A new lysine biosynthetic enzyme from a bacterial endosymbiont shaped by genetic drift and genome reduction.

The effect of population bottlenecks and genome reduction on enzyme function is poorly understood. Candidatus Liberibacter solanacearum is a bacterium with a reduced genome that is transmitted vertically to the egg of an infected psyllid-a population bottleneck that imposes genetic drift and is predicted to affect protein structure and function. Here, we define the function of Ca.

Predicting Long-Time-Scale Kinetics under Variable Experimental Conditions with Kinetica.jl.

Predicting the degradation processes of molecules over long time scales is a key aspect of industrial materials design. However, it is made computationally challenging by the need to construct large networks of chemical reactions that are relevant to the experimental conditions that kinetic models must mirror, with every reaction requiring accurate kinetic data. Here, we showcase , a new software package for constructing large-scale chemical reaction networks in a fully automated fashion by exploring chemical reaction space with a kinetics-driven algorithm; coupled to efficient machine-learning models of activation energies for sampled elementary reactions, we show how this approach readily enables generation and kinetic characterization of networks containing ∼10 chemical species and ≃10-10 reactions.

High-throughput property-driven generative design of functional organic molecules.

The design of molecules and materials with tailored properties is challenging, as candidate molecules must satisfy multiple competing requirements that are often difficult to measure or compute. While molecular structures produced through generative deep learning will satisfy these patterns, they often only possess specific target properties by chance and not by design, which makes molecular discovery via this route inefficient. In this work, we predict molecules with (Pareto-)optimal properties by combining a generative deep learning model that predicts three-dimensional conformations of molecules with a supervised deep learning model that takes these as inputs and predicts their electronic structure.

On the utility of microfluidic systems to study protein interactions: advantages, challenges, and applications.

Within the complex milieu of a cell, which comprises a large number of different biomolecules, interactions are critical for function. In this post-reductionist era of biochemical research, the 'holy grail' for studying biomolecular interactions is to be able to characterize them in native environments. While there are a limited number of in situ experimental techniques currently available, there is a continuing need to develop new methods for the analysis of biomolecular complexes that can cope with the additional complexities introduced by native-like solutions.

Diagnostic accuracy and performance of artificial intelligence in measuring left atrial volumes and function on multiphasic CT in patients with atrial fibrillation.

Objectives: To evaluate the effectiveness of a novel artificial intelligence (AI) algorithm for fully automated measurement of left atrial (LA) volumes and function using cardiac CT in patients with atrial fibrillation.

Methods: We included 79 patients (mean age 63 ± 12 years; 35 with atrial fibrillation (AF) and 44 controls) between 2017 and 2020 in this retrospective study. Images were analyzed by a trained AI algorithm and an expert radiologist.

Site-specific modifications to AAV8 capsid yields enhanced brain transduction in the neonatal MPS IIIB mouse.

Mucopolysaccharidosis type IIIB (MPS IIIB) is an autosomal recessive lysosomal disease caused by defective production of the enzyme α-N-acetylglucosaminidase. It is characterized by severe and complex central nervous system degeneration. Effective therapies will likely target early onset disease and overcome the blood-brain barrier.

The First Purification of Functional Proteins from the Unculturable, Genome-Reduced, Bottlenecked α-Proteobacterium 's Liberibacter solanacearum'.

Liberibacter solanacearum' is an unculturable α-proteobacterium that is the causal agent of zebra chip disease of potato-a major problem in potato-growing areas, because it affects growth and yield. Developing effective treatments for ' L. solanacearum' has been hampered by the difficulty in functionally characterizing the proteins of this organism, largely because they are not easily expressed and purified in standard expression systems.

Assessment of free fatty acids and cholesteryl esters delivered in liposomes as novel class of antibiotic.

Background: Healthcare associated infections (HAI) with multidrug-resistant (MDR) bacteria continue to be a global threat, highlighting an urgent need for novel antibiotics. In this study, we assessed the potential of free fatty acids and cholesteryl esters that form part of the innate host defense as novel antibacterial agents for use against MDR bacteria.

Methods: Liposomes of six different phospholipid mixtures were employed as carrier for six different fatty acids and four different cholesteryl esters.

Preferred transduction with AAV8 and AAV9 via thalamic administration in the MPS IIIB model: A comparison of four rAAV serotypes.

Sanfilippo syndrome type B (MPS IIIB) is a lysosomal storage disease caused by a deficiency of N-acetyl-glucosaminidase (NAGLU) activity. Since early therapeutic intervention is likely to yield the most efficacious results, we sought to determine the possible therapeutic utility of rAAV in early gene therapy based interventions. Currently, the application of recombinant adeno-associated virus (AAV) vectors is one of the most widely used gene transfer systems, and represents a promising approach in the treatment of MPS IIIB.

Mucopolysaccharidosis IIIB confers enhanced neonatal intracranial transduction by AAV8 but not by 5, 9 or rh10.

Sanfilippo syndrome type B (mucopolysaccharidosis IIIB, MPS IIIB) is a lysosomal storage disease resulting from deficiency of N-acetyl-glucosaminidase (NAGLU) activity. To determine the possible therapeutic utility of recombinant adeno-associated virus (rAAV) in early gene therapy-based interventions, we performed a comprehensive assessment of transduction and biodistribution profiles of four central nervous system (CNS) administered rAAV serotypes, -5, -8, -9 and -rh10. To simulate optimal earliest treatment of the disease, each rAAV serotype was injected into the CNS of neonatal MPS IIIB and control animals.

The renin-angiotensin system and prevention of age-related functional decline: where are we now?

Declining physical function is a major health problem for older adults as it is associated with multiple comorbidities and mortality. Exercise has been shown to improve physical function, though response to exercise is variable. Conversely, drugs targeting the renin-angiotensin system (RAS) pathway, including angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs), are also reported to improve physical function.

Mucopolysaccharidosis III (Sanfilippo Syndrome)- disease presentation and experimental therapies.

Sanfilippo Syndrome or Mucopolysaccharidosis Ill (MPS Ill) is a group of lysosomal storage diseases resulting from a deficiency of one of four lysosomal enzymes: Type A - heparan N-sulfatase (SGSH), Type B - a-N-acetylglucosaminidase (NAGLU), Type C - acetyl CoA a-glucosaminide acetyltransferase (HGSNAT) and Type D - N-acetylglucosamine-6-sulfatase (GNS). Each of these enzymes is necessary for degradation of heparan sulfate. Deficiency of any of these enzymes manifests as a neurodegenerative disorder with accompanying somatic manifestations.

Pemphigus vulgaris: the manifestations and long-term management of 55 patients with oral lesions.

Perhaps surprisingly, the manifestations and management of patients with pemphigus vulgaris and oral lesions have been detailed only infrequently. The present study has examined the clinical features, diagnosis and management of a cohort of 55 patients, including three adolescents, with pemphigus vulgaris predominantly affecting the oral mucosa. There was about a 6-month delay from the onset of symptoms until presentation for diagnosis, longer in men than in women.

Systemic corticosteroids in the phenytoin hypersensitivity syndrome.

A patient is described with the characteristic features of phenytoin hypersensitivity syndrome (PHS) including fever, erythroderma, tibial and facial oedema, pinhead-sized facial pustules and abnormal liver function tests. The use of systemic corticosteroids in this condition is not established. We report the resolution of all the features of PHS with systemic corticosteroids and recurrence on withdrawal, and further remission on reinstitution of systemic corticosteroids.

Bacillary angiomatosis with cutaneous and oral lesions in an HIV-infected patient from the U.K.

We describe an HIV positive patient with histologically confirmed cutaneous and oral lesions of bacillary angiomatosis, an unusual clinical presentation. As far as we are aware, this is the first reported case of cutaneous bacillary angiomatosis in the U.K.

Acrodermatitis chronica atrophicans: a case report and review of the literature.

We report a 55-year-old woman with acrodermatitis chronica atrophicans (ACA) and a peripheral sensory neuropathy. ACA is an uncommon late cutaneous manifestation of Lyme disease, which follows disseminated Borrelia burgdorferi infection. This is the second published case from the U.