Design of Prestressing Tendons for Strengthening Steel Truss Bridges

The paper introduces a design space for the design of prestressing tendons concentric with members for strengthening steel truss bridges. The design space contains all feasible solutions for the cross-sectional area of the tendon and the level of prestressing that satisfy the following criteria: (1) tendon yielding; (2) member buckling; and (3) member fracture and yielding. In the tendon design, two options for the degree of prestressing and backup are available. The prestressing option controls the amount of fatigue crack propagation under cyclic loadings, while the backup option provides the tendon area capable of replacing or backing up the member.     

Proteomics Unveils Post-Mortem Changes in Beef Muscle Proteins and Provides Insight into Variations in Meat Quality Traits of Crossbred Young Steers and Heifers Raised in Feedlot

Proteomics has been widely used to study muscle biology and meat quality traits from different species including beef. Beef proteomics studies allow a better understanding of the biological processes related to meat quality trait determination. This study aimed to decipher by means of two-dimensional electrophoresis (2D-PAGE), mass spectrometry and bioinformatics the changes in post-mortem muscle with a focus on proteins differentially expressed in the Longissimus thoracis (LT) muscle of immunocastrated young heifers and steers. Carcass traits, chemical composition, pH, instrumental color (L*, a*, b*), cooking loss and Warner-Bratzler shear force (WBSF) of meat from F1 Montana-Nellore cattle were also evaluated. Backfat thickness (BFT) and intramuscular fat content (IMF) were 46.8% and 63.6% higher in heifers (p < 0.05), respectively, while evaporation losses (EL) were 10.22% lower compared to steers. No differences (p > 0.05) were observed for tenderness evaluated by WBSF (3, 10, and 17 days post-mortem), pH, and color traits (L*, a* and b*) between the experimental groups. The study revealed several proteins to be differentially expressed proteins in heifers compared steers (p < 0.05). In heifers, proteins involved in nutrient transport (TF, ALB, and MB), energy metabolism (ALDOA, GAPDH, and PKM), and oxidative stress and response to stress (HSPA8 and CA3) were associated with a greater BFT and IMF deposition. The higher expression of these proteins indicated greater oxidative capacity and lower glycolytic activity in the LT muscle of heifers. In steers, there was greater abundance of protein expression related to muscle contraction and proteins of structure (ACTA1, TPM2 and TNNT3), energy metabolism (ENO1, ENO3, PYGM, PGM1 and TPI1) and ATP metabolism (ATP5F1B, PEBP1 and AK1), indicating greater glycogenolysis in LT muscle, suggesting a shift in the glycolytic/oxidative fibers of steers.     

CD73-Mediated Formation of Extracellular Adenosine Is Responsible for Adenosine A2A Receptor-Mediated Control of Fear Memory and Amygdala Plasticity

Adenosine A_2A receptors (A_2AR) control fear memory and the underlying processes of synaptic plasticity in the amygdala. In other brain regions, A_2AR activation is ensured by ATP-derived extracellular adenosine formed by ecto-5′-nucleotidase or CD73. We now tested whether CD73 is also responsible to provide for the activation of A_2AR in controlling fear memory and amygdala long-term potentiation (LTP). The bilateral intracerebroventricular injection of the CD73 inhibitor αβ-methylene ADP (AOPCP, 1 nmol/ventricle/day) phenocopied the effect of the A_2AR blockade by decreasing the expression of fear memory, an effect disappearing in CD73-knockout (KO) mice and in forebrain neuronal A_2AR-KO mice. In the presence of PPADS (20 μM) to eliminate any modification of ATP/ADP-mediated P2 receptor effects, both AOPCP (100 μM) and the A_2AR antagonist, {"type":"entrez-protein","attrs":{"text":"SCH58261","term_id":"1052882304","term_text":"SCH58261"}}SCH58261 (50 nM), decreased LTP magnitude in synapses of projection from the external capsula into the lateral amygdala, an effect eliminated in slices from both forebrain neuronal A_2AR-KO mice and CD73-KO mice. These data indicate a key role of CD73 in the process of A_2AR-mediated control of fear memory and underlying synaptic plasticity processes in the amygdala, paving the way to envisage CD73 as a new therapeutic target to interfere with abnormal fear-like emotional processing.     

Stearoyl CoA Desaturase-1 Silencing in Glioblastoma Cells: Phospholipid Remodeling and Cytotoxicity Enhanced upon Autophagy Inhibition

Modulation of lipid metabolism is a well-established cancer hallmark, and SCD1 has been recognized as a key enzyme in promoting cancer cell growth, including in glioblastoma (GBM), the deadliest brain tumor and a paradigm of cancer resistance. The central goal of this work was to identify, by MS, the phospholipidome alterations resulting from the silencing of SCD1 in human GBM cells, in order to implement an innovative therapy to fight GBM cell resistance. With this purpose, RNAi technology was employed, and low serum-containing medium was used to mimic nutrient deficiency conditions, at which SCD1 is overexpressed. Besides the expected increase in the saturated to unsaturated fatty acid ratio in SCD1 silenced-GBM cells, a striking increase in polyunsaturated chains, particularly in phosphatidylethanolamine and cardiolipin species, was noticed and tentatively correlated with an increase in autophagy (evidenced by the increase in LC3BII/I ratio). The contribution of autophagy to mitigate the impact of SCD1 silencing on GBM cell viability and growth, whose modest inhibition could be correlated with the maintenance of energetically associated mitochondria, was evidenced by using autophagy inhibitors. In conclusion, SCD1 silencing could constitute an important tool to halt GBM resistance to the available treatments, especially when coupled with a mitochondria disrupter chemotherapeutic.     

The Future of Point-of-Care Nucleic Acid Amplification Diagnostics after COVID-19: Time to Walk the Walk

Since the onset of the COVID-19 pandemic, over 610 million cases have been diagnosed and it has caused over 6.5 million deaths worldwide. The crisis has forced the scientific community to develop tools for disease control and management at a pace never seen before. The control of the pandemic heavily relies in the use of fast and accurate diagnostics, that allow testing at a large scale. The gold standard diagnosis of viral infections is the RT-qPCR. Although it provides consistent and reliable results, it is hampered by its limited throughput and technical requirements. Here, we discuss the main approaches to rapid and point-of-care diagnostics based on RT-qPCR and isothermal amplification diagnostics. We describe the main COVID-19 molecular diagnostic tests approved for self-testing at home or for point-of-care testing and compare the available options. We define the influence of specimen selection and processing, the clinical validation, result readout improvement strategies, the combination with CRISPR-based detection and the diagnostic challenge posed by SARS-CoV-2 variants for different isothermal amplification techniques, with a particular focus on LAMP and recombinase polymerase amplification (RPA). Finally, we try to shed light on the effect the improvement in molecular diagnostics during the COVID-19 pandemic could have in the future of other infectious diseases.     

Aphid BCR4 Structure and Activity Uncover a New Defensin Peptide Superfamily

Aphids (Hemiptera: Aphidoidea) are among the most detrimental insects for agricultural plants, and their management is a great challenge in agronomical research. A new class of proteins, called Bacteriocyte-specific Cysteine-Rich (BCR) peptides, provides an alternative to chemical insecticides for pest control. BCRs were initially identified in the pea aphid Acyrthosiphon pisum. They are small disulfide bond-rich proteins expressed exclusively in aphid bacteriocytes, the insect cells that host intracellular symbiotic bacteria. Here, we show that one of the A. pisum BCRs, BCR4, displays prominent insecticidal activity against the pea aphid, impairing insect survival and nymphal growth, providing evidence for its potential use as a new biopesticide. Our comparative genomics and phylogenetic analyses indicate that BCRs are restricted to the aphid lineage. The 3D structure of BCR4 reveals that this peptide belongs to an as-yet-unknown structural class of peptides and defines a new superfamily of defensins.     

Spatial–Spectral Analysis of Hyperspectral Images Reveals Early Detection of Downy Mildew on Grapevine Leaves

Downy mildew is a highly destructive disease of grapevine. Currently, monitoring for its symptoms is time-consuming and requires specialist staff. Therefore, an automated non-destructive method to detect the pathogen before the visible symptoms appear would be beneficial for early targeted treatments. The aim of this study was to detect the disease early in a controlled environment, and to monitor the disease severity evolution in time and space. We used a hyperspectral image database following the development from 0 to 9 days post inoculation (dpi) of three strains of Plasmopara viticola inoculated on grapevine leaves and developed an automatic detection tool based on a Support Vector Machine (SVM) classifier. The SVM obtained promising validation average accuracy scores of 0.96, a test accuracy score of 0.99, and it did not output false positives on the control leaves and detected downy mildew at 2 dpi, 2 days before the clear onset of visual symptoms at 4 dpi. Moreover, the disease area detected over time was higher than that when visually assessed, providing a better evaluation of disease severity. To our knowledge, this is the first study using hyperspectral imaging to automatically detect and show the spatial distribution of downy mildew on grapevine leaves early over time.     

Identification of Potential New Aedes aegypti Juvenile Hormone Inhibitors from N-Acyl Piperidine Derivatives: A Bioinformatics Approach

Aedes aegypti mosquitoes transmit several human pathogens that cause millions of deaths worldwide, mainly in Latin America. The indiscriminate use of insecticides has resulted in the development of species resistance to some such compounds. Piperidine, a natural alkaloid isolated from Piper nigrum, has been used as a hit compound due to its larvicidal activity against Aedes aegypti. In the present study, piperidine derivatives were studied through in silico methods: pharmacophoric evaluation (PharmaGist), pharmacophoric virtual screening (Pharmit), ADME/Tox prediction (Preadmet/Derek 10.0^®), docking calculations (AutoDock 4.2) and molecular dynamics (MD) simulation on GROMACS-5.1.4. MP-416 and MP-073 molecules exhibiting ΔG binding (MMPBSA −265.95 ± 1.32 kJ/mol and −124.412 ± 1.08 kJ/mol, respectively) and comparable to holo (ΔG binding = −216.21 ± 0.97) and pyriproxyfen (a well-known larvicidal, ΔG binding= −435.95 ± 2.06 kJ/mol). Considering future in vivo assays, we elaborated the theoretical synthetic route and made predictions of the synthetic accessibility (SA) (SwissADME), lipophilicity and water solubility (SwissADME) of the promising compounds identified in the present study. Our in silico results show that MP-416 and MP-073 molecules could be potent insecticides against the Aedes aegypti mosquitoes.     

A new algorithm for finding faces in wireframes

The problem of identifying the topology implied by wireframe drawings of polyhedral objects requires the identification of face loops, loops of edges which correspond to a face in the object the drawing portrays.In this paper, we survey the advantages and limitations of known approaches, and present and discuss test results which illustrate the successes and failures of a currently popular approach based on Dijkstra’s Algorithm. We conclude that the root cause of many failure cases is that the underlying algorithm assumes that the cost of traversing an edge is fixed.We propose a new polynomial-order algorithm for finding faces in wireframes. This algorithm could be adapted to any graph-theoretical least-cost circuit problem where the cost of traversing an edge is not fixed but context-dependent.