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1.
Clin Microbiol Rev ; : e0011823, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38899876

RESUMO

SUMMARYStaphylococcus capitis is divided into two subspecies, S. capitis subsp. ureolyticus (renamed urealyticus in 1992; ATCC 49326) and S. capitis subsp. capitis (ATCC 27840), and fits with the archetype of clinically relevant coagulase-negative staphylococci (CoNS). S. capitis is a commensal bacterium of the skin in humans, which must be considered an opportunistic pathogen of interest particularly as soon as it is identified in a clinically relevant specimen from an immunocompromised patient. Several studies have highlighted the potential determinants underlying S. capitis pathogenicity, resistance profiles, and virulence factors. In addition, mobile genetic element acquisitions and mutations contribute to S. capitis genome adaptation to its environment. Over the past decades, antibiotic resistance has been identified for S. capitis in almost all the families of the currently available antibiotics and is related to the emergence of multidrug-resistant clones of high clinical significance. The present review summarizes the current knowledge concerning the taxonomic position of S. capitis among staphylococci, the involvement of this species in human colonization and diseases, the virulence factors supporting its pathogenicity, and the phenotypic and genomic antimicrobial resistance profiles of this species.

2.
Nat Methods ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744918

RESUMO

The combination of native electrospray ionization with top-down fragmentation in mass spectrometry (MS) allows simultaneous determination of the stoichiometry of noncovalent complexes and identification of their component proteoforms and cofactors. Although this approach is powerful, both native MS and top-down MS are not yet well standardized, and only a limited number of laboratories regularly carry out this type of research. To address this challenge, the Consortium for Top-Down Proteomics initiated a study to develop and test protocols for native MS combined with top-down fragmentation of proteins and protein complexes across 11 instruments in nine laboratories. Here we report the summary of the outcomes to provide robust benchmarks and a valuable entry point for the scientific community.

3.
Br J Neurosurg ; : 1-6, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38741545

RESUMO

Although glioblastoma is the commonest primary brain tumour in adults, its location in the cerebellum is extremely rare. We present thirteen cases (3 female, 10 male; median age at presentation 56 [age range 21-77]) of surgically managed, histologically confirmed, primary cerebellar glioblastoma (cGB) over a 17 year period (2005-2022). Pre-operative radiological diagnosis was challenging given cGB rarity, although MRI demonstrated ring enhancement in all cases. Surgical management included posterior fossa craniectomy and debulking in 11 cases and burr hole biopsy in two. CSF diversion was necessary in four cases. No evidence of IDH or ATRX gene mutations was found when tested. Survival ranged from 1 to 22 months after diagnosis (mean 10.9 months). We also seek to understand why glioblastoma is rare in this location and discuss potential reasons for this. We hypothesise that increasing anatomical distance from germinal regions and decreased local endogenous neural stem cell activity (which has been associated with glioblastoma) may explain why glioblastoma is rare in the cerebellum. We hereby seek to add to the limited literature on cGB as this is the largest UK cGB series to date.

4.
Phys Med Biol ; 69(11)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38718813

RESUMO

Objective.This study aims to characterize radiological properties of selected additive manufacturing (AM) materials utilizing both material extrusion and vat photopolymerization technologies. Monochromatic synchrotron x-ray images and synchrotron treatment beam dosimetry were acquired at the hutch 3B and 2B of the Australian Synchrotron-Imaging and Medical Beamline.Approach.Eight energies from 30 keV up to 65 keV were used to acquire the attenuation coefficients of the AM materials. Comparison of theoretical, and experimental attenuation data of AM materials and standard solid water for MV linac was performed. Broad-beam dosimetry experiment through attenuated dose measurement and a Geant4 Monte Carlo simulation were done for the studied materials to investigate its attenuation properties specific for a 4 tesla wiggler field with varying synchrotron radiation beam qualities.Main results.Polylactic acid (PLA) plus matches attenuation coefficients of both soft tissue and brain tissue, while acrylonitrile butadiene styrene, Acrylonitrile styrene acrylate, and Draft resin have close equivalence to adipose tissue. Lastly, PLA, co-polyester plus, thermoplastic polyurethane, and White resins are promising substitute materials for breast tissue. For broad-beam experiment and simulation, many of the studied materials were able to simulate RMI457 Solid Water and bolus within ±10% for the three synchrotron beam qualities. These results are useful in fabricating phantoms for synchrotron and other related medical radiation applications such as orthovoltage treatments.Significance and conclusion.These 3D printing materials were studied as potential substitutes for selected tissues such as breast tissue, adipose tissue, soft-tissue, and brain tissue useful in fabricating 3D printed phantoms for synchrotron imaging, therapy, and orthovoltage applications. Fabricating customizable heterogeneous anthropomorphic phantoms (e.g. breast, head, thorax) and pre-clinical animal phantoms (e.g. rodents, canine) for synchrotron imaging and radiotherapy using AM can be done based on the results of this study.


Assuntos
Síncrotrons , Austrália , Método de Monte Carlo , Radioterapia/instrumentação , Radioterapia/métodos , Radiometria/instrumentação , Radiometria/métodos , Humanos
6.
PLoS One ; 19(3): e0299243, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38446817

RESUMO

Tsetse flies, the sole biological vectors of trypanosomiasis, are predominantly controlled using visual traps and targets baited with attractant lures. Formulation of the lures is informed by compositions of odors from vertebrate hosts preferred by specific tsetse species. However, there are no effective lures for Glossina austeni, a major vector of trypanosomiasis along eastern-coastal region of Africa. Formulation of the lure can be informed by knowledge of G. austeni, preferred vertebrate hosts. We thus sought to understand these hosts by assessment of putative bloodmeal sources of this tsetse fly in Arabuko Sokoke National Reserve where this species is naturally present. We sampled tsetse flies using NGU traps, isolated non-teneral G. austeni flies based on their feeding status, and identified vertebrate source of bloodmeals in their midgut contents using vertebrate 16S rRNA-PCR High-Resolution Melting analysis. We analyzed the relative vertebrate species frequencies in the bloodmeals using Fisher's exact tests. Overall, we trapped 122 flies, most of which (66.39%) were non-teneral, among which we successfully identified the vertebrate bloodmeals in 30 samples. Specifically, we detected putative suni antelope (Neotragus moschatus), harnessed bushbuck (Tragelaphus scriptus), buffalo (Syncerus caffer) and cattle (Bos taurus) derived bloodmeals. Putative suni antelope bloodmeals were significantly more frequent (63.22%), than those of the harnessed bushbuck (23.33%), buffalo (10.00%) or cattle (3.33%) (p < 0.05 Fisher's exact tests) among the samples analyzed. Suni antelope thus appears to predominate vertebrate bloodmeal source for G. austeni in the reserve, coincident with findings reported elsewhere, and is therefore a viable candidate for bioprospecting for G. austeni responsive attractants.


Assuntos
Antílopes , Bison , Tripanossomíase , Moscas Tsé-Tsé , Animais , Bovinos , Quênia , Búfalos , RNA Ribossômico 16S
7.
J Am Pharm Assoc (2003) ; : 102079, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38556246

RESUMO

Barriers to medication error reporting in inpatient settings and primary care clinics are well known and can be categorized as psychological, logistical, knowledge, and workplace. These barriers have not been explored well at Federally Qualified Health Centers (FQHC) where limited pharmacy services may exist. METHODS: This prospective, cross-sectional study surveyed 161 medical professionals at a large FQHC clinic with a small pharmacy team to explore their understanding of medication error categories and the influence of barriers to medication error reporting on their decision to report. RESULTS: Thirty-six (22.4%) respondents completed the survey. Nearly 40% of respondents would not report a near miss error and were influenced by workplace/environmental barriers significantly more than those who would report. Regardless of reporting experience or patient-care role, assessed barrier categories influence the decision to report similarly. CONCLUSION: Near miss medication errors are inconsistently reported. Efforts to improve reporting should emphasize addressing workplace/environmental barriers.

8.
Laryngoscope ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38506422

RESUMO

Here we present the first case of sebaceous carcinoma of the middle ear. We discuss the treatment course and post treatment results after 11 years of follow up. We further summarize the available literature of sebaceous carcinoma of the temporal bone, which prior to this case was exclusively limited to the external auditory canal. Laryngoscope, 2024.

9.
Sci Rep ; 14(1): 6189, 2024 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-38485968

RESUMO

Despite the general consensus that the warming over the high latitudes northern forests (HLNF) has led to enhanced photosynthetic activity and contributed to the greening trend, isolating the impact of temperature increase on photosynthesis and greenness has been difficult due to the concurring influence of the CO2 fertilization effect. Here, using an ensemble of simulations from biogeochemical models that have contributed to the Trends in Net Land Atmosphere Carbon Exchange project (TRENDY), we identify an emergent relationship between the simulation of the climate-driven temporal changes in both gross primary productivity (GPP) and greenness (Leaf Area Index, LAI) and the model's spatial sensitivity of these quantities to growing-season (GS) temperature. Combined with spatially-resolved observations of LAI and GPP, we estimate that GS-LAI and GS-GPP increase by 17.0 ± 2.4% and 24.0 ± 3.0% per degree of warming, respectively. The observationally-derived sensitivities of LAI and GPP to temperature are about 40% and 71% higher, respectively, than the mean of the ensemble of simulations from TRENDY, primarily due to the model underestimation of the sensitivity of light use efficiency to temperature. We estimate that the regional mean GS-GPP increased 28.2 ± 5.1% between 1983-1986 and 2013-2016, much larger than the 5.8 ± 1.4% increase from the CO2 fertilization effect implied by Wenzel et al. This suggests that warming, not CO2 fertilization, is primarily responsible for the observed dramatic changes in the HLNF biosphere over the last century.


Assuntos
Dióxido de Carbono , Florestas , Fotossíntese , Clima , Estações do Ano , Ecossistema , Mudança Climática
10.
Heliyon ; 10(2): e23999, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38293437

RESUMO

Enhancing the durability of structural elements is a viable approach to promote sustainability in civil engineering. Research has shown that well-maintained slabs outperform degraded ones, which deteriorate rapidly due to insufficient upkeep. The occurrence of cracking and deformation in slabs subjected to sustained loads significantly impacts their functionality. However, the implementation of appropriate retrofitting techniques utilizing locally available materials can effectively minimize deflection and crack propagation while also improving flexural capacity. This particular study aimed to evaluate the flexural performance of slabs that were retrofitted using bamboo fibre laminate (BFL). Also, the study investigated two alternative replacement methods alongside the conventional mix; one involved replacing all fine aggregates with ceramic fine aggregate and the other involved a complete replacement of coarse aggregates with ceramic coarse aggregate. These mixes were represented in both the retrofitted and non-retrofitted samples. The retrofitting process included using the combined external bonding and near surface-mounted method. Twelve slab samples were made, with six being non-retrofitted and the other six retrofitted with BFL. Each of the samples had dimensions of 300 mm × 300 mm × 50 mm for reinforced concrete (RC) slabs. The slabs were tested employing the three point-bending system, and the retrofitted slabs with the conventional mix exhibited the highest ultimate failure load and flexural strength (62.1 kN), which compared to the non-retrofitted slabs of the same mix was a 60.76% increase. Additionally, the study did a thorough analysis of the presence of flexural and diagonal shear cracks, as well as the occurrence of debonding between BFL and the slabs. Non-destructive tests were also conducted on the slab samples to further confirm accurate results. These findings offer helpful insights into the development and application of a sustainable retrofitting material that can remarkably improve RC slabs.

11.
Clin Chem ; 70(3): 497-505, 2024 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-38102065

RESUMO

BACKGROUND: Cardiac troponin measurements are indispensable for the diagnosis of myocardial infarction and provide useful information for long-term risk prediction of cardiovascular disease. Accelerated diagnostic pathways prevent unnecessary hospital admission, but require reporting cardiac troponin concentrations at low concentrations that are sometimes below the limit of quantification. Whether analytical imprecision at these concentrations contributes to misclassification of patients is debated. CONTENT: The International Federation of Clinical Chemistry Committee on Clinical Application of Cardiac Bio-Markers (IFCC C-CB) provides evidence-based educational statements on analytical and clinical aspects of cardiac biomarkers. This mini-review discusses how the reporting of low concentrations of cardiac troponins impacts on whether or not assays are classified as high-sensitivity and how analytical performance at low concentrations influences the utility of troponins in accelerated diagnostic pathways. Practical suggestions are made for laboratories regarding analytical quality assessment of cardiac troponin results at low cutoffs, with a particular focus on accelerated diagnostic pathways. The review also discusses how future use of cardiac troponins for long-term prediction or management of cardiovascular disease may require improvements in analytical quality. SUMMARY: Clinical guidelines recommend using cardiac troponin concentrations as low as the limit of detection of the assay to guide patient care. Laboratories, manufacturers, researchers, and external quality assessment providers should extend analytical performance monitoring of cardiac troponin assays to include the concentration ranges applicable in these pathways.


Assuntos
Bioensaio , Infarto do Miocárdio , Humanos , Química Clínica , Hospitalização , Infarto do Miocárdio/diagnóstico , Troponina
12.
Science ; 382(6675): 1165-1170, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38060669

RESUMO

Catalysts that distinguish between electronically distinct carbon-hydrogen (C-H) bonds without relying on steric effects or directing groups are challenging to design. In this work, cobalt precatalysts supported by N-alkyl-imidazole-substituted pyridine dicarbene (ACNC) pincer ligands are described that enable undirected, remote borylation of fluoroaromatics and expansion of scope to include electron-rich arenes, pyridines, and tri- and difluoromethoxylated arenes, thereby addressing one of the major limitations of first-row transition metal C-H functionalization catalysts. Mechanistic studies established a kinetic preference for C-H bond activation at the meta-position despite cobalt-aryl complexes resulting from ortho C-H activation being thermodynamically preferred. Switchable site selectivity in C-H borylation as a function of the boron reagent was thereby preliminarily demonstrated using a single precatalyst.

13.
Sci Rep ; 13(1): 21480, 2023 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-38057401

RESUMO

Bone quality is commonly used to diagnose bone diseases such as osteoporosis, with many studies focusing on microarchitecture for fracture prediction. In this study a bovine distal femur was imaged using both micro-computed tomography (µCT) and tomosynthesis using focal construct geometry (FCG) for comparison of microarchitectural parameters. Six regions of interest (ROIs) were compared between the two imaging modalities, with both global and adaptive methods used to binarize the images. FCG images were downsampled to the same pixel size as the µCT images. Bone morphometrics were determined using BoneJ, for each imaging modality, binarization technique and ROI. Bone area/total area was found to have few significant differences between FCG and µCT (p < 0.05 for two of six ROIs). Fractal Dimension had only one significant difference (p < 0.05 for one of six ROIs) between µCT and downsampled FCG (where pixel size was equalized). Trabecular thickness and trabecular spacing were observed to follow trends as observed for the corresponding µCT images, although many absolute values were significantly different (p < 0.05 for between one and six ROIs depending on image types used). This study demonstrates the utility of tomosynthesis for measurement of microarchitectural morphometrics.


Assuntos
Osso e Ossos , Osteoporose , Animais , Bovinos , Microtomografia por Raio-X/métodos , Raios X , Fêmur/diagnóstico por imagem , Densidade Óssea
14.
Microbiome Res Rep ; 2(1): 1, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38059211

RESUMO

Recent years have seen the development of high-accuracy and high-throughput genetic manipulation techniques, which have greatly improved our understanding of genetically tractable microbes. However, challenges remain in establishing genetic manipulation techniques in novel organisms, owing largely to exogenous DNA defence mechanisms, lack of selectable markers, lack of efficient methods to introduce exogenous DNA and an inability of genetic vectors to replicate in their new host. In this review, we describe some of the techniques that are available for genetic manipulation of novel microorganisms. While many reviews exist that focus on the final step in genetic manipulation, the editing of recipient DNA, we particularly focus on the first step in this process, the transfer of exogenous DNA into a strain of interest. Examples illustrating the use of these techniques are provided for a selection of human gut bacteria in which genetic tractability has been established, such as Bifidobacterium, Bacteroides and Roseburia. Ultimately, this review aims to provide an information source for researchers interested in developing genetic manipulation techniques for novel bacterial strains, particularly those of the human gut microbiota.

15.
PNAS Nexus ; 2(12): pgad338, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38059262

RESUMO

The rapid adoption of glyphosate-resistant crops at the end of the 20th century caused a simplification of weed management that relied heavily on glyphosate for weed control. However, the effectiveness of glyphosate has diminished. A greater understanding of trends related to glyphosate use will shed new light on weed adaptation to a product that transformed global agriculture. Objectives were to (1) quantify the change in weed control efficacy from postemergence (POST) glyphosate use on troublesome weeds in corn and soybean and (2) determine the extent to which glyphosate preceded by a preemergence (PRE) improved the efficacy and consistency of weed control compared to glyphosate alone. Herbicide evaluation trials from 24 institutions across the United States of America and Canada from 1996 to 2021 were compiled into a single database. Two subsets were created; one with glyphosate applied POST, and the other with a PRE herbicide followed by glyphosate applied POST. Within each subset, mean and variance of control ratings for seven problem weed species were regressed over time for nine US states and one Canadian province. Mean control with POST glyphosate alone decreased over time while variability in control increased. Glyphosate preceded by a labeled PRE herbicide showed little change in mean control or variability in control over time. These results illustrate the rapid adaptation of agronomically important weed species to the paradigm-shifting product glyphosate. Including more diversity in weed management systems is essential to slowing weed adaptation and prolonging the usefulness of existing and future technologies.

16.
Clin Res Cardiol ; 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38117299

RESUMO

BACKGROUND: Anxiety and limited patient comprehension may pose significant barriers when informing elderly patients about complex procedures such as transcatheter aortic valve implantation (TAVI). OBJECTIVES: We aimed to evaluate the utility of medical graphics to improve the patient informed consent (IC) before TAVI. METHODS: In this prospective, randomized dual center study, 301 patients were assigned to a patient brochure containing medical graphics (Comic group, n = 153) or sham information (Control group, n = 148) on top of usual IC. Primary outcomes were patient understanding of central IC-related aspects and periprocedural anxiety assessed by the validated Spielberger State Trait Anxiety Inventory (STAI), both analyzed by cognitive status according to the Montreal Cognitive Assessment (MoCA). RESULTS: Patient understanding was significantly higher in the Comic group [mean number of correct answers 12.8 (SD 1.2) vs. 11.3 (1.8); mean difference 1.5 (95% CI 1.2-1.8); p < 0.001]. This effect was more pronounced in the presence of cognitive dysfunction (MoCA < 26) [12.6 (1.2) in the Comic vs. 10.9 (1.6) in the Control group; mean difference 1.8 (1.4-2.2), p < 0.001]. Mean STAI score declined by 5.7 (95% CI 5.1-6.3; p < 0.001) in the Comic and 0.8 points (0.2-1.4; p = 0.015) in the Control group. Finally, mean STAI score decreased in the Comic group by 4.7 (3.8-5.6) in cognitively impaired patients and by 6.6 (95% CI 5.8 to 7.5) in patients with normal cognitive function (p < 0.001 each). CONCLUSIONS: Our results prove beneficial effects for using medical graphics to inform elderly patients about TAVI by improving patient understanding and reducing periprocedural anxiety (DRKS00021661; 23/Oct/2020). Medical graphics entailed significant beneficial effects on the primary endpoints, patient understanding and periprocedural anxiety, compared to the usual patient informed consent (IC) procedure. Patient understanding of IC-related aspects was significantly higher in the Comic group, with a more pronounced benefit in patients with cognitive impairment (p for IC method and cognitive status < 0.001, respectively; p for IC method x MoCA category interaction = 0.017). There further was a significant decline of periprocedural anxiety in patients with and without cognitive impairment (p for IC method x measuring time point < 0.001; p for IC method x MoCA category x measuring time point interaction = 0.018).

17.
Open Heart ; 10(2)2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38151261

RESUMO

BACKGROUND: There have been relatively few studies detailing the real-world effectiveness and safety of accelerated diagnostic protocols (ADP), using high sensitivity cardiac troponin (hs-cTn). OBJECTIVE: To analyse the safety and effectiveness of early emergency department (ED) discharge following implementation of the European Society of Cardiology (ESC) 0/3-hour ADP for suspected acute coronary syndromes (ACS). METHOD: We prospectively studied 2 cohorts of consecutive suspected ACS presentations to ED before (n=1642) and after (n=1376, 2 centres) implementation of the ESC 0/3-hour ADP incorporating limit of detection rule out. Safety was defined by MACE (major adverse cardiac events) inclusive of type 1 myocardial infarction (MI) in patients discharged from ED, and clinical effectiveness by percentage ED discharge. Continuous variables and categorical data were evaluated by independent t-test and χ2 test, respectively. Time-to-event data were analysed as survival data and converted to Kaplan-Meier curves for interpretation. RESULTS: In the preimplementation period, there was a higher prevalence of MI. Discharge from ED increased by >100% (from 27.1% to 56.5% of the cohort) with no safety signal (MACE rate 4/444 (0.9%) vs 4/769 (0.52%), p=0.430 for the 2011 and 2018 cohort, respectively). This correlated with a marked reduction in length of stay overall but a more modest reduction for those discharged from ED (6 hours 10 min vs 5 hours 25 min, p<0.001) for the 2011 and 2018 cohort, respectively. There were improvements in presentation to blood draw (163-90 min, p<0.001). Time from presentation to first ECG actually increased (16.2 vs 31.2 min, p<0.001). Analysis of hs-cTn values and ECGs revealed a maximum ED discharge rate of 69%, by applying the 0/3-hour protocol, implying potential for increasing safe ED discharge. CONCLUSIONS: Implementation of an ADP with hs-cTn is safe and effective for early rule-out and discharge of suspected ACS but require considerable resources and education to optimise maximal patient flow.


Assuntos
Síndrome Coronariana Aguda , Cardiologia , Infarto do Miocárdio , Humanos , Síndrome Coronariana Aguda/diagnóstico , Troponina T , Infarto do Miocárdio/diagnóstico , Eletrocardiografia/métodos
18.
Cancers (Basel) ; 15(24)2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38136356

RESUMO

Background: Neurofibromatosis type 1 (NF1) is a genetic disorder characterized by heterozygous germline NF1 gene mutations that predispose patients to developing plexiform neurofibromas, which are benign but often disfiguring tumors of the peripheral nerve sheath induced by loss of heterozygosity at the NF1 locus. These can progress to malignant peripheral nerve sheath tumors (MPNSTs). There are no approved drug treatments for adults with NF1-related inoperable plexiform neurofibromas, and only one drug (selumetinib), which is an FDA-approved targeted therapy for the treatment of symptomatic pediatric plexiform neurofibromas, highlighting the need for additional drug screening and development. In high-throughput screening, the effectiveness of drugs against cell lines is often assessed by measuring in vitro potency (AC50) or the area under the curve (AUC). However, the variability of dose-response curves across drugs and cell lines and the frequency of partial effectiveness suggest that these measures alone fail to provide a full picture of overall efficacy. Methods: Using concentration-response data, we combined response effectiveness (EFF) and potency (AC50) into (a) a score characterizing the effect of a compound on a single cell line, S = log[EFF/AC50], and (b) a relative score, ΔS, characterizing the relative difference between a reference (e.g., non-tumor) and test (tumor) cell line. ΔS was applied to data from high-throughput screening (HTS) of a drug panel tested on NF1-/- tumor cells, using immortalized non-tumor NF1+/- cells as a reference. Results: We identified drugs with sensitivity, targeting expected pathways, such as MAPK-ERK and PI3K-AKT, as well as serotonin-related targets, among others. The ΔS technique used here, in tandem with a supplemental ΔS web tool, simplifies HTS analysis and may provide a springboard for further investigations into drug response in NF1-related cancers. The tool may also prove useful for drug development in a variety of other cancers.

19.
Science ; 382(6672): 787-792, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37972156

RESUMO

Secondary organic aerosol (SOA) is ubiquitous in the atmosphere and plays a pivotal role in climate, air quality, and health. The production of low-volatility dimeric compounds through accretion reactions is a key aspect of SOA formation. However, despite extensive study, the structures and thus the formation mechanisms of dimers in SOA remain largely uncharacterized. In this work, we elucidate the structures of several major dimer esters in SOA from ozonolysis of α-pinene and ß-pinene-substantial global SOA sources-through independent synthesis of authentic standards. We show that these dimer esters are formed in the particle phase and propose a mechanism of nucleophilic addition of alcohols to a cyclic acylperoxyhemiacetal. This chemistry likely represents a general pathway to dimeric compounds in ambient SOA.

20.
Nat Commun ; 14(1): 7305, 2023 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-37951938

RESUMO

Knowledge of deeply-rooted non-ammonia oxidising Thaumarchaeota lineages from terrestrial environments is scarce, despite their abundance in acidic soils. Here, 15 new deeply-rooted thaumarchaeotal genomes were assembled from acidic topsoils (0-15 cm) and subsoils (30-60 cm), corresponding to two genera of terrestrially prevalent Gagatemarchaeaceae (previously known as thaumarchaeotal Group I.1c) and to a novel genus of heterotrophic terrestrial Thaumarchaeota. Unlike previous predictions, metabolic annotations suggest Gagatemarchaeaceae perform aerobic respiration and use various organic carbon sources. Evolutionary divergence between topsoil and subsoil lineages happened early in Gagatemarchaeaceae history, with significant metabolic and genomic trait differences. Reconstruction of the evolutionary mechanisms showed that the genome expansion in topsoil Gagatemarchaeaceae resulted from extensive early lateral gene acquisition, followed by progressive gene duplication throughout evolutionary history. Ancestral trait reconstruction using the expanded genomic diversity also did not support the previous hypothesis of a thermophilic last common ancestor of the ammonia-oxidising archaea. Ultimately, this study provides a good model for studying mechanisms driving niche partitioning between spatially related ecosystems.


Assuntos
Ecossistema , Solo , Filogenia , Archaea/metabolismo , Genômica , Microbiologia do Solo , Oxirredução , Amônia/metabolismo
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