epidemiology , Male , Female , Elasmobranchii/parasitology , Copepoda/classification , Isopoda/classification , Sympatry
6.
Ecol Evol ; 14(5): e11201, 2024 May.
Article in English | MEDLINE | ID: mdl-38799386

ABSTRACT

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.

7.
J Clin Med ; 13(10)2024 May 07.
Article in English | MEDLINE | ID: mdl-38792297

ABSTRACT

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.

9.
Conserv Biol ; : e14263, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38578170

ABSTRACT

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.

10.
bioRxiv ; 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38464173

ABSTRACT

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.

11.
Alzheimers Dement ; 20(2): 1459-1464, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38085800

ABSTRACT

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.


Subject(s)
Alzheimer Disease , Amyloidosis , Cognitive Dysfunction , Humans , Mice , Animals , Alzheimer Disease/therapy , Alzheimer Disease/drug therapy , Amyloid beta-Protein Precursor/genetics , Amyloid beta-Protein Precursor/metabolism , Mice, Transgenic , Amyloidosis/therapy , Amyloidosis/metabolism , Disease Models, Animal , Amyloid beta-Peptides/metabolism , Plaque, Amyloid/pathology
12.
J Anim Ecol ; 93(1): 83-94, 2024 01.
Article in English | MEDLINE | ID: mdl-37984847

ABSTRACT

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.


Subject(s)
Fishes , Fresh Water , Animals , Seasons , Ecosystem , Estuaries
13.
Allergy ; 79(1): 104-115, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37650296

ABSTRACT

BACKGROUND: Atopic dermatitis (AD) is characterized by Staphylococcus aureus (S. aureus) colonization. Longitudinal early life data delineating relationships of S. aureus colonization, barrier function, and AD outcomes are lacking. We define longitudinal S. aureus endotypes and AD pathogenesis in early life. METHODS: We defined longitudinal S. aureus skin colonization phenotypes across two annual visits (non-colonized: V1- V2- , early transient: V1+ V2- , late-onset: V1- V2+ , persistent: V1+ V2+ ) in the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children cohort. We analyzed AD severity, sensitization, and skin barrier function across phenotypes, and performed mediation analyses between colonization and FLG expression. RESULTS: Persistent S. aureus colonization was associated with increased SCORAD at V1 (33.5 vs. 19.0, p = .004) and V2 (40.1 vs.16.9, p < .001), and lower non-lesional (NL) FLG at V2 (1.77 vs. 4.09, p = .029) compared to the non-colonized phenotype, with early transient and late-onset colonization as intermediate phenotypes. Children colonized at V2 demonstrated a decrease in NL-FLG expression from V1 to V2 compared to those non-colonized at V2 (p = .0012), who maintained expression. This effect remained significant even after adjusting for V1 colonization and SCORAD (p = .011). CONCLUSIONS: Our findings are the first to present longitudinal quantitative FLG expression and S. aureus skin colonization in early life and suggest that a decrease in NL-FLG drives later colonization. Hence, therapies to maintain NL-FLG expression may prevent S. aureus colonization. Further, a longitudinal AD endotype of persistent colonization is characterized by increased AD severity, sensitization, and decreasing NL-FLG.


Subject(s)
Dermatitis, Atopic , Filaggrin Proteins , Staphylococcus aureus , Staphylococcus aureus/physiology , Skin/microbiology , Humans , Dermatitis, Atopic/microbiology , Infant , Child, Preschool , Male , Female , Patient Acuity , Filaggrin Proteins/genetics
14.
Am J Primatol ; 86(2): e23586, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38151775

ABSTRACT

Ranging dynamics are physical and behavioral representations of how different socioecological factors affect an organism's spatial decisions and space use strategies. Western lowland gorillas (Gorilla gorilla gorilla) are a model species to investigate the drivers of spatial dynamics based on both the natural variation in socioecological factors within the species and compared with their mountain gorilla counterparts. In this study, we evaluate the influences of resource seasonality and social dynamics on variation in home range size, utilization, and intergroup overlap among multiple gorilla groups over an 8-year study period in the northern Republic of Congo. This study shows that western lowland gorillas can have small home ranges comparable to mountain gorillas, rather than universally larger home ranges as previously supposed, and that home ranges are stable through time. The largest source of variation in space use was the degree of intergroup home range overlap. The study groups did not demonstrate intraspecific variation in range size nor changes in intergroup overlap with respect to seasonality of fruit resources, but all groups demonstrated expansion of monthly range and core area with group size, matching predictions of intragroup feeding competition. These findings highlight the potential impact of intergroup relationships on space use and prompt further research on the role of social dynamics in ranging strategies. In this study, we reveal a greater degree of variability and flexibility in gorilla ranging behavior than previously realized which is relevant to improving comparative studies and informing conservation strategies on behalf of these endangered primates.


Subject(s)
Gorilla gorilla , Hominidae , Animals , Fruit , Congo , Forests
15.
Alzheimers Dement ; 20(3): 1807-1814, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38126555

ABSTRACT

INTRODUCTION: We investigated associations of Alzheimer's disease (AD) serum biomarkers with longitudinal changes in cognitive function from mid- to late life among women. METHODS: The study population included 192 women with the median age of 53.3 years at baseline, from the Study of Women's Health Across the Nation Michigan Cohort, followed up over 14 years. Associations between baseline serum amyloid ß (Aß)42, the Aß42/40 ratio, phosphorylated tau181 (p-tau181), and total tau with longitudinal changes in cognition were evaluated using linear mixed effects models. RESULTS: After adjusting for confounders, lower Aß42/40 ratios were associated with faster declines in the Digit Span Backward Test. Higher p-tau181 also showed a borderline statistically significant association with more rapid decline in the Symbol Digit Modalities Test. DISCUSSION: Our findings suggest that mid-life serum AD biomarkers could be associated with accelerated cognitive decline from mid- to late life in women. Future studies with larger samples are needed to validate and extend our findings. HIGHLIGHTS: This study investigates midlife serum AD biomarkers on longitudinal cognitive function changes in women. Mid-life serum AD biomarkers are associated with accelerated cognitive decline. A decrease in the Aß42/40 ratio was associated with a faster decline in the DSB score. A higher p-tau181 concentration was associated with a faster decline in the SDMT score.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Humans , Female , Middle Aged , Alzheimer Disease/epidemiology , Amyloid beta-Peptides , tau Proteins , Cognition , Biomarkers
17.
Antib Ther ; 6(4): 277-297, 2023 Oct.
Article in English | MEDLINE | ID: mdl-38075238

ABSTRACT

Background: Due to COVID-19, pandemic preparedness emerges as a key imperative, necessitating new approaches to accelerate development of reagents against infectious pathogens. Methods: Here, we developed an integrated approach combining synthetic, computational and structural methods with in vitro antibody selection and in vivo immunization to design, produce and validate nature-inspired nanoparticle-based reagents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results: Our approach resulted in two innovations: (i) a thermostable nasal vaccine called ADDoCoV, displaying multiple copies of a SARS-CoV-2 receptor binding motif derived epitope and (ii) a multivalent nanoparticle superbinder, called Gigabody, against SARS-CoV-2 including immune-evasive variants of concern (VOCs). In vitro generated neutralizing nanobodies and electron cryo-microscopy established authenticity and accessibility of epitopes displayed by ADDoCoV. Gigabody comprising multimerized nanobodies prevented SARS-CoV-2 virion attachment with picomolar EC50. Vaccinating mice resulted in antibodies cross-reacting with VOCs including Delta and Omicron. Conclusion: Our study elucidates Adenovirus-derived dodecamer (ADDomer)-based nanoparticles for use in active and passive immunization and provides a blueprint for crafting reagents to combat respiratory viral infections.

19.
Primates ; 2023 Dec 16.
Article in English | MEDLINE | ID: mdl-38103142

ABSTRACT

Planning is a type of problem solving in which a course of future action is devised via mental computation. Potential advantages of planning for tool use include reduced effort to gather tools, closer alignment to an efficient tool design, and increased foraging efficiency. Chimpanzees (Pan troglodytes troglodytes) in the Goualougo Triangle use a variety of different types of tools. We hypothesized that procurement strategy (brought to the termite nest, manufactured or acquired at the termite nest, or borrowed from others) reflects planning for current needs, with tool transport behavior varying by tool type and by age and sex class. It is also possible that chimpanzees anticipate the need for tools at future times, which would be evidenced by transporting multiple tool types for a sequential task. One year of video recordings at termite nests were systematically screened for tool procurement; data comprised 299 tool procurement events across 66 chimpanzees. In addition, we screened video recordings of leaf sponging and honey gathering, which resulted in another 38 procurement events. Fishing probes, which are typically used during a single visit, were typically transported to termite nests, while puncturing tools, which are durable and remain on site, were more often acquired at termite nests. Most tools transported in multiples were fishing probes, perhaps in anticipation that a single probe might not last through an entire foraging bout or might be transferred to another chimpanzee. We further documented that chimpanzees transported tool sets, comprising multiple different tool types used in sequence. Mature chimpanzees transported tools more often than did immatures. These observations suggest that chimpanzees plan tool use flexibly, reflecting the availability of raw materials and the likelihood that specific tool types will be needed for particular tasks. Developmental studies and further integration of behavioral, spatial, and archaeological data will help to illuminate the decision making and time depth of planning associated with tool technologies in living primates and hominin ancestors.

20.
ACS Catal ; 13(21): 14189-14198, 2023 Nov 03.
Article in English | MEDLINE | ID: mdl-37942270

ABSTRACT

Supported bimetallic catalysts commonly exhibit higher rates of reaction compared to their monometallic counterparts, but the origin of these enhancements is often poorly defined. The recent discovery that cooperative redox enhancement effects in Au-Pd systems promote bimetallic catalysis in thermochemical oxidation is an important development in this field. This effect aligns two important research fields, thermo- and electrocatalysis, but questions relating to the generality and origin of the effect remain. Here, we demonstrate that these effects can be observed in reactions over a range of bimetal combinations and reveal the origin using a combination of electrochemical and material characterization. We disclose that the observed activity enhancement in thermochemical systems is a result of the electrochemical polarization of two disparate catalytic sites. This forms an alternative operating potential for a given bimetallic system that increases the driving force of each of the composite half reactions in oxidative dehydrogenation. We therefore uncover the physicochemical descriptors that dictate whether these enhancement effects will be exhibited by a particular combination of supported metal catalysts and determine the magnitude of the effect.

SELECTION OF CITATIONS
SEARCH DETAIL
...