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1.
Biochem Soc Trans ; 52(2): 517-527, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38572868

RESUMO

Cellular signalling is a complex process and involves cascades of enzymes that, in response to a specific signal, give rise to exact cellular responses. Signalling scaffold proteins organise components of these signalling pathways in space and time to co-ordinate signalling outputs. In this review we introduce a new class of mechanically operated signalling scaffolds that are built into the cytoskeletal architecture of the cell. These proteins contain force-dependent binary switch domains that integrate chemical and mechanical signals to introduce quantised positional changes to ligands and persistent alterations in cytoskeletal architecture providing mechanomemory capabilities. We focus on the concept of spatial organisation, and how the cell organises signalling molecules at the plasma membrane in response to specific signals to create order and distinct signalling outputs. The dynamic positioning of molecules using binary switches adds an additional layer of complexity to the idea of scaffolding. The switches can spatiotemporally organise enzymes and substrates dynamically, with the introduction of ∼50 nm quantised steps in distance between them as the switch patterns change. Together these different types of signalling scaffolds and the proteins engaging them, provide a way for an ordering of molecules that extends beyond current views of the cell.


Assuntos
Citoesqueleto , Transdução de Sinais , Humanos , Citoesqueleto/metabolismo , Animais , Mecanotransdução Celular , Membrana Celular/metabolismo
2.
Ecol Lett ; 27(3): e14393, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38430049

RESUMO

Long-term (press) disturbances like the climate crisis and other anthropogenic pressures are fundamentally altering ecosystems and their functions. Many critical ecosystem functions, such as biogeochemical cycling, are facilitated by microbial communities. Understanding the functional consequences of microbiome responses to press disturbances requires ongoing observations of the active populations that contribute to functions. This study leverages a 7-year time series of a 60-year-old coal seam fire (Centralia, Pennsylvania, USA) to examine the resilience of soil bacterial microbiomes to a press disturbance. Using 16S rRNA and 16S rRNA gene amplicon sequencing, we assessed the interannual dynamics of the active subset and the 'whole' bacterial community. Contrary to our hypothesis, the whole communities demonstrated greater resilience than active subsets, suggesting that inactive members contributed to overall structural resilience. Thus, in addition to selection mechanisms of active populations, perceived microbiome resilience is also supported by mechanisms of dispersal, persistence, and revival from the local dormant pool.


Assuntos
Microbiota , Resiliência Psicológica , Solo/química , RNA Ribossômico 16S/genética , Microbiologia do Solo , Bactérias/genética , Microbiota/fisiologia
3.
J Pediatr Orthop ; 44(5): e469-e473, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38477339

RESUMO

OBJECTIVE: Pelvic osteotomies relieve tension of the bladder and fascial closures during bladder exstrophy repair. Multiple techniques for postoperative immobilization of the pelvis and lower extremities have been described. The primary aim of this study was to assess differences in short and long-term changes in pubic rami diastasis when comparing Bryant traction to spica cast immobilization. Secondary aims included a comparison of length of stay, skin-related complications, and urologic outcomes. METHODS: We performed a single-institutional retrospective review of bladder exstrophy patients younger than 18 months of age who underwent posterior pelvic osteotomy and bladder exstrophy closure from April 2005 to April 2020. Short-term and long-term pubic rami diastasis were defined as postoperative measurements ≤6 months and ≥12 months, respectively. Secondary outcomes included length of stay, pressure ulcer, skin rash/abrasion, urethrocutaneous fistula, and bladder or fascial dehiscence rates. Multivariable logistic regression assessed for an association between immobilization type and degree of diastasis while controlling for age at the time of diastasis measurement and sex. RESULTS: Fifteen patients underwent Bryant traction and 36 patients underwent spica cast immobilization. In both the short-term and long-term, there was a greater reduction in pubic diastasis in the spica cast group ( P = 0.002 and P = 0.05, respectively). After adjustments, there were higher odds of having a greater reduction in pubic rami diastasis in both the short-term (odds ratio: 2.71, 95% CI: 1.52-4.86, P = 0.001) and long-term (odds ratio: 2.41, 95% CI: 1.00-5.80, P = 0.05). Length of stay was significantly higher in Bryant's traction group (26 vs 19 d, P < 0.001). Rates of pressure ulcers were higher in the Bryant traction group (26.7% vs 0%, P = 0.005). Rates of skin rash/abrasions, urethrocutaneous fistula, and bladder/fascial dehiscence did not differ. CONCLUSIONS: Spica cast immobilization is a safe and effective immobilization method. Compared with Bryant traction, spica cast immobilization was associated with a greater reduction in postoperative pubic diastasis both short and long-term, along with a shorter length of hospitalization and reduced rate of pressure ulcers. LEVEL OF EVIDENCE: Level III-therapeutic study.


Assuntos
Extrofia Vesical , Exantema , Fístula , Lesão por Pressão , Humanos , Lactente , Extrofia Vesical/cirurgia , Procedimentos Cirúrgicos Urológicos/métodos , Estudos Retrospectivos
4.
Orthop J Sports Med ; 12(3): 23259671241237810, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38532765

RESUMO

Background: Little is known on how meniscal morphology develops during skeletal growth and maturation and its subsequent relationship with the corresponding bony anatomy. Hypotheses: (1) Meniscal dimensions and morphology would change by age during skeletal growth and maturation in different ways in boys compared with girls. (2) Morphological features of the medial and lateral menisci would correlate to medial and lateral femoral condyle curvatures. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Anatomic features of the medial and lateral menisci were measured on magnetic resonance imaging scans from 269 unique knees (age, 3-18 years; 51% female) with no prior history of injury, congenital or growth-related skeletal disorders, or bony deformities. Morphological shape-based measurements were normalized to tibial plateau width or determined as ratios of meniscal dimensions. The association between age and anatomy was analyzed with linear regression. Two-way analysis of variance with the Holm-Sídák post hoc method was used to compare anatomy between sexes in different age groups. Linear regression was used to evaluate the relationship between femoral condyle curvature radius and meniscal morphology in each compartment after adjusting for age and sex. Results: Meniscal length, width, horn distance, mean cross-sectional area (CSA), and mean height increased with age in both sexes (R2 > 0.1; P < .001). Age-related changes in meniscal morphology were seen in normalized length, width, horn distance, and mean height; width-to-length ratio; horn distance-to-length ratio (lateral meniscus only); normalized mean CSA (except lateral meniscus in girls); and mean tip angle (R2 > 0.04; P < .02). Sex-based differences were also found, with some morphological differences (normalized length and height) throughout development (P < .03) and size differences (length, width, and mean CSA) in later development (P < .01). After adjusting for age and sex, there were significant correlations between medial condyle curvature radius and normalized width, width-to-length ratio, horn distance, horn distance-to-length ratio, mean CSA, and mean height of the medial meniscus (P≤ .041) and between lateral condyle curvature radius and normalized length, mean height, and mean tip angle of the lateral meniscus (P≤ .004). Conclusion: Age-related changes in meniscal dimensions and morphology, most notably a nonuniform growth pattern in meniscal geometry, occurred during skeletal growth and maturation, with different trends in boys than in girls.

5.
Am J Sports Med ; 51(14): 3706-3713, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37924211

RESUMO

BACKGROUND: Meniscal injuries are extremely common. Several anatomic features of the knee, including the tibial plateau morphology, have been shown to influence knee biomechanics and the risk of ligamentous injuries. Little is known, however, how these morphological features influence the risk of isolated meniscal injuries in the anterior cruciate ligament (ACL)-intact knee. HYPOTHESIS: There are differences in the slopes and concavity of the tibial plateau between patients with isolated meniscal tears and matched uninjured controls. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: In total, 89 patients with first-instance isolated medial (n = 37) or lateral (n = 52) meniscal injuries requiring surgical treatment (mean age, 16 ± 1 years; 35% female) were matched to 89 controls with uninjured knees and no previous injuries (mean age, 16 ± 2 years; 35% female) based on age and sex. Magnetic resonance imaging scans (preoperative for injured group) were used to measure the coronal slope of the tibial plateau, posterior slope of the medial and lateral tibial plateaus, and maximum depth of the medial tibial plateau. General linear models were used to evaluate the differences in tibial plateau morphology between the knees with and without meniscal injuries, with and without adjustment for age and sex. RESULTS: Compared with matched controls, patients with surgically treated isolated meniscal tears had a smaller lateral tibial slope (by 2.2° [medial meniscal injury] and 1.6° [lateral meniscal injury]; P < .02), a smaller medial tibial slope (by 2.3° [medial meniscal injury] and 2.4° [lateral meniscal injury]; P < .001) and a larger medial tibial depth (by 0.8 mm [medial meniscal injury] and 0.9 mm [lateral meniscal injury]; P < .001). There were no differences in coronal tibial slope between the injured and uninjured groups. There were no differences in quantified anatomic features between the isolated medial and lateral meniscal injury groups. The same trends were observed after adjusting for age and sex. CONCLUSION: This study suggests that patients with an isolated meniscal tear requiring surgery have a smaller posterior tibial slope and a larger medial tibial depth (more concave medial tibial plateau) than matched uninjured controls. This is contrary to what is known for ACL tears, in which a steeper posterior tibial slope and a shallower medial tibial depth have been associated with an increased risk of ACL tear.


Assuntos
Lesões do Ligamento Cruzado Anterior , Traumatismos do Joelho , Humanos , Feminino , Adolescente , Masculino , Estudos de Coortes , Tíbia/diagnóstico por imagem , Tíbia/cirurgia , Tíbia/anatomia & histologia , Ligamento Cruzado Anterior/cirurgia , Articulação do Joelho/cirurgia , Meniscos Tibiais/diagnóstico por imagem , Meniscos Tibiais/cirurgia , Traumatismos do Joelho/diagnóstico por imagem , Traumatismos do Joelho/cirurgia , Lesões do Ligamento Cruzado Anterior/cirurgia , Imageamento por Ressonância Magnética , Estudos Retrospectivos
6.
Otol Neurotol ; 44(10): e747-e754, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37875014

RESUMO

OBJECTIVE: The objective of the current study was to present the results of an international working group survey identifying perceived limitations of existing facial nerve grading scales to inform the development of a novel grading scale for assessing early postoperative facial paralysis that incorporates regional scoring and is anchored in recovery prognosis and risk of associated complications. STUDY DESIGN: Survey. SETTING: A working group of 48 multidisciplinary clinicians with expertise in skull base, cerebellopontine angle, temporal bone, or parotid gland surgery. RESULTS: House-Brackmann grade is the most widely used system to assess facial nerve function among working group members (81%), although more than half (54%) agreed that the system they currently use does not adequately estimate the risk of associated complications, such as corneal injury, and confidence in interrater and intrarater reliability is generally low. Simplicity was ranked as the most important attribute of a novel postoperative facial nerve grading system to increase the likelihood of adoption, followed by reliability and accuracy. There was widespread consensus (91%) that the eye is the most critical facial region to focus on in the early postoperative setting. CONCLUSIONS: Members were invited to submit proposed grading systems in alignment with the objectives of the working group for subsequent validation. From these data, we plan to develop a simple, clinically anchored, and reproducible staging system with regional scoring for assessing early postoperative facial nerve function after surgery of the skull base, cerebellopontine angle, temporal bone, or parotid gland.


Assuntos
Nervo Facial , Paralisia Facial , Humanos , Nervo Facial/cirurgia , Reprodutibilidade dos Testes , Paralisia Facial/diagnóstico , Paralisia Facial/etiologia , Face , Cabeça , Complicações Pós-Operatórias/diagnóstico
7.
Environ Microbiol ; 25(10): 1785-1795, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37139849

RESUMO

Soil viruses are important components of the carbon (C) cycle, yet we still know little about viral ecology in soils. We added diverse 13 C-labelled carbon sources to soil and we used metagenomic-SIP to detect 13 C assimilation by viruses and their putative bacterial hosts. These data allowed us to link a 13 C-labelled bacteriophage to its 13 C-labelled Streptomyces putative host, and we used qPCR to track the dynamics of the putative host and phage in response to C inputs. Following C addition, putative host numbers increased rapidly for 3 days, and then more gradually, reaching maximal abundance on Day 6. Viral abundance and virus:host ratio increased dramatically over 6 days, and remained high thereafter (8.42 ± 2.94). From Days 6 to 30, virus:host ratio remained high, while putative host numbers declined more than 50%. Putative host populations were 13 C-labelled on Days 3-30, while 13 C-labelling of phage was detected on Days 14 and 30. This dynamic suggests rapid growth and 13 C-labelling of the host fueled by new C inputs, followed by extensive host mortality driven by phage lysis. These findings indicate that the viral shunt promotes microbial turnover in soil following new C inputs, thereby altering microbial community dynamics, and facilitating soil organic matter production.


Assuntos
Bacteriófagos , Streptomyces , Bacteriófagos/genética , Solo , Microbiologia do Solo , Carbono/análise , Isótopos/análise
8.
Otolaryngol Clin North Am ; 56(3): 567-576, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36964095

RESUMO

Microsurgical removal of acoustic neuroma has advanced tremendously; however, complications still occur. Facial nerve injury is the most common detrimental complication and should take precedence over gross tumor removal in cases where there is an unfavorable tumor-facial nerve interface. Cerebrospinal fluid leakage can occur even with meticulous closure techniques and is generally treatable with either lumbar-subarachnoid drainage or revision wound closure. Meningitis is a serious complication that requires a high index of suspicion in the postoperative period. Other less common complications include intraoperative and postoperative vascular injuries. Early identification and treatment can prevent devastating outcomes.


Assuntos
Traumatismos do Nervo Facial , Neuroma Acústico , Humanos , Neuroma Acústico/cirurgia , Vazamento de Líquido Cefalorraquidiano/etiologia , Vazamento de Líquido Cefalorraquidiano/terapia , Nervo Facial , Traumatismos do Nervo Facial/complicações , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
9.
J Neurosurg ; 138(3): 621-628, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36866795

RESUMO

OBJECTIVE: Meningioma prognostication and treatment continues to evolve with an increasing understanding of tumor biology. In this study, the authors aimed to test conventional predictors of meningioma recurrence, histopathology variables for which there exists some controversy (brain invasion), as well as a novel molecular-based location paradigm. METHODS: This is a retrospective study of a consecutive series of patients with WHO grade I-III meningioma resected at The University of Texas Southwestern Medical Center between 1994 and 2015. Time to meningioma recurrence (i.e., recurrence-free survival [RFS]) was the primary endpoint measured. Kaplan-Meier curves were constructed and compared using log-rank tests. Cox univariate and multivariate analyses were performed to identify predictors of RFS. RESULTS: A total of 703 consecutive patients with meningioma underwent resection at The University of Texas Southwestern Medical Center between the years 1994 and 2015. A total of 158 patients were excluded for insufficient follow-up (< 3 months). The median age of the cohort was 55 years (range 16-88 years) and 69.5% (n = 379) were female. The median follow-up was 48 months (range 3-289 months). There was not a significantly increased risk of recurrence in patients with evidence of brain invasion, in patients with otherwise WHO grade I meningioma (Cox univariate HR 0.92, 95% CI 0.44-1.91, p = 0.82, power 4.4%). Adjuvant radiosurgery to subtotally resected WHO grade I meningiomas did not prolong the time to recurrence (n = 52, Cox univariate HR 0.21, 95% CI 0.03-1.61, p = 0.13, power 71.6%). Location (midline skull base, lateral skull base, and paravenous) was significantly associated with RFS (p < 0.01, log-rank test). In patients with high-grade meningiomas (WHO grade II or III), location was predictive of RFS (p = 0.03, log-rank test), with paravenous meningiomas exhibiting the highest rates of recurrence. Location was not significant on multivariate analysis. CONCLUSIONS: The data suggest that brain invasion does not increase the risk of recurrence in otherwise WHO grade I meningioma. Adjuvant radiosurgery to subtotally resected WHO grade I meningiomas did not prolong the time to recurrence. Location categorized by distinct molecular signatures did not predict RFS in a multivariate model. Larger studies are needed to confirm these findings.


Assuntos
Neoplasias Meníngeas , Meningioma , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Meningioma/cirurgia , Estudos Retrospectivos , Cabeça , Encéfalo , Neoplasias Meníngeas/cirurgia
10.
mBio ; 14(2): e0358422, 2023 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-36877031

RESUMO

Bacteria catalyze the formation and destruction of soil organic matter, but the bacterial dynamics in soil that govern carbon (C) cycling are not well understood. Life history strategies explain the complex dynamics of bacterial populations and activities based on trade-offs in energy allocation to growth, resource acquisition, and survival. Such trade-offs influence the fate of soil C, but their genomic basis remains poorly characterized. We used multisubstrate metagenomic DNA stable isotope probing to link genomic features of bacteria to their C acquisition and growth dynamics. We identify several genomic features associated with patterns of bacterial C acquisition and growth, notably genomic investment in resource acquisition and regulatory flexibility. Moreover, we identify genomic trade-offs defined by numbers of transcription factors, membrane transporters, and secreted products, which match predictions from life history theory. We further show that genomic investment in resource acquisition and regulatory flexibility can predict bacterial ecological strategies in soil. IMPORTANCE Soil microbes are major players in the global carbon cycle, yet we still have little understanding of how the carbon cycle operates in soil communities. A major limitation is that carbon metabolism lacks discrete functional genes that define carbon transformations. Instead, carbon transformations are governed by anabolic processes associated with growth, resource acquisition, and survival. We use metagenomic stable isotope probing to link genome information to microbial growth and carbon assimilation dynamics as they occur in soil. From these data, we identify genomic traits that can predict bacterial ecological strategies which define bacterial interactions with soil carbon.


Assuntos
Traços de História de Vida , Solo/química , Microbiologia do Solo , Bactérias/genética , Bactérias/metabolismo , Carbono/metabolismo , Isótopos/metabolismo , Metagenômica
11.
Nat Commun ; 14(1): 776, 2023 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-36774346

RESUMO

Deviations from mirror symmetry in the development of bilateral organisms are common but the mechanisms of initial symmetry breaking are insufficiently understood. The actin cytoskeleton of individual cells self-organises in a chiral manner, but the molecular players involved remain essentially unidentified and the relationship between chirality of an individual cell and cell collectives is unclear. Here, we analysed self-organisation of the chiral actin cytoskeleton in individual cells on circular or elliptical patterns, and collective cell alignment in confined microcultures. Screening based on deep-learning analysis of actin patterns identified actin polymerisation regulators, depletion of which suppresses chirality (mDia1) or reverses chirality direction (profilin1 and CapZß). The reversed chirality  is mDia1-independent but requires the function of actin-crosslinker α-actinin1. A robust correlation between the effects of a variety of actin assembly regulators on chirality of individual cells and cell collectives is revealed. Thus, actin-driven cell chirality may underlie tissue and organ asymmetry.


Assuntos
Citoesqueleto de Actina , Actinas
12.
Am J Sports Med ; 51(1): 49-57, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36412922

RESUMO

BACKGROUND: Anterior cruciate ligament (ACL) revision surgery is challenging for both patients and surgeons. Understanding the risk factors for failure after bridge-enhanced ACL restoration (BEAR) may help with patient selection for ACL restoration versus ACL reconstruction. PURPOSE: To identify the preoperative risk factors for ACL revision surgery within the first 2 years after BEAR. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Data from the prospective BEAR I, II, and III trials were used to determine the preoperative risk factors for ACL revision surgery. All patients with a complete ACL tear (aged 13-47 years, depending on the trial), who met all other inclusion/exclusion criteria and underwent a primary BEAR procedure within 30 to 50 days from the injury (dependent on the trial), were included. Demographic data (age, sex, body mass index), baseline patient-reported outcomes (International Knee Documentation Committee [IKDC] subjective score, Marx activity score), preoperative imaging results (ACL stump length, notch size, tibial slope), and intraoperative findings (knee hyperextension, meniscal status) were evaluated to determine their contribution to the risk of ipsilateral ACL revision surgery. RESULTS: A total of 123 patients, with a median age of 17.6 years (interquartile range, 16-23 years), including 67 (54%) female patients, met study criteria. Overall, 18 (15%) patients required ACL revision surgery in the first 2 years after the BEAR procedure. On bivariate analyses, younger age (P = .011), having a contact injury at the time of the initial tear (P = .048), and increased medial tibial slope (MTS; P = .029) were associated with a higher risk of ipsilateral revision surgery. Multivariable logistic regression analyses identified 2 independent predictors of revision: patient age and MTS. The odds of ipsilateral revision surgery were decreased by 32% for each 1-year increase in age (odds ratio, 0.684 [95% CI, 0.517-0.905]; P = .008) and increased by 28% for each 1° increase in MTS (odds ratio, 1.280 [95% CI, 1.024-1.601]; P = .030). Sex, baseline IKDC or Marx score, knee hyperextension, and meniscal status were not significant predictors of revision. CONCLUSION: Younger age and higher MTS were predictors of ipsilateral ACL revision surgery after the BEAR procedure. Younger patients with higher tibial slopes should be aware of the increased risk for revision surgery when deciding to undergo ACL restoration.


Assuntos
Lesões do Ligamento Cruzado Anterior , Ligamento Cruzado Anterior , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Masculino , Ligamento Cruzado Anterior/cirurgia , Estudos Prospectivos , Reoperação , Estudos de Casos e Controles , Articulação do Joelho/cirurgia , Lesões do Ligamento Cruzado Anterior/cirurgia , Fatores de Risco
13.
Plant Commun ; 4(1): 100502, 2023 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-36463410

RESUMO

FtsH proteases are membrane-embedded proteolytic complexes important for protein quality control and regulation of various physiological processes in bacteria, mitochondria, and chloroplasts. Like most cyanobacteria, the model species Synechocystis sp. PCC 6803 contains four FtsH homologs, FtsH1-FtsH4. FtsH1-FtsH3 form two hetero-oligomeric complexes, FtsH1/3 and FtsH2/3, which play a pivotal role in acclimation to nutrient deficiency and photosystem II quality control, respectively. FtsH4 differs from the other three homologs by the formation of a homo-oligomeric complex, and together with Arabidopsis thaliana AtFtsH7/9 orthologs, it has been assigned to another phylogenetic group of unknown function. Our results exclude the possibility that Synechocystis FtsH4 structurally or functionally substitutes for the missing or non-functional FtsH2 subunit in the FtsH2/3 complex. Instead, we demonstrate that FtsH4 is involved in the biogenesis of photosystem II by dual regulation of high light-inducible proteins (Hlips). FtsH4 positively regulates expression of Hlips shortly after high light exposure but is also responsible for Hlip removal under conditions when their elevated levels are no longer needed. We provide experimental support for Hlips as proteolytic substrates of FtsH4. Fluorescent labeling of FtsH4 enabled us to assess its localization using advanced microscopic techniques. Results show that FtsH4 complexes are concentrated in well-defined membrane regions at the inner and outer periphery of the thylakoid system. Based on the identification of proteins that co-purified with the tagged FtsH4, we speculate that FtsH4 concentrates in special compartments in which the biogenesis of photosynthetic complexes takes place.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Synechocystis , Peptídeo Hidrolases , Complexo de Proteína do Fotossistema II/genética , Complexo de Proteína do Fotossistema II/metabolismo , Filogenia , Tilacoides/metabolismo , Cloroplastos/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Synechocystis/genética , Synechocystis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Metaloproteases/genética , Metaloproteases/metabolismo
14.
Front Cell Neurosci ; 16: 1014629, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36467609

RESUMO

The Mercator projection map of the world provides a useful, but distorted, view of the relative scale of countries. Current cellular models suffer from a similar distortion. Here, we undertook an in-depth structural analysis of the molecular dimensions in the cell's computational machinery, the MeshCODE, that is assembled from a meshwork of binary switches in the scaffolding proteins talin and vinculin. Talin contains a series of force-dependent binary switches and each domain switching state introduces quantised step-changes in talin length on a micrometre scale. The average dendritic spine is 1 µm in diameter so this analysis identifies a plausible Gearbox-like mechanism for dynamic regulation of synaptic function, whereby the positioning of enzymes and substrates relative to each other, mechanically-encoded by the MeshCODE switch patterns, might control synaptic transmission. Based on biophysical rules and experimentally derived distances, this analysis yields a novel perspective on biological digital information.

15.
Open Mind (Camb) ; 6: 169-182, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36439072

RESUMO

Language is not only used to transmit neutral information; we often seek to persuade by arguing in favor of a particular view. Persuasion raises a number of challenges for classical accounts of belief updating, as information cannot be taken at face value. How should listeners account for a speaker's "hidden agenda" when incorporating new information? Here, we extend recent probabilistic models of recursive social reasoning to allow for persuasive goals and show that our model provides a pragmatic account for why weakly favorable arguments may backfire, a phenomenon known as the weak evidence effect. Critically, this model predicts a systematic relationship between belief updates and expectations about the information source: weak evidence should only backfire when speakers are expected to act under persuasive goals and prefer the strongest evidence. We introduce a simple experimental paradigm called the Stick Contest to measure the extent to which the weak evidence effect depends on speaker expectations, and show that a pragmatic listener model accounts for the empirical data better than alternative models. Our findings suggest further avenues for rational models of social reasoning to illuminate classical decision-making phenomena.

16.
Appl Environ Microbiol ; 88(22): e0083922, 2022 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-36300927

RESUMO

Tracking the metabolic activity of whole soil communities can improve our understanding of the transformation and fate of carbon in soils. We used stable isotope metabolomics to trace 13C from nine labeled carbon sources into the water-soluble metabolite pool of an agricultural soil over time. Soil was amended with a mixture of all nine sources, with one source isotopically labeled in each treatment. We compared changes in the 13C enrichment of metabolites with respect to carbon source and time over a 48-day incubation and contrasted differences between soluble sources (glucose, xylose, amino acids, etc.) and insoluble sources (cellulose and palmitic acid). Whole soil metabolite profiles varied singularly by time, while the composition of 13C-labeled metabolites differed primarily by carbon source (R2 = 0.68) rather than time (R2 = 0.07), with source-specific differences persisting throughout incubations. The 13C labeling of metabolites from insoluble carbon sources occurred slower than that from soluble sources but yielded a higher average atom percent (atom%) 13C in metabolite markers of biomass (amino acids and nucleic acids). The 13C enrichment of metabolite markers of biomass stabilized between 5 and 15 atom% 13C by the end of incubations. Temporal patterns in the 13C enrichment of tricarboxylic acid cycle intermediates, nucleobases (uracil and thymine), and by-products of DNA salvage (allantoin) closely tracked microbial activity. Our results demonstrate that metabolite production in soils is driven by the carbon source supplied to the community and that the fate of carbon in metabolites do not generally converge over time as a result of ongoing microbial processing and recycling. IMPORTANCE Carbon metabolism in soil remains poorly described due to the inherent difficulty of obtaining information on the microbial metabolites produced by complex soil communities. Our study demonstrates the use of stable isotope probing (SIP) to study carbon metabolism in soil by tracking 13C from supplied carbon sources into metabolite pools and biomass. We show that differences in the metabolism of sources influence the fate of carbon in soils. Heterogeneity in 13C-labeled metabolite profiles corresponded with compositional differences in the metabolically active populations, providing a basis for how microbial community composition correlates with the quality of soil carbon. Our study demonstrates the application of SIP-metabolomics in studying soils and identifies several metabolite markers of growth, activity, and other aspects of microbial function.


Assuntos
Carbono , Solo , Carbono/metabolismo , Microbiologia do Solo , Isótopos , Aminoácidos
17.
Orthop J Sports Med ; 10(10): 23259671221127326, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36263311

RESUMO

Background: The cross-sectional area (CSA) of the anterior cruciate ligament (ACL) and reconstructed graft has direct implications on its strength and knee function. Little is known regarding how the CSA changes along the ligament length and how those changes vary between treated and native ligaments over time. Hypothesis: It was hypothesized that (1) the CSA of reconstructed ACLs and restored ACLs via bridge-enhanced ACL restoration (BEAR) is heterogeneous along the length. (2) Differences in CSA between treated and native ACLs decrease over time. (3) CSA of the surgically treated ACLs is correlated significantly with body size (ie, height, weight, body mass index) and knee size (ie, bicondylar and notch width). Study Design: Cohort study; Level of evidence, 2. Methods: Magnetic resonance imaging scans of treated and contralateral knees of 98 patients (n = 33 ACL reconstruction, 65 BEAR) at 6, 12, and 24 months post-operation were used to measure the ligament CSA at 1% increments along the ACL length (tibial insertion, 0%; femoral insertion, 100%). Statistical parametric mapping was used to evaluate the differences in CSA between 6 and 24 months. Correlations between body and knee size and treated ligament CSA along its length were also assessed. Results: Hamstring autografts had larger CSAs than native ACLs at all time points (P < .001), with region of difference decreasing from proximal 95% of length (6 months) to proximal 77% of length (24 months). Restored ACLs had larger CSAs than native ACLs at 6 and 12 months, with larger than native CSA only along a small midsubstance region at 24 months (P < .001). Graft CSA was correlated significantly with weight (6 and 12 months), bicondylar width (all time points), and notch width (24 months). Restored ACL CSA was significantly correlated with bicondylar width (6 months) and notch width (6 and 12 months). Conclusion: Surgically treated ACLs remodel continuously within the first 2 years after surgery, leading to ligaments/grafts with heterogeneous CSAs along the length, similar to the native ACL. While reconstructed ACLs remained significantly larger, the restored ACL had a CSA profile comparable with that of the contralateral native ACL. In addition to size and morphology differences, there were fundamental differences in factors contributing to CSA profile between the ACL reconstruction and BEAR procedures. Registration: NCT02664545 (ClinicalTrials.gov identifier).

19.
Otol Neurotol ; 43(8): e846-e855, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35941601

RESUMO

OBJECTIVE: This study aimed to assess the durability of audiological outcomes after radiation and surgery in the management of vestibular schwannoma. STUDY DESIGN: Retrospective review. SETTING: Tertiary academic center. PATIENTS: Adults with sporadic vestibular schwannoma and serviceable hearing at the time of intervention. INTERVENTIONS: Gamma Knife, middle cranial fossa, or retrosigmoid approaches. MAIN OUTCOME MEASURES: Pure-tone audiometry and speech discrimination scores. RESULTS: Postintervention serviceable hearing (class A/B) was preserved in 70.4% (n = 130; mean follow-up, 3.31 yr; range, 0-15.25 yr). Of the 49 patients treated with radiation, 19 (39.6%) had serviceable hearing at last follow-up, compared with 38 (46.9% of 81) who underwent retrosigmoid (n = 36 [44.4%]) and middle cranial fossa (n = 45 [55.6%]) approaches (odds ratio [OR], 1.40; 95% confidence interval [CI], 0.67-2.82; p = 0.47). A matched analysis by age, tumor volume, and preintervention hearing (n = 38) also found no difference in hearing preservation (HP) likelihood between surgery and radiation (OR, 2.33; 95% CI, 0.24-35.91; p = 0.59). After initial HP, 4 (9.5%) surgical versus 10 (37.0%) radiated patients subsequently lost residual serviceable (A/B) hearing (OR, 0.18; 95% CI, 0.06-0.69; p = 0.01) at a mean 3.74 ± 3.58 and 4.73 ± 3.83 years after surgery and radiation, respectively. Overall, 5- and 10-year HP rates (A/B) after initially successful HP surgery were 84.4 and 63.0%, respectively. However, survival estimates declined to 48.9% at 5 years and 32.7% at 10 years when patients with immediate postoperative serviceable hearing loss were also included, which were comparable to radiation-HP rates at 5 and 10 years of 28.0 and 14.2%, respectively ( p = 0.75). CONCLUSIONS: After vestibular schwannoma intervention, overall HP was similar between radiated and surgical cohorts. However, when successful, surgical approaches offered more durable hearing outcomes at long-term follow-up.


Assuntos
Neuroma Acústico , Adulto , Audiometria de Tons Puros , Fossa Craniana Média/cirurgia , Audição , Humanos , Neuroma Acústico/radioterapia , Neuroma Acústico/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
20.
Environ Microbiol ; 24(11): 5230-5247, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35920035

RESUMO

Soil dwelling microorganisms are key players in the terrestrial carbon cycle, driving both the degradation and stabilization of soil organic matter. Bacterial community structure and function vary with respect to land use; yet the ecological drivers of this variation remain poorly described and difficult to predict. We conducted a multi-substrate DNA-stable isotope probing experiment across cropland, old-field, and forest habitats to link carbon mineralization dynamics with the dynamics of bacterial growth and carbon assimilation. We tracked the movement of 13 C derived from five distinct carbon sources as it was assimilated into bacterial DNA over time. We show that carbon mineralization, community composition, and carbon assimilation dynamics all differed with respect to land use. We also show that microbial community dynamics affect carbon assimilation dynamics and are associated with soil DNA content. Soil DNA yield is easy to measure and may be useful in predicting microbial community dynamics linked to soil carbon cycling. Soil dwelling microorganisms are key players in the terrestrial carbon cycle, driving both the degradation and stabilization of soil organic matter. Microbial communities vary with respect to land use, but we still have an incomplete understanding of how variation in community structure links to variation in community function. DNA stable isotope probing (DNA-SIP) is a high-resolution method that can identify specific microbial taxa that assimilate carbon in situ. We conducted a large-scale multi-substrate DNA-SIP experiment to explore differences in bacterial activity across land-use regimes. We show that microbial community dynamics vary with land use, that these dynamics are linked to soil carbon cycling, and that they are associated with easily measured soil properties.


Assuntos
Microbiota , Solo , Solo/química , Carbono/metabolismo , Microbiologia do Solo , Bactérias , Isótopos/metabolismo
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