Biology subjects

Punt, M.

Publications and source records attributed to Punt, M..

4 recordsLinked to original sources

bioRxiv2025

An open-source, externally validated neural network algorithm to recognize daily life gait of older adults based on the lower-back sensor

BackgroundAccurate gait recognition from daily physical activities is a critical first step for further fall risk assessment and rehabilitation monitoring based on inertial sensors. However, most openly available models are based on healthy young adults ambulating in structured conditions. ObjectiveThis study aimed to develop an open-source and externally validated algorithm for daily-life gait recognition of older adults based on acceleration and angular velocity, as well as acceleration data only, and explore the effect of the use of data augmentation in the model training. MethodsA convolutional neural network was trained for gait recognition. The data for model training was lower-back inertial sensor data from 20 older adults (mean age 76 years old), with annotated synchronized activity labels in semi-structured and daily-life conditions. The data was randomly split into training, validation, and testing datasets by participants, and the model was trained multiple times using these different splits. The model was trained based on data from six channels (accelerations and angular velocities) and three channels (accelerations only) under conditions with and without data augmentation, respectively. External validation was evaluated based on lower-back sensor data collected from 47 stroke survivors (mean age 72.3 years old) in balance and walking tests. ResultsFor the testing dataset, the median accuracy ranged from 94 % to 98 %, precision from 63 % to 85 %, sensitivity from 95 % to 97 %, F1-score from 76 % to 90 %, and specificity from 94 % to 98 %. For the external validation dataset, the median accuracy ranged from 97 % to 100 %, precision from 99.9 % to 100 %, sensitivity from 71 % to 100 %, F1-score from 83 % to 100 %, and specificity 100 %. ConclusionsBased on lower-back-worn inertial sensor data, we provide an accurate, open-source, and externally validated daily-life gait recognition algorithm for older adults, with one model for six-axis input data and another for three-axis input data. Besides, we found when training the model, the use of data augmentation is especially helpful on the model based on acceleration data only.

bioengineering↗

bioRxiv2022

High sorbic acid resistance of Penicillium roqueforti is mediated by the SORBUS gene cluster

Penicillium roqueforti is a major food-spoilage fungus known for its high resistance to the food preservative sorbic acid. Here, we demonstrate that the minimum inhibitory concentration of undissociated sorbic acid (MICu) ranges between 4.2 and 21.2 mM when 34 P. roqueforti strains were grown on malt extract broth. A genome-wide association study revealed that the six most resistant strains contained the 180 kbp gene cluster SORBUS, which was absent in the other 28 strains. In addition, a SNP analysis revealed five genes outside the SORBUS cluster that may be linked to sorbic acid resistance. A partial SORBUS knock-out (>100 of 180 kbp) in a resistant strain reduced sorbic acid resistance to similar levels as observed in the sensitive strains. Whole genome transcriptome analysis revealed a small set of genes present in both resistant and sensitive P. roqueforti strains that were differentially expressed in the presence of the weak acid. These genes could explain why P. roqueforti is more resistant to sorbic acid when compared to other fungi, even in the absence of the SORBUS cluster. Together, the MICu of 21.2 mM makes P. roqueforti among the most sorbic acid-resistant fungi, if not the most resistant fungus, which is mediated by the SORBUS gene cluster. Author summaryChemical preservatives, such as sorbic acid, are often used in food to prevent spoilage by fungi, yet some fungi are particularly well-suited to deal with these preservatives. First, we investigated the resistance of 34 Penicillium roqueforti strains to various food preservatives. This revealed that some strains were highly resistant to sorbic acid, while others are more sensitive. Next, we used DNA sequencing to compare the genetic variation between these strains and discovered a specific genetic region (SORBUS) that is unique to the resistant strains. Through comparative analysis with other fungal species the SORBUS region was studied in more detail and with the use of genetic engineering tools we removed this unique region. Finally, the mutant lacking the SORBUS region was confirmed to have lost its sorbic acid resistance. This finding is of particular interest as it suggests that only some, not all, P. roqueforti strains are potent spoilers and that specific genetic markers could help in the identification of resistant strains.

genomics↗

bioRxiv2021

Human islet expression levels of Prostaglandin E2 synthetic enzymes, but not prostaglandin EP3 receptor, are positively correlated with markers of β-cell function and mass in non-diabetic obesity

Elevated islet production of prostaglandin E2 (PGE2), an arachidonic acid metabolite, and expression of Prostaglandin E2 Receptor subtype EP3 (EP3) are well-known contributors to the {beta}-cell dysfunction of type 2 diabetes (T2D). Yet, many of the same pathophysiological conditions exist in obesity, and little is known about how the PGE2 production and signaling pathway influences non-diabetic beta-cell function. In this work, plasma arachidonic acid and PGE2 metabolite levels were quantified in a cohort of non-diabetic and T2D human subjects to identify their relationship with glycemic control, obesity, and systemic inflammation. In order to link these findings to processes happening at the islet level, cadaveric human islets were subject to gene expression and functional assays. Interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) mRNA levels, but not those of EP3, positively correlated with donor body mass index (BMI). IL-6 expression also strongly correlated with the expression of COX-2 and other PGE2 synthetic pathway genes. Insulin secretion assays using an EP3-specific antagonist confirmed functionallyrelevant up-regulation of PGE2 production. Yet, islets from obese donors were not dysfunctional, secreting just as much insulin in basal and stimulatory conditions as those from non-obese donors as a percent of content. Islet insulin content, on the other hand, was increased with both donor BMI and islet COX-2 expression, while EP3 expression was unaffected. We conclude up-regulated islet PGE2 production may be part of the {beta}-cell adaption response to obesity and insulin resistance that only becomes dysfunctional when both ligand and receptor are highly expressed in T2D.

pharmacology and toxicology↗

bioRxiv2020

Mono-ubiquitination of Rabphilin 3A by UBE3A serves a non-degradative function

Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by brain-specific loss of UBE3A, an E3 ubiquitin protein ligase. A substantial number of possible ubiquitination targets of UBE3A have been identified, although evidence of being direct UBE3A substrates is often lacking. Here we identified the synaptic protein Rabphilin-3a (RPH3A), an effector of the RAB3A small GTPase involved in axonal vesicle priming and docking, as a ubiquitination target of UBE3A. We found that the UBE3A and RAB3A binding sites on RPH3A partially overlap, and that RAB3A binding to RPH3A interferes with UBE3A binding. We confirmed previous observations that RPH3A levels are critically dependent on RAB3A binding but, rather surprisingly, we found that the reduced RPH3A levels in the absence of RAB3A are not mediated by UBE3A. Indeed, while we found that RPH3A is ubiquitinated in a UBE3A-dependent manner in mouse brain, UBE3A mono-ubiquitinates RPH3A and does not facilitate RPH3A degradation. Moreover, we found that an AS-linked UBE3A missense mutation in the UBE3A region that interacts with RPH3A, abrogates the interaction with RPH3A. In conclusion, our results identify RPH3A as a novel target of UBE3A and suggest that UBE3A-dependent ubiquitination of RPH3A serves a non-degradative function.

neuroscience↗