Miracle-dz/UniFAR-FTUs huggingface dataset:
Autophagy induction by thiostrepton for the improvement of anticancer therapy

ABSTRACT Macroautophagy/autophagy induction by caloric restriction mimetics (CRMs) is a strategy to stimulate anticancer immune responses of immunogenic cell death (ICD)-inducing chemotherapeutics. We designed a phenotypic screening campaign in which we identified pharmacological agents that have CRM properties (i.e., non-cytotoxic induction of autophagic flux that reduces cytoplasmic protein acetylation) and simultaneously act as ICD amplifiers (i.e. with the capacity to enhance the release of adenosine triphosphate, ATP, from stressed and dying cancer cells). This approach led to the identification of thiostrepton, a natural cyclic oligopeptide antibiotic, as an agent that enhances chemotherapy-induced anticancer immune responses in vivo, in immunocompetent mice bearing syngeneic tumors. Interestingly, both the pro-autophagic and the anticancer effects of thiostrepton rely on the activation of TFEB (transcription factor EB) and TFE3 (transcription factor E3). In summary, thiostrepton represents a novel CRM and ICD amplifier that may be useful for cancer therapy.
Contrast response in a comprehensive network model of macaque V1

The response to contrast is one of the most important functions of the macaque primary visual cortex, V1, but up to now there has not been an adequate theory for it. To fill this gap in our understanding of cortical function, we built and analyzed a new large-scale, biologically constrained model of the input layer, 4Cα, of macaque V1. We called the new model CSY2. We challenged CSY2 with a three-parameter family of visual stimuli that varied in contrast, orientation, and spatial frequency. CSY2 accurately simulated experimental data and made many new predictions. It accounted for 1) the shapes of firing-rate-versus-contrast functions, 2) orientation and spatial frequency tuning versus contrast, and 3) the approximate contrast-invariance of cortical activity maps. Post-analysis revealed that the mechanisms that were needed to produce the successful simulations of contrast response included strong recurrent excitation and inhibition that find dynamic equilibria across the cortical surface, dynamic feedback between L6 and L4, and synaptic dynamics like inhibitory synaptic depression.
Laser Induced Graphene Paper Heaters with Multimodally Patternable Electrothermal Performance for Low-Energy Manufacturing of Composites.

Low-energy manufacturing of polymeric composites through two-dimensional electrothermal heaters is a promising strategy over traditional autoclave and oven. Laser induced graphene paper (LIGP) is a recent emergent multifunctional material with merits of one-step computer aided design and manufacturing (CAD/CAM) as well as flexible thin nature. To fully explore its capabilities of in situ heating, herein, we adventurously propose and investigate the customizable manufacture and modulation of LIGP enabled heaters with multimodally patternable performance. Developed by two modes (uniform & nonuniform) of laser processing, the LIGP heaters (LIGP-H) show distinctively unique characteristics, including high working range (> 600 °C), fast stabilization (< 8 s), high temperature efficiency (~370 °C·cm2/W), and superb robustness. Most innovatively, the non-uniform processing could section LIGP-H into subzones with independently controlled heating performance, rendering various designable patterns. The above unique characteristics guarantee the LIGP-H highly reliable for in situ curing composites with flat, curve and even inhomogeneous structures. With enormous energy-saving (~85%), superb curing accuracy, and comparable mechanical strength, the proposed device is advantageous for assuring high-quality and high-efficient manufacturing.
Input and output pathways determining potassium budgets in two paddy fields subjected to countermeasures against radiocesium in Fukushima, Japan

Countermeasures to reduce radiocesium (134Cs and 137Cs) uptake by crops have been implemented in farmlands affected by the Fukushima nuclear accident in 2011. A widely practiced countermeasure is the application of potassium (K). Long-term soil K maintenance is a key issue due to the long physical half-life of 137Cs (30 years). Information on input and output pathways determining plant-available K budgets can provide a base for the development of maintenance strategies. Therefore, in this study we evaluated these pathways in paddy fields subjected to K fertilization as a countermeasure. We selected two fields with different soil textures and drainage conditions and quantified input and output via fertilization, irrigation, precipitation, straw return to soil, plant harvesting, surface runoff, and percolation during the cropping period in 2018. The major input pathways were fertilization, straw return, and irrigation due to a large inflow volume with spill-over irrigation. The major output pathways consisted of plant harvesting, surface runoff, and percolation. However, 85% of K in harvested plants was brought back by straw return; in practice, harvesting was a minor pathway. The K budgets during the study period were negative (−20 and −289 kg ha−1) and especially severe in clay loam soil with high output via percolation. This could probably be attributed to the low cation exchange capacity and high permeability from the low total C and clay contents. Losses via surface runoff stemmed from excessive irrigation volumes in both fields. Around 70% of the total K output via surface runoff and percolation was discharged before mid-summer drainage. Accordingly, controlling the irrigation volume during this period in addition to increasing cation exchange capacity and decreasing permeability may improve the negative budgets.
Targeted domain assembly for fast functional profiling of metagenomic datasets with S3A

Abstract Motivation The understanding of the ever-increasing number of metagenomic sequences accumulating in our databases demands for approaches that rapidly ‘explore’ the content of multiple and/or large metagenomic datasets with respect to specific domain targets, avoiding full domain annotation and full assembly. Results S3A is a fast and accurate domain-targeted assembler designed for a rapid functional profiling. It is based on a novel construction and a fast traversal of the Overlap-Layout-Consensus graph, designed to reconstruct coding regions from domain annotated metagenomic sequence reads. S3A relies on high-quality domain annotation to efficiently assemble metagenomic sequences and on the design of a new confidence measure for a fast evaluation of overlapping reads. Its implementation is highly generic and can be applied to any arbitrary type of annotation. On simulated data, S3A achieves a level of accuracy similar to that of classical metagenomics assembly tools while permitting to conduct a faster and sensitive profiling on domains of interest. When studying a few dozens of functional domains—a typical scenario—S3A is up to an order of magnitude faster than general purpose metagenomic assemblers, thus enabling the analysis of a larger number of datasets in the same amount of time. S3A opens new avenues to the fast exploration of the rapidly increasing number of metagenomic datasets displaying an ever-increasing size. Availability and implementation S3A is available at http://www.lcqb. upmc.fr/S3A_ASSEMBLER/. Supplementary information Supplementary data are available at Bioinformatics online.
Ultrasensitive Stress Biomarker Detection Using Polypyrrole Nanotube Coupled to a Field-Effect Transistor

Stress biomarkers such as hormones and neurotransmitters in bodily fluids can indicate an individual’s physical and mental state, as well as influence their quality of life and health. Thus, sensitive and rapid detection of stress biomarkers (e.g., cortisol) is important for management of various diseases with harmful symptoms, including post-traumatic stress disorder and depression. Here, we describe rapid and sensitive cortisol detection based on a conducting polymer (CP) nanotube (NT) field-effect transistor (FET) platform. The synthesized polypyrrole (PPy) NT was functionalized with the cortisol antibody immunoglobulin G (IgG) for the sensitive and specific detection of cortisol hormone. The anti-cortisol IgG was covalently attached to a basal plane of PPy NT through an amide bond between the carboxyl group of PPy NT and the amino group of anti-cortisol IgG. The resulting field-effect transistor-type biosensor was utilized to evaluate various cortisol concentrations. Cortisol was sensitively measured to a detection limit of 2.7 × 10−10 M (100 pg/mL), with a dynamic range of 2.7 × 10−10 to 10−7 M; it exhibited rapid responses (<5 s). We believe that our approach can serve as an alternative to time-consuming and labor-intensive health questionnaires; it can also be used for diagnosis of underlying stress-related disorders.
Special Issue on E-Health Services

The importance of e-health to citizens, patients, health providers, governments, and other stakeholders is rapidly increasing. E-health services have a range of advantages. For instance, e-health may improve access to services, reduce costs, and improve self-management. E-health may allow previously underserved populations to gain access to services. Services utilizing apps, social media, or online video are rapidly gaining ground in most countries. In this special issue, we present a range of up-to-date studies from around the world, providing important insights into central topics relating to e-health services.
A novel technique for performing gallbladder tumor biopsy using a stent delivery system and biopsy forceps

A 79-year-old man presented to our hospital with a gallbladder tumor diagnosed using abdominal ultrasonography (AUS). AUS, contrast-enhanced computed tomography, and magnetic resonance imaging showed a protruded lesion at the gallbladder fundus (▶Fig. 1, ▶Fig. 2). Endoscopic retrograde cholangiography (ERC) was performed, and cholecystography revealed a contrast agent defect at the gallbladder fundus (▶Fig. 3). We placed a 0.025-inch guidewire into the gallbladder and inserted a biliary stent delivery system, composed of a guide catheter and pusher tube (MAJ510; Olympus Medical Systems, Tokyo, Japan) (▶Fig. 4). After removing the guidewire and guide catheter, we inserted biopsy forceps (radial Jaw 4 Pediatric Biopsy Forceps; Boston Scientific Japan, Tokyo, Japan) through the pusher tube and performed biopsy of the gallbladder fundus legion (▶Video 1). The biopsy specimen was sufficient to diagnose gallbladder cancer (▶Fig. 5). Tumor recurrence was not seen for 3 years after surgery. Although other endoscopic methods for diagnosing gallbladder cancers have been previously reported [1–3], use of biopsy forceps specimens for diagnosing gallbladder cancer is novel to our knowledge. We have previously reported the utility of a biliary stent delivery system in removing a foreign body from the bile duct [4, 5]. The technique used here enabled us to insert biopsy forceps into the gallbladder safely and easily, and to obtain a sufficient biopsy sample. Moreover, this method may contribute to reducing complications after ERC, such as acute pancreatitis and duodenal perforation caused by the biopsy forceps injuring the duodenal papilla. Careful and accurate biopsy is important for prevention of gallbladder perforation. We placed an endoscopic naso-gallbladder drainage tube at the end of this procedure to reduce the bile juice leakage in case of gallbladder perforation. In conclusion, we report a novel technique to obtain a sample of the gallbladder using a stent delivery system using a biopsy forceps. Endoscopy_UCTN_Code_TTT_1AR_2AD
Isolation of Lobane and Prenyleudesmane Diterpenoids from the Soft Coral Lobophytum varium

Further chemical investigation of the EtOAc extract of the soft coral Lobophytum varium resulted in the discovery of eleven new diterpenoids lobovarols F–P (1–11) of lobane– and prenyleudesmane–types, along with two known metabolites (12 and 13). The structures of the new metabolites were established by spectroscopic analyses, including 2D NMR experiments. The absolute configuration of 1 was determined using Mosher’s method. The complete assignment of 1H and 13C NMR spectroscopic data of 12 and 13 and the identification of pyran-derived moieties in the prenyleudesmanes were reported for the first time. Anti-inflammatory activities of the isolated compounds in suppressing elastase release and superoxide anion generation in human neutrophils were disclosed for 1, 2, 4, 12, and 13. A stereospecific biosynthesis for lobanes and prenyleudesmanes from the related prenylgermacranes could explain the coexistence of lobanes and prenylgermacranes in L. varium.
Cell Wall Invertase Is Essential for Ovule Development through Sugar Signaling Rather Than Provision of Carbon Nutrients1[OPEN]

Ovule-specific silencing of cell wall invertase inhibits initiation of the ovule by disrupting sugar signaling but without inducing carbon starvation. Ovule formation is essential for realizing crop yield because it determines seed number. The underlying molecular mechanism, however, remains elusive. Here, we show that cell wall invertase (CWIN) functions as a positive regulator of ovule initiation in Arabidopsis (Arabidopsis thaliana). In situ hybridization revealed that CWIN2 and CWIN4 were expressed at the placenta region where ovule primordia initiated. Specific silencing of CWIN2 and CWIN4 using targeted artificial microRNA driven by an ovule-specific SEEDSTICK promoter (pSTK) resulted in a substantial reduction of CWIN transcript and activity, which blocked ovule initiation and aggravated ovule abortion. There was no induction of carbon (C) starvation genes in the transgenic lines, and supplementing newly forming floral buds with extra C failed to recover the ovule phenotype. This indicates that suppression of CWIN did not lead to C starvation. A group of hexose transporters was downregulated in the transgenic plants. Among them, two representative ones were spatially coexpressed with CWIN2 and CWIN4, suggesting a coupling between CWIN and hexose transporters for ovule initiation. RNA-sequencing analysis identified differentially expressed genes encoding putative extracellular receptor-like kinases, MADS-box transcription factors, including STK, and early auxin response genes in response to CWIN-silencing. Our data demonstrate the essential role of CWIN in ovule initiation, which is most likely to occur through sugar signaling instead of C nutrient contribution. We propose that CWIN-mediated sugar signaling may be perceived by, and transmitted through, hexose transporters or receptor-like kinases to regulate ovule formation by modulating downstream auxin signaling and MADS-box transcription factors.
A Rare Case of Pneumococcal and Meningococcal Mixed Meningitis in an Infant with Cardiac Dysfunction

Meningitis is commonly caused by a viral, bacterial, fungal, or parasitic infection that involves the cerebrospinal fluid (CSF) and leads to inflammation of the protective membranes covering the brain and spinal cord. Among bacterial pathogens responsible for meningitis, Streptococcus pneumoniae is notorious for causing more than 50 of all cases of bacterial meningitis. Neisseria meningitis is also a major cause of bacterial meningitis. Here, we report a rare case of a 13-month-old infant with cardiac dysfunction associated with meningitis caused by co-infection with Streptococcus pneumoniae and Neisseria meningitides. Cardiac dysfunction is a condition where the heart pumping becomes less effective and the heart cannot pump sufficient blood to meet the bodyâ��s needs. Bacteria were isolated by culture and detected by polymerase chain reaction (PCR) on CSF. The patient was treated with vancomycin, ceftriaxone, and rifampin followed by three months of follow-up without any clinical symptoms. This raises the possibility of finding other cases of mixed neonatal meningitis in the future since the incidence of meningitis is currently increasing in the region. Â© 2018, Archives of Clinical Infectious Diseases.
High-Throughput Particle Concentration Using Complex Cross-Section Microchannels

High throughput particle/cell concentration is crucial for a wide variety of biomedical, clinical, and environmental applications. In this work, we have proposed a passive spiral microfluidic concentrator with a complex cross-sectional shape, i.e., a combination of rectangle and trapezoid, for high separation efficiency and a confinement ratio less than 0.07. Particle focusing in our microfluidic system was observed in a single, tight focusing line, in which higher particle concentration is possible, as compared with simple rectangular or trapezoidal cross-sections with similar flow area. The sharper focusing stems from the confinement of Dean vortices in the trapezoidal region of the complex cross-section. To quantify this effect, we introduce a new parameter, complex focusing number or CFN, which is indicative of the enhancement of inertial focusing of particles in these channels. Three spiral microchannels with various widths of 400 µm, 500 µm, and 600 µm, with the corresponding CFNs of 4.3, 4.5, and 6, respectively, were used. The device with the total width of 600 µm was shown to have a separation efficiency of ~98%, and by recirculating, the output concentration of the sample was 500 times higher than the initial input. Finally, the investigation of results showed that the magnitude of CFN relies entirely on the microchannel geometry, and it is independent of the overall width of the channel cross-section. We envision that this concept of particle focusing through complex cross-sections will prove useful in paving the way towards more efficient inertial microfluidic devices.
Proteomics of Brucella

Brucella spp. are Gram negative intracellular bacteria responsible for brucellosis, a worldwide distributed zoonosis. A prominent aspect of the Brucella life cycle is its ability to invade, survive and multiply within host cells. Comprehensive approaches, such as proteomics, have aided in unravelling the molecular mechanisms underlying Brucella pathogenesis. Technological and methodological advancements such as increased instrument performance and multiplexed quantification have broadened the range of proteome studies, enabling new and improved analyses, providing deeper and more accurate proteome coverage. Indeed, proteomics has demonstrated its contribution to key research questions in Brucella biology, i.e., immunodominant proteins, host-cell interaction, stress response, antibiotic targets and resistance, protein secretion. Here, we review the proteomics of Brucella with a focus on more recent works and novel findings, ranging from reconfiguration of the intracellular bacterial proteome and studies on proteomic profiles of Brucella infected tissues, to the identification of Brucella extracellular proteins with putative roles in cell signaling and pathogenesis. In conclusion, proteomics has yielded copious new candidates and hypotheses that require future verification. It is expected that proteomics will continue to be an invaluable tool for Brucella and applications will further extend to the currently ill-explored aspects including, among others, protein processing and post-translational modification.
HSF1: Primary Factor in Molecular Chaperone Expression and a Major Contributor to Cancer Morbidity

Heat shock factor 1 (HSF1) is the primary component for initiation of the powerful heat shock response (HSR) in eukaryotes. The HSR is an evolutionarily conserved mechanism for responding to proteotoxic stress and involves the rapid expression of heat shock protein (HSP) molecular chaperones that promote cell viability by facilitating proteostasis. HSF1 activity is amplified in many tumor contexts in a manner that resembles a chronic state of stress, characterized by high levels of HSP gene expression as well as HSF1-mediated non-HSP gene regulation. HSF1 and its gene targets are essential for tumorigenesis across several experimental tumor models, and facilitate metastatic and resistant properties within cancer cells. Recent studies have suggested the significant potential of HSF1 as a therapeutic target and have motivated research efforts to understand the mechanisms of HSF1 regulation and develop methods for pharmacological intervention. We review what is currently known regarding the contribution of HSF1 activity to cancer pathology, its regulation and expression across human cancers, and strategies to target HSF1 for cancer therapy.
Can Improved Legume Varieties Optimize Iron Status in Low- and Middle-Income Countries? A Systematic Review.

Iron and zinc deficiencies are some of the most widespread micronutrient deficiencies in low- and middle-income countries (LMIC). Dietary diversification, food fortification, nutrition education, and supplementation can be used to control micronutrient deficiencies. Legumes are important staple foods in most households in LMIC. Legumes are highly nutritious (good sources of essential minerals, fiber, and low glycemic index) and offer potential benefits in addressing nutrition insecurity in LMIC. Several efforts have been made to increase micronutrient intake by use of improved legumes. Improved legumes have a higher nutrient bioavailability, lower phytate, or reduced hard-to-cook (HTC) defect. We hypothesize that consumption of improved legumes leads to optimization of zinc and iron status and associated health outcomes. Therefore, the objective of this review is to examine the evidence on the efficacy of interventions using improved legumes. Nine relevant studies are included in the review. Consumption of improved legumes resulted in a ≥1.5-fold increase in iron intake. Several studies noted modest improvements in biomarkers of iron status [hemoglobin (Hb), serum ferritin (SF), and transferrin receptor] associated with consumption of improved legumes. Currently, no efficacy studies assessing the relation between consumption of improved legumes and zinc status are available in the literature. Evidence shows that, in addition to repletion of biomarkers of iron status, consumption of improved legumes is associated with both clinical and functional outcomes. The prevalence of iron deficiency (ID) decreases with consumption of improved legumes, with increases of ≤3.0 g/L in Hb concentrations. Improvement in cognition and brain function in women has been reported as well. However, further research is necessary in more at-risk groups and also to show if the reported improvements in status markers translate to improved health outcomes. Evidence from the included studies shows potential from consumption of improved legumes suggesting them to be a sustainable solution to improve iron status.