Measurement Of Activity Research Articles

High-throughput discovery of inhibitory protein fragments with AlphaFold.

Peptides can bind to specific sites on larger proteins and thereby function as inhibitors and regulatory elements. Peptide fragments of larger proteins are particularly attractive for achieving these functions due to their inherent potential to form native-like binding interactions. Recently developed experimental approaches allow for high-throughput measurement of protein fragment inhibitory activity in living cells. However, it has thus far not been possible to predict de novo which of the many possible protein fragments bind to protein targets, let alone act as inhibitors. We have developed a computational method, FragFold, that employs AlphaFold to predict protein fragment binding to full-length proteins in a high-throughput manner. Applying FragFold to thousands of fragments tiling across diverse proteins revealed peaks of predicted binding along each protein sequence. Comparisons with experimental measurements establish that our approach is a sensitive predictor of fragment function: Evaluating inhibitory fragments from known protein-protein interaction interfaces, we find 87% are predicted by FragFold to bind in a native-like mode. Across full protein sequences, 68% of FragFold-predicted binding peaks match experimentally measured inhibitory peaks. Deep mutational scanning experiments support the predicted binding modes and uncover superior inhibitory peptides in high throughput. Further, FragFold is able to predict previously unknown protein binding modes, explaining prior genetic and biochemical data. The success rate of FragFold demonstrates that this computational approach should be broadly applicable for discovering inhibitory protein fragments across proteomes.

Disrupted basolateral amygdala circuits supports negative valence bias in depressive states

Negative bias is an essential characteristic of depressive episodes leading patients to attribute more negative valence to environmental cues. This negative bias affects all levels of information processing including emotional response, attention and memory, leading to the development and maintenance of depressive symptoms. In this context, pleasant stimuli become less attractive and unpleasant ones more aversive, yet the related neural circuits underlying this bias remain largely unknown. By studying a mice model for depression chronically receiving corticosterone (CORT), we showed a negative bias in valence attribution to olfactory stimuli that responds to antidepressant drug. This result paralleled the alterations in odor value assignment we observed in bipolar depressed patients. Given the crucial role of amygdala in valence coding and its strong link with depression, we hypothesized that basolateral amygdala (BLA) circuits alterations might support negative shift associated with depressive states. Contrary to humans, where limits in spatial resolution of imaging tools impair easy amygdala segmentation, recently unravelled specific BLA circuits implicated in negative and positive valence attribution could be studied in mice. Combining CTB and rabies-based tracing with ex vivo measurements of neuronal activity, we demonstrated that negative valence bias is supported by disrupted activity of specific BLA circuits during depressive states. Chronic CORT administration induced decreased recruitment of BLA-to-NAc neurons preferentially involved in positive valence encoding, while increasing recruitment of BLA-to-CeA neurons preferentially involved in negative valence encoding. Importantly, this dysfunction was dampened by chemogenetic hyperactivation of BLA-to-NAc neurons. Moreover, altered BLA activity correlated with durable presynaptic connectivity changes coming from the paraventricular nucleus of the thalamus, recently demonstrated as orchestrating valence assignment in the amygdala. Together, our findings suggest that specific BLA circuits alterations might support negative bias in depressive states and provide new avenues for translational research to understand the mechanisms underlying depression and treatment efficacy.

Acquired Low Factor XIII Activity Is Associated with an Increased Need for Blood Transfusions in Patients with Gastrointestinal Bleedings

BackgroundFactor XIII plays a key role within the coagulation cascade.ObjectiveWe aimed to investigate the relevance of factor XIII activity on the outcome of patients with gastrointestinal bleedings.MethodsIn this retrospective, single-center study patients with gastrointestinal bleeding and measurement of factor XIII activity were included. The primary endpoint was the number of red blood cell transfusions in patients with reduced factor XIII activity (< 70%) compared to patients with normal activity. Additionally, the influence of factor XIII substitution was assessed.ResultsNinety-seven patients (median age: 64 [IQR 55, 77] years, 31 (32%) females) were included in the analysis. Fifty-six (58%) patients suffered from an upper gastrointestinal bleeding. 66 (68%) patients had a factor XIII activity < 70% and 24 (36%) of those received factor XIII substitution. Patients with reduced FXIII activity needed significantly more red blood cell transfusions than patients with normal activity (9 [5, 12] vs. 4 [1, 8], p < 0.001). Patients receiving factor XIII substitution showed a trend toward a decreased need for transfusions after substitution (0 [0, 5] vs. 3 [1, 6], p = 0.066). Factor XIII activity correlated negatively with the INR (rs = -0.24, p = 0.018) and positively with hemoglobin levels (rs = 0.28, p = 0.006) and with thrombocyte counts (rs = 0.30, p = 0.003).ConclusionThe present study shows an association of factor XIII activity with the requirement of blood transfusions in patients with gastrointestinal bleedings and indicates a potential benefit of factor XIII substitution. Factor XIII activity seems to be dependent from the amount of blood loss and the global coagulation parameters.

Oxazolidinone antibiotics impair ex vivo megakaryocyte differentiation from hematopoietic progenitor cells and their maturation into platelets.

Oxazolidinones (linezolid and tedizolid) adverse reactions include thrombocytopenia, the mechanism of which is still largely unknown. In cultured cells, oxazolidinones impair mitochondrial protein synthesis and oxidative metabolism. As mitochondrial activity is essential for megakaryocyte differentiation and maturation into platelets, we examined whether oxazolidinones impair these processes ex vivo and alter, in parallel, the activity of mitochondrial cytochrome c-oxidase (CYTOX; enzyme partly encoded by the mitochondrial genome) and cell morphology. Human CD34+ cells were isolated, incubated with cytokines (up to 14 days) and clinically relevant oxazolidinone concentrations or in control conditions, and used for (i) clonogenic assays [counting of megakaryocyte (CFU-Mk), granulocyte-monocyte (CFU-GM), burst-forming unit-erythroid (BFU-E) colonies]; (ii) the measure of the expression of megakaryocyte surface antigens (CD34 to CD41 and CD42); (iii) counting of proplatelets; (iv) the measurement of CYTOX activity; and (v) cell morphology (optic and electron microscopy). Oxazolidinones caused a significant decrease in BFU-E but not CFU-Mk or CFU-GM colonies. Yet, the megakaryocytic lineage was markedly affected, with a decreased differentiation of CD34+ into CD41+/CD42+ cells, an abolition of proplatelet formation and striking decrease in the numbers of large polylobulated nucleus megakaryocytes, with a complete loss of intracellular demarcation membrane system, disappearance of mitochondria, and suppression of CYTOX activity. These alterations were more marked in cells incubated with tedizolid than linezolid. These data suggest that oxazolidinones may induce thrombocytopenia by impairing megakaryocytic differentiation through mitochondrial dysfunction. Pharmacological interventions to prevent this toxicity might therefore be difficult as mitochondrial toxicity is most probably inherently linked to their antibacterial activity.

Neuroimaging model of visceral manipulation in awake rat.

It is unclear to what extent measurements of brain activity are affected by background, and experimentally unrelated, interoceptive processes. To advance our understanding of ongoing visceral activity's influence on brain states, here we provide a proof of concept, anesthesia-free animal model of visceral manipulation during simultaneous BOLD fMRI. We successfully demonstrated BOLD activation during gastric distension of the unanesthetized rat in both classically reported (cerebellum, hippocampus) and novel (inferior colliculus) regions. This paradigm establishes an important foundation for further interrogation of viscera-brain interactions.

The German version of the Pregnancy Physical Activity Questionnaire: a translation, cross-cultural adaptation, reliability and validity assessment

BackgroundValidated and internationally standardised measurement instruments are a prerequisite for ensuring that physical activity during pregnancy is comparable and for deriving physical activity recommendations. In Germany, there has been no adapted version of the internationally used Pregnancy Physical Activity Questionnaire (PPAQ) until now. This study’s aim centred around translating the original English version into German (PPAQ-G) and determining its reliability as well as validity in a German population.MethodsThe PPAQ was translated into German using the forward-backwards technique. Its reliability and validity were tested. Thirty-four correctly completed questionnaires were analysed. The test–retest reliability was presented using the intraclass correlation coefficient (ICC) and Spearman correlation coefficient. Validity was tested by using accelerometer (n = 23) and determined by Spearman correlation coefficient.ResultsIn the transcultural adjustment, two questions were amended to describe intensity more precisely, and two other questions were adapted to reflect the units of measurement used in Germany. The ICC indicated a reliability of r = 0.79 for total activity (without sitting), and the intensity subcategories ranged from r = 0.70 (moderate-intensity activities) to r = 0.90 (sitting). Although, validity assessment showed no significant correlation for sedentary, moderate or vigorous intensity, there were significant correlations for total activity (light and above; r = 0.49; p < 0.05) and for light activity (r = 0.65; p < 0.01).ConclusionsThe PPAQ-G showed good reliability for use on pregnant German women and a moderately accurate measurement of physical activity. It can be used nationally for epidemiological studies, and it also enables international comparisons of physical activity during pregnancy.Trial registrationDRKS00023426; Registration date 20 May 2021.

The audio-visual incongruency asymmetry. Natural sounds in an urban visual setting are more relaxing than urban sounds in visual nature

Audio-visual interactions play a crucial role in environmental perception. Incongruent audio-visual environments, although prominent in the urban fabric, have been underlit in research. Contrasting exposures to visually natural environments combined with urban sounds, as well as the reverse scenario of visually urban environments with natural sounds, are explored for their restorative potential, both at the cognitive level by means of self-reported evaluations and instinctively through measurements of electrodermal activity. The test panel (n=67) results point at a strong audio-visual urban-nature incongruency asymmetry. Eventful natural sounds in an urban setting were perceived as more pleasant and relaxing than eventful urban sounds in a green environment. So augmenting an urban environment with natural sounds, even in absence of any visual natural features, could be an interesting soundscape intervention. In contrast, a visually natural environment paired with urban sounds is strongly negatively perceived. The findings further contribute to a growing body of literature emphasizing the importance of the sonic environment in designing restorative spaces.

Characteristics of Selected Bioactive Compounds and Malting Parameters of Hemp (Cannabis sativa L.) Seeds and Malt.

Hemp (Cannabis sativa L.) seeds are an interesting raw material for malting regarding its relatively high bioactive compounds concentration and proven advantageous properties in different food products and dietary supplements. In the first stage of the study, important seeds properties relevant to the malting process including moisture content, seed viability, and water absorption capacity were determined. However, a few parameters determining the seeds' usability for malt preparation, such as germination ability and water sensitivity, are different in comparison to typical malting raw materials such as barley or wheat. However, they make it possible to obtain high-quality hemp malt. In the next stage of research, spectroscopic and chromatographic analyses, including measurements of antioxidant activity and protein separation by SEC-HPLC, were conducted. The results showed that the malting process improved the total antioxidant potential of hemp seeds by 15%, leading to an increase in the concentration of lower molecular weight proteins and oligopeptides-below molecular mass of 10 kDa-responsible for this high antioxidant activity. The processing of hemp seeds reduced the phytate content while increasing phosphate fractions with fewer phosphate groups, which may have a beneficial effect on nutritional value. These results suggest that malting hemp seeds needs optimalization of the process but can increase its nutritional value as a promising raw material in the food industry.

Subjective measurement of physical activity and sedentary behaviour in children and adolescents with cerebral palsy: a scoping review

Purpose Physical activity is essential for maintaining overall health. Cost-effective and easily administered outcome instruments are valuable for clinical practice and large-scale population studies. The scoping review aimed to identify and map subjective instruments developed or validated to measure habitual physical activity and/or sedentary behaviour in children and adolescents with cerebral palsy aged 0–18 years across all levels of the GMFCS-E&R. Materials and methods This scoping review was conducted in accordance with the JBI methodology for scoping reviews and searched the databases PubMed, CINAHL, Web of Science, Cochrane Database of Systematic Reviews, JBI Database of Systematic Reviews and Implementation Reports, Embase and Pedro to identify articles. Results From 288 full-text references, 13 studies met the inclusion criteria. Nine instruments measured habitual physical activity and/or sedentary behaviour in children and adolescents with cerebral palsy aged 18 months to 18 years. Six subjective instruments were tested for ambulatory children, while three instruments were tested in children and adolescents at GMFCS-E&R level I–V. Conclusion and implications Reporting of the psychometric properties were found on reliability in three instruments, while data on validity were reported in all instruments. Further studies assessing the psychometric properties of subjective instruments in the target population are needed.

Neuroelectrophysiology-compatible electrolytic lesioning.

Lesion studies have historically been instrumental for establishing causal connections between brain and behavior. They stand to provide additional insight if integrated with multielectrode techniques common in systems neuroscience. Here, we present and test a platform for creating electrolytic lesions through chronically implanted, intracortical multielectrode probes without compromising the ability to acquire neuroelectrophysiology. A custom-built current source provides stable current and allows for controlled, repeatable lesions in awake-behaving animals. Performance of this novel lesioning technique was validated using histology from ex vivo and in vivo testing, current and voltage traces from the device, and measurements of spiking activity before and after lesioning. This electrolytic lesioning method avoids disruptive procedures, provides millimeter precision over the extent and submillimeter precision over the location of the injury, and permits electrophysiological recording of single-unit activity from the remaining neuronal population after lesioning. This technique can be used in many areas of cortex, in several species, and theoretically with any multielectrode probe. The low-cost, external lesioning device can also easily be adopted into an existing electrophysiology recording setup. This technique is expected to enable future causal investigations of the recorded neuronal population's role in neuronal circuit function, while simultaneously providing new insight into local reorganization after neuron loss.

A highly sensitive, accurate, and stable method for measuring pectin depolymerase activity

Pectin depolymerase is widely utilized in various industrial sectors. However, the traditional methods for determining its enzymatic activity have limitations, such as cumbersome operations and a significant impact of enzyme solution dilution ratios on activity. The 3-methyl-2-benzothiazolinone hydrazone (MBTH) method can be employed to address these issues, but pectin precipitation and strong background commonly arise in this method. We have successfully overcome these challenges by employing a low-temperature and high-alkaline environment, and further optimized the reagent compositions and detection wavelength to improve the method. Consequently, enzyme hydrolysis follows a zero-order reaction within 60 min, which is helpful for the endpoint measurement of pectinase activity. The developed calibration curve for pectinase concentration and hydrolysis rate demonstrates linearity (R2 = 0.9945) within the range of 2.5–15.8 mU/mL of pectinase. This method exhibits high sensitivity, accuracy, and stability, making it suitable for routine determination of pectin depolymerase activity in research and applications.

Connectome-constrained networks predict neural activity across the fly visual system

We can now measure the connectivity of every neuron in a neural circuit1–9, but we cannot measure other biological details, including the dynamical characteristics of each neuron. The degree to which measurements of connectivity alone can inform the understanding of neural computation is an open question10. Here we show that with experimental measurements of only the connectivity of a biological neural network, we can predict the neural activity underlying a specified neural computation. We constructed a model neural network with the experimentally determined connectivity for 64 cell types in the motion pathways of the fruit fly optic lobe1–5 but with unknown parameters for the single-neuron and single-synapse properties. We then optimized the values of these unknown parameters using techniques from deep learning11, to allow the model network to detect visual motion12. Our mechanistic model makes detailed, experimentally testable predictions for each neuron in the connectome. We found that model predictions agreed with experimental measurements of neural activity across 26 studies. Our work demonstrates a strategy for generating detailed hypotheses about the mechanisms of neural circuit function from connectivity measurements. We show that this strategy is more likely to be successful when neurons are sparsely connected—a universally observed feature of biological neural networks across species and brain regions.

Cytotoxic properties, glycolytic effects and high-resolution respirometry mitochondrial activities of Eriocephalus racemosus against MDA-MB 231 triple-negative breast cancer

IntroductionTriple-negative breast cancer (TNBC) represents a significant global health crisis due to its resistance to conventional therapies and lack of specific molecular targets. This study explored the potential of Eriocephalus racemosus (E. racemosus) as an alternative treatment for TNBC. The cytotoxic properties and high-resolution respirometry mitochondrial activities of E. racemosus against the MDA-MB 231 TNBC cell line were evaluated.MethodsHexane solvent and bioactive fraction extractions of E. racemosus were performed, while mass spectrometry-based metabolite profiling was used to identify the phytochemical constituents of the extracts. The extracts were further tested against MDA-MB 231 TNBC cells to determine their cytotoxicity. The mode of cell death was determined using flow cytometry. The activities of caspases 3, 8, and 9 were assessed using a multiplex activity assay kit. Glycolytic activity and High-resolution respirometry measurements of mitochondrial function in the MDA-MB 231 cell line were conducted using the Seahorse XFp and Oroboros O2K.ResultsMetabolite profiling of E. racemosus plant crude extracts identified the presence of coumarins, flavonoids, sesquiterpenoids, triterpenoids, and unknown compounds. The extracts demonstrated promising cytotoxic activities, with a half maximal inhibitory concentration (IC50) of 12.84 µg/mL for the crude hexane extract and 15.49 µg/mL for the bioactive fraction. Further, the crude hexane and bioactive fraction extracts induced apoptosis in the MDA-MB-231 TNBC cells, like the reference drug cisplatin (17.44%, 17.26% and 20.25%, respectively) compared to untreated cells. Caspase 3 activities confirmed the induction of apoptosis in both cisplatin and the plant crude extracts, while caspase 8 and 9 activities confirmed the activation of both the intrinsic and extrinsic apoptosis pathways. Increased levels of glycolytic activity were observed in the hexane crude extract. High-resolution respiratory measurements showed elevated mitochondrial activities in all mitochondrial states except for complex-IV activity.ConclusionThese findings support further exploration of E. racemosus as a potential therapeutic agent for TNBC, offering a promising avenue for the development of targeted treatments with minimal adverse effects.

Transcriptome analysis reveals the anti-Parkinson's activity of Mangiferin in zebrafish

As the global population ages, the incidence of Parkinson's Disease (PD) continues to rise, imposing significant social and economic burdens. Mangiferin (MGF), a polyphenolic, bioactive compound has been shown to play a role in the prevention and treatment of PD. This study investigates the neuroprotective effects of MGF in an MPTP-induced zebrafish model of PD through transcriptome analysis. Initially, optimal concentrations for modeling were determined using various MPTP and MGF combinations. The zebrafish were then divided into control, MPTP-treated, and MGF co-treated groups. Subsequent evaluations included hatching rates, mortality rates, growth and development conditions, spontaneous motor abilities, as well as measurements of enzymatic activities of SOD, CAT, and levels of GSH. Ultimately, the therapeutic efficacy of MGF on the PD model in zebrafish was assessed through transcriptome sequencing. The results demonstrated that MPTP treatment induced PD-associated symptoms in zebrafish, while MGF treatment significantly improved the motor abilities and survival rates of the PD model zebrafish, effectively reducing oxidative stress and ameliorating PD symptoms. Transcriptome sequencing further revealed that MGF may mitigate mitochondrial-related oxidative stress in PD zebrafish by modulating the expression of critical genes including lrrk2, vps35, atp13a, dnajc6, and uchl1. Differential gene expression analysis indicated that these genes are primarily involved in vital signaling pathways, such as neuroactive ligand-receptor interaction, and the calcium signaling pathway. In summary, our study provides robust scientific evidence supporting MGF as a potential therapeutic candidate for PD by preserving mitochondrial homeostasis and elucidating its mechanisms of action.

Selective attention and sensitivity to auditory disturbances in a virtually-real Classroom: Comparison of adults with and without AD(H)D.

Many people, and particularly individuals with Attention Deficit (Hyperactivity) Disorder (AD(H)D), find it difficult to maintain attention during classroom learning. However, traditional paradigms used to evaluate attention do not capture the complexity and dynamic nature of real-life classrooms. Using a novel Virtual Reality platform, coupled with measurement of neural activity, eye-gaze and skin conductance, here we studied the neurophysiological manifestations of attention and distractibility, under realistic learning conditions. Individuals with AD(H)D exhibited higher neural responses to irrelevant sounds and reduced speech tracking of the teacher, relative to controls. Additional neurophysiological measures, such the power of alpha-oscillations and frequency of gaze-shifts away from the teacher, contributed to explaining variance in self-reported AD(H)D symptoms across the sample. These ecologically-valid findings provide critical insight into the neurophysiological mechanisms underlying individual differences in the capacity for sustained attention and the proneness to distraction and mind-wandering, experienced in real-life situations.

Transcriptional activation of PINK1 by MyoD1 mediates mitochondrial homeostasis to induce renal calcification in pediatric nephrolithiasis

This study aims to uncover the molecular mechanisms underlying pediatric kidney stone formation induced by renal calcium deposition by utilizing high-throughput sequencing data to reveal the regulation of PINK1 by MyoD1. We performed transcriptome sequencing on peripheral blood samples from healthy children and children with kidney stones to obtain differentially expressed genes (DEGs). Genes related to mitochondrial oxidative stress were obtained from the Genecards website and intersected with DEGs to obtain candidate target genes. Additionally, we conducted protein-protein interaction (PPI) analysis using the STRING database to identify core genes involved in pediatric kidney stone disease (KSD) and predicted their transcription factors using the hTFtarget database. We assessed the impact of MyoD1 on the activity of the PINK1 promoter using dual-luciferase reporter assays and investigated the enrichment of MyoD1 on the PINK1 promoter through chromatin immunoprecipitation (ChIP) experiments. To validate our hypothesis, we selected HK-2 cells and established an in vitro kidney stone model induced by calcium oxalate monohydrate (COM). We evaluated the expression levels of various genes, cell viability, volume of adherent crystals in each group, as well as mitochondrial oxidative stress in cells by measuring mitochondrial membrane potential (Δψm), superoxide dismutase (SOD) activity, reactive oxygen species (ROS), and malondialdehyde (MDA) content. Mitochondrial autophagy was assessed using mtDNA fluorescence staining and Western blot analysis of PINK1-related proteins. Apoptosis-related proteins were evaluated using Western blot analysis, and cell apoptosis was measured using flow cytometry. Furthermore, we developed a rat model of KSD and assessed the expression levels of various genes, as well as the pathologic changes in rat renal tissues using H&E and von Kossa staining, transmission electron microscopy (TEM), and the expression of creatinine, blood urea nitrogen, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) to evaluate the mitochondrial oxidative stress in vivo (through measurement of Δψm, SOD activity, ROS, and MDA content). Mitochondrial autophagy was evaluated by Western blot analysis of PINK1-associated proteins. Apoptosis-related proteins were detected using Western blot analysis, and cellular apoptosis was examined using cell flow cytometry and TUNEL staining. Bioinformatics analysis revealed that the PINK1 gene is upregulated and vital in pediatric kidney stone patients. Our in vitro and in vivo experiments demonstrated that silencing PINK1 could inhibit kidney stone formation by suppressing mitochondrial oxidative stress both in vitro and in vivo. We identified MyoD1 as an upstream transcription factor of PINK1 that contributes to the occurrence of pediatric kidney stones through the activation of PINK1. Our in vivo and in vitro experiments collectively confirmed that silencing MyoD1 could inhibit mitochondrial oxidative stress, mitochondrial autophagy, and cellular apoptosis in a rat model of kidney stones by downregulating PINK1 expression, consequently suppressing the formation of kidney stones. In this study, we discovered that MyoD1 may promote kidney stone formation and development in pediatric patients by transcriptionally activating PINK1 to induce mitochondrial oxidative stress.

Photocatalytic performance of CuO NPs: An experimental approach for process parameter optimization for Rh B dye

Optimization of process parameters for photocatalytic activity measurement of CuO nanoparticles (NPs) was the focus of this study. CuO NPs were prepared following chemical co-precipitation method and characterized using X-ray diffraction (XRD), ultraviolet visible (UV–vis) spectroscopy, field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), Brunauer-Emmett-Teller (BET) and Fourier transform infrared spectroscopy (FTIR). Subsequent studies concentrated on optimizing pH of Rhodamine B (Rh B) dye, catalyst doses, and concentration of hydrogen peroxide (H2O2) for effective photocatalytic degradation. This optimization process was intended to properly investigate the photocatalytic activity of CuO NPs using Rh B dye (5 ppm), a frequently encountered organic pollutant. After 180 min of UV irradiation at optimized condition (pH 10, 0.3125 mg/mL NPs, 9000 ppm H2O2) a degradation rate of 60 percent was recorded. These findings maximized the degradation efficiency of CuO NPs to exploit as a potential photocatalyst.

NinjaNIRS: an open hardware solution for wearable whole-head high-density functional near-infrared spectroscopy.

Functional near-infrared spectroscopy (fNIRS) technology has been steadily advancing since the first measurements of human brain activity over 30 years ago. Initially, efforts were focused on increasing the channel count of fNIRS systems and then to moving from sparse to high density arrays of sources and detectors, enhancing spatial resolution through overlapping measurements. Over the last ten years, there have been rapid developments in wearable fNIRS systems that place the light sources and detectors on the head as opposed to the original approach of using fiber optics to deliver the light between the hardware and the head. The miniaturization of the electronics and increased computational power continues to permit impressive advances in wearable fNIRS systems. Here we detail our design for a wearable fNIRS system that covers the whole head of an adult human with a high-density array of 56 sources and up to 192 detectors. We provide characterization of the system showing that its performance is among the best in published systems. Additionally, we provide demonstrative images of brain activation during a ball squeezing task. We have released the hardware design to the public, with the hope that the community will build upon our foundational work and drive further advancements.

Continuous locomotor activity monitoring to assess animal welfare following intracranial surgery in mice.

Locomotor activity can serve as a readout to identify discomfort and pain. Therefore, monitoring locomotor activity following interventions that induce potential discomfort may serve as a reliable method for evaluating animal health, complementing conventional methods such as body weight measurement. In this study, we used the digital ventilated cage (DVC®) system for the assessment of circadian locomotor activity, in addition to body weight monitoring, following intracranial stereotaxic surgery in an Alzheimer's disease mouse model (C57BL/6J/APPswe/PSEN1dE9). Stereotaxic surgery did not affect the organization of circadian locomotor activity of both 7-8-week-old and 19-21-week-old mice. However, we observed that both young and old mice exhibited a significant decrease in activity during the dark phase. Also, our study shows that changes in locomotor activity exhibit higher sensitivity in detecting alterations indicative of animal health compared to measuring body weight. In contrast to 7-8-week-old mice, where we observed no genotypic differences in locomotor activity, 19-21-week-old APP/PS1 mice showed increased locomotor activity compared to wild-type mice. Furthermore, our analyses revealed that a subset of the 7-8-week-old mice showed increased locomotor activity during the initial peak of the dark phase. One mouse experienced sudden death early in life, possibly due to epileptic seizures. Altogether, our findings affirm continuous activity measurements as used in the DVC® as a highly valuable objective method for post-surgical welfare monitoring. Its discerning capacity not only facilitates circadian locomotor rhythm assessment but also enables the identification of individual aberrant activity patterns, possibly indicative of epileptic seizures.

Screening for Fabry disease in patients with left ventricular hypertrophy in China: A multicentre and prospective study.

Left ventricular hypertrophy (LVH) is frequently detected via echocardiography in individuals with Fabry disease (FD), sometimes leading to confusion with hypertrophic cardiomyopathy (HCM) of other aetiologies. Considering this diagnosis challenge, FD should be included in the list of differential diagnosis for patients presenting with LVH. To address this concern, we conducted a prospective screening study in China, using dried blood spot (DBS) testing, to evaluate patients with unexplained LVH. Our study was designed as a nationwide, multicentre prospective investigation. A total of 1015 patients from 55 different centres who were diagnosed with LVH by echocardiography were screened in the study from September 2022 to December 2023. Demographic information, biochemistry data, echocardiography parameters and clinical observations were meticulously collected from all participants. The DBS method was used to assess α-galactosidase A (α-Gal A) activity in males and both α-Gal A and globotriaosylsphingosine (lyso-Gb3) levels in females. The final screening population included 906 patients (589 males, 65%) with LVH, characterized by a mean maximal myocardial thickness of 14.8±4.6mm and an average age of 56.9±17.2years. In total, 43 patients (38 males, 5 females) exhibited low α-Gal A activity measurement (<2.2μmol/L), while 21 patients (10 males, 11 females) presented low α-Gal A activity or elevated lyso-Gb3 levels (>1.1ng/mL). Among these patients, eight individuals (7 males and 1 female) were genetically confirmed to harbour pathogenic GLA mutations, resulting in a total prevalence of 0.88%. Compared with patients without FD, patients with FD tended to have proteinuria (75% vs. 21.2%, P=0.001), family history of HCM (37.5% vs. 2.3%, P<0.01) and neuropathic pain (37.5% vs. 4.4%, P<0.01) but lower systolic blood pressure (118.5±12.5 vs. 143.3±29.3mmHg, P=0.017). Five mutations were previously recognized as associated with FD while the remaining two, p.Asp313Val (c.938A>T) and c.547+3A>G, were deemed potentially pathogenic. Subsequent familial validation post-diagnosis identified an additional 14 confirmed cases. This pioneering screening study for FD among Chinese patients with unexplained LVH using DBS measurement, revealed an FD detection rate of 0.88%. Our findings confirmed that the combined measurement of lyso-Gb3 and α-Gal A activity is beneficial for primary screening of FD in patients with LVH. Given the availability of efficacious therapies and the value of cascade screening in extended families, early detection of FD in LVH patients is clinically important.