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Abstract Manganese oxide (α-MnO2) nanoparticles are highly recognised for their use in supercapacitor applications. This study demonstrates the successful synthesis of flower-like and nanorods hollandite α-MnO2 by a simple one-pot hydrothermal technique at various reaction times. The synthesised nanoparticles were characterised by various physicochemical and electrochemical characterisation techniques. The influence of the various reaction times on the structural and morphological properties was evaluated by X-ray diffraction (XRD) and scanning electron microscope. XRD patterns revealed that the synthesized MnO2 nanoparticles are tetragonal structures with crystallite sizes ranging from 13.69 to 20.37 nm estimated from the Williamson–Hall method. Moreover, the functional groups and surface area were examined by Fourier transform infrared spectroscopy and Bruner–Emmert–Teller, respectively. Furthermore, the compositional elements were studied by X-ray photoemission spectroscopy and energy-dispersive X-ray spectroscopy. Finally, the electrochemical performances were studied using cyclic voltammetry, galvanostatic charge–discharge and electrochemical impedance spectroscopy (EIS). The GCD characteristics revealed that the optimised α-MnO2 has a good capacitive behaviour, which predicts the potential application in energy storage. Electrochemical studies revealed that the 3 h-MnO2 sample exhibited a superior electrochemical behaviour and demonstrated a high specific capacitance of 132 F/g at a current density of 1A/g.

Abstract Background Duchenne muscular dystrophy (DMD) is a severe form of muscular dystrophy without an effective treatment, caused by mutations in the DMD gene, leading to the absence of dystrophin. DMD results in muscle weakness, loss of ambulation, and death at an early age. Metabolomics studies in mdx mice, the most used model for DMD, reveal changes in metabolites associated with muscle degeneration and aging. In DMD, the tongue muscles exhibit unique behavior, initially showing partial protection against inflammation but later experiencing fibrosis and loss of muscle fibers. Certain metabolites and proteins, like TNF-α and TGF-β, are potential biomarkers for dystrophic muscle characterization. Methods To investigate disease progression and aging, we utilized young (1 month old) and old (21–25 months old) mdx and wild-type tongue muscles. Metabolite changes were analyzed using 1H nuclear magnetic resonance, while TNF-α and TGF-β were assessed using Western blotting to examine inflammation and fibrosis. Morphometric analysis was conducted to assess the extent of myofiber damage between groups. Results The histological analysis of the mid-belly tongue showed no differences between groups. No differences were found between the concentrations of metabolites from wild-type or mdx whole tongues of the same age. The metabolites alanine, methionine, and 3-methylhistidine were higher, and taurine and glycerol were lower in young tongues in both wild type and mdx (p 0.05). Conclusions Surprisingly, histological, metabolite, and protein analysis reveal that the tongue of old mdx remains partially spared from the severe myonecrosis observed in other muscles. The metabolites alanine, methionine, 3-methylhistidine, taurine, and glycerol may be effective for specific assessments, although their use for disease progression monitoring should be cautious due to age-related changes in the tongue muscle. Acetic acid, phosphocreatine, isoleucine, succinate, creatine, TNF-α, and TGF-β do not vary with aging and remain constant in spared muscles, suggesting their potential as specific biomarkers for DMD progression independent of aging.

Abstract To evaluate the impact of elevator travel on intraocular pressure after vitreoretinal surgery with gas tamponade. Patients undergoing pars plana vitreoretinal surgery with and without gas insertion were recruited on post-operative day 1. All intraocular pressures were measured three times by Tono-Pen AVIA (Reichert, USA) on the fourth floor and, after rapid ascent in an elevator, on the 12th floor of the hospital. All patients were observed and asked for any symptoms of pain or nausea for at least 15 min. In this study, 54 patients were recruited. Twenty-seven patients underwent vitreoretinal procedures with gas insertion, while 27 patients without gas insertion acted as controls. The mean age of patients was 60.9 years. The mean changes in intraocular pressure of the patients with gas insertion (+ 1.39 mmHg) were greater than those without gas insertion (− 0.43 mmHg) and statistically significantly different (95% CI 1.17–2.48, P

Micro-dystrophin gene replacement therapies for Duchenne muscular dystrophy (DMD) are currently in clinical trials, but have not been thoroughly investigated for their efficacy on cardiomyopathy progression to heart failure. We previously validated Fiona/dystrophin-utrophin-deficient (dko) mice as a DMD cardiomyopathy model that progresses to reduced ejection fraction indicative of heart failure. Adeno-associated viral (AAV) vector delivery of an early generation micro-dystrophin prevented cardiac pathology and functional decline through 1 year of age in this new model. We now show that gene therapy using a micro-dystrophin optimized for skeletal muscle efficacy (AAV-μDys5), and which is currently in a clinical trial, is able to fully prevent cardiac pathology and cardiac strain abnormalities and maintain normal (>45%) ejection fraction through 18 months of age in Fiona/dko mice. Early treatment with AAV-μDys5 prevents inflammation and fibrosis in Fiona/dko hearts. Collagen in cardiac fibrotic scars becomes more tightly packed from 12 to 18 months in Fiona/dko mice, but the area of fibrosis containing tenascin C does not change. Increased tight collagen correlates with unexpected improvements in Fiona/dko whole-heart function that maintain impaired cardiac strain and strain rate. This study supports micro-dystrophin gene therapy as a promising intervention for preventing DMD cardiomyopathy progression.

Urban air mobility is expected to play a role in improving transportation of people and goods in growing urban areas while contributing to sustainable urban growth and zero-emissions future aviation. The research presented herein computationally investigated the performance of control laws for a generic Urban Air Taxi (UAT) subjected to empirically-developed urban airflow disturbances. This involved developing a representative flight dynamics model of a UAT in steady level cruise flight with an inner-loop autopilot. Active Disturbance Rejection Control (ADRC) and Proportional-Integral-Derivative (PID) control laws were implemented to investigate the controlled and uncontrolled acceleration responses and compare them to the acceleration limits in ISO 2631. Using a linear flight dynamics model, ADRC demonstrated improved performance over PID control with equal initial tuning effort. PID was able to reduce passenger accelerations to unharmful, though still uncomfortable, levels while ADRC further reduced the lateral accelerations to comfortable levels.

Music has played a central role in Indian religious experience for millennia. The origins of Indian music include the recitation of the sacred syllable OM and Sanskrit Mantras in ancient Vedic fire sacrifices. The notion of Sound Absolute, first in the Upanishads as Śabda-Brahman and later as Nāda-Brahman, formed the theological background for music, Sangīta, designed as a vehicle of liberation founded upon the worship of Hindu deities expressed in rāgas, or specific melodic formulas. Nearly all genres of music in India, classical or devotional, share this theoretical and practical understanding, extending to other Indic religions like Buddhism, Jainism, and Sikhism. What is less documented is how rāga music has been adopted by non-Indic communities in South Asia: Judaism (Bene Israel), Christianity (Catholic), and Islam (Chishti Sufi). After briefly outlining the relation between religion and the arts, the Indian aesthetics of Rasa, and the basic notions of sacred sound and music in Hinduism, this essay reveals the presence of rāga music, specifically the structure or melodic pattern of the morning rāga known as Bhairava, in compositions praising the divinity of each non-Indic tradition: Adonai, Jesus, and Allah. As similar tone patterns appear in the religious experiences of these communities, they reveal the phenomenon of “shared religious soundscapes” relevant to the comparative study of religion and music, or Musicology of Religion.

The finite element method (FEM) is widely used to simulate a variety of physics phenomena. Approaches that integrate FEM with neural networks (NNs) are typically leveraged as an alternative to conducting expensive FEM simulations in order to reduce the computational cost without significantly sacrificing accuracy. However, these methods can produce biased predictions that deviate from those obtained with FEM, since these hybrid FEM-NN approaches rely on approximations trained using physically relevant quantities. In this work, an uncertainty estimation framework is introduced that leverages ensembles of Bayesian neural networks to produce diverse sets of predictions using a hybrid FEM-NN approach that approximates internal forces on a deforming solid body. The uncertainty estimator developed herein reliably infers upper bounds of bias/variance in the predictions for a wide range of interpolation and extrapolation cases using a three-element FEM-NN model of a bar undergoing plastic deformation. This proposed framework offers a powerful tool for assessing the reliability of physics-based surrogate models by establishing uncertainty estimates for predictions spanning a wide range of possible load cases.

Inadequate diastolic closure of the aortic valve causes aortic regurgitation (AR). Diastolic regurgitation towards the left ventricle (LV) causes LV volume overload, resulting in eccentric LV remodelling. Transthoracic echocardiography (TTE) is the first line examination in the work-up of AR. TTE allows quantification of left ventricular end-diastolic diameter and volume and left ventricular ejection fraction, which are key elements in the clinical decision making regarding the timing of valve surgery. The qualitative echocardiographic features contributing to the AR severity grading are discussed: fluttering of the anterior mitral valve leaflet, density and shape of the continuous wave Doppler signal of the AR jet, colour flow imaging of the AR jet width, and holodiastolic flow reversal in the descending thoracic aorta and abdominal aorta. Volumetric assessment of the AR is performed by measuring the velocity time integral of the left ventricular outflow tract (LVOT) and transmitral valve (MV) plane, and diameters of LVOT and MV. We explain how the regurgitant fraction and effective regurgitant orifice area (EROA) can be calculated. Alternatively, the proximal isovelocity surface area can be used to determine the EROA. We overview the utility of pressure half time and vena contracta width to assess AR severity. Further, we discuss the role of transoesophageal echocardiography, echocardiography speckle tracking strain imaging, cardiac magnetic resonance imaging and computed tomography of the thoracic aorta in the work-up of AR. Finally, we overview the criteria for valve surgery in AR.

Aortic stenosis (AS) causes left ventricular outflow obstruction. Severe AS has major haemodynamic implications in critically ill patients, in whom increased cardiac output and oxygen delivery are often required. Transthoracic echocardiography (TTE) plays a key role in the AS severity grading. In this review, we will give an overview of how to use the simplified Bernoulli equation to convert the echo Doppler measured velocities (cm s-1) to AS peak and mean gra­dient (mm Hg) and how to calculate the aortic valve area (AVA), using the continuity equation, based on the principle of preservation of flow. TTE allows quantification of compensatory left ventricular (LV) hypertrophy, assessment of LV systolic function, and determination of LV diastolic function and LV loading. Subsequently, the obtained results from the TTE study need to be integrated to establish the AS severity grading. The pitfalls of echocardiographic AS severity assessment are explained, and how to deal with inconsistency between AVA and mean gradient. The contribution of transoesophageal echocardiography, low-dose dobutamine stress echo (in case of low-flow low-gradient AS), echocardiography strain imaging, cardiac magnetic resonance imaging, cardiac multidetector computed tomography and the relatively new concept of Flow Pressure Gradient Classification to the work-up for aortic stenosis is discussed. Finally, the treatment of AS is overviewed. Elective aortic valve replacement is indicated in patients with severe symptomatic AS. In the ICU, afterload reduction by vasodilator therapy and treatment of pulmonary and venous congestion by diuretics could be considered.

Clinical manifestations and courses of eye diseases in children are profoundly variable, from minor irritations, pain, infections, inflammations, ocular misalignment, refractive errors and visual impairment, to permanent blindness [...]

Doping ZnS nanoparticles with different metal and/or non-metal ions is one of the ways to improve their properties. That is because dopants introduce strain into the lattice of the ZnS nanoparticles. The influence of Ti on the ZnS nanoparticles was investigated on the structural properties, optical properties, and also electrical impedance spectroscopy (EIS). The presence of Ti in the crystal lattice of the ZnS introduced strain into the crystal structure, hence causing a lattice expansion and reducing the crystallite sizes of the ZnS nanoparticles. Ti doping was observed to increase the energy band gap of ZnS nanoparticles and also reduce the charge carrier recombination. Doping Ti into ZnS was observed to decrease the charge transfer resistance of ZnS nanoparticles with an increase in dopant concentration indicating an improved charge transfer mobility owing to the presence of strain in the crystal lattice.

Summary: Mutations in the gene encoding for dystrophin leads to structural and functional deterioration of cardiomyocytes and is a hallmark of cardiomyopathy in Duchenne muscular dystrophy (DMD) patients. Administration of recombinant adeno-associated viral vectors delivering microdystrophin or ribonucleotide reductase (RNR), under muscle-specific regulatory control, rescues both baseline and high workload-challenged hearts in an aged, DMD mouse model. However, only RNR treatments improved both systolic and diastolic function under those conditions. Cardiac-specific recombinant adeno-associated viral treatment of RNR holds therapeutic promise for improvement of cardiomyopathy in DMD patients. Key Words: cardiomyopathy, diastolic dysfunction, dystrophin, ribonucleotide reductase, recombinant adeno-associated virus vectors

In heart failure with reduced ejection fraction (HFrEF), cardiogenic edema develops from impaired cardiac function, pathological remodeling, chronic inflammation, endothelial dysfunction, neurohormonal activation, and altered nitric oxide-related pathways. Pre-clinical HFrEF studies have shown that treatment with sodium–glucose cotransporter-2 inhibitors (SGLT-2i) stimulates natriuretic and osmotic/diuretic effects, improves overall cardiac function, attenuates maladaptive cardiac remodeling, and reduces chronic inflammation, oxidative stress, and endothelial dysfunction. Here, we review the mechanisms and effects of SGLT-2i therapy on cardiogenic edema in various models of HFrEF. Overall, the data presented suggest a high translational importance of these studies, and pre-clinical studies show that SGLT-2i therapy has a marked effect on suppressing the progression of HFrEF through multiple mechanisms, including those that affect the development of cardiogenic edema.

Symptomatic heart failure with reduced ejection fraction (HFrEF) is characterized by edema and chronic pathological activation of the classical renin–angiotensin–aldosterone system (RAAS). The soluble (pro)renin receptor (s(P)RR) is released into circulation by proteolytic cleavage of tissue expressed (P)RR and is a candidate biomarker of RAAS activation. However, previous studies linked elevated levels of s(P)RR in patients with HFrEF to renal dysfunction. Utilizing prospectively enrolled patients with comparable rEF, we show that increased plasma levels of s(P)RR are associated with symptomatic HF (characterized by edema), independent of chronic renal dysfunction. We also found that s(P)RR levels were positively correlated with patient plasma renin activity (PRA). Normotensive mice with dilated cardiomyopathy (DCM) and HFrEF, without renal dysfunction, showed plasma s(P)RR and PRA patterns similar to human HFrEF patients. Plasma s(P)RR levels positively correlated with PRA and systemic edema, but not with EF, resembling findings in patients with HFrEF without chronic kidney dysfunction. In female DCM mice with elevated PRA levels and plasma s(P)RR levels, a randomized, blinded trial comparing the direct renin inhibitor, aliskiren vs. vehicle control, showed that direct renin inhibition normalized PRA, lowered s(P)RR, and prevented symptomatic HFrEF. Considered in light of previous findings, these data suggest that, in HFrEF, in the absence of renal dysfunction, elevation of plasma s(P)RR levels is caused by increased PRA and associated with the development of systemic edema.

Gene replacement for Duchenne muscular dystrophy (DMD) with micro-dystrophins has entered clinical trials, but efficacy in preventing heart failure is unknown. Although most patients with DMD die from heart failure, cardiomyopathy is undetectable until the teens, so efficacy from trials in young boys will be unknown for a decade. Available DMD animal models were sufficient to demonstrate micro-dystrophin efficacy on earlier onset skeletal muscle pathology underlying loss of ambulation and respiratory insufficiency in patients. However, no mouse models progressed into heart failure, and dog models showed highly variable progression insufficient to evaluate efficacy of micro-dystrophin or other therapies on DMD heart failure. To overcome this barrier, we have generated the first DMD mouse model to our knowledge that reproducibly progresses into heart failure. This model shows cardiac inflammation and fibrosis occur prior to reduced function. Fibrosis does not continue to accumulate, but inflammation persists after function declines. We used this model to test micro-dystrophin gene therapy efficacy on heart failure prevention for the first time. Micro-dystrophin prevented declines in cardiac function and prohibited onset of inflammation and fibrosis. This model will allow identification of committed pathogenic steps to heart failure and testing of genetic and nongenetic therapies to optimize cardiac care for patients with DMD.

Alpha2-antiplasmin (α2AP), the fast-reacting, serine protease inhibitor (serpin) of plasmin, was originally thought to play a key role in protection against uncontrolled, plasmin-mediated proteolysis of coagulation factors and other molecules. However, studies of humans and mice with genetic deficiency of α2AP have expanded our understanding of this serpin, particularly in disease states. Epidemiology studies have shown an association between high α2AP levels and increased risk or poor outcome in cardiovascular diseases. Mechanistic studies in disease models indicate that α2AP stops the body's own fibrinolytic system from dissolving pathologic thrombi that cause venous thrombosis, pulmonary embolism, arterial thrombosis, and ischemic stroke. In addition, α2AP fosters the development of microvascular thrombosis and enhances matrix metalloproteinase-9 expression. Through these mechanisms and others, α2AP contributes to brain injury, hemorrhage and swelling in experimental ischemic stroke. Recent studies also show that α2AP is required for the development of stasis thrombosis by inhibiting the early activation of effective fibrinolysis. In this review, we will discuss the key role played by α2AP in controlling thrombosis and fibrinolysis and, we will consider its potential value as a therapeutic target in cardiovascular diseases and ischemic stroke.

Pathological sodium-water retention or edema/congestion is a primary cause of heart failure (HF) decompensation, clinical symptoms, hospitalization, reduced quality of life, and premature mortality. Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) based therapies reduce hospitalization due to HF, improve functional status, quality, and duration of life in patients with HF with reduced ejection fraction (HFrEF) independently of their glycemic status. The pathophysiologic mechanisms and molecular pathways responsible for the benefits of SGLT-2i in HFrEF remain inconclusive, but SGLT-2i may help HFrEF by normalizing salt-water homeostasis to prevent clinical edema/congestion. In HFrEF, edema and congestion are related to compromised cardiac function. Edema and congestion are further aggravated by renal and pulmonary abnormalities. Treatment of HFrEF patients with SGLT-2i enhances natriuresis/diuresis, improves cardiac function, and reduces natriuretic peptide plasma levels. In this review, we summarize current clinical research studies related to outcomes of SGLT-2i treatment in HFrEF with a specific focus on their contribution to relieving or preventing edema and congestion, slowing HF progression, and decreasing the rate of rehospitalization and cardiovascular mortality.

Gene therapy approaches for DMD using recombinant adeno-associated viral (rAAV) vectors to deliver miniaturized (or micro) dystrophin genes to striated muscles have shown significant progress. However, concerns remain about the potential for immune responses against dystrophin in some patients. Utrophin, a developmental paralogue of dystrophin, may provide a viable treatment option. Here we examine the functional capacity of an rAAV-mediated microutrophin (μUtrn) therapy in the mdx4cv mouse model of DMD. We found that rAAV-μUtrn led to improvement in dystrophic histopathology & mostly restored the architecture of the neuromuscular and myotendinous junctions. Physiological studies of tibialis anterior muscles indicated peak force maintenance, with partial improvement of specific force. A fundamental question for μUtrn therapeutics is not only can it replace critical functions of dystrophin, but whether full-length utrophin impacts the therapeutic efficacy of the smaller, highly expressed μUtrn. As such, we found that μUtrn significantly reduced the spacing of the costameric lattice relative to full-length utrophin. Further, immunostaining suggested the improvement in dystrophic pathophysiology was largely influenced by favored correction of fast 2b fibers. However, unlike μUtrn, μdystrophin (μDys) expression did not show this fiber type preference. Interestingly, μUtrn was better able to protect 2a and 2d fibers in mdx:utrn-/- mice than in mdx4cv mice where the endogenous full-length utrophin was most prevalent. Altogether, these data are consistent with the role of steric hindrance between full-length utrophin & μUtrn within the sarcolemma. Understanding the stoichiometry of this effect may be important for predicting clinical efficacy.

The washing of layered double hydroxides (LDH) material is mostly purposed to discard the unreacted products after the reaction has been completed. However, this study demonstrated that the washing stage can also be targeted to optimise the electrochemical performance of LDH by using an appropriate solvent. Solvents, namely, ethanol, acetone, and an ethanol–acetone solution (2:1) were used for the washing of LDH and the impacts thereof on the structural, physical, chemical, morphological, and electrochemical properties were investigated. Using Williamson–Hall analysis, we observed modifications on the crystalline domain. The specific surface area and pore parameters for all the samples were also differently affected. The Fourier transform infrared (FTIR) measurements displayed evident changes in the basic sites. The electrochemical performances of samples were analysed. The sample washed with the ethanol–acetone solution exhibited a specific capacitance of 1807.26 Fg−1 at 10 mVs−1, which is higher than that of other samples as well as low internal resistance compared to its counterpart. This demonstrates that the use of an appropriate solvent during the washing stage of LDH affects the electrochemical properties.

The fascinating features of 2D nanomaterials for various applications have prompted increasing research into single and few-layer metal dichalcogenides nanosheets using improved nanofabrication and characterization techniques. MoS2 has recently been intensively examined among layered metal dichalcogenides and other diverse transition metal-based materials, that have previously been studied in various applications. In this research, we report mixed-phase Mn-doped MoS2 nanoflowers for supercapacitor performance studies. The confirmation of the successfully prepared Mn-doped MoS2 nanoflowers was characterized by XRD, SEM-EDS, RAMAN, and BET research techniques. The mixed-phase of the as-synthesized electrode material was confirmed by the structural changes observed in the XRD and RAMAN studies. The surface area from the BET measurement was calculated to be 46.0628 m2/g, and the adsorption average pore size of the electrode material was 11.26607 nm. The electrochemical performance of the Mn-doped MoS2 electrode material showed a pseudo-capacitive behavior, with a specific capacitance of 70.37 Fg−1, and with a corresponding energy density of 3.14 Whkg−1 and a power density of 4346.35 Wkg−1. The performance of this metal-doped MoS2-based supercapacitor device can be attributed to its mixed phase, which requires further optimization in future works.

This research work describes the synthesis of ZnO nanostructures doped with Ho3+ ions using a conventional sol–gel synthesis method. The nanostructured produced exhibited a wurtzite hexagonal structure in both ZnO and ZnO:Ho3+ (0.25, 0.5, 0.75 mol%) samples. The change in morphology with addition of Ho3+ dopants was observed, which was assigned to Ostwald ripening effect occurring during the nanoparticles’ growth. The photoluminescence emission properties of the doped samples revealed that Ho3+ was emitting through its electronic transitions. Moreover, reduced surface defects were observed in the Holmium doped samples whose analysis was undertaken using an X-ray Photoelectron Spectroscopy (XPS) technique. Finally, enhanced room temperature ferromagnetism (RT-FM) for Ho3+-doped ZnO (0.5 mol%) samples with a peak-to-peak line width of 452 G was detected and found to be highly correlated to the UV–VIS transmittance results.

As a subfield in the study of religion and music, the theology of music is generally understood in Western terms. Yet to fully encompass the rich heritage of music in world religions, the theology of music must welcome non-Western traditions. After introducing ancient Greek and Biblical narratives regarding the origins of music, including metaphysical concepts, narratives of music as Divine Gift, musical angels, and the sacred origin of the notes and scales, this article explores music in Hindu religion through the lens of theology. We find that Indian music is also ‘given by the gods’ (i.e., Brahmā, Vishnu, and Śiva), associated with ‘musical angels,’ and originally formed from metaphysical principles (i.e., OM and the concept of Nāda-Brahman). What is demonstrated here, representing a long continuity, is how these same ideas are viable in the performance of Indian classical music today. Citing examples of compositions of Dhrupad and Khayal from the standard repertoire, this article reveals how modern-day classical songs contain references to sacred sound principles and the divine origins of music, both in their lyrics and in the unfoldment of musical notes (Svaras) and melodic patterns (Rāgas).

Abstract Background Beak and feather disease virus (BFDV) is an important disease causing agent affecting psittacines. BFDV is highly infectious and can present as acute, chronic or subclinical disease. The virus causes immunodeficiency and is often associated with secondary infections. No commercial vaccine is available and yields of recombinant BFDV capsid protein (CP) expressed in insect cells and bacteria are yet to be seen as commercially viable, although both systems produced BFDV CP that could successfully assemble into virus-like particles (VLPs). Plants as expression systems are increasingly becoming favourable for the production of region-specific and niche market products. The aim of this study was to investigate the formation and potential for purification of BFDV VLPs in Nicotiana benthamiana. Methods The BFDV CP was transiently expressed in N. benthamiana using an Agrobacterium-mediated system and plant expression vectors that included a bean yellow dwarf virus (BeYDV)-based replicating DNA vector. Plant-produced BFDV CP was detected using immunoblotting. VLPs were purified using sucrose cushion and CsCl density gradient centrifugation and visualised using transmission electron microscopy. Results In this study we demonstrate that the BFDV CP can be successfully expressed in N. benthamiana, albeit at relatively low yield. Using a purification strategy based on centrifugation we demonstrated that the expressed CP can self-assemble into VLPs that can be detected using electron microscopy. These plant-produced BFDV VLPs resemble those produced in established recombinant expression systems and infectious virions. It is possible that the VLPs are spontaneously incorporating amplicon DNA produced from the replicating BeYDV plant vector. Conclusions This is the first report of plant-made full-length BFDV CP assembling into VLPs. The putative pseudovirions could be used to further the efficacy of vaccines against BFDV.

CRISPR/Cas9-mediated gene editing is an emerging strategy to treat Duchenne muscular dystrophy. Here the authors develop multiple CRISPR/Cas9-based approaches to correct different dystrophin gene mutations, and show significant restoration of dystrophin expression in skeletal and cardiac muscle in mice.

Despite recent advances, chronic heart failure remains a significant and growing unmet medical need, reaching epidemic proportions carrying substantial morbidity, mortality, and costs. A safe and convenient therapeutic agent that produces sustained inotropic effects could ameliorate symptoms and improve functional capacity and quality of life. The authors discovered that small amounts of 2-deoxy-ATP (dATP) activate cardiac myosin leading to enhanced contractility in normal and failing heart muscle. Cardiac myosin activation triggers faster myosin cross-bridge cycling with greater force generation during each contraction. They describe the rationale and results of a translational medicine effort to increase dATP levels using a gene therapy strategy that up-regulates ribonucleotide reductase, the rate-limiting enzyme for dATP synthesis, selectively in cardiomyocytes. In small and large animal models of heart failure, a single dose of this gene therapy has led to sustained inotropic effects with no toxicity or safety concerns identified to date. Further animal studies are being conducted with the goal of testing this agent in patients with heart failure.