Nanobase.org: a repository for DNA and RNA nanostructures.

We introduce a new online database of nucleic acid nanostructures for the field of DNA and RNA nanotechnology. The database implements an upload interface, searching and database browsing. Each deposited nanostructures includes an image of the nanostructure, design file, an optional 3D view, and additional metadata such as experimental data, protocol or literature reference. The database accepts nanostructures in any preferred format used by the uploader for the nanostructure design. We further provide a set of conversion tools that encourage design file conversion into common formats (oxDNA and PDB) that can be used for setting up simulations, interactive editing or 3D visualization. The aim of the repository is to provide to the DNA/RNA nanotechnology community a resource for sharing their designs for further reuse in other systems and also to function as an archive of the designs that have been achieved in the field so far. Nanobase.org is available at https://nanobase.org/.

Dynamic changes in thymic sub-populations during acute and long-term infections with virulent and virulence-attenuated Salmonella Typhimurium strains in C57BL/6 and autoimmune-prone lpr mice.

SALMONELLA: Typhimurium infection in mice results in drastic loss of immature CD4- CD8- double negative (DN) and CD4+ CD8+ double positive (DP) thymic subsets compared to mature single positive (SP) subsets. We investigated changes in thymocyte sub-populations post infection with a wild type (WT) virulent strain and ΔrpoS, a virulence-attenuated strain, of Salmonella Typhimurium in C57BL/6 (B6) and Fas-deficient autoimmune-prone lpr mice. The WT strain caused acute thymic atrophy with greater loss of thymocytes in lpr mice compared to B6 mice. Infection with ΔrpoS caused progressive thymic atrophy in B6 and lpr mice. Analysis of thymocyte subsets revealed that immature thymocytes including the DN, immature single positive (ISP), and DP thymocytes underwent extensive loss. SP thymocytes were more resistant to loss in WT-infected B6 mice, whereas WT-infected lpr and ΔrpoS-infected mice exhibited depletion of SP thymocytes. Overall, thymocyte sub-populations exhibited differential susceptibilities depending on bacterial virulence and the host background.

Monolithic light concentration by core-shell TiO2nanostructures templated by monodisperse polymer colloidal monolayers.

Nanostructured dielectric overlayers can be used to increase light absorption in nanometer-thin films used for various optoelectronic applications. Here, the self-assembly of a close-packed monolayer of polystyrene nanospheres is used to template a core-shell polystyrene-TiO2light-concentrating monolithic structure. This is enabled by the growth of TiO2at temperatures below the polystyrene glass-transition temperature via atomic layer deposition. The result is a monolithic, tailorable nanostructured overlayer fabricated by simple chemical methods. The design of this monolith can be tailored to generate significant absorption increases in thin film light absorbers. Finite-difference, time domain simulations are used to explore the design polystyrene-TiO2core-shell monoliths that maximize light absorption in a 40 nm GaAs-on-Si substrate as a model for a photoconductive antenna THz emitter. An optimized core-shell monolith structure generated a greater than 60-fold increase of light absorption at a single wavelength in the GaAs layer of the simulated model device.

Mitochondrial dynamics, positioning and function mediated by cytoskeletal interactions.

The ability of a mitochondrion to undergo fission and fusion, and to be transported and localized within a cell are central not just to proper functioning of mitochondria, but also to that of the cell. The cytoskeletal filaments, namely microtubules, F-actin and intermediate filaments, have emerged as prime movers in these dynamic mitochondrial shape and position transitions. In this review, we explore the complex relationship between the cytoskeleton and the mitochondrion, by delving into: (i) how the cytoskeleton helps shape mitochondria via fission and fusion events, (ii) how the cytoskeleton facilitates the translocation and anchoring of mitochondria with the activity of motor proteins, and (iii) how these changes in form and position of mitochondria translate into functioning of the cell.

Accelerated rate of progression of bioprosthetic aortic stenosis in patients with renal disease.

BACKGROUND: Renal disease can lead to more rapid progression of aortic stenosis. However, there are limited case report data investigating the impact of renal disease on the rate of prosthetic aortic valve stenosis. We sought to quantify the rate of progression of bioprosthetic aortic stenosis in patients with renal disease. METHODS: Patients with bioprosthetic aortic valves and at least two transthoracic echocardiograms six or more months apart were included. Echocardiographic data from patients with end-stage renal disease (ESRD), chronic kidney disease (CKD) stages 3-4, and normal renal function were compared using ANOVA and Kruskal-Wallis tests. RESULTS: One hundred fifteen patients (43 ESRD, 52 CKD, and 20 controls) were included in this study. Changes in dimensionless index (DI) (units/year) for patients with normal renal function, CKD, and ESRD were .025 ± .13, -.040 ± .08, -.10 ± .13, respectively, leading to calculated changes in aortic valve area (AVA) (cm2 /year) of .04 ± .28, -.13 ± .29, -.42 ± .72, respectively. Change in peak gradient (m/sec/year) was significantly lower for patients with normal renal function compared to ESRD; -.077 ± 5.98 versus 7.18 ± 17.9. In the ESRD group, a nonsignificant trend toward greater change in DI/year was seen in TAVR compared to SAVR: -.14 ± .16 versus -.08 ± .11. CONCLUSION: Our results confirm limited available data reporting an accelerated rate of bioprosthetic stenosis in patients with CKD and ESRD. These data not only quantify this progression but may also inform clinical decision-making and valve selection in patients with renal disease.

Conventional and Emerging Markers in Stem Cell Isolation and Characterization.

Stem cells have emerged as a promising source of cell-based therapy in regenerative medicine with several stem cell-based products currently in clinical trials. Despite the immense therapeutic potential, their isolation from some of the emerging sources and their characterization has been naïve owing to the lack of standard markers for the same. Some biomarkers have now been well established for the isolation and characterization of stem cells. However, there are emerging markers that can be used in addition to these conventional markers or independent of them to establish the identity of the stem cells. In this review, an attempt has been made to describe a few conventionally used markers and emerging markers for the identification, isolation and characterization of stem cells from various niches across the three germ layer origins.

Direct oral anticoagulants and warfarin in patients with cirrhosis: a comparison of outcomes.

Anticoagulation management in patients with cirrhosis presents several challenges as a result of alterations in hemostasis. Historically vitamin k antagonists and low molecular weight heparins have been the agents of choice in this patient population. Direct oral anticoagulants (DOACs) may provide an alternative to traditional anticoagulant therapy. To evaluate the rate of major bleeding among patients receiving DOACs or warfarin with cirrhosis. A retrospective, observational, cohort study of adult patients admitted between January 2012 and July 2018 with diagnosis of cirrhosis receiving anticoagulation with DOAC or warfarin therapy was performed. Patients were stratified based on the receipt of a DOAC or warfarin. The primary endpoint was incidence of major bleeding at 90 days. Secondary endpoints included stroke or embolic event at 90 days as well as rehospitalization and mortality at 1 year. One hundred sixty-seven patients were included for analysis; of which 110 received warfarin and 57 received a DOAC. The most commonly used DOAC was apixaban (52.6%) followed by rivaroxaban (45.6%) and dabigratran (1.8%). The incidence of major bleeding was similar between warfarin and DOAC groups (9.1% vs. 5.2% p = 0.381). No difference in the rate of stroke or recurrent embolic event at 90 days was identified between the two groups (0% vs. 1.58% p = 0.341; 1.8% vs. 1.8% p = 0.731). In conclusion DOACs appear to be a safe alternative to warfarin in patients with mild to moderate cirrhosis. Further studies are warranted to confirm these findings.

Clinical Applications of Induced Pluripotent Stem Cells - Stato Attuale.

In an adult human body, somatic stem cells are present in small amounts in almost all organs with the function of general maintenance and prevention of premature aging. But, these stem cells are not pluripotent and are unable to regenerate large cellular loss caused by infarctions or fractures especially in cells with limited replicative ability such as neurons and cardiomyocytes. These limitations gave rise to the idea of inducing pluripotency to adult somatic cells and thereby restoring their regeneration, replication and plasticity. Though many trials and research were focused on inducing pluripotency, a solid breakthrough was achieved by Yamanaka in 2006. Yamanaka's research identified 4 genes (OCT-4, SOX-2, KLF-4 and c-MYC) as the key requisite for inducing pluripotency in any somatic cells (iPSCs). Our study, reviews the major methods used for inducing pluripotency, differentiation into specific cell types and their application in both cell regeneration and disease modelling. We have also highlighted the current status of iPSCs in clinical applications by analysing the registered clinical trials. We believe that this review will assist the researchers to decide the parameters such as induction method and focus their efforts towards clinical application of iPSCs.

Evaluation of the Parasight Platform for Malaria Diagnosis.

The World Health Organization estimates that nearly 500 million malaria tests are performed annually. While microscopy and rapid diagnostic tests (RDTs) are the main diagnostic approaches, no single method is inexpensive, rapid, and highly accurate. Two recent studies from our group have demonstrated a prototype computer vision platform that meets those needs. Here we present the results from two clinical studies on the commercially available version of this technology, the Sight Diagnostics Parasight platform, which provides malaria diagnosis, species identification, and parasite quantification. We conducted a multisite trial in Chennai, India (Apollo Hospital [n = 205]), and Nairobi, Kenya (Aga Khan University Hospital [n = 263]), in which we compared the device to microscopy, RDTs, and PCR. For identification of malaria, the device performed similarly well in both contexts (sensitivity of 99% and specificity of 100% at the Indian site and sensitivity of 99.3% and specificity of 98.9% at the Kenyan site, compared to PCR). For species identification, the device correctly identified 100% of samples with Plasmodium vivax and 100% of samples with Plasmodium falciparum in India and 100% of samples with P. vivax and 96.1% of samples with P. falciparum in Kenya, compared to PCR. Lastly, comparisons of the device parasite counts with those of trained microscopists produced average Pearson correlation coefficients of 0.84 at the Indian site and 0.85 at the Kenyan site.

Computer-vision-based technology for fast, accurate and cost effective diagnosis of malaria.

BACKGROUND: Microscopy has long been considered to be the gold standard for diagnosis of malaria despite the introduction of newer assays. However, it has many challenges like requirement of trained microscopists and logistic issues. A vision based device that can diagnose malaria, provide speciation and estimate parasitaemia was evaluated. METHODS: The device was evaluated using samples from 431 consented patients, 361 of which were initially screened by RDT and microscopy and later analysed by PCR. It was a prospective, non-randomized, blinded trial. Quantification of parasitaemia was performed by two experienced technicians. Samples were subjected to diagnosis by Sight Dx digital imaging scanning. RESULTS: The sensitivity and specificity of the SightDx P1 device for analysed samples were found to be 97.05 and 96.33%, respectively, when compared to PCR. When compared to microscopy, sensitivity and specificity were found to be 94.4 and 95.6%, respectively. The device was able to speciate 73.3% of the PCR Plasmodium falciparum positive samples and 91.4% of PCR Plasmodium vivax positive samples. CONCLUSION: The ability of the device to detect parasitaemia as compared with microscopy, was within 50% in 71.3% of cases and demonstrated a correlation coefficient of 0.89.

Mechanical Properties Affect Primary T Cell Activation in 3D Bioprinted Hydrogels.

T cells play a critical role in the adaptive immune response of the body, especially against intracellular pathogens and cancer. In vitro, T cell activation studies typically employ planar (two-dimensional, 2D) culture systems that do not mimic native cell-to-extracellular matrix (ECM) interactions, which influence activation. The goal of this work was to study T cell responses in a cell line (EL4) and primary mouse T cells in three-dimensional (3D) bioprinted matrices of varied stiffness. Cell-laden hydrogels were 3D bioprinted from gelatin methacryloyl (GelMA) using a digital light processing (DLP)-based 3D bioprinter operated with visible light (405 nm). Mechanical characterization revealed that the hydrogels had pathophysiologically relevant stiffnesses for a lymph node-mimetic tissue construct. EL4, a mouse T cell lymphoma line, or primary mouse T cells were 3D bioprinted and activated using a combination of 10 ng/mL of phorbol myristate acetate (PMA) and 0.1 µM of ionomycin. Cellular responses revealed differences between 2D and 3D cultures and that the biomechanical properties of the 3D bioprinted hydrogel influence T cell activation. Cellular responses of the 2D and 3D cultures in a soft matrix (19.83 ± 2.36 kPa) were comparable; however, they differed in a stiff matrix (52.95 ± 1.36 kPa). The fraction of viable EL4 cells was 1.3-fold higher in the soft matrix than in the stiff matrix. Furthermore, primary mouse T cells activated with PMA and ionomycin showed 1.35-fold higher viable cells in the soft matrix than in the stiff matrix. T cells bioprinted in a soft matrix and a stiff matrix released 7.4-fold and 5.9-fold higher amounts of interleukin-2 (IL-2) than 2D cultured cells, respectively. Overall, the study demonstrates the changes in the response of T cells in 3D bioprinted scaffolds toward engineering an ex vivo lymphoid tissue-mimetic system that can faithfully recapitulate T cell activation and unravel pathophysiological characteristics of T cells in infectious biology, autoimmunity, and cancers.

Emotion and motion: Toward emotion recognition based on standing and walking.

Emotion recognition is key to interpersonal communication and to human-machine interaction. Body expression may contribute to emotion recognition, but most past studies focused on a few motions, limiting accurate recognition. Moreover, emotions in most previous research were acted out, resulting in non-natural motion, which is unapplicable in reality. We present an approach for emotion recognition based on body motion in naturalistic settings, examining authentic emotions, natural movement, and a broad collection of motion parameters. A lab experiment using 24 participants manipulated participants' emotions using pretested movies into five conditions: happiness, relaxation, fear, sadness, and emotionally-neutral. Emotion was manipulated within subjects, with fillers in between and a counterbalanced order. A motion capture system measured posture and motion during standing and walking; a force plate measured center of pressure location. Traditional statistics revealed nonsignificant effects of emotions on most motion parameters; only 7 of 229 parameters demonstrate significant effects. Most significant effects are in parameters representing postural control during standing, which is consistent with past studies. Yet, the few significant effects suggest that it is impossible to recognize emotions based on a single motion parameter. We therefore developed machine learning models to classify emotions using a collection of parameters, and examined six models: k-nearest neighbors, decision tree, logistic regression, and the support vector machine with radial base function and linear and polynomial functions. The decision tree using 25 parameters provided the highest average accuracy (45.8%), more than twice the random guess for five conditions, which advances past studies demonstrating comparable accuracies, due to our naturalistic setting. This research suggests that machine learning models are valuable for emotion recognition in reality and lays the foundation for further progress in emotion recognition models, informing the development of recognition devices (e.g., depth camera), to be used in home-setting human-machine interactions.

Subcutaneous entomophthoromycosis masquerading as soft tissue neoplasm in breastfeeding mother.

Subcutaneous entomophthoromycosis is an infection caused by saprophytic, ubiquitous and highly opportunistic fungal pathogens. Individuals with immune disorders are frequently susceptible to these infections. Entomophthoromycosis is a rare fungal infection that primarily affects children andmen, and is known to cause infection in healthy individuals. Diagnosis of the disease is by demonstration of fungal elements using special stains, and the disease responds well to oral antifungal agents. Long-term antifungal agents reduce the need for surgical intervention when the disease presents as a mass. We report a case of an immunocompetent nursing mother in her 20s who presented with a soft tissue mass in her right arm. It was diagnosed as subcutaneous entomophthoromycosis and treated with long-term fluconazole. The lesion showed a significant reduction in size following treatment for 2 months. Subcutaneous fungal infection presenting as a mass-forming lesion in extremities may mimic a neoplasm. Fungal infection should be ruled out in inflammatory cell-rich lesions seen on histopathological examination.

High throughput screening identifies auranofin and pentamidine as potent compounds that lower IFN-γ-induced Nitric Oxide and inflammatory responses in mice: DSS-induced colitis and Salmonella Typhimurium-induced sepsis.

Interferon-gamma (IFN-γ) is a type II interferon produced primarily by T cells and natural killer cells. IFN-γ induces the expression of inducible nitric oxide synthase (NOS2) to catalyze Nitric Oxide (NO) production in various immune and non-immune cells. Excessive IFN-γ-activated NO production is implicated in several inflammatory diseases, including peritonitis and inflammatory bowel diseases. In this study, we screened the LOPAC®1280 library in vitro on the H6 mouse hepatoma cell line to identify novel non-steroidal small molecule inhibitors of IFN-γ-induced NO production. Compounds with the highest inhibitory activity were validated, which led to identifying the lead compounds: pentamidine, azithromycin, rolipram, and auranofin. Auranofin was the most potent compound determined based on IC50 and goodness of fit analyses. Mechanistic investigations revealed that majority of the lead compounds suppress the IFN-γ-induced transcription of Nos2 without negatively affecting NO-independent processes, such as the IFN-γ-induced transcription of Irf1, Socs1 and MHC class 1 surface expression. However, all four compounds lower IFN-γ-induced reactive oxygen species amounts. In addition, auranofin significantly reduced IFN-γ-mediated NO and IL6 production in resident as well as thioglycolate-elicited peritoneal macrophages (PMs). Finally, in vivo testing of the lead compounds in the pre-clinical DSS-induced ulcerative colitis mice model revealed pentamidine and auranofin to be the most potent and protective lead compounds. Also, pentamidine and auranofin greatly increase the survival of mice in another inflammatory model: Salmonella Typhimurium-induced sepsis. Overall, this study identifies novel anti-inflammatory compounds targeting IFN-γ-induced NO-dependent processes to alleviate two distinct inflammatory models of disease.

Characterizing Salmonella Typhimurium-induced Septic Peritonitis in Mice.

Sepsis is a dysregulated host immune response to microbial invasion or tissue damage, leading to organ injury at a site distant from that of the infection or damage. Currently, the widely used mice models of sepsis include lipopolysaccharide (LPS)-induced endotoxemia, cecal ligation and puncture (CLP), and monobacterial infection model systems. This protocol describes a method to study the host responses during Salmonella Typhimurium infection-induced septic peritonitis in mice. S. Typhimurium, a Gram-negative intracellular pathogen, causes typhoid-like disease in mice. This protocol elaborates the culture preparation, induction of septic peritonitis in mice through intraperitoneal injection, and methods to study systemic host responses. Furthermore, the assessment of bacterial burden in different organs and the flow cytometric analysis of increased neutrophil numbers in the peritoneal lavage is presented. Salmonella Typhimurium-induced sepsis in mice leads to an increase in proinflammatory cytokines and rapid infiltration of neutrophils in the peritoneal cavity, leading to lower survival. Every step in this protocol has been optimized, resulting in high reproducibility of the pathogenesis of septic peritonitis. This model is useful for studying immunological responses during bacterial sepsis, the roles of different genes in disease progression, and the effects of drugs to attenuate sepsis.

Thermal processes of miniature thermomagnetic generators in resonant self-actuation mode.

This paper presents an investigation of the heat transfer processes in miniature thermomagnetic generators (TMGs) that are based on the recently developed concept of resonant self-actuation of a cantilever enabling efficient conversion of thermal into electrical energy. A lumped element model (LEM) is introduced to describe the dynamics of heat intake during mechanical contact between a thermomagnetic (TM) film and heat source, and of heat dissipation. The key parameters governing heat intake and dissipation are the heat transfer coefficient at contact and the thermal resistance R b of the bonding layer between TM film and cantilever, respectively. The effects of these parameters on the performance metrics are investigated for different heat source temperatures above the Curie temperature of the TM film. LEM simulations reveal critical values of κ and R b , above which stable performance of energy generation occurs characterized by large stroke and frequency resulting in large power.

Lumped Element Model for Thermomagnetic Generators Based on Magnetic SMA Films.

This paper presents a lumped element model (LEM) to describe the coupled dynamic properties of thermomagnetic generators (TMGs) based on magnetic shape memory alloy (MSMA) films. The TMG generators make use of the concept of resonant self-actuation of a freely movable cantilever, caused by a large abrupt temperature-dependent change of magnetization and rapid heat transfer inherent to the MSMA films. The LEM is validated for the case of a Ni-Mn-Ga film with Curie temperature TC of 375 K. For a heat source temperature of 443 K, the maximum power generated is 3.1 µW corresponding to a power density with respect to the active material's volume of 80 mW/cm3. Corresponding LEM simulations allow for a detailed study of the time-resolved temperature change of the MSMA film, the change of magnetic field at the position of the film and of the corresponding film magnetization. Resonant self-actuation is observed at 114 Hz, while rapid temperature changes of about 10 K occur within 1 ms during mechanical contact between heat source and Ni-Mn-Ga film. The LEM is used to estimate the effect of decreasing TC on the lower limit of heat source temperature in order to predict possible routes towards waste heat recovery near room temperature.

Notch Signalling: A Potential Therapeutic Pathway in Oral Squamous Cell Carcinoma.

Cancer, a set of diseases characterized by abnormal cell growth resulting from alteration in the expression pattern of diverse genes, is one of the prominent causes of mortality and morbidity worldwide. This modification of various genes leads to altered signalling cascades and changes in the molecular network. These changes eventually give rise to cellular dysfunction and then to systemic failure causing death. Of the several pathways that are aberrantly activated in cancer, Notch signalling pathway is a prominent one. Notch signalling pathway is a juxtracrine signalling pathway which activates the genes associated with cell proliferation, survival and angiogenesis. Notch signalling pathway components are seen to be upregulated in several types of cancer. Oral squamous cell carcinoma (OSCC) is a predominant category of oral cancer where aberrant activation of Notch signalling causes tumour progression and metastasis. In this review, we discuss the Notch signalling pathway, its components, forms and its role in the progression and metastasis of oral squamous cell carcinoma.

Artificial intelligence in colonoscopy.

Colorectal cancer remains a leading cause of morbidity and mortality in the United States. Advances in artificial intelligence (AI), specifically computer aided detection and computer-aided diagnosis offer promising methods of increasing adenoma detection rates with the goal of removing more pre-cancerous polyps. Conversely, these methods also may allow for smaller non-cancerous lesions to be diagnosed in vivo and left in place, decreasing the risks that come with unnecessary polypectomies. This review will provide an overview of current advances in the use of AI in colonoscopy to aid in polyp detection and characterization as well as areas of developing research.