Abstract
The role of aflatoxins (AFs) in the biology of producing strains,
Aspergillus
sect. Flavi, is still a matter of debate. Over recent years, research has pointed to how environmental factors ...altering the redox balance in the fungal cell can switch on the synthesis of AF. Notably, it has been known for decades that oxidants promote AF synthesis. More recent evidence has indicated that AF synthesis is controlled at the transcriptional level: reactive species that accumulate in fungal cells in the stationary growth phase modulate the expression of aflR, the main regulator of AF synthesis—through the oxidative stress related transcription factor AP-1. Thus, AFs are largely synthesized and secreted when (i) the fungus has exploited most nutritional resources; (ii) the hyphal density is high; and (iii) reactive species are abundant in the environment. In this study, we show that AFs efficiently scavenge peroxides and extend the lifespan of
E. coli
grown under oxidative stress conditions. We hypothesize a novel role for AF as an antioxidant and suggest its biological purpose is to extend the lifespan of AFs-producing strains of
Aspergillus
sect. Flavi under highly oxidizing conditions such as when substrate resources are depleted, or within a host.
Although the antibacterial activity and toxicity to humans and animals of the mycotoxin patulin are well known, its role in the postharvest decay of apples by Penicillium expansum has never been ...investigated. In the present study the gene disruption technique was used to alter the sequence of 6-methyl-salicylic acid synthase, an enzyme involved in the first committed step of patulin biosynthesis. Thirty-nine mutants were obtained, however only two of them (M5 and M21) passed the sub-cultural and molecular confirmation tests. They proved to produce 33–41% less patulin than their wild-type (WT) strain, although no difference in the growth and morphology of the colony was observed. Moreover, the mutants showed a significantly reduced pathogenicity and virulence on artificially inoculated apples. In particular, a 33–34% and 47–54% reduction of disease incidence and severity were recorded for M5 and M21, respectively. As confirmation, when the biomass of the mutants was quantified in vivo by Real-time PCR, a significant difference was recorded as compared to the WT and even between mutants. Moreover, when patulin production potential of mutants was restored by exogenous application of the mycotoxin, their ability to cause the disease was not significantly different from that of WT. Finally, mutants showed an increased susceptibility to the application of the antioxidant quercetin, their pathogenicity and virulence being significantly reduced at only 1/100 of the concentration needed for the WT. Based on these findings, patulin seems to have a role in the development of blue mold decay on apples.
►Patulin ecological role has never been elucidated. ►Gene disruption was used to alter the sequence of 6-methylsalicylic acid synthase. ►Mutants were significantly less pathogenic/virulent on apples unless missing patulin was added. ►Mutants were more susceptible to the antioxidant quercetin than the wild type. ►Patulin seems to have a role in blue mold pathogenic development on apples.
Abstract
We introduce a physics-informed Bayesian neural network with flow-approximated posteriors using multiplicative normalizing flows for detailed uncertainty quantification (UQ) at the physics ...event-level. Our method is capable of identifying both heteroskedastic aleatoric and epistemic uncertainties, providing granular physical insights. Applied to deep inelastic scattering (DIS) events, our model effectively extracts the kinematic variables
x
,
Q
2
, and
y
, matching the performance of recent deep learning regression techniques but with the critical enhancement of event-level UQ. This detailed description of the underlying uncertainty proves invaluable for decision-making, especially in tasks like event filtering. It also allows for the reduction of true inaccuracies without directly accessing the ground truth. A thorough DIS simulation using the H1 detector at HERA indicates possible applications for the future electron–ion collider. Additionally, this paves the way for related tasks such as data quality monitoring and anomaly detection. Remarkably, our approach effectively processes large samples at high rates.
Abstract Outcomes after posterior cruciate ligament (PCL) reconstructive surgery have historically been inferior to outcomes after reconstruction of the anterior cruciate ligament (ACL). As such, ...some surgeons may be reluctant to recommend reconstruction of the PCL. However, recent technologic advances have substantially improved PCL reconstructive surgical outcomes. These advances include better understanding of PCL diagnosis and surgical indications; recognition of the need for repair or reconstruction of associated injuries, especially injuries to the posterolateral and posteromedial corners of the knee; PCL-specific surgical instruments including mechanical tensioning devices to restore anatomic tibial step-off; improved graft fixation techniques including primary and backup methods of fixation; use of strong graft material including advances in the procurement, processing, and usage of allograft tissue; improved surgical techniques; and advances in the understanding of knee ligament structure and biomechanics, resulting in more accurate surgical tunnel placement, achieving anatomic graft insertion sites while minimizing graft bending. Today, PCL reconstructive surgery often results in excellent function with a return to the patient’s preinjury level of activity. In contrast to accelerated rehabilitation after ACL reconstructive surgery, slow and deliberate postoperative rehabilitation is recommended to allow early healing to occur after PCL reconstructive surgery.
We investigate the properties of the hidden-charm pentaquark-like resonances first observed by the LHCb Collaboration in 2015, by measuring the polarization transfer KLL between the incident photon ...and the outgoing proton in the exclusive photoproduction of J/ψ near threshold. We present a first estimate of the sensitivity of this observable to the pentaquark photocouplings and hadronic branching ratios, and extend our predictions to the case of the initial-state helicity correlation ALL, using a polarized target. These results serve as a benchmark for the SBS experiment at Jefferson Lab, which proposes to measure for the first time the helicity correlations ALL and KLL in J/ψ exclusive photoproduction, in order to determine the pentaquark photocouplings and branching ratios.
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The standard model for diffusion and surface kinetics driven growth of a single spherical particle in solution is applied incorrectly throughout the literature. This leads to ...inaccurate values for parameter values, such as the diffusion and surface kinetics coefficients. The model cannot even distinguish between diffusion or surface kinetics driven growth.
It is shown that crystal growth occurs in two distinct stages. The standard model only holds during the late time. Fitting to experimental data, including the early time, leads to incorrect values for the coefficients. It is shown that diffusion and surface kinetics are interchangeable in the model and so indistinguishable. The growth is controlled by a single non-dimensional group. Previous studies, where more independent parameters are calculated have redundancy. The Gibbs-Thomson relation plays an important role but, in the cases studied here, this is only noticeable during the first growth stage where the model does not hold. For the first time an explicit relation for the variation of the radius with time is given. Excellent agreement with experimental data on CdSe growth is shown.
Background
About 5% of Wilms tumors present with vascular extension, which sometimes extends to the right atrium. Vascular extension does not affect the prognosis, but impacts the surgical strategy, ...which is complex and not fully standardized. Our goal is to identify elements of successful surgical management of Wilms tumors with vascular extensions.
Patients and Methods
A retrospective study of pediatric Wilms tumors treated at three sites (January 1999–June 2019) was conducted. The inclusion criterion was the presence of a renal vein and vena cava thrombus at diagnosis. Tumor stage, pre and postoperative treatment, preoperative imaging, operative report, pathology, operative complications, and follow-up data were reviewed.
Results
Of the 696 pediatric patients with Wilms tumors, 69 (9.9%) met the inclusion criterion. In total, 24 patients (37.5%) had a right atrial extension and two presented with Budd–Chiari syndrome at diagnosis. Two died at diagnosis owing to pulmonary embolism. All patients received neoadjuvant chemotherapy and thrombus regressed in 35.6% of cases. Overall, 14 patients had persistent intra-atrial thrombus extension (58%) and underwent cardiopulmonary bypass. Most thrombi (72%) were removed intact with nephrectomy. Massive intraoperative bleeding occurred during three procedures. Postoperative renal insufficiency was identified as a risk factor for patient survival (
p
= 0.01). With a median follow-up of 9 years (range: 0.5–20 years), overall survival was 89% and event-free survival was 78%.
Conclusions
Neoadjuvant chemotherapy with proper surgical strategy resulted in a survival rate comparable to that of children with Wilms tumors without intravascular extension. Clinicians should be aware that postoperative renal insufficiency is associated with worse survival outcomes.
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