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1.
Mar Drugs ; 22(7)2024 Jun 28.
Article in English | MEDLINE | ID: mdl-39057411

ABSTRACT

In our continuing search for biologically active new chemical entities from marine organisms, we have isolated a new cyclic depsipeptide, PM170453 (1), from a cyanobacterium of the genus Lyngbya sp., collected in the Indo-Pacific Ocean. Structure elucidation of the isolated compound was determined by spectroscopic methods including MS, 1H, 13C and 2D-NMR. To solve the supply problem for 1 and progress pharmaceutical development, the total synthesis of 1 that involves a total of 20 chemical steps in a convergent process was carried out. Its in vitro cytotoxic activity against four human tumor cell lines, as well as the inhibition of the interaction between the programmed cell death protein 1 PD-1 and its ligand PD-L1 were also evaluated.


Subject(s)
Antineoplastic Agents , Cyanobacteria , Depsipeptides , Depsipeptides/pharmacology , Depsipeptides/isolation & purification , Depsipeptides/chemistry , Depsipeptides/chemical synthesis , Humans , Cyanobacteria/chemistry , Cell Line, Tumor , Antineoplastic Agents/pharmacology , Antineoplastic Agents/isolation & purification , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Aquatic Organisms , B7-H1 Antigen/antagonists & inhibitors , Pacific Ocean , Peptides, Cyclic/pharmacology , Peptides, Cyclic/chemistry , Peptides, Cyclic/isolation & purification
2.
Nature ; 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39085604

ABSTRACT

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels1 are essential for pacemaking activity and neural signalling2,3. Drugs inhibiting HCN1 are promising candidates for management of neuropathic pain4 and epileptic seizures5. The general anaesthetic propofol (2,6-di-iso-propylphenol) is a known HCN1 allosteric inhibitor6 with unknown structural basis. Here, using single-particle cryo-electron microscopy and electrophysiology, we show that propofol inhibits HCN1 by binding to a mechanistic hotspot in a groove between the S5 and S6 transmembrane helices. We found that propofol restored voltage-dependent closing in two HCN1 epilepsy-associated polymorphisms that act by destabilizing the channel closed state: M305L, located in the propofol-binding site in S5, and D401H in S6 (refs. 7,8). To understand the mechanism of propofol inhibition and restoration of voltage-gating, we tracked voltage-sensor movement in spHCN channels and found that propofol inhibition is independent of voltage-sensor conformational changes. Mutations at the homologous methionine in spHCN and an adjacent conserved phenylalanine in S6 similarly destabilize closing without disrupting voltage-sensor movements, indicating that voltage-dependent closure requires this interface intact. We propose a model for voltage-dependent gating in which propofol stabilizes coupling between the voltage sensor and pore at this conserved methionine-phenylalanine interface in HCN channels. These findings unlock potential exploitation of this site to design specific drugs targeting HCN channelopathies.

3.
Seizure ; 120: 194-200, 2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39032348

ABSTRACT

PURPOSE: To describe four patients with subacute encephalopathy with seizures in alcoholics (SESA) syndrome and to review its clinical, electroencephalogram (EEG), neuroimaging and diagnostic criteria. METHODS: We conducted a retrospective analysis of a series of prospectively collected patients who met the previously established criteria for SESA syndrome. Subsequently, we reviewed all cases published in the English language from the initial description to the present. RESULTS: We found 34 patients diagnosed with SESA syndrome to date, including the four cases of SESA in this report. Fourteen out of 34 (41.1 %) patients were over 60 years of age. Twelve (35.2 %) were abstinent from alcohol and in 4 (11.7 %) there was excessive alcohol consumption. Triggering causes were unknown in 18 cases (53.0 %). All cases (100 %) presented with an altered mental status. Fourteen (41.1 %) subjects had a history of epileptic seizures in the context of acute withdrawal syndrome (AWS). Twenty (58.8 %) patients had focal motor seizures (FMSs), 24 (70.5 %) bilateral tonic-clonic seizures (BTCSs), and 15 (44.1 %) focal impaired awareness seizures (FIASs). In 8 (23.5 %), criteria for focal nonconvulsive status epilepticus (NCSE) were met. Twenty-eight (82.3 %) subjects had transient neurological deficits. In 29 (85.2 %) subjects, lateralized periodic discharges (LPDs) were observed in the EEG. Areas of increased T2/FLAIR signal and restricted diffusion were mentioned in 22 subjects (64.7 %). Transfer to the intensive care unit (ICU) was necessary in 8 (23.5 %) subjects. Thirteen (38.2 %) had recurrent episodes. Enduring cerebral sequelae had been mentioned in 9 (26.4 %) cases. The most used anti-seizure medication (ASM) was levetiracetam, followed by phenytoin and lacosamide. CONCLUSION: SESA syndrome represents a well-defined subtype of focal NCSE in patients with chronic alcoholism. Its prompt recognition can facilitate the initiation of early ASM therapy and help implement a video-EEG evaluation and neuroimaging strategy.

4.
Front Immunol ; 15: 1386590, 2024.
Article in English | MEDLINE | ID: mdl-39076984

ABSTRACT

Aluminum hydroxide has long been employed as a vaccine adjuvant for its safety profile, although its precise mechanism of action remains elusive. In this study, we investigated the transcriptomic responses in sheep spleen following repetitive vaccination with aluminum adjuvanted vaccines and aluminum hydroxide alone. Notably, this work represents the first exploration of the sheep spleen transcriptome in such conditions. Animals were splitted in 3 treatment groups: vaccine group, adjuvant alone group and control group. A total of 18 high-depth RNA-seq libraries were sequenced, resulting in a rich dataset which also allowed isoform-level analysis. The comparisons between vaccine-treated and control groups (V vs C) as well as between vaccine-treated and adjuvant-alone groups (V vs A) revealed significant alterations in gene expression profiles, including protein coding genes and long non-coding RNAs. Among the differentially expressed genes, many were associated with processes such as endoplasmic reticulum (ER) stress, immune response and cell cycle. The analysis of co-expression modules further indicated a correlation between vaccine treatment and genes related to ER stress and unfolded protein response. Surprisingly, adjuvant-alone treatment had little impact on the spleen transcriptome. Additionally, the role of alternative splicing in the immune response was explored. We identified isoform switches in genes associated with immune regulation and inflammation, potentially influencing protein function. In conclusion, this study provides valuable insights into the transcriptomic changes in sheep spleen following vaccination with aluminum adjuvanted vaccines and aluminum hydroxide alone. These findings shed light on the molecular mechanisms underlying vaccine-induced immune responses and emphasize the significance of antigenic components in aluminum adjuvant mechanism of action. Furthermore, the analysis of alternative splicing revealed an additional layer of complexity in the immune response to vaccination in a livestock species.


Subject(s)
Adjuvants, Immunologic , Spleen , Transcriptome , Vaccination , Animals , Spleen/immunology , Spleen/metabolism , Sheep , Gene Expression Profiling , Vaccines/immunology , Aluminum Hydroxide/immunology , Alternative Splicing
5.
BMC Psychol ; 12(1): 349, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38877593

ABSTRACT

BACKGROUND: During the COVID-19 pandemic, young people have experienced numerous personal losses across various aspects, impacting their quality of life. This study aimed to explore and analyze the losses experienced by physiotherapy students during the first year of the COVID-19 pandemic. METHODS: A qualitative phenomenological study was conducted using an open-format exercise carried out during the Clinical Specialties class from February to May 2021. Thirty-four (83% female) third-year physical therapy students participated. ATLAS.ti software was used for the analysis and coding by three researchers. RESULTS: Analysis of the categories revealed various losses experienced by the participants, including losses in psychological well-being, physical health, the social sphere (friendships, relationships with partners and family members, and experiences of death), spiritual losses (loss of freedom and identity), leisure time (travel, recreational activities and physical exercise), and different losses related to university studies (motivation and enthusiasm and clinical practices). CONCLUSION: The COVID-19 pandemic has led to significant losses among physiotherapy students, with losses in the social sphere being the most prevalent. This study can serve as a foundation for developing resources aimed at enhancing the well-being of physiotherapy students, promoting optimal academic performance, improving self-care, and reducing psychosocial problems.


Subject(s)
COVID-19 , Qualitative Research , Humans , COVID-19/psychology , COVID-19/epidemiology , Female , Male , Young Adult , Adult , Quality of Life/psychology , Students, Health Occupations/psychology , Pandemics , SARS-CoV-2
7.
J Neurointerv Surg ; 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38906690

ABSTRACT

BACKGROUND: Several antithrombotic treatments during emergent carotid artery stenting (eCAS) have been proposed, but an appropriate protocol to balance risk-benefit is not well known. OBJECTIVE: To investigate the efficacy and safety of tirofiban compared with aspirin in patients with acute ischemic stroke undergoing eCAS. METHODS: We conducted a retrospective single-center study of the prospective ARTISTA Registry, including patients with atherosclerotic internal carotid artery occlusion treated with eCAS. Two groups, according to antiplatelet drug, were studied: aspirin (250-500 mg single-dose) versus tirofiban (500 µg bolus+200 µg/h). Primary outcomes were the rate of in-stent thrombosis and symptomatic intracranial hemorrhage (sICH) within the first 24 hours. RESULTS: During the period 2019-2023, 181 patients were included, 103 received aspirin, 78 tirofiban; 149 (82.3%) had tandem lesions. The primary efficacy outcome occurred in 9 (9.4%) in the aspirin group, as compared with 1 (1.3%) in the tirofiban group (adjusted odds ratio (aOR)=0.11, 95% CI 0.01 to 0.98; P=0.048). The primary safety outcome was detected in 12 (11.7%) in the aspirin group, as compared with 2 (2.6%) in the tirofiban group (aOR=0.16, 95% CI 0.03 to 0.87; P=0.034). The tirofiban group presented a lower risk of parenchymal hemorrhage (18 (17.4%) vs 4 (5.2%), aOR=0.27, 95% CI 0.09 to 0.88; P=0.029) and an increased rate of excellent recanalization (expanded Treatment in Cerebral Infarction (eTICI) 2c-3) (50 (48.5%) vs 54 (69.2%); aOR=2.15, 95% CI 1.12 to 4.13; P=0.02). There were no differences in functional outcomes or mortality at 3 months. CONCLUSIONS: Periprocedural antithrombotic therapy with tirofiban was associated with a lower risk of in-stent thrombosis and sICH at 24 hours from eCAS compared with aspirin. Prospective randomized clinical trials are needed to confirm our results.

8.
Nat Biotechnol ; 2024 May 07.
Article in English | MEDLINE | ID: mdl-38714897

ABSTRACT

A central challenge in developing personalized cancer cell immunotherapy is the identification of tumor-reactive T cell receptors (TCRs). By exploiting the distinct transcriptomic profile of tumor-reactive T cells relative to bystander cells, we build and benchmark TRTpred, an antigen-agnostic in silico predictor of tumor-reactive TCRs. We integrate TRTpred with an avidity predictor to derive a combinatorial algorithm of clinically relevant TCRs for personalized T cell therapy and benchmark it in patient-derived xenografts.

9.
J Med Food ; 2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38742994

ABSTRACT

Declines in estrogen levels occur in women transitioning to menopause. Estrogen hormones play important roles in multiple systems of the body, and estrogen loss is associated with a variety of symptoms that can decrease quality of life. The gut microbiota is involved in regulating endogenous estrogen levels. A portion of estrogen glucuronides can be reactivated in the gut by the microbial enzyme ß-glucuronidase, and the resulting free estrogens can return to the bloodstream. Here, we carried out in vitro screening of ß-glucuronidase activities for 84 strains belonging to 16 different species of lactic acid bacteria and bifidobacteria and found that one and three strains of Levilactobacillus brevis and Lacticasebacillus rhamnosus, respectively, can deconjugate estrogens. Among these strains, L. brevis KABP052 had the highest ß-glucuronidase activity. Moreover, in an exploratory, randomized, double-blind, placebo-controlled trial, we demonstrated that serum estrogen levels in healthy peri- and postmenopausal women given a probiotic formula containing KABP052 were maintained over time, whereas levels significantly decreased in the group given a placebo. Significantly higher levels of estradiol (31.62 ± 7.97 pg/mL vs. 25.12 ± 8.17 pg/mL) and estrone (21.38 ± 8.57 pg/mL vs. 13.18 ± 8.77 pg/mL) were observed in the probiotic versus placebo group after 12 weeks of intervention. This clinical study demonstrated for the first time the estrogen modulation capacity of a probiotic formula containing a bacterial strain having ß-glucuronidase activity in women during the menopausal transition and formed the basis for future investigations using probiotics in the menopausal population.

10.
Article in English | MEDLINE | ID: mdl-38802040

ABSTRACT

OBJECTIVE: The long term benefit of carotid angioplasty and stenting (CAS) can be reduced by recurrent stroke related to in stent re-stenosis (ISR). An individualised predictive tool is needed to identify ISR events. A nomogram for individual risk assessment of ISR ≥ 70% after CAS is proposed. METHODS: A national observational, prospective, multicentre registry was conducted between January 2015 and December 2020. Cohorts of patients with symptomatic or asymptomatic severe carotid stenosis who underwent CAS with a follow up of at least one year after CAS were included. Duplex ultrasound was used to assess in stent re-stenosis. Pre-operative factors were compared between the non-ISR and ISR groups. Kaplan-Meier and Cox regression were used for variable selection. The nomogram was formulated and validated by concordance indices and calibration curves. An in stent re-stenosis risk table was generated for risk stratification. RESULTS: A total of 354 patients were included in the analysis. The ISR rate of ≥ 70% was 7.6% (n = 27). Peripheral arterial disease (hazard ratio [HR] 3.18, 95% confidence interval [CI] 1.23 - 8.24, p = .017), anterior communicating artery absence (HR 3.38, 95% CI 1.27 - 8.94, p = .016), diabetes mellitus (HR 3.34, 95% CI 1.21 - 9.26, p = .020), female sex (HR 2.99, 95% CI 1.04 - 8.60, p = .041), and pre-procedure pathological ultrasound vasoreactivity (HR 3.87, 95% CI 1.43 -10.50, p = .008), as independent risk factors for ISR of ≥ 70%, were included in the nomogram. The concordance index at 12 and 24 months was 0.83. In low risk groups, ISR of ≥ 70% occurred in 4.8% of patients during follow up compared with 56.2% of patients in the high risk groups (p < .001). CONCLUSION: The nomogram and risk evaluation score have good predictive ability for ISR. They can be used as practical clinical tools for individualised risk assessment.

11.
J Chromatogr A ; 1726: 464967, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38749275

ABSTRACT

Infant formulas (IF) can contain harmful chemical substances, such as pesticides and mycotoxins, resulting from the contamination of raw materials and inputs used in the production chain, which can cause adverse effects to infants. Therefore, the quick, easy, cheap, effective, rugged, and safe (QuEChERS) methodology prior ultra-high performance liquid chromatography coupled to triple quadrupole mass spectrometry (UHPL-QqQ-MS/MS) analysis was applied for the determination of 23 contaminants, in 30 samples of Brazilian IF. The method was validated in terms of limit of detection (0.2 to 0.4 µg/kg), limits of quantification (1 and 10 µg/kg), and recovery (64 % to 122 %); precision values, in terms of relative standard deviation (RSD), were ≤ 20 %. Fenitrothion, chlorpyrifos, and bifenthrin were the pesticides detected in the samples, but the values did not exceed the limit set by the European Union (EU), and ANVISA, and they were detected under their limits of quantification. Additionally, suspect screening and unknown analysis were conducted to tentatively identify 32 substances, including some compounds not covered in this study, such as pesticides, hormones, and veterinary drugs. Carbofuran was identified, confirmed and quantified in 10 % of the samples.


Subject(s)
Food Contamination , Infant Formula , Limit of Detection , Tandem Mass Spectrometry , Tandem Mass Spectrometry/methods , Chromatography, High Pressure Liquid/methods , Brazil , Infant Formula/chemistry , Food Contamination/analysis , Pesticides/analysis , Humans , Pesticide Residues/analysis , Reproducibility of Results , Mycotoxins/analysis , Infant , Pyrethrins/analysis
12.
Nucleic Acids Res ; 52(W1): W324-W332, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38686803

ABSTRACT

Drug discovery aims to identify potential therapeutic compounds capable of modulating the activity of specific biological targets. Molecular docking can efficiently support this process by predicting binding interactions between small molecules and macromolecular targets and potentially accelerating screening campaigns. SwissDock is a computational tool released in 2011 as part of the SwissDrugDesign project, providing a free web-based service for small-molecule docking after automatized preparation of ligands and targets. Here, we present the latest version of SwissDock, in which EADock DSS has been replaced by two state-of-the-art docking programs, i.e. Attracting Cavities and AutoDock Vina. AutoDock Vina provides faster docking predictions, while Attracting Cavities offers more accurate results. Ligands can be imported in various ways, including as files, SMILES notation or molecular sketches. Targets can be imported as PDB files or identified by their PDB ID. In addition, advanced search options are available both for ligands and targets, giving users automatized access to widely-used databases. The web interface has been completely redesigned for interactive submission and analysis of docking results. Moreover, we developed a user-friendly command-line access which, in addition to all options of the web site, also enables covalent ligand docking with Attracting Cavities. The new version of SwissDock is freely available at https://www.swissdock.ch/.


Subject(s)
Molecular Docking Simulation , Software , Ligands , Drug Discovery/methods , User-Computer Interface , Internet , Proteins/chemistry , Proteins/metabolism , Small Molecule Libraries/chemistry , Small Molecule Libraries/pharmacology , Protein Binding , Binding Sites
14.
Mar Environ Res ; 197: 106464, 2024 May.
Article in English | MEDLINE | ID: mdl-38583356

ABSTRACT

Seagrass meadows are biodiversity hotspots for invertebrate species including decapods. Understanding the drivers of species abundance, richness and diversity of decapod assemblages is crucial for the conservation of such hotspots, but how drivers act across multiple spatial scales remains unexplored. Here we describe the decapod assemblages of Posidonia oceanica seagrass meadows and assess the influence of attributes from three increasing spatial scales (habitat, landscape, and geographical levels) on the assemblages' structure and composition, as well as the variability partitioning among each one of these levels. Overall, geographical level attributes (i.e., inlet aperture, confinement) affected the most the decapod assemblages, while we only found a modest contribution from habitat (e.g., detritus biomass, sediment organic matter) and landscape attributes (e.g., fragmentation). We suggest that decapod assemblages are driven by the interaction of multiple processes occurring at different scales and other highly stochastic phenomena such as larval dispersion and recruitment.


Subject(s)
Alismatales , Decapoda , Animals , Ecosystem , Biodiversity , Biomass
15.
Rev. esp. quimioter ; 37(2): 158-162, abr. 2024. tab, graf
Article in English | IBECS | ID: ibc-231649

ABSTRACT

Objectives. We assessed the in vitro activity of delafloxacin and the synergy between cefotaxime and delafloxacin among cefotaxime non-susceptible invasive isolates of Streptococcus pneumoniae (CNSSP). Material and methods. A total of 30 CNSSP (cefotaxime MIC > 0.5 mg/L) were studied. Serotyping was performed by the Pneumotest-Latex and Quellung reaction. Minimum inhibitory concentrations (MICs) of delafloxacin, levofloxacin, penicillin, cefotaxime, erythromycin and vancomycin were determined by gradient diffusion strips (GDS). Synergistic activity of delafloxacin plus cefotaxime against clinical S. pneumoniae isolates was evaluated by the GDS cross method. Results. Delafloxacin showed a higher pneumococcal activity than its comparator levofloxacin (MIC50, 0.004 versus 0.75 mg/L and MIC90, 0.047 versus >32 mg/L). Resistance to delafloxacin was identified in 7/30 (23.3%) isolates, belonging to serotypes 14 and 9V. Synergy between delafloxacin and cefotaxime was detected in 2 strains (serotypes 19A and 9V). Antagonism was not observed. Addition of delafloxacin increased the activity of cefotaxime in all isolates. Delafloxacin susceptibility was restored in 5/7 (71.4%) strains. Conclusions. CNSSP showed a susceptibility to delafloxacin of 76.7%. Synergistic interactions between delafloxacin and cefotaxime were observed in vitro among CNSSP by GDS cross method. (AU)


Objetivos. Evaluamos la actividad in vitro de delafloxacino y la sinergia entre cefotaxima y delafloxacino entre aislados invasivos de Streptococcus pneumoniae no sensibles a cefotaxima (SPNSC). Material y métodos. Se estudiaron un total de 30 SPNSC (CIM de cefotaxima > 0,5 mg/L). El serotipado se realizó mediante la reacción Pneumotest-Latex y Quellung. Las concentraciones mínimas inhibitorias (CMI) de delafloxacino, levofloxacino, penicilina, cefotaxima, eritromicina y vancomicina se determinaron mediante tiras de difusión en gradiente (GDS). La actividad sinérgica de delafloxacino y cefotaxima frente aislados clínicos de S. pneumoniae se evaluó mediante el método cruzado GDS. Resultados. Delafloxacino mostró una mayor actividad neumocócica que su comparador levofloxacino (CIM50, 0,004 versus 0,75 mg/L y MIC90, 0,047 versus > 32 mg/L). Se identificó resistencia a delafloxacino en 7/30 (23,3%) aislados, pertenecientes a los serotipos 14 y 9V. Se detectó sinergia entre delafloxacino y cefotaxima en 2 cepas (serotipos 19A y 9V). No se observó antagonismo. La adición de delafloxacino aumentó la actividad de cefotaxima en todos los aislados. La sensibilidad a delafloxacino se restableció en 5/7 (71,4%) cepas. Conclusiones. SPNSC mostraron una susceptibilidad a delafloxacino del 76,7%. Se observaron interacciones sinérgicas in vitro entre delafloxacino y cefotaxima entre SPNSC mediante el método cruzado GDS. (AU)


Subject(s)
Humans , Streptococcus pneumoniae , Drug Synergism , Cefotaxime , Levofloxacin , Penicillins , Erythromycin , Vancomycin
16.
Violence Vict ; 39(1): 21-37, 2024 03 07.
Article in English | MEDLINE | ID: mdl-38453372

ABSTRACT

This study examined 1,134 cases of violence against women in intimate partner relationships with violations of protective orders in a monitoring period of up to 15 months. The dynamics of time and violence were analyzed in the cases of multiple violation versus one-time violation, with the objective of identifying and thus neutralizing the risk factors for this type of recidivism. The results showed that early violation, serious physical violence, death threats, as well as jealousy, harassment, and control are related to multiple violation. This article discusses the results in comparison with other research and proposes measures to avoid revictimizations.


Subject(s)
Intimate Partner Violence , Spouse Abuse , Humans , Female , Spouse Abuse/prevention & control , Sexual Behavior , Sexual Partners , Risk Factors , Violence , Intimate Partner Violence/prevention & control
17.
Rev Esp Geriatr Gerontol ; 59(4): 101488, 2024.
Article in Spanish | MEDLINE | ID: mdl-38552373

ABSTRACT

Advance care planning is a deliberative process that aims to help patients define goals and preferences for future care and treatment at a times when they have limited decision-making capacity. This study aims to analyze models of advance care planning in elderly individuals living in nursing homes. We reviewed papers published in Cochrane, PubMed and Embase. A total of 26 studies were selected, including a total of 44,131 people over 65 years of age. We analyzed the types of intervention (interviews, videos, workshops, documentation, etc.) and their results derived from the application. We conclude that no study implements a standardized intervention model. These interventions include decision-making (transfers to hospital, resucitation orders) and the adequacy of therapeutic effort (antibiotherapy, nutrition, serotherapy, etc.). Other outcomes are implementation barriers (time and training).


Subject(s)
Advance Care Planning , Nursing Homes , Nursing Homes/organization & administration , Humans , Aged , Homes for the Aged/organization & administration
18.
Vet Pathol ; 61(4): 604-608, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38440930

ABSTRACT

Mannheimia haemolytica-associated abomasitis has been clinically described as a cause of sudden death in lambs, but it is poorly characterized. We describe the pathological features of a severe fibrinonecrotizing abomasitis in 3 lambs that died suddenly. All 3 abomasums had a thickened submucosa due to edema and necrotic areas delimited by bands of degenerate neutrophils with slender nuclei (oat cells) and angiocentric distributions. The overlying mucosa was congested. Myriads of gram-negative coccobacilli were observed within the oat cell bands. M. haemolytica was isolated from the abomasum in all 3 animals and was serotyped as A2 in one of them. Pericarditis and pleuritis were observed in 2 of the lambs. Clostridium spp. were isolated in 1 lamb and detected by immunohistochemistry in the 3 animals, suggesting clostridial co-infection. M. haemolytica should be considered among the differential diagnoses of necrotizing abomasitis in lambs.


Subject(s)
Abomasum , Mannheimia haemolytica , Necrosis , Pasteurellaceae Infections , Sheep Diseases , Animals , Mannheimia haemolytica/isolation & purification , Sheep Diseases/pathology , Sheep Diseases/microbiology , Sheep , Abomasum/pathology , Abomasum/microbiology , Pasteurellaceae Infections/veterinary , Pasteurellaceae Infections/pathology , Pasteurellaceae Infections/microbiology , Necrosis/veterinary , Necrosis/pathology , Necrosis/microbiology , Stomach Diseases/veterinary , Stomach Diseases/pathology , Stomach Diseases/microbiology , Male , Female , Immunohistochemistry/veterinary
19.
Plant Cell ; 36(7): 2465-2490, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38513609

ABSTRACT

Plants in habitats with unpredictable conditions often have diversified bet-hedging strategies that ensure fitness over a wider range of variable environmental factors. A striking example is the diaspore (seed and fruit) heteromorphism that evolved to maximize species survival in Aethionema arabicum (Brassicaceae) in which external and endogenous triggers allow the production of two distinct diaspores on the same plant. Using this dimorphic diaspore model, we identified contrasting molecular, biophysical, and ecophysiological mechanisms in the germination responses to different temperatures of the mucilaginous seeds (M+ seed morphs), the dispersed indehiscent fruits (IND fruit morphs), and the bare non-mucilaginous M- seeds obtained by pericarp (fruit coat) removal from IND fruits. Large-scale comparative transcriptome and hormone analyses of M+ seeds, IND fruits, and M- seeds provided comprehensive datasets for their distinct thermal responses. Morph-specific differences in co-expressed gene modules in seeds, as well as in seed and pericarp hormone contents, identified a role of the IND pericarp in imposing coat dormancy by generating hypoxia affecting abscisic acid (ABA) sensitivity. This involved expression of morph-specific transcription factors, hypoxia response, and cell wall remodeling genes, as well as altered ABA metabolism, transport, and signaling. Parental temperature affected ABA contents and ABA-related gene expression and altered IND pericarp biomechanical properties. Elucidating the molecular framework underlying the diaspore heteromorphism can provide insight into developmental responses to globally changing temperatures.


Subject(s)
Brassicaceae , Fruit , Gene Expression Regulation, Plant , Germination , Seeds , Temperature , Germination/genetics , Germination/physiology , Seeds/genetics , Seeds/physiology , Seeds/growth & development , Seeds/metabolism , Brassicaceae/genetics , Brassicaceae/physiology , Brassicaceae/metabolism , Fruit/genetics , Fruit/physiology , Fruit/growth & development , Fruit/metabolism , Plant Growth Regulators/metabolism , Transcriptome/genetics , Plant Dormancy/genetics , Plant Dormancy/physiology , Abscisic Acid/metabolism
20.
Front Plant Sci ; 15: 1358312, 2024.
Article in English | MEDLINE | ID: mdl-38525145

ABSTRACT

The transition from germinating seeds to emerging seedlings is one of the most vulnerable plant life cycle stages. Heteromorphic diaspores (seed and fruit dispersal units) are an adaptive bet-hedging strategy to cope with spatiotemporally variable environments. While the roles and mechanisms of seedling traits have been studied in monomorphic species, which produce one type of diaspore, very little is known about seedlings in heteromorphic species. Using the dimorphic diaspore model Aethionema arabicum (Brassicaceae), we identified contrasting mechanisms in the germination responses to different temperatures of the mucilaginous seeds (M+ seed morphs), the dispersed indehiscent fruits (IND fruit morphs), and the bare non-mucilaginous M- seeds obtained from IND fruits by pericarp (fruit coat) removal. What follows the completion of germination is the pre-emergence seedling growth phase, which we investigated by comparative growth assays of early seedlings derived from the M+ seeds, bare M- seeds, and IND fruits. The dimorphic seedlings derived from M+ and M- seeds did not differ in their responses to ambient temperature and water potential. The phenotype of seedlings derived from IND fruits differed in that they had bent hypocotyls and their shoot and root growth was slower, but the biomechanical hypocotyl properties of 15-day-old seedlings did not differ between seedlings derived from germinated M+ seeds, M- seeds, or IND fruits. Comparison of the transcriptomes of the natural dimorphic diaspores, M+ seeds and IND fruits, identified 2,682 differentially expressed genes (DEGs) during late germination. During the subsequent 3 days of seedling pre-emergence growth, the number of DEGs was reduced 10-fold to 277 root DEGs and 16-fold to 164 shoot DEGs. Among the DEGs in early seedlings were hormonal regulators, in particular for auxin, ethylene, and gibberellins. Furthermore, DEGs were identified for water and ion transporters, nitrate transporter and assimilation enzymes, and cell wall remodeling protein genes encoding enzymes targeting xyloglucan and pectin. We conclude that the transcriptomes of seedlings derived from the dimorphic diaspores, M+ seeds and IND fruits, undergo transcriptional resetting during the post-germination pre-emergence growth transition phase from germinated diaspores to growing seedlings.

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