De novo and inherited dominant variants in U4 and U6 snRNAs cause retinitis pigmentosa.

The U4 small nuclear RNA (snRNA) forms a duplex with the U6 snRNA and, together with U5 and ∼30 proteins, is part of the U4/U6.U5 tri-snRNP complex, located at the core of the major spliceosome. Recently, recurrent variants in the U4 RNA, transcribed from the gene, and in at least two other genes were discovered to cause neurodevelopmental disorder.

Personalized μ-transcranial alternating current stimulation improves online brain-computer interface control.

Objective: A motor imagery (MI)-based brain-computer interface (BCI) enables users to engage with external environments by capturing and decoding electroencephalography (EEG) signals associated with the imagined movement of specific limbs. Despite significant advancements in BCI technologies over the past 40 years, a notable challenge remains: many users lack BCI proficiency, unable to produce sufficiently distinct and reliable MI brain patterns, hence leading to low classification rates in their BCIs. The objective of this study is to enhance the online performance of MI-BCIs in a personalized, biomarker-driven approach using transcranial alternating current stimulation (tACS).

Personalized μ-transcranial alternating current stimulation improves online brain-computer interface control.

Objective: A motor imagery (MI)-based brain-computer interface (BCI) enables users to engage with external environments by capturing and decoding electroencephalography (EEG) signals associated with the imagined movement of specific limbs. Despite significant advancements in BCI technologies over the past 40 years, a notable challenge remains: many users lack BCI proficiency, unable to produce sufficiently distinct and reliable MI brain patterns, hence leading to low classification rates in their BCIs. The objective of this study is to enhance the online performance of MI-BCIs in a personalized, biomarker-driven approach using transcranial alternating current stimulation (tACS).

Preclinical evaluation of the efficacy and safety of AAV8-TNAP-D10 in Alpl-/- and AlplPrx1/Prx1 mouse models for the treatment of early and late-onset hypophosphatasia.

We previously documented successful resolution of skeletal and dental disease in the infantile and late-onset murine models of hypophosphatasia (HPP), with a single injection of an adeno-associated serotype 8 vector encoding mineral-targeted TNAP (AAV8-TNAP-D10). Here, we conducted dosing studies in both HPP mouse models. A single escalating dose from 4x108 up to 4x1010 (vg/b) was intramuscularly injected into 4-day-old Alpl-/- mice (an infantile HPP model) and a single dose from 4x106 up to 4x109 (vg/b) was administered to 8-week-old AlplPrx1/Prx1 mice (a late-onset HPP model).

Personalized whole-brain activity patterns predict human corticospinal tract activation in real-time.

Background: Transcranial magnetic stimulation (TMS) interventions could feasibly treat stroke-related motor impairments, but their effects are highly variable. Brain state-dependent TMS approaches are a promising solution to this problem, but inter-individual variation in lesion location and oscillatory dynamics can make translating them to the poststroke brain challenging. Personalized brain state-dependent approaches specifically designed to address these challenges are needed.

Variants in the AGBL5 gene are responsible for autosomal recessive Retinitis pigmentosa with hearing loss.

The AGBL5 gene encodes for the Cytoplasmic Carboxypeptidase 5 (CCP5), an α-tubulin deglutamylase that cleaves the γ-carboxyl-linked branching point of glutamylated tubulin. To date, pathogenic variants in AGBL5 have been associated only with isolated retinitis pigmentosa (RP). Hearing loss has not been reported in AGBL5-caused retinal disease.

Novel AIRTrode-based wearable electrode supports long-term, online brain-computer interface operations.

Non-invasive electroencephalograms (EEG)-based brain-computer interfaces (BCIs) play a crucial role in a diverse range of applications, including motor rehabilitation, assistive and communication technologies, holding potential promise to benefit users across various clinical spectrums. Effective integration of these applications into daily life requires systems that provide stable and reliable BCI control for extended periods. Our prior research introduced the AIRTrode, a self-adhesive (A), injectable (I), and room-temperature (RT) spontaneously-crosslinked hydrogel electrode (AIRTrode).

Exploring non-coding variants and evaluation of antisense oligonucleotides for splicing redirection in Usher syndrome.

Exploring non-coding regions is increasingly gaining importance in the diagnosis of inherited retinal dystrophies. Deep-intronic variants causing aberrant splicing have been identified, prompting the development of antisense oligonucleotides (ASOs) to modulate splicing. We performed a screening of five previously described deep-intronic variants among monoallelic patients with Usher syndrome (USH) or isolated retinitis pigmentosa.

Personalized whole-brain activity patterns predict human corticospinal tract activation in real-time.

Background: Transcranial magnetic stimulation (TMS) interventions could feasibly treat stroke-related motor impairments, but their effects are highly variable. Brain state-dependent TMS approaches are a promising solution to this problem, but inter-individual variation in lesion location and oscillatory dynamics can make translating them to the poststroke brain challenging. Personalized brain state-dependent approaches specifically designed to address these challenges are therefore needed.

Hebbian plasticity induced by temporally coincident BCI enhances post-stroke motor recovery.

Functional electrical stimulation (FES) can support functional restoration of a paretic limb post-stroke. Hebbian plasticity depends on temporally coinciding pre- and post-synaptic activity. A tight temporal relationship between motor cortical (MC) activity associated with attempted movement and FES-generated visuo-proprioceptive feedback is hypothesized to enhance motor recovery.

Inherited phosphate and pyrophosphate disorders: New insights and novel therapies changing the oral health landscape.

Background: Mineral metabolism is critical for proper development of hard tissues of the skeleton and dentition. The dentoalveolar complex includes the following 4 mineralized tissues: enamel, dentin, cementum, and alveolar bone. Developmental processes of these tissues are affected by inherited disorders that disrupt phosphate and pyrophosphate homeostasis, although manifestations are distinct from those in the skeleton.

STUB1 Mutations as Possible Genetic Modifiers in Spinocerebellar Ataxia Type 8.

Background: Spinocerebellar ataxia type 8 (SCA8) is a dominantly inherited expansion disorder with highly variable penetrance. ATXN8OS/ATXN8 expanded alleles have been identified in association with other types of hereditary ataxias, pointing to a possible genetic synergism.

Objectives: We aimed to further investigate the molecular background of patients with SCA8 diagnosis.

Zinc-alkaline phosphatase at sites of aortic calcification.

Zinc (Zn) is a normal trace element in mineralizing tissues, but it is unclear whether it is primarily bound to the mineral phase or to organic molecules involved in the mineralization process, or both. Tissue-nonspecific alkaline phosphatase (TNAP) is a Zn metalloenzyme with two Zn ions bound to the M1 and M2 catalytic sites that functions to control the phosphate/pyrophosphate ratio during biomineralization. Here, we studied aortas from Tagln-Cre ; Hprt TNAP overexpressor (TNAP-OE) mice that develop severe calcification.

Evaluating the Feasibility of Visual Imagery for an EEG-Based Brain-Computer Interface.

Visual imagery, or the mental simulation of visual information from memory, could serve as an effective control paradigm for a brain-computer interface (BCI) due to its ability to directly convey the user's intention with many natural ways of envisioning an intended action. However, multiple initial investigations into using visual imagery as a BCI control strategies have been unable to fully evaluate the capabilities of true spontaneous visual mental imagery. One major limitation in these prior works is that the target image is typically displayed immediately preceding the imagery period.

Combining detrended cross-correlation analysis with Riemannian geometry-based classification for improved brain-computer interface performance.

Riemannian geometry-based classification (RGBC) gained popularity in the field of brain-computer interfaces (BCIs) lately, due to its ability to deal with non-stationarities arising in electroencephalography (EEG) data. Domain adaptation, however, is most often performed on sample covariance matrices (SCMs) obtained from EEG data, and thus might not fully account for components affecting covariance estimation itself, such as regional trends. Detrended cross-correlation analysis (DCCA) can be utilized to estimate the covariance structure of such signals, yet it is computationally expensive in its original form.

Glycoproteomic profile of human tissue-nonspecific alkaline phosphatase expressed in osteoblasts.

Tissue-nonspecific alkaline phosphatase (TNALP) is a glycoprotein expressed by osteoblasts that promotes bone mineralization. TNALP catalyzes the hydrolysis of the mineralization inhibitor inorganic pyrophosphate and ATP to provide inorganic phosphate, thus controlling the inorganic pyrophosphate/inorganic phosphate ratio to enable the growth of hydroxyapatite crystals. N-linked glycosylation of TNALP is essential for protein stability and enzymatic activity and is responsible for the presence of different bone isoforms of TNALP associated with functional and clinical differences.

Deciphering complexity: variants linked to an atypical retinal dystrophy phenotype.

exemplifies the remarkable clinical and genetic heterogeneity observed in inherited retinal dystrophies. Our research describes the clinical and molecular characteristics of a patient manifesting an atypical retinal dystrophy pattern, marked by the identification of both a previously unreported and a rarely encountered variant. Whole-exome sequencing was performed to identify potential causative variants.

Transfer learning promotes acquisition of individual BCI skills.

Subject training is crucial for acquiring brain-computer interface (BCI) control. Typically, this requires collecting user-specific calibration data due to high inter-subject neural variability that limits the usability of generic decoders. However, calibration is cumbersome and may produce inadequate data for building decoders, especially with naïve subjects.

Differential effects of the lipidic and ionic microenvironment on NPP1's phosphohydrolase and phosphodiesterase activities.

Ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) is an enzyme present in matrix vesicles (MV). NPP1 participates on the regulation of bone formation by producing pyrophosphate (PP) from adenosine triphosphate (ATP). Here, we have used liposomes bearing dipalmitoylphosphatidylcholine (DPPC), sphingomyelin (SM), and cholesterol (Chol) harboring NPP1 to mimic the composition of MV lipid rafts to investigate ionic and lipidic influence on NPP1 activity and mineral propagation.

Do Media Extracellular Vesicles and Extracellular Vesicles Bound to the Extracellular Matrix Represent Distinct Types of Vesicles?

Mineralization-competent cells, including hypertrophic chondrocytes, mature osteoblasts, and osteogenic-differentiated smooth muscle cells secrete media extracellular vesicles (media vesicles) and extracellular vesicles bound to the extracellular matrix (matrix vesicles). Media vesicles are purified directly from the extracellular medium. On the other hand, matrix vesicles are purified after discarding the extracellular medium and subjecting the cells embedded in the extracellular matrix or bone or cartilage tissues to an enzymatic treatment.

Inferring individual evaluation criteria for reaching trajectories with obstacle avoidance from EEG signals.

During reaching actions, the human central nerve system (CNS) generates the trajectories that optimize effort and time. When there is an obstacle in the path, we make sure that our arm passes the obstacle with a sufficient margin. This comfort margin varies between individuals.

Annexin A5 stabilizes matrix vesicle-biomimetic lipid membranes: unravelling a new role of annexins in calcification.

Matrix vesicles are a special class of extracellular vesicles thought to actively contribute to both physiologic and pathologic mineralization. Proteomic studies have shown that matrix vesicles possess high amounts of annexin A5, suggesting that the protein might have multiple roles at the sites of calcification. Currently, Annexin A5 is thought to promote the nucleation of apatitic minerals close to the inner leaflet of the matrix vesicles' membrane enriched in phosphatidylserine and Ca.