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Heart failure (HF) is a complex clinical syndrome characterized by exercise intolerance. However, most diagnostic assessments are performed at rest, when many patients are asymptomatic. To better understand the underlying pathophysiology, examination during exercise is needed. Hydraulic force, a newly identified mechanism of diastolic filling, is proportional to the difference in short-axis areas
Atmospheric particulate matter (PM) contains different components that can elicit varying adverse health effects in humans and animals. Studies on PM toxicity and its underlying mechanisms in the middle ear are limited, and they generally use a PM standard. However, as PM composition varies temporally and geographically, it is crucial to identify the toxic PM constituents according to season and r
Cas9 nucleases are widely used for genome editing and engineering. Cas9 enzymes encoded by CRISPR-Cas defence systems of various prokaryotic organisms possess different properties such as target site preferences, size, and DNA cleavage efficiency. Here, we biochemically characterized CoCas9 from Capnocytophaga ochracea, a bacterium that inhabits the oral cavity of humans and contributes to plaque
Type II CRISPR-Cas9 RNA-guided nucleases are widely used for genome engineering. Type II-A SpCas9 protein from Streptococcus pyogenes is the most investigated and highly used enzyme of its class. Nevertheless, it has some drawbacks, including a relatively big size, imperfect specificity and restriction to DNA targets flanked by an NGG PAM sequence. Cas9 orthologs from other bacterial species may p
Cas12e proteins (formerly CasX) form a distinct subtype of Class II type V CRISPR-Cas effectors. Recently, it was shown that DpbCas12e from Deltaproteobacteria and PlmCas12e from Planctomycetes can introduce programmable double-stranded breaks in mammalian genomes. Thus, along with Cas9 and Cas12a Class II effectors, Cas12e could be harnessed for genome editing and engineering. The location of cle
Saturated fatty acids impose lipotoxic stress on pancreatic β cells, leading to β cell failure and diabetes. In this study, we investigate the critical role of organellar Ca2+ disturbance on defective autophagy and β cell lipotoxicity. Palmitate, a saturated fatty acid, induced perilysosomal Ca2+ elevation, sustained mTOR complex 1 (mTORC1) activation on the lysosomal membrane, suppression of the
CRISPR-Cas defense systems opened up the field of genome editing due to the ease with which effector Cas nucleases can be programmed with guide RNAs to access desirable genomic sites. Type II-A SpCas9 from Streptococcus pyogenes was the first Cas9 nuclease used for genome editing and it remains the most popular enzyme of its class. Nevertheless, SpCas9 has some drawbacks including a relatively lar
Protozoan parasites of the genus Leishmania cause leishmaniasis, a disease with variable clinical manifestations that affects millions of people worldwide. Infection with L. donovani can result in fatal visceral disease. In Panama, Colombia, and Costa Rica, L. panamensis is responsible for most of the reported cases of cutaneous and mucocutaneous leishmaniasis. Studying a large number of drug cand
The use of CRISPR-Cas bacterial adaptive immunity system components for targeted DNA changes has opened broad prospects for programmable genome editing of higher organisms. The most widely used gene editors are based on the Cas9 effectors of the type II CRISPR-Cas systems. In complex with guide RNAs, Cas9 proteins are able to directionally introduce double-stranded breaks into DNA regions that are
Chagas disease (CD), caused by Trypanosoma cruzi, is a neglected tropical illness affecting 6-8 million people in Latin America. Reaching scholarly consensus on the host response to T. cruzi infection remains a significant challenge, primarily due to substantial heterogeneity in outcomes driven by both the choice of animal model and the infecting parasite's discrete typing unit (DTU). This var
Fishes of the genus Pterois possess spines that provoke intense pain, which can last for weeks. Since the first toxicological description of their spine venom, a significant amount of research has been published regarding their biochemical characterization. This minireview presents research published from 1959 to 2024 on bioactive substances found in Pterois species. Pterois venom mainly con
Pathological processes often change the mechanical properties of cells. Increased rigidity could be a marker of cellular malfunction. Erythrocytes are a type of cell that deforms to squeeze through tiny capillaries; changes in their rigidity can dramatically affect their functionality. Furthermore, differences in the homeostatic elasticity of the cell can be used as a tool for diagnosis and even f
Soil biodiversity monitoring requires standardized and practical sample storage methods, particularly for large-scale surveys. Yet, the influence of the soil storage conditions on eDNA-based assessments of microbial and faunal communities remains a key concern. Here, we assessed whether air-drying of soils at room temperature alters microbial (prokaryotes, fungi, micro-eukaryotes) and faunal (nema
Clinical characteristics.Spinocerebellar ataxia type 4 (SCA4) is a progressive neurologic disease characterized by cerebellar involvement (gait ataxia, balance disturbances, eye movement abnormalities), brain stem involvement (dysarthria, dysphagia), sensory neuropathy, motor neuron involvement (muscle wasting and spasticity), autonomic dysfunction (especially orthostatic hypotension), and cogniti
An elderly, right-handed, male patient presented to the emergency department at a middle sized hospital with a few hours' history of mild confusion and a difficulty expressing himself verbally. Past medical history consisted of hypertension and cured hairy cell leukemia. CT scan of the brain showed a 5 cm infarction in the left occipital lobe, and a corresponding P2 occlusion was seen. The patient
In this paper we study how transforming regular reinforcement learning environments into goal-conditioned environments can let agents learn to solve tasks autonomously and reward-free. We show that an agent can learn to solve tasks by selecting its own goals in an environment-agnostic way, at training times comparable to externally guided reinforcement learning. Our method is independent of the un
Humans have a propensity for rhythmicity, notably expressed in the domains of lan-guage and music. It is expressed through the abilities to produce and perceive rhyth-mic signals, as well as entrainment, which is the ability to synchronise movements inrelation to external rhythmic stimuli (e.g., dancing). However, it remains unclear asto how, why or when this rhythmic propensity evolved.A comparat
