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1.
J Am Chem Soc ; 2024 Jul 02.
Article de Anglais | MEDLINE | ID: mdl-38953583

RÉSUMÉ

Van der Waals (vdW) magnets both allow exploration of fundamental 2D physics and offer a route toward exploiting magnetism in next generation information technology, but vdW magnets with complex, noncollinear spin textures are currently rare. We report here the syntheses, crystal structures, magnetic properties and magnetic ground states of four bulk vdW metal-organic magnets (MOMs): FeCl2(pym), FeCl2(btd), NiCl2(pym), and NiCl2(btd), pym = pyrimidine and btd = 2,1,3-benzothiadiazole. Using a combination of neutron diffraction and bulk magnetometry we show that these materials are noncollinear magnets. Although only NiCl2(btd) has a ferromagnetic ground state, we demonstrate that low-field hysteretic metamagnetic transitions produce states with net magnetization in zero-field and high coercivities for FeCl2(pym) and NiCl2(pym). By combining our bulk magnetic data with diffuse scattering analysis and broken-symmetry density-functional calculations, we probe the magnetic superexchange interactions, which when combined with symmetry analysis allow us to suggest design principles for future noncollinear vdW MOMs. These materials, if delaminated, would prove an interesting new family of 2D magnets.

2.
Nature ; 2024 Jun 17.
Article de Anglais | MEDLINE | ID: mdl-38885696

RÉSUMÉ

Harnessing genetic diversity in major staple crops through the development of new breeding capabilities is essential to ensure food security1. Here we examined the genetic and phenotypic diversity of the A.E. Watkins landrace collection2 of bread wheat (Triticum aestivum), a major global cereal, through whole-genome re-sequencing (827 Watkins landraces and 208 modern cultivars) and in-depth field evaluation spanning a decade. We discovered that modern cultivars are derived from just two of the seven ancestral groups of wheat and maintain very long-range haplotype integrity. The remaining five groups represent untapped genetic sources, providing access to landrace-specific alleles and haplotypes for breeding. Linkage disequilibrium (LD) based haplotypes and association genetics analyses link Watkins genomes to the thousands of high-resolution quantitative trait loci (QTL), and significant marker-trait associations identified. Using these structured germplasm, genotyping and informatics resources, we revealed many Watkins-unique beneficial haplotypes that can confer superior traits in modern wheat. Furthermore, we assessed the phenotypic effects of 44,338 Watkins-unique haplotypes, introgressed from 143 prioritised QTL in the context of modern cultivars, bridging the gap between landrace diversity and current breeding. This study establishes a framework for systematically utilising genetic diversity in crop improvement to achieve sustainable food security.

4.
J Fish Biol ; 2024 May 09.
Article de Anglais | MEDLINE | ID: mdl-38721880

RÉSUMÉ

Marine predators are vital to the healthy functioning of coastal ecosystems, but to understand their roles, it is necessary to elucidate their movement ecology, particularly in relation to one another. A decade's worth of acoustic telemetry data (2011-2020) from Algoa Bay, South Africa, was investigated to determine how two mesopredatory species (teleosts: dusky kob Argyrosomus japonicus, n = 11, and leervis Lichia amia, n = 16) and two top predatory species (sharks: ragged-tooth sharks Carcharias taurus, n = 45, and white sharks Carcharodon carcharias, n = 31) used and shared this bay ecosystem. Multi-annual seasonal fidelity to the bay was exhibited by all species, but differences in residency were observed among species. Similarly, species used space in the bay differently-the teleosts moved less and had movements restricted to the central and western inshore regions of the bay. Conversely, the sharks roamed more, but detections were concentrated in the western part of the bay for C. taurus and in the eastern part of the bay for C. carcharias. Social network analysis showed that species segregated in space and time on a fine scale. However, there was some interaction observed between C. taurus, L. amia, and A. japonicus, but to varying degrees. This is likely because of strong habitat preferences exhibited by each species and predator-prey relationships between these predatory guilds. Results highlight that the sheltered marine Algoa Bay is a resource-rich environment, supporting multiple predators with different hunting strategies albeit similar prey preferences. Finally, these species are likely afforded some protection by the current Greater Addo Elephant National Park Marine Protected Area in the bay but are vulnerable to fishing pressure when they leave this ecosystem.

5.
Transl Anim Sci ; 8: txae058, 2024.
Article de Anglais | MEDLINE | ID: mdl-38800101

RÉSUMÉ

Demands of domestic and foreign market specifications of carcass weight and fat cover, of beef cattle, have led to the development of cattle growth models that predict fat cover to assist on-farm managers make management decisions. The objectives of this paper are 4-fold: 1) conduct a brief review of the biological basis of adipose tissue accretion, 2) briefly review live and carcass assessments of beef cattle, and carcass grading systems used to develop quantitative compositional and quality indices, 3) review fat deposition models: Davis growth model (DGM), French National Institute for Agricultural Research growth model (IGM), Cornell Value Discovery System (CVDS), and BeefSpecs drafting tool (BeefSpecsDT), and 4) appraise the process of translating science and practical skills into research/decision support tools that assist the Beef industry improve profitability. The r2 for live and carcass animal assessments, using several techniques across a range of species and traits, ranged from 0.61 to 0.99 and from 0.52 to 0.99, respectively. Model evaluations of DGM and IGM were conducted using Salers heifers (n = 24) and Angus-Hereford steers (n = 15) from an existing publication and model evaluations of CVDS and BeefSpecsDT were conducted using Angus steers (n = 33) from a research trial where steers were grain finished for 101 d in a commercial feedlot. Evaluating the observed and predicted fat mass (FM) is the focus of this review. The FM mean bias for Salers heifers were 7.5 and 1.3 kg and the root mean square error of prediction (RMSEP) were 31.2 and 27.8 kg and for Angus-Hereford steers the mean bias were -4.0 and -10.5 kg and the RMSEP were 9.14 and 21.5 kg for DGM and IGM, respectively. The FM mean bias for Angus steers were -5.61 and -2.93 kg and the RMSEP were 12.3 and 13.4 kg for CVDS and BeefSpecsDT, respectively. The decomposition for bias, slope, and deviance were 21%, 12%, and 68% and 5%, 4%, and 91% for CVDS and BeefSpecsDT, respectively. The modeling efficiencies were 0.38 and 0.27 and the models were within a 20 kg level of tolerance 91% and 88% for CVDS and BeefSpecsDT, respectively. Fat deposition models reported in this review have the potential to assist the beef industry make on-farm management decisions on live cattle before slaughter and improve profitability. Modelers need to continually assess and improve their models but with a caveat of 1) striving to minimize inputs, and 2) choosing on-farm inputs that are readily available.

6.
Sci Rep ; 14(1): 8245, 2024 04 08.
Article de Anglais | MEDLINE | ID: mdl-38589670

RÉSUMÉ

The human skin microbiome comprises diverse populations that differ temporally between body sites and individuals. The virome is a less studied component of the skin microbiome and the study of bacteriophages is required to increase knowledge of the modulation and stability of bacterial communities. Staphylococcus species are among the most abundant colonisers of skin and are associated with both health and disease yet the bacteriophages infecting the most abundant species on skin are less well studied. Here, we report the isolation and genome sequencing of 40 bacteriophages from human skin swabs that infect coagulase-negative Staphylococcus (CoNS) species, which extends our knowledge of phage diversity. Six genetic clusters of phages were identified with two clusters representing novel phages, one of which we characterise and name Alsa phage. We identified that Alsa phages have a greater ability to infect the species S. hominis that was otherwise infected less than other CoNS species by the isolated phages, indicating an undescribed barrier to phage infection that could be in part due to numerous restriction-modification systems. The extended diversity of Staphylococcus phages here enables further research to define their contribution to skin microbiome research and the mechanisms that limit phage infection.


Sujet(s)
Bactériophages , Humains , Bactériophages/génétique , Coagulase/génétique , Génome viral , Peau/microbiologie , Phages de Staphylococcus/génétique , Staphylococcus/génétique
7.
J Natl Cancer Inst ; 2024 Apr 24.
Article de Anglais | MEDLINE | ID: mdl-38656931

RÉSUMÉ

INTRODUCTION: While contact days-days with healthcare contact outside home-are increasingly adopted as a measure of time toxicity and treatment burden, they could also serve as a surrogate of treatment-related harm. We sought to assess the association between contact days and patient-reported outcomes, and the prognostic ability of contact days. METHODS: We conducted a secondary analysis of CO.17 that evaluated cetuximab vs supportive care in patients with advanced colorectal cancer. CO.17 collected EORTC-QLQ-C30 instrument data. We assessed the association between number of contact days in a window and changes in physical function and global health status, and the association between number of contact days in the first 4 weeks with overall survival (OS). RESULTS: There was a negative association between the number of contact days and change in physical function (per each additional contact day at 4 weeks, 1.50 point decrease; and 8 weeks, 1.06 point decrease, p < .0001 for both), but not with global health status. This negative association was seen in patients receiving cetuximab, but not supportive care. More contact days in the first 4 weeks was associated with worse OS for all comers and patients receiving cetuximab (per each additional contact day; all comers, aHR 1.07, 95% CI, 1.05- 1.10; and cetuximab, aHR 1.08, 95%CI 1.05- 1.11, p < .0001 for both). CONCLUSIONS: In this secondary analysis of a clinical trial, more contact days early in the course was associated with declines in physical function and worse survival in all-comers and in participants receiving cancer-directed treatment. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT00079066.

8.
New Phytol ; 2024 Apr 26.
Article de Anglais | MEDLINE | ID: mdl-38666346

RÉSUMÉ

Barley (Hordeum vulgare) is an important global cereal crop and a model in genetic studies. Despite advances in characterising barley genomic resources, few mutant studies have identified genes controlling root architecture and anatomy, which plays a critical role in capturing soil resources. Our phenotypic screening of a TILLING mutant collection identified line TM5992 exhibiting a short-root phenotype compared with wild-type (WT) Morex background. Outcrossing TM5992 with barley variety Proctor and subsequent SNP array-based bulk segregant analysis, fine mapped the mutation to a cM scale. Exome sequencing pinpointed a mutation in the candidate gene HvPIN1a, further confirming this by analysing independent mutant alleles. Detailed analysis of root growth and anatomy in Hvpin1a mutant alleles exhibited a slower growth rate, shorter apical meristem and striking vascular patterning defects compared to WT. Expression and mutant analyses of PIN1 members in the closely related cereal brachypodium (Brachypodium distachyon) revealed that BdPIN1a and BdPIN1b were redundantly expressed in root vascular tissues but only Bdpin1a mutant allele displayed root vascular defects similar to Hvpin1a. We conclude that barley PIN1 genes have sub-functionalised in cereals, compared to Arabidopsis (Arabidopsis thaliana), where PIN1a sequences control root vascular patterning.

9.
BMJ Open Ophthalmol ; 9(1)2024 Apr 22.
Article de Anglais | MEDLINE | ID: mdl-38653537

RÉSUMÉ

OBJECTIVE: Microbial keratitis (MK) is a significant cause of blindness in sub-Saharan Africa. We investigated the feasibility of using a novel corneal impression membrane (CIM) for obtaining and processing samples by culture, PCR and whole-genome sequencing (WGS) in patients presenting with suspected MK in Malawi. METHODS AND ANALYSIS: Samples were collected from patients presenting with suspected MK using a 12 mm diameter polytetrafluoroethylene CIM disc. Samples were processed using culture and PCR for Acanthamoeba, herpes simplex virus type 1 (HSV-1) and the bacterial 16S rRNA gene. Minimum inhibitory concentrations of isolates to eight antimicrobials were measured using susceptibility strips. WGS was used to characterise Staphylococcus aureus isolates. RESULTS: 71 eyes of 71 patients were included. The overall CIM isolation rate was 81.7% (58 positive samples from 71 participants). 69 (81.2%) of isolates were Gram-positive cocci. Coagulase-negative Staphylococcus 31.8% and Streptococcus species 14.1% were the most isolated bacteria. Seven (9.9%) participants were positive for HSV-1. Fungi and Acanthamoeba were not detected. Moxifloxacin and chloramphenicol offered the best coverage for both Gram-positive and Gram-negative isolates when susceptibility was determined using known antimicrobial first quartile concentrations and European Committee on Antimicrobial Susceptibility Testing breakpoints, respectively. WGS identified known virulence genes associated with S. aureus keratitis. CONCLUSIONS: In a resource-poor setting, a CIM can be used to safely sample the cornea in patients presenting with suspected MK, enabling identification of causative microorganisms by culture and PCR. Although the microbiological spectrum found was limited to the dry season, these preliminary results could be used to guide empirical treatment.


Sujet(s)
Infections bactériennes de l'oeil , Humains , Projets pilotes , Malawi/épidémiologie , Mâle , Femelle , Adulte , Adulte d'âge moyen , Infections bactériennes de l'oeil/microbiologie , Infections bactériennes de l'oeil/épidémiologie , Infections bactériennes de l'oeil/traitement médicamenteux , Jeune adulte , Bactéries/isolement et purification , Bactéries/effets des médicaments et des substances chimiques , Bactéries/génétique , Tests de sensibilité microbienne , Cornée/microbiologie , Kératite/microbiologie , Kératite/traitement médicamenteux , Kératite/épidémiologie , Antibactériens/pharmacologie , Antibactériens/usage thérapeutique , Sujet âgé , Réaction de polymérisation en chaîne , Adolescent , Acanthamoeba/isolement et purification , Acanthamoeba/génétique , Acanthamoeba/effets des médicaments et des substances chimiques , ARN ribosomique 16S/génétique
10.
Curr Biol ; 34(10): 2039-2048.e3, 2024 05 20.
Article de Anglais | MEDLINE | ID: mdl-38653244

RÉSUMÉ

Compacted soil layers adversely affect rooting depth and access to deeper nutrient and water resources, thereby impacting climate resilience of crop production and global food security. Root hair plays well-known roles in facilitating water and nutrient acquisition. Here, we report that root hair also contributes to root penetration into compacted layers. We demonstrate that longer root hair, induced by elevated auxin response during a root compaction response, improves the ability of rice roots to penetrate harder layers. This compaction-induced auxin response in the root hair zone is dependent on the root apex-expressed auxin synthesis gene OsYUCCA8 (OsYUC8), which is induced by compaction stress. This auxin source for root hair elongation relies on the auxin influx carrier AUXIN RESISTANT 1 (OsAUX1), mobilizing this signal from the root apex to the root hair zone. Mutants disrupting OsYUC8 and OsAUX1 genes exhibit shorter root hairs and weaker penetration ability into harder layers compared with wild type (WT). Root-hair-specific mutants phenocopy these auxin-signaling mutants, as they also exhibit an attenuated root penetration ability. We conclude that compaction stress upregulates OsYUC8-mediated auxin biosynthesis in the root apex, which is subsequently mobilized to the root hair zone by OsAUX1, where auxin promotes root hair elongation, improving anchorage of root tips to their surrounding soil environment and aiding their penetration ability into harder layers.


Sujet(s)
Acides indolacétiques , Oryza , Racines de plante , Oryza/métabolisme , Oryza/génétique , Oryza/croissance et développement , Racines de plante/métabolisme , Racines de plante/croissance et développement , Acides indolacétiques/métabolisme , Protéines végétales/métabolisme , Protéines végétales/génétique , Régulation de l'expression des gènes végétaux , Sol/composition chimique
11.
Proc Natl Acad Sci U S A ; 121(18): e2322692121, 2024 Apr 30.
Article de Anglais | MEDLINE | ID: mdl-38652744

RÉSUMÉ

Food intake and energy balance are tightly regulated by a group of hypothalamic arcuate neurons expressing the proopiomelanocortin (POMC) gene. In mammals, arcuate-specific POMC expression is driven by two cis-acting transcriptional enhancers known as nPE1 and nPE2. Because mutant mice lacking these two enhancers still showed hypothalamic Pomc mRNA, we searched for additional elements contributing to arcuate Pomc expression. By combining molecular evolution with reporter gene expression in transgenic zebrafish and mice, here, we identified a mammalian arcuate-specific Pomc enhancer that we named nPE3, carrying several binding sites also present in nPE1 and nPE2 for transcription factors known to activate neuronal Pomc expression, such as ISL1, NKX2.1, and ERα. We found that nPE3 originated in the lineage leading to placental mammals and remained under purifying selection in all mammalian orders, although it was lost in Simiiformes (monkeys, apes, and humans) following a unique segmental deletion event. Interestingly, ablation of nPE3 from the mouse genome led to a drastic reduction (>70%) in hypothalamic Pomc mRNA during development and only moderate (<33%) in adult mice. Comparison between double (nPE1 and nPE2) and triple (nPE1, nPE2, and nPE3) enhancer mutants revealed the relative contribution of nPE3 to hypothalamic Pomc expression and its importance in the control of food intake and adiposity in male and female mice. Altogether, these results demonstrate that nPE3 integrates a tripartite cluster of partially redundant enhancers that originated upon a triple convergent evolutionary process in mammals and that is critical for hypothalamic Pomc expression and body weight homeostasis.


Sujet(s)
Poids , Consommation alimentaire , Éléments activateurs (génétique) , Hypothalamus , Pro-opiomélanocortine , Danio zébré , Animaux , Pro-opiomélanocortine/métabolisme , Pro-opiomélanocortine/génétique , Souris , Hypothalamus/métabolisme , Consommation alimentaire/génétique , Consommation alimentaire/physiologie , Danio zébré/génétique , Danio zébré/métabolisme , Femelle , Mâle , Souris transgéniques , Humains , Facteurs de transcription/métabolisme , Facteurs de transcription/génétique , Mammifères/métabolisme , Mammifères/génétique
12.
Sci Rep ; 14(1): 7174, 2024 Mar 26.
Article de Anglais | MEDLINE | ID: mdl-38531931

RÉSUMÉ

We report on a new ground-level neutron monitor design for studying cosmic rays and fluxes of solar energetic particles at the Earth's surface. The first-of-its-kind instrument, named the NM-2023 after the year it was standardised and following convention, will be installed at a United Kingdom Meteorological Office observatory (expected completion mid 2024) and will reintroduce such monitoring in the UK for the first time since ca. 1984. Monte Carlo radiation transport code is used for the development and application of parameterised models to investigate alternative neutron detectors, their location and bulk material geometry in a realistic cosmic ray neutron field. Benchmarked against a model of the current and most widespread design standardised in 1964 (the NM-64), two main parameterisation studies are conducted; a simplified standard model and a concept slab parameterisation. We show that the NM-64 standard is well optimised for the intended large-diameter boron trifluoride (BF 3 ) proportional counters but not for multiple smaller diameter counters. The new design (based on a novel slab arrangement) produces comparable counting efficiencies to an NM-64 with six BF 3 counters and has the added advantage of being more compact, lower cost and avoids the use of highly toxic BF 3 .

13.
Sci Adv ; 10(10): eadj6834, 2024 Mar 08.
Article de Anglais | MEDLINE | ID: mdl-38457492

RÉSUMÉ

Sleep deprivation enhances risk for serious injury and fatality on the roads and in workplaces. To facilitate future management of these risks through advanced detection, we developed and validated a metabolomic biomarker of sleep deprivation in healthy, young participants, across three experiments. Bi-hourly plasma samples from 2 × 40-hour extended wake protocols (for train/test models) and 1 × 40-hour protocol with an 8-hour overnight sleep interval were analyzed by untargeted liquid chromatography-mass spectrometry. Using a knowledge-based machine learning approach, five consistently important variables were used to build predictive models. Sleep deprivation (24 to 38 hours awake) was predicted accurately in classification models [versus well-rested (0 to 16 hours)] (accuracy = 94.7%/AUC 99.2%, 79.3%/AUC 89.1%) and to a lesser extent in regression (R2 = 86.1 and 47.8%) models for within- and between-participant models, respectively. Metabolites were identified for replicability/future deployment. This approach for detecting acute sleep deprivation offers potential to reduce accidents through "fitness for duty" or "post-accident analysis" assessments.


Sujet(s)
Privation de sommeil , Sommeil , Humains , Privation de sommeil/métabolisme , Vigilance , Métabolomique , Apprentissage machine
14.
Trends Plant Sci ; 29(7): 814-822, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38402016

RÉSUMÉ

The root angle plays a critical role in efficiently capturing nutrients and water from different soil layers. Steeper root angles enable access to mobile water and nitrogen from deeper soil layers, whereas shallow root angles facilitate the capture of immobile phosphorus from the topsoil. Thus, understanding the genetic regulation of the root angle is crucial for breeding crop varieties that can efficiently capture resources and enhance yield. Moreover, this understanding can contribute to developing varieties that effectively sequester carbon in deeper soil layers, supporting global carbon mitigation efforts. Here we review and consolidate significant recent discoveries regarding the molecular components controlling root angle in cereal crop species and outline the remaining research gaps in this field.


Sujet(s)
Grains comestibles , Racines de plante , Racines de plante/génétique , Racines de plante/anatomie et histologie , Racines de plante/croissance et développement , Grains comestibles/génétique , Régulation de l'expression des gènes végétaux , Produits agricoles/génétique , Sol/composition chimique , Azote/métabolisme
15.
Trends Plant Sci ; 2024 Feb 13.
Article de Anglais | MEDLINE | ID: mdl-38355326

RÉSUMÉ

Spatiotemporal soil heterogeneity and the resulting edaphic stress cycles can be decisive for crop growth. However, our understanding of the acclimative value of root responses to heterogeneous soil conditions remains limited. We outline a framework to evaluate the acclimative value of root responses that distinguishes between stress responses that are persistent and reversible upon stress release, termed 'plasticity' and 'elasticity', respectively. Using energy balances, we provide theoretical evidence that the advantage of plasticity over elasticity increases with the number of edaphic stress cycles and if responses lead to comparatively high energy gains. Our framework provides a conceptual basis for assessing the acclimative value of root responses to soil heterogeneity and can catalyse research on crop adaptations to heterogeneous belowground environments.

16.
Subst Use Addctn J ; 45(2): 201-210, 2024 Apr.
Article de Anglais | MEDLINE | ID: mdl-38258818

RÉSUMÉ

BACKGROUND: Although the sale of nonprescription syringes in pharmacies is legal in most states, people who inject drugs (PWID) continue to face obstacles to syringe purchase like stigma, prohibitive costs, restrictive policies, and stocking issues. We examined the consistency of syringe pricing as another possible barrier. METHODS: We analyzed data on syringe prices and other relevant variables from 153 unique secret shopper visits to 2 retail chain pharmacies in Massachusetts (MA), New Hampshire (NH), Oregon (OR), and Washington (WA) as part of the fidelity component of a large pharmacy-focused intervention study. Pretax prices from purchases made between August 2019 and May 2021 were adjusted for inflation to 2022 dollars, and a linear regression of the price of a 10-pack of syringes was constructed to examine the determinants of syringe pricing. RESULTS: The average real price of a 10-pack of syringes across all states was $4.53 (SD = 0.99), with wide variability between pharmacies (max = $11.44, min = $1.70) and between states (mean OR = $5.76, WA = $4.74, MA = $4.33, NH = $4.30). Forty-seven percent (n = 72) of the purchases were taxed despite syringes being tax exempt in MA and WA, and not having a sales tax in NH or OR. The results of the regression suggest that certain needle gauges were associated with lower overall prices, while 1 pharmacy chain and 2 syringe brands were associated with higher overall prices. CONCLUSIONS: The high variability in syringe pricing presents another barrier to pharmacy-based syringe access since high prices may leave PWID no choice but to reuse or share needles, especially in areas with limited alternatives or without a syringe service program. Leadership from healthcare systems, pharmacy chains, and state and local policymakers is essential to reduce stigma and to implement policies that streamline syringe purchases, eliminate the taxation of exempt syringes in accordance with state laws, and reduce the variation in syringe prices.


Sujet(s)
Pharmacies , Toxicomanie intraveineuse , Humains , Aiguilles , Médicaments sans ordonnance , Massachusetts
17.
medRxiv ; 2024 Jan 21.
Article de Anglais | MEDLINE | ID: mdl-38293201

RÉSUMÉ

Post-infection inflammatory syndromes have been increasingly recognized as a cause of host damage in a variety of infectious diseases including tuberculosis, bacterial meningitis, and COVID-19. Recently, a post-infectious inflammatory response syndrome (PIIRS) was described in non-HIV-infected cryptococcal fungal meningoencephalitis (CM) as a major cause of mortality. Inflammatory syndromes are particularly severe in neurological infections due to the skull's rigid structure which limits unchecked tissue expansion from inflammatory-induced edema. In the present studies, neurologic transcriptional pathway analysis utilizing a murine PIIRS model demonstrated a predominance of Janus kinase/signal transducer and activator of transcription (JAK/STAT) activation. JAK/STAT inhibitor treatment resulted in improvements in CNS damage markers, reductions in intrathecal CD44hiCD62lo CD4+ effector CD4+ T-cells and MHC II+ inflammatory myeloid cells, and weight gains in mice, the latter after treatment with antifungals. Based on these data, pathway-driven steroid-sparing human treatment for steroid-refractory PIIRS was initiated using short courses of the JAK/STAT inhibitor ruxolitinib. These were well tolerated and reduced activated HLA-DR+ CD4+ and CD8+ cells and inflammatory monocytes as well as improved brain imaging. Together, these findings support the role of JAK/STAT in PIIRS as well as further study of JAK/STAT inhibitors as potential adjunctive therapy for PIRS and other neural inflammatory syndromes.

18.
Elife ; 122024 Jan 31.
Article de Anglais | MEDLINE | ID: mdl-38294329

RÉSUMÉ

Seedling root traits impact plant establishment under challenging environments. Pearl millet is one of the most heat and drought tolerant cereal crops that provides a vital food source across the sub-Saharan Sahel region. Pearl millet's early root system features a single fast-growing primary root which we hypothesize is an adaptation to the Sahelian climate. Using crop modeling, we demonstrate that early drought stress is an important constraint in agrosystems in the Sahel where pearl millet was domesticated. Furthermore, we show that increased pearl millet primary root growth is correlated with increased early water stress tolerance in field conditions. Genetics including genome-wide association study and quantitative trait loci (QTL) approaches identify genomic regions controlling this key root trait. Combining gene expression data, re-sequencing and re-annotation of one of these genomic regions identified a glutaredoxin-encoding gene PgGRXC9 as the candidate stress resilience root growth regulator. Functional characterization of its closest Arabidopsis homolog AtROXY19 revealed a novel role for this glutaredoxin (GRX) gene clade in regulating cell elongation. In summary, our study suggests a conserved function for GRX genes in conferring root cell elongation and enhancing resilience of pearl millet to its Sahelian environment.


Pearl millet is a staple food for over 90 million people living in regions of Africa and India that typically experience high temperatures and little rainfall. It was domesticated about 4,500 years ago in the Sahel region of West Africa and is one of the most heat and drought tolerant cereal crops worldwide. In most plants, organs known as roots absorb water and essential nutrients from the soil. Young pearl millet plants develop a fast-growing primary root, but it is unclear how this unique feature helps the crop to grow in hot and dry conditions. Using weather data collected from the Sahel over a 20-year period, Fuente, Grondin et al. predicted by modelling that early drought stress is the major factor limiting pearl millet growth and yield in this region. Field experiments found that plants with primary roots that grow faster within soil were better at tolerating early drought than those with slower growing roots. Further work using genetic approaches revealed that a gene known as PgGRXC9 promotes the growth of the primary root. To better understand how this gene works, the team examined a very similar gene in a well-studied model plant known as Arabidopsis. This suggested that PgGRXC9 helps the primary root to grow by stimulating cell elongation within the root. Since it is well adapted to dry conditions, pearl millet is expected to play an important role in helping agriculture adjust to climate change. The findings of Fuente, Grondin et al. may be used by plant breeders to create more resilient and productive varieties of pearl millet.


Sujet(s)
Arabidopsis , Pennisetum , Sécheresses , Pennisetum/génétique , Glutarédoxines , Étude d'association pangénomique , Produits agricoles
19.
Clin Cancer Res ; 30(6): 1121-1130, 2024 Mar 15.
Article de Anglais | MEDLINE | ID: mdl-38170586

RÉSUMÉ

PURPOSE: Sidedness is prognostic and predictive of anti-EGFR efficacy in metastatic colorectal cancer (mCRC). Transverse colon has been historically excluded from several analyses of sidedness and the optimal division between left- and right-sided colorectal cancer is unclear. We investigated transverse colon primary tumor location as a biomarker in mCRC. EXPERIMENTAL DESIGN: Pooled analysis of CCTG/AGITG CO.17 and CO.20 trials of cetuximab in chemotherapy-refractory mCRC. Outcomes of patients with RAS/BRAF wild-type (WT) mCRC from CO.17 and KRAS WT mCRC from CO.20 were analyzed according to location. RESULTS: A total of 553 patients were analyzed, 32 (5.8%) with cancers from the transverse, 101 (18.3%) from right, and 420 from (75.9%) left colon. Transverse mCRC failed to reach significant benefit from cetuximab versus best supportive care (BSC) for overall survival [OS; median, 5.9 vs. 2.1 months; HR, 0.63; 95% confidence interval (CI), 0.28-1.42; P=0.26] and progression-free survival (PFS; median, 1.8 vs. 1.3 months; HR, 0.57; 95% CI, 0.26-1.28; P=0.16). Analyzing exclusively patients randomized to cetuximab, right-sided and transverse had comparable outcomes for OS (median, 5.6 vs. 5.9 months; HR, 0.82; 95% CI, 0.50-1.34; P=0.43) and PFS (median, 1.9 vs. 1.8 months; HR, 0.78; 95% CI, 0.49-1.26; P=0.31). Patients with left-sided mCRC had superior outcomes with cetuximab compared with transverse for OS (median, 9.7 vs. 5.9 months; HR, 0.42; 95% CI, 0.27-0.67; P=0.0002) and PFS (median, 3.8 vs. 1.8 months; HR, 0,49; 95% CI, 0.31-0.76; P=0.001). Location was not prognostic in patients treated with BSC alone. CONCLUSIONS: Transverse mCRC has comparable prognostic and predictive features with right-sided mCRC.


Sujet(s)
Côlon transverse , Tumeurs du côlon , Tumeurs colorectales , Tumeurs du rectum , Humains , Cétuximab/usage thérapeutique , Tumeurs colorectales/traitement médicamenteux , Tumeurs colorectales/génétique , Côlon transverse/anatomopathologie , Essais contrôlés randomisés comme sujet , Tumeurs du côlon/traitement médicamenteux , Tumeurs du côlon/génétique , Tumeurs du rectum/traitement médicamenteux , Marqueurs biologiques , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique
20.
J Nurs Meas ; 32(1): 117-128, 2024 Mar 14.
Article de Anglais | MEDLINE | ID: mdl-37348886

RÉSUMÉ

The Connor-Davidson Resilience Scale is a commonly used measure of resilience. However, while resilience is considered multidimensional, the specific dimensions embedded within this scale remain equivocal. The aim of this article was to contribute to this debate by analyzing responses from a large sample obtained within a mental health setting. Baseline data from 672 consecutive referrals to a publicly funded outpatient service for adults with anxiety and depression were subjected to exploratory factor analysis. Outcome data from 349 of these participants who had completed treatment were analyzed using confirmatory factor analysis. Both analytical strategies suggested that two dimensions were evident (Adaptability and Tenacity), although comparisons of Adaptability and Tenacity across sociodemographic, diagnostic, psychological distress, and functional impairment variables provided little support for their discriminability. The practical utility to mental health nurses of subcomponents of resilience remains clinically persuasive yet empirically elusive with current instrumentation.


Sujet(s)
Trouble dépressif , Tests psychologiques , Résilience psychologique , Adulte , Humains , Psychométrie , Reproductibilité des résultats , Anxiété/diagnostic , Anxiété/psychologie , Troubles anxieux
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