Modulation of plant autophagy during pathogen attack

In plants, the highly conserved catabolic process of autophagy has long been known as a means of maintaining cellular homeostasis and coping with abiotic stress conditions. Accumulating evidence has linked autophagy to immunity against invading pathogens, regulating plant cell death, and antimicrobial defences. In turn, it appears that phytopathogens have evolved ways not only to evade autophagic clearance but also to modulate and co-opt autophagy for their own benefit. In this review, we summarize and discuss the emerging discoveries concerning how pathogens modulate both host and self-autophagy machineries to colonize their host plants, delving into the arms race that determines the fate of interorganismal interaction.Fil: Leary, Alexandre Y. Imperial College London; Reino UnidoFil: Sanguankiattichai, Nattapong. University of Oxford; Reino UnidoFil: Duggan, Cian. Imperial College London; Reino UnidoFil: Tumtas, Yasin. Imperial College London; Reino UnidoFil: Pandey, Pooja. Imperial College London; Reino UnidoFil: Segretin, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Salguero Linares, Jose. Imperial College London; Reino UnidoFil: Savage, Zachary D. Imperial College London; Reino UnidoFil: Yow, Rui Jin. Imperial College London; Reino UnidoFil: Bozkurt, Tolga O.. Imperial College London; Reino Unid

AlphaFold2-multimer guided high-accuracy prediction of typical and atypical ATG8-binding motifs

Macroautophagy/autophagy is an intracellular degradation process central to cellular homeostasis and defense against pathogens in eukaryotic cells. Regulation of autophagy relies on hierarchical binding of autophagy cargo receptors and adaptors to ATG8/LC3 protein family members. Interactions with ATG8/LC3 are typically facilitated by a conserved, short linear sequence, referred to as the ATG8/LC3 interacting motif/region (AIM/LIR), present in autophagy adaptors and receptors as well as pathogen virulence factors targeting host autophagy machinery. Since the canonical AIM/LIR sequence can be found in many proteins, identifying functional AIM/LIR motifs has proven challenging. Here, we show that protein modelling using Alphafold-Multimer (AF2-multimer) identifies both canonical and atypical AIM/LIR motifs with a high level of accuracy. AF2-multimer can be modified to detect additional functional AIM/LIR motifs by using protein sequences with mutations in primary AIM/LIR residues. By combining protein modelling data from AF2-multimer with phylogenetic analysis of protein sequences and protein-protein interaction assays, we demonstrate that AF2-multimer predicts the physiologically relevant AIM motif in the ATG8-interacting protein 2 (ATI-2) as well as the previously uncharacterized noncanonical AIM motif in ATG3 from potato (Solanum tuberosum). AF2-multimer also identified the AIM/LIR motifs in pathogen-encoded virulence factors that target ATG8 members in their plant and human hosts, revealing that cross-kingdom ATG8-LIR/AIM associations can also be predicted by AF2-multimer. We conclude that the AF2-guided discovery of autophagy adaptors/receptors will substantially accelerate our understanding of the molecular basis of autophagy in all biological kingdoms

Association of polymorphisms in APOE, p53, and p21 with primary open-angle glaucoma in Turkish patients

Purpose To investigate the association between Apolipoprotein E (APOE), tumor suppressor protein p53 (p53), and cyclin-dependent kinase inhibitor 1A (p21) genes and primary open-angle glaucoma (POAG) in a cohort of Turkish subjects. Methods Seventy-five POAG patients (49 women, 26 men) and 119 healthy subjects (67 women, 52 men) were genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Allele and genotype frequencies between healthy subjects and glaucoma patients were compared by the χ2 test, and intraocular pressure (IOP), cup/disc ratio (C/D) and visual field indices (MD and PSD) were compared among different APOE, p53, and p21 genotypes in POAG group. A p value 0.05). POAG subjects with the ε2ε3 genotype had a worse PSD value (median=2.2) than those with the ε3ε4 genotype (median=1.77; p=0.01) and POAG subjects with the ε3ε3 genotype had worse MD and PSD values (median= -7.4 and 3.4, respectively) than those with the ε3ε4 genotype (median= -4.1 and 1.77, respectively; p=0.034 and 0.028, respectively). Conclusions Our study found no link between polymorphisms in APOE, p53, and p21 genes and POAG in Turkish patients, although a larger sample is required to elucidate the role of these polymorphisms in the pathogenesis and course of glaucoma

The Science Behind the Springs: Using Biomechanics and Finite Element Modeling to Predict Outcomes in Spring-Assisted Sagittal Synostosis Surgery

Spring-assisted surgery for the correction of scaphocephaly has gained popularity over the past 2 decades. Our unit utilizes standardized torsional springs with a central helix for spring-assisted surgery. This design allows a high degree of accuracy and reproducibility of the force vectors and force distance curves. In this manuscript, we expand on the biomechanical testing and properties of these springs. Standardization of design has enabled us to study the springs on bench and in vivo and a comprehensive repository of calvarial remodeling and spring dynamics has been acquired and analyzed. Finite element modeling is a technique utilized to predict the outcomes of spring-assisted surgery. We have found this to be a useful tool, in planning our surgical strategy and improving outcomes. This technique has also contributed significantly to the process of informed consent preoperatively. In this article, we expand on our spring design and dynamics as well as the finite element modeling used to predict and improve outcomes. In our unit, this practice has led to a significant improvement in patient outcomes and parental satisfaction and we hope to make our techniques available to a wider audience

SOME ASPECTS OF ENERGY SAVING OF BURDEN MATERIAL IN THE BLAST FURNACE

To determine the possibility of self-stabilization effect for burden surface texture and gas flow in operating blast furnace under the proper conditions was experimentally proved for the first time, as well as the reasons of the effect disruption

Complications of Tranexamic Acid in Orthopedic Lower Limb Surgery: A Meta-Analysis of Randomized Controlled Trials

Objective. Tranexamic acid (TXA) is increasingly used in orthopedic surgery to reduce blood loss; however, there are concerns about the risk of venous thromboembolic (VTE) complications. The aim of this study was to evaluate TXA safety in patients undergoing lower limb orthopedic surgical procedures. Design. A meta-analysis was performed on the PubMed, Web of Science, and Cochrane Library databases in January 2020 using the following string (Tranexamic acid) AND ((knee) OR (hip) OR (ankle) OR (lower limb)) to identify RCTs about TXA use in patients undergoing every kind of lower limb surgical orthopedic procedures, with IV, IA, or oral administration, and compared with a control arm to quantify the VTE complication rates. Results. A total of 140 articles documenting 9,067 patients receiving TXA were identified. Specifically, 82 studies focused on TKA, 41 on THA, and 17 on other surgeries, including anterior cruciate ligament reconstruction, intertrochanteric fractures, and meniscectomies. The intravenous TXA administration protocol was studied in 111 articles, the intra-articular in 45, and the oral one in 7 articles. No differences in terms of thromboembolic complications were detected between the TXA and control groups neither in the overall population (2.4% and 2.8%, respectively) nor in any subgroup based on the surgical procedure and TXA administration route. Conclusions. There is an increasing interest in TXA use, which has been recently broadened from the most common joint replacement procedures to the other types of surgeries. Overall, TXA did not increase the risk of VTE complications, regardless of the administration route, thus supporting the safety of using TXA for lower limb orthopedic surgical procedures

Photonuclear reactions with Zinc: A case for clinical linacs

The use of bremsstrahlung photons produced by a linac to induce photonuclear reactions is wide spread. However, using a clinical linac to produce the photons is a new concept. We aimed to induce photonuclear reactions on zinc isotopes and measure the subsequent transition energies and half-lives. For this purpose, a bremsstrahlung photon beam of 18 MeV endpoint energy produced by the Philips SLI-25 linac has been used. The subsequent decay has been measured with a well-shielded single HPGe detector. The results obtained for transition energies are in good agreement with the literature data and in many cases surpass these in accuracy. For the half-lives, we are in agreement with the literature data, but do not achieve their precision. The obtained accuracy for the transition energies show what is achievable in an experiment such as ours. We demonstrate the usefulness and benefits of employing clinical linacs for nuclear physics experiments