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1.
Artigo em Inglês | MEDLINE | ID: mdl-38668744

RESUMO

A Gram-stain-negative bacterium, designated LG-4T, was isolated from sediment of Qiantang River in Zhejiang Province, PR China. Cells were strictly aerobic, non-spore-forming, non-motile and short-rod-shaped (1.0-1.2 µm long and 0.7-0.8 µm wide). Growth occurred at 15-42 °C (optimum, 30 °C), at pH 5.0-9.0 (pH 7.0) and at 0-2.0 % (w/v) NaCl (optimum, 0.5 % NaCl). Strain LG-4T showed 95.75-96.90 % 16S rRNA gene sequence similarity to various type strains of the genera Tabrizicola, Pseudotabrizicola, Phaeovulum, Rhodobacter and Wagnerdoeblera of the family Paracoccaceae, and the most closely related strain was Tabrizicola soli ZQBWT (96.90 % similarity). The phylogenomic tree showed that strain LG-4T clustered in the family Paracoccaceae and was positioned outside of the clade composed of the genera Wagnerdoeblera and Falsigemmobacter. The average nucleotide identity and digital DNA-DNA hybridization values between strain LG-4T and the related type strains were in the range of 74.19-77.56 % and 16.70-25.80 %, respectively. The average amino acid identity (AAI) values between strain LG-4T and related type strains of the family Paracoccaceae were 60.94-69.73 %, which are below the genus boundary (70 %). The evolutionary distance (ED) values between LG-4T and the related genera of the family Paracoccaceae were 0.21-0.34, which are within the recommended standard (≥0.21-0.23) for defining a novel genus in the family Paracoccaceae. The predominant cellular fatty acids were C18 : 1 ω7c, C19 : 0 cyclo ω8c, C18 : 0 and C16 : 0, the isoprenoid quinone was Q-10, and the major polar lipids were phospholipid, phosphatidylglycerol, phosphatidylcholine, aminolipid and two unknown polar lipids. The genome size was 4.7 Mb with 68.6 mol% G+C content. On the basis of distinct phylogenetic relationships, low AAI values and high ED values, and differential phenotypic, physiological and biochemical characteristics, strain LG-4T represents a novel species of a new genus in the family Paracoccaceae, for which the name Ruixingdingia sedimenti gen. nov., sp. nov. is proposed. The type strain is LG-4T (=MCCC 1K08849T=KCTC 8136T).


Assuntos
Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Sedimentos Geológicos , Hibridização de Ácido Nucleico , Filogenia , RNA Ribossômico 16S , Rios , Análise de Sequência de DNA , RNA Ribossômico 16S/genética , Ácidos Graxos/química , Ácidos Graxos/análise , DNA Bacteriano/genética , China , Sedimentos Geológicos/microbiologia , Rios/microbiologia , Fosfolipídeos/análise , Ubiquinona/análogos & derivados
2.
Cognition ; 247: 105745, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38569229

RESUMO

Here's an all-too-familiar scenario: Person A is staring at person B, and then B turns toward A, and A immediately looks away (a phenomenon we call 'gaze deflection'). Beyond perceiving lower-level properties here - such as the timing of the eye/head turns - you can also readily perceive seemingly higher-level social dynamics: A got caught staring, and frantically looked away in embarrassment! It seems natural to assume that such social impressions are based on more fundamental representations of what happened when - but here we show that social gaze dynamics are unexpectedly powerful in that they can actually alter (and even reverse) the perceived temporal order of the underlying events. Across eight experiments, observers misperceived B as turning before A, when in fact they turned simultaneously - and even when B was turning after A. Additional controls confirmed that this illusion depends on visual processing (vs. being driven solely by higher-level interpretations), and that it is specific to the perception of social agents (vs. non-social objects). This demonstrates how social perception is tightly integrated into our perceptual experience of the world, and can have powerful consequences for one of the most basic properties that we can perceive: what happens when.

3.
Rev Mal Respir ; 2024 Apr 11.
Artigo em Francês | MEDLINE | ID: mdl-38609767

RESUMO

INTRODUCTION: The second COPD Biennial organized by the COPD working group of the French Society of Respiratory Diseases took place in Paris (Cochin) on 13th December 2023. STATE OF THE ART: Major trends in 2023 were discussed; they encompassed concepts, definitions, biologics, care pathways, pulmonary rehabilitation and complex situations entailed by respiratory infections, cardiovascular comorbidities and pulmonary hypertension, and modalities of oxygen therapy and ventilation. PERSPECTIVES: The different talks underlined major changes in COPD including the concepts of pre-COPD, etiotypes, health trajectories and new definitions of exacerbation. Recent results in biologics for COPD open the door to new pharmacological options. Assessment of current care pathways in France highlighted some causes for concern. For example, pulmonary rehabilitation is a key but insufficiently practiced element. Respiratory infections require careful assessment and treatments. Diagnosis and treatment of cardiovascular comorbidities and pulmonary hypertension are of paramount importance. As of late, oxygen therapy and ventilation modalities have evolved, and are beginning to afford more personalized options. CONCLUSIONS: As regards COPD, a personalized approach is crucial, placing the patient at the center of the care pathway and facilitating coordination between healthcare providers.

4.
Phys Rev Lett ; 132(13): 131002, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38613275

RESUMO

We present the measurements of all-particle energy spectrum and mean logarithmic mass of cosmic rays in the energy range of 0.3-30 PeV using data collected from LHAASO-KM2A between September 2021 and December 2022, which is based on a nearly composition-independent energy reconstruction method, achieving unprecedented accuracy. Our analysis reveals the position of the knee at 3.67±0.05±0.15 PeV. Below the knee, the spectral index is found to be -2.7413±0.0004±0.0050, while above the knee, it is -3.128±0.005±0.027, with the sharpness of the transition measured with a statistical error of 2%. The mean logarithmic mass of cosmic rays is almost heavier than helium in the whole measured energy range. It decreases from 1.7 at 0.3 PeV to 1.3 at 3 PeV, representing a 24% decline following a power law with an index of -0.1200±0.0003±0.0341. This is equivalent to an increase in abundance of light components. Above the knee, the mean logarithmic mass exhibits a power law trend towards heavier components, which is reversal to the behavior observed in the all-particle energy spectrum. Additionally, the knee position and the change in power-law index are approximately the same. These findings suggest that the knee observed in the all-particle spectrum corresponds to the knee of the light component, rather than the medium-heavy components.

5.
J Magn Reson Imaging ; 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38400842

RESUMO

BACKGROUND: The neurotoxic potential of gadolinium (Gd)-based contrast agents (GBCAs) retention in the brains of patients with type 2 diabetes mellitus (T2DM) is unclear. PURPOSE: To determine the deposition and clearance of GBCAs in T2DM rats and the mechanism by which Gd enhances nucleotide-binding oligomerization domain-3 (NLRP3) inflammasome activation. STUDY TYPE: Cross-sectional, prospective. ANIMAL MODEL: 104 T2DM male Wistar rats. FIELD STRENGTH/SEQUENCE: 9.4-T, T1-weighted fast spin echo sequence. ASSESSMENT: T2DM (male Wistar rats, n = 52) and control group (healthy, male Wistar rats, n = 52) rats received saline, gadodiamide, Gd-diethylenetriaminepentaacetic acid, and gadoterate meglumine for four consecutive days per week for 7 weeks. The distribution and clearance of Gd in the certain brain were assessed by MRI (T1 signal intensity and relaxation rate R1, on the last day of each week), inductively coupled plasma mass-spectroscopy, ultraperformance liquid chromatography mass spectrometry, and transmission electron microscopy. Behavioral tests, histopathological features, and the effects of GBCAs on neuroinflammation were also analyzed. STATISTICAL TESTS: One-way analysis of variance, bonferroni method, and unpaired t-test. A P-value <0.05 was considered statistically significant. RESULTS: The movement distance and appearance time in the open field test of the T2DM rats in the gadodiamide group were significantly shorter than in the other groups. Furthermore, the expression of NLRP3, Pro-Caspase-1, interleukin-1ß (IL-1ß), and apoptosis-associated speck-like protein containing a CARD protein in neurons was significantly higher in the gadodiamide group than in the saline group, as shown by Western blot. Gadodiamide also induced differentiation of microglia into M1 type, decreased the neuronal mitochondrial membrane potential, and significantly increased neuronal apoptosis from flow cytometry. DATA CONCLUSION: T2DM may affect both the deposition and clearance of GBCAs in the brain. Informed by the T2DM model, gadodiamide could mediate the neuroinflammatory response by NLRP3 inflammasome activation. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 1.

7.
J Neurosci ; 44(4)2024 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-38124193

RESUMO

K+-Cl- cotransporter-2 (KCC2) critically controls neuronal chloride homeostasis and maintains normal synaptic inhibition by GABA and glycine. Nerve injury diminishes synaptic inhibition in the spinal cord via KCC2 impairment. However, how KCC2 regulates nociceptive input to spinal excitatory and inhibitory neurons remains elusive. Here, we show that basal GABA reversal potentials were significantly more depolarized in vesicular GABA transporter (VGAT)-expressing inhibitory neurons than those in vesicular glutamate transporter-2 (VGluT2)-expressing excitatory neurons in spinal cords of male and female mice. Strikingly, inhibiting KCC2 with VU0463271 increased currents elicited by puff NMDA and the NMDAR-mediated frequency of mEPSCs in VGluT2, but not in VGAT, dorsal horn neurons. Notably, VU0463271 had no effect on EPSCs monosynaptically evoked from the dorsal root in VGluT2 neurons. Furthermore, VU0463271 augmented α2δ-1-NMDAR interactions and their protein levels in spinal cord synaptosomes. In Cacna2d1 KO mice, VU0463271 had no effect on puff NMDA currents or the mEPSC frequency in dorsal horn neurons. Disrupting α2δ-1-NMDAR interactions with α2δ-1 C-terminus mimicking peptide diminished VU0463271-induced potentiation in the mEPSC frequency and puff NMDA currents in VGluT2 neurons. Additionally, intrathecal injection of VU0463271 reduced mechanical and thermal thresholds in wild-type mice, but not in Cacna2d1 KO mice. VU0463271-induced pain hypersensitivity in mice was abrogated by co-treatment with the NMDAR antagonist, pregabalin (an α2δ-1 inhibitory ligand), or α2δ-1 C-terminus mimicking peptide. Our findings suggest that KCC2 controls presynaptic and postsynaptic NMDAR activity specifically in excitatory dorsal horn neurons. KCC2 impairment preferentially potentiates nociceptive transmission between spinal excitatory interneurons via α2δ-1-bound NMDARs.Significance statementImpaired function of potassium-chloride cotransporter-2 (KCC2), a key regulator of neuronal inhibition, in the spinal cord plays a major role in neuropathic pain. This study unveils that KCC2 controls spinal nociceptive synaptic strength via NMDA receptors in a cell type- and synapse type-specific manner. KCC2 inhibition preferentially augments presynaptic and postsynaptic NMDA receptor activity in spinal excitatory interneurons via α2δ-1 (previously known as a calcium channel subunit). Importantly, spinal KCC2 impairment triggers pain hypersensitivity through α2δ-1-coupled NMDA receptors. These findings pinpoint the cell and molecular substrates for the reciprocal relationship between spinal synaptic inhibition and excitation in chronic neuropathic pain. Targeting both KCC2 and α2δ-1­NMDA receptor complexes could be an effective strategy in managing neuropathic pain conditions.


Assuntos
Receptores de N-Metil-D-Aspartato , Simportadores , Animais , Feminino , Masculino , Camundongos , Ácido gama-Aminobutírico/metabolismo , N-Metilaspartato/farmacologia , Peptídeos/farmacologia , Células do Corno Posterior/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Medula Espinal/metabolismo , Simportadores/genética , Simportadores/metabolismo , Sinapses/metabolismo
8.
Phys Rev Lett ; 131(15): 151001, 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37897763

RESUMO

The diffuse Galactic γ-ray emission, mainly produced via interactions between cosmic rays and the interstellar medium and/or radiation field, is a very important probe of the distribution, propagation, and interaction of cosmic rays in the Milky Way. In this Letter, we report the measurements of diffuse γ rays from the Galactic plane between 10 TeV and 1 PeV energies, with the square kilometer array of the Large High Altitude Air Shower Observatory (LHAASO). Diffuse emissions from the inner (15°10 TeV). The energy spectrum in the inner Galaxy regions can be described by a power-law function with an index of -2.99±0.04, which is different from the curved spectrum as expected from hadronic interactions between locally measured cosmic rays and the line-of-sight integrated gas content. Furthermore, the measured flux is higher by a factor of ∼3 than the prediction. A similar spectrum with an index of -2.99±0.07 is found in the outer Galaxy region, and the absolute flux for 10≲E≲60 TeV is again higher than the prediction for hadronic cosmic ray interactions. The latitude distributions of the diffuse emission are consistent with the gas distribution, while the longitude distributions show clear deviation from the gas distribution. The LHAASO measurements imply that either additional emission sources exist or cosmic ray intensities have spatial variations.

9.
Eur Rev Med Pharmacol Sci ; 27(19): 9309-9314, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37843344

RESUMO

OBJECTIVE: Hyperlipidemic acute pancreatitis (HLAP) remains one of the major digestive emergencies with increasing health risks. Oral refeeding tolerant (ORT) and enteral tube feeding tolerant (ETFT) are commonly used for nutritional management in HLAP. However, the differences between ORT and ETFT are yet to be characterized. PATIENTS AND METHODS: This study included consecutive patients admitted to the Ordos Central Hospital between January 2019 and April 2023, with predefined inclusion criteria. RESULTS: A total of 335 HLAP patients were recruited according to the inclusion criteria. 268 patients were diagnosed with moderately severe acute pancreatitis (MSAP), of which 193 were in the OFT group and 75 in the ETFT group. In the ETFT group, abdominal pain and abdominal distension were significantly higher than that in the OFT group. No significant result was identified in the laboratory data. However, the OFT group showed a higher hospitalization and cost, as well as exocrine insufficiency and newly onset diabetes, than the ETFT group. CONCLUSIONS: Based on the incidence of HLAP retrieved in this study, MSAP is the major type with increasing clinical value. From the nutritional management sense, patients who received OFT showed higher hospitalization and cost, as well as lower exocrine insufficiency and newly onset diabetes.


Assuntos
Diabetes Mellitus , Hiperlipidemias , Pancreatite , Humanos , Pancreatite/diagnóstico , Doença Aguda , Hiperlipidemias/epidemiologia , Hiperlipidemias/diagnóstico , Estudos Retrospectivos , Diabetes Mellitus/epidemiologia
10.
Front Immunol ; 14: 1217718, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37575247

RESUMO

Data regarding response to SARS-CoV-2 immunization in pediatric patients with predominantly antibody deficiency (PAD) is limited. We evaluated SARS-CoV-2 immunization response by anti-SARS-CoV-2-spike antibody level in 15 pediatric PAD patients. These data were compared to a published cohort of adult PAD patients (n=62) previously analyzed following SARS-CoV-2 immunization at our single center institution. We evaluated demographics, clinical characteristics, immunophenotype, infection history, and past medication use by chart review. Following a two-dose monovalent initial series SARS-CoV-2 immunization, mean anti-SARS-CoV-2-spike antibody levels were significantly higher in pediatric PAD patients compared to adult PAD patients (2,890.7 vs. 140.1 U/mL; p<0.0001). Pediatric PAD patients with low class-switched memory B-cells, defined as <2% of total CD19+ B-cells, had significantly lower mean anti-SARS-CoV-2-spike antibody levels than those without (p=0.02). Following a third-dose monovalent SARS-CoV-2 immunization, the mean anti-SARS-CoV-2-spike antibody levels in pediatric PAD patients significantly increased (2,890.7 to 18,267.2 U/mL; p<0.0001). These data support Centers for Disease Control guidelines regarding three-part SARS-CoV-2 vaccine series, including in the pediatric PAD patient demographic.


Assuntos
COVID-19 , Doenças da Imunodeficiência Primária , Vacinas , Adulto , Humanos , Criança , Vacinas contra COVID-19 , COVID-19/prevenção & controle , SARS-CoV-2 , Vacinação , Anticorpos Antivirais
12.
Lancet Gastroenterol Hepatol ; 8(9): 803-815, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37336228

RESUMO

BACKGROUND: In eosinophilic gastrointestinal diseases, the role of eosinophils in disease pathogenesis and the effect of eosinophil depletion on patient outcomes are unclear. Benralizumab, an eosinophil-depleting monoclonal antibody that targets the interleukin-5 receptor α, might eliminate gastric tissue eosinophils and improve outcomes in eosinophilic gastritis. We aimed to assess the efficacy and safety of benralizumab in patients with eosinophilic gastritis. METHODS: We conducted a single-site, randomised, double-blind, placebo-controlled, phase 2 trial at Cincinnati Children's Hospital Medical Center (Cincinnati, OH, USA). Individuals aged 12-60 years with symptomatic, histologically active eosinophilic gastritis (peak gastric eosinophil count ≥30 eosinophils per high-power field [eos/hpf] in at least five hpfs) and blood eosinophilia (>500 eosinophils per µL [eos/µL]) were randomly assigned (1:1, block size of four) to benralizumab 30 mg or placebo, stratified by the use of glucocorticoids for gastric disease. Investigators, study staff, and study participants were masked to treatment assignment; statisticians were unmasked when analysing data. Treatments were administered subcutaneously once every 4 weeks for a 12-week double-blind period (three total injections). The primary endpoint was the proportion of patients who achieved histological remission (peak gastric eosinophil count <30 eos/hpf) at week 12. Key secondary endpoints were the changes from baseline to week 12 in peak gastric eosinophil count, blood eosinophil count, eosinophilic gastritis histology (total, inflammatory, and structural feature scores), Eosinophilic Gastritis Endoscopic Reference System (EG-REFS) score, and patient-reported outcome symptom measures (Severity of Dyspepsia Assessment [SODA] and Patient-Reported Outcome Measurement Information System [PROMIS] short-form questionnaire). After the 12-week double-blind period, patients were eligible for entry into two open-label extension (OLE) periods up to week 88, in which all patients received benralizumab. Efficacy was analysed in the intention-to-treat (ITT) population and safety was assessed in all patients who received at least one dose of study drug. The trial was registered on ClinicalTrials.gov, NCT03473977, and is completed. FINDINGS: Between April 23, 2018, and Jan 13, 2020, 34 patients were screened, and 26 were subsequently randomly assigned to benralizumab (n=13) or placebo (n=13) and included in the ITT and safety populations (mean age 19·5 years [SD 7·3]; 19 [73%] male patients and seven [27%] female patients). At week 12, ten (77% [95% CI 50 to 92]) of 13 patients who received benralizumab and one (8% [1 to 33]) of 13 who received placebo achieved histological remission (difference 69 percentage points [95% CI 32 to 85]; p=0·0010). Changes from baseline to week 12 were significantly greater in the benralizumab group versus the placebo group for peak gastric eosinophil counts (mean -137 eos/hpf [95% CI -186 to -88] vs -38 eos/hpf [-94 to 18]; p=0·0080), eosinophilic gastritis histology total score (mean -0·31 [-0·42 to -0·20] vs -0·02 [-0·16 to 0·12]; p=0·0016), histology inflammatory score (mean -0·46 [-0·60 to -0·31] vs -0·04 [-0·22 to 0·13]; p=0·0006), and blood eosinophil counts (median -1060 eos/µL [IQR -1740 to -830] vs -160 eos/µL [-710 to 120]; p=0·0044). Changes were not significantly different between the groups for eosinophilic gastritis histology structural score (mean -0·07 [95% CI -0·19 to 0·05] vs 0·03 [-0·09 to 0·15]; p=0·23), EG-REFS score (mean -1·0 [-2·3 to 0·3] vs -0·5 [-2·0 to 1·0]; p=0·62), or in patient-reported outcomes (SODA and PROMIS). During the double-blind period, treatment-emergent adverse events occurred in 11 (85%) of 13 patients in the benralizumab group and six (46%) of 13 in the placebo group; the most common treatment-emergent adverse events were headache (six [46%] vs two [15%] patients), nausea (three [23%] vs two [15%]), and vomiting (two [15%] vs three [23%]). There were no treatment-related deaths. Two patients had serious adverse events (dizziness and rhabdomyolysis in one patient; aspiration in one patient) during the OLE periods, which were considered unrelated to study treatment. INTERPRETATION: Benralizumab treatment induced histological remission, as defined by absence of tissue eosinophilia, in most patients with eosinophilic gastritis. However, the persistence of histological, endoscopic, and other features of the disease suggest a co-existing, eosinophil-independent pathogenic mechanism and the need for broader targeting of type 2 immunity. FUNDING: AstraZeneca and the Division of Intramural Research (National Institute of Allergy and Infectious Diseases, US National Institutes of Health).


Assuntos
Asma , Eosinofilia , Estados Unidos , Criança , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Asma/complicações , Asma/tratamento farmacológico , Progressão da Doença , Eosinofilia/tratamento farmacológico
13.
Science ; 380(6652): 1390-1396, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37289911

RESUMO

Some gamma-ray bursts (GRBs) have a tera-electron volt (TeV) afterglow, but the early onset of this has not been observed. We report observations with the Large High Altitude Air Shower Observatory (LHAASO) of the bright GRB 221009A, which serendipitously occurred within the instrument's field of view. More than 64,000 photons >0.2 TeV were detected within the first 3000 seconds. The TeV flux began several minutes after the GRB trigger and then rose to a peak ~10 seconds later. This was followed by a decay phase, which became more rapid ~650 seconds after the peak. We interpret the emission using a model of a relativistic jet with half-opening angle of ~0.8°. This is consistent with the core of a structured jet and could explain the high isotropic energy of this GRB.

14.
Antonie Van Leeuwenhoek ; 116(7): 687-695, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37156982

RESUMO

A Gram-stain-negative, rod-shaped, polar flagellated or stalked and non-spore-forming bacterium, designated LB-2T, was isolated from activated sludge. Growth was observed at 20-30 °C (optimum 28 °C), pH 6.0-8.0 (optimum pH 7.0) and salinity of 0-0.5% (w/v; optimum 0.5%). Phylogenetic analysis based on the 16S rRNA gene indicated that strain LB-2T belongs to the genus Sphingomonas and showed the highest sequence similarity (96.7%) and less than 96.7% similarities to other type strains. The genome size of strain LB-2T was 4.10 Mb, with 66.8 mol% G + C content. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strains LB-2T and S. canadensis FWC47T were 77.8% and 21%, respectively. The predominant cellular fatty acids were summed feature 8 (C18:1ω7c and/or C18 : 1ω6c) and C16:0. The major polar lipids were aminolipid, glycolipid, sphingoglycolipid, phosphatidylcholine, phosphatidylglycerol, four unidentified lipids, glycophospholipid, phosphatidylethanolamine and diphosphatidylglycerol. The predominant respiratory quinone was Q-10 and the major polyamine was sym-homospermidine. On the basis of phenotypic, genotypic and phylogenetic evidences, strain LB-2T represents a novel species in the genus Sphingomonas, for which the name Sphingomonas caeni sp. nov. is proposed. The type strain is LB-2T (GDMCC 1.3630T = NBRC 115,102T).


Assuntos
Fosfolipídeos , Sphingomonas , Fosfolipídeos/química , Esgotos , Filogenia , RNA Ribossômico 16S/genética , Ubiquinona/química , Ácidos Graxos/química , DNA , Análise de Sequência de DNA , Técnicas de Tipagem Bacteriana , DNA Bacteriano/genética
15.
Nat Immunol ; 24(6): 979-990, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37188942

RESUMO

Antiviral CD8+ T cell immunity depends on the integration of various contextual cues, but how antigen-presenting cells (APCs) consolidate these signals for decoding by T cells remains unclear. Here, we describe gradual interferon-α/interferon-ß (IFNα/ß)-induced transcriptional adaptations that endow APCs with the capacity to rapidly activate the transcriptional regulators p65, IRF1 and FOS after CD4+ T cell-mediated CD40 stimulation. While these responses operate through broadly used signaling components, they induce a unique set of co-stimulatory molecules and soluble mediators that cannot be elicited by IFNα/ß or CD40 alone. These responses are critical for the acquisition of antiviral CD8+ T cell effector function, and their activity in APCs from individuals infected with severe acute respiratory syndrome coronavirus 2 correlates with milder disease. These observations uncover a sequential integration process whereby APCs rely on CD4+ T cells to select the innate circuits that guide antiviral CD8+ T cell responses.


Assuntos
Antivirais , COVID-19 , Humanos , Calibragem , Células Apresentadoras de Antígenos , Linfócitos T CD8-Positivos , Antígenos CD40 , Interferon-alfa , Linfócitos T CD4-Positivos
16.
Acta Crystallogr F Struct Biol Commun ; 79(Pt 6): 144-150, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37223975

RESUMO

The crystal structure of the G-rich human telomeric DNA Tel22 has been determined at 1.35 Šresolution in space group P6. Tel22 forms a non-canonical DNA structure called the G-quadruplex. The space group and unit-cell parameters are comparable to those in the crystal structures with PDB codes 6ip3 (1.40 Šresolution) and 1kf1 (2.15 Šresolution). The G-quadruplexes are highly similar in all of the structures. However, this structure of Tel22 displays clear density for polyethylene glycol and two potassium ions, which are located outside the ion channel in the G-quadruplex and play an important role in stabilizing the crystal contacts. In addition, 111 water molecules were identified (compared with 79 and 68 in PDB entries 6ip3 and 1kf1, respectively) that participate in intricate and extensive networks providing high stability to the G-quadruplex.


Assuntos
Quadruplex G , Humanos , Conformação de Ácido Nucleico , Cristalografia por Raios X , DNA/química , Íons , Potássio/química , Telômero
17.
Brain Sci ; 13(3)2023 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-36979245

RESUMO

Although endovascular treatment is a promising approach, blood blister-like aneurysms (BBAs) still present treatment challenges. This study aimed to assess the effectiveness and safety of flow diverter device-assisted coiling (FDDAC) for the treatment of BBAs, which are broad based and friable with a high rebleeding risk. Eight patients (five females and three males) who presented with subarachnoid hemorrhages (SAH) due to BBA ruptures between May 2020 and May 2022 were retrospectively enrolled. All patients were treated by flow diverter device (Tubridge) adjunctive coil embolization using a semi-deploying technique. The demographic information, angiographic data, interval between admission and treatment, materials, therapy, clinical outcomes (including periprocedural and intraprocedural mortality and morbidity), and follow-up results of all patients were reviewed. The mean age of the patients with BBAs was 48.5 years (range 31-62 years); aneurysm sizes ranged from 2.2 × 1.7 mm to 4.6 × 3.2 mm, and the median Hunt-Hess score was 3. All aneurysms were completely closed at follow-up, and all 8 patients had excellent clinical outcomes (modified Rankin scores = 0-2) at discharge. Angiograms showed complete aneurysm occlusion after 6 months to 1 year. In addition, there were no cases of re-rupture, re-treatment, or recurrence of the aneurysms. FDDAC is safe to use in patients with BBAs and provides an alternative treatment option for this disease.

18.
East Asian Arch Psychiatry ; 33(1): 15-20, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36991551

RESUMO

OBJECTIVE: To determine whether meaning in life (MIL) was associated with a lower risk of depression in people from low-income families during the COVID-19 pandemic. METHODS: Individuals from low-income families were recruited at a community centre during the fourth wave of the COVID-19 pandemic in Hong Kong. Levels of MIL were assessed using the Meaning in Life Questionnaire (MLQ). Severity of depressive symptoms was assessed using the Patient Health Questionnaire-9 (PHQ-9). Scores of ≥24 on the Presence of Meaning subscale (MLQ-P) and Search for Meaning subscale (MLQ-S) were considered high. A score of ≥10 on the PHQ-9 was indicative of clinical depression. Correlations between MLQ and PHQ-9 scores were examined, along with associations between presence of/search for meaning and risk of clinical depression. RESULTS: Among 102 participants, 64 (62.7%) had clinical depression; 14 (13.7%) had both high presence of meaning and high search for meaning. The MLQ score was correlated with the PHQ-9 score (r = -0.56, p < 0.001). The adjusted risk ratio for depression was 0.31 (p = 0.006) in participants with both high presence of meaning and high search for meaning. CONCLUSION: Among people with lower socioeconomic status, MIL may be important for protecting against depression during the COVID-19 pandemic.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Hong Kong/epidemiologia , Depressão/epidemiologia , Depressão/diagnóstico , Pandemias , Inquéritos e Questionários
19.
Am Nat ; 201(4): 610-618, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36958001

RESUMO

AbstractConventional analyses suggest that the metabolism of heterotrophs is thermally more sensitive than that of autotrophs, implying that warming leads to pronounced trophodynamic imbalances. However, these analyses inappropriately combine within- and across-taxa trends. Our new analysis separates these, revealing that 92% of the difference in the apparent thermal sensitivity between autotrophic and heterotrophic protists does indeed arise from within-taxa responses. Fitness differences among taxa adapted to different temperature regimes only partially compensate for the positive biochemical relationship between temperature and growth rate within taxa, supporting the hotter-is-partially-better hypothesis. Our work highlights the importance of separating within- and across-taxa responses when comparing temperature sensitivities between groups, which is relevant to how trophic imbalances and carbon fluxes respond to warming.


Assuntos
Temperatura Alta , Temperatura , Processos Autotróficos
20.
Int J Technol Assess Health Care ; 39(1): e11, 2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36779272

RESUMO

OBJECTIVES: To report the processes used to design and implement an assessment tool to inform funding decisions for competing health innovations in a tertiary hospital. METHODS: We designed an assessment tool for health innovation proposals with three components: "value to the institution," "novelty," and "potential for adoption and scaling." The "value to the institution" component consisted of twelve weighted value attributes identified from the host institution's annual report; weights were allocated based on a survey of the hospital's leaders. The second and third components consisted of open-ended questions on "novelty" and "barriers to implementation" to support further dialogue. Purposive literature review was performed independently by two researchers for each assessment. The assessment tool was piloted during an institutional health innovation funding cycle. RESULTS: We used 17 days to evaluate ten proposals. The completed assessments were shared with an independent group of panellists, who selected five projects for funding. Proposals with the lowest scores for "value to the institution" had less perceived impact on the patient-related value attributes of "access," "patient centeredness," "health outcomes," "prevention," and "safety." Similar innovations were reported in literature in seven proposals; potential barriers to implementation were identified in six proposals. We included a worked example to illustrate the assessment process. CONCLUSIONS: We developed an assessment tool that is aligned with local institutional priorities. Our tool can augment the decision-making process when funding health innovation projects. The tool can be adapted by others facing similar challenges of trying to choose the best health innovations to fund.


Assuntos
Centros Médicos Acadêmicos , Humanos , Inquéritos e Questionários
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