Assessment of Domestic Well-Being: From Perception to Measurement

Nowadays, there are plenty of sensing devices that enable the measurement of physiological, environmental, and behavioral parameters of people 24 hours a day, seven days a week and provide huge quantities of different data. Data and signals coming from sensing devices, installed in indoor or outdoor environments or often worn by the users, generate heterogeneous and complex structured datasets, most of the time not uniformly structured. The artificial intelligence (AI) algorithms applied to these sets of data have demonstrated capabilities to infer indices related to a subject's status and well-being [1]. Well-being is a key parameter in the World Health Organization (WHO) definition of health, considering its physical, mental, and social spheres. Quantitatively assessing a subject's well-being is of paramount importance if we want to assess the whole status of a person, which is particularly useful in the case of ageing people living alone. Assessment allows for continuous remote monitoring to improve people's quality of life (QoL) according to their perceptions, needs, and preferences. Technology undoubtedly plays a pivotal role in this regard, providing us new tools to support the objective evaluation of a subject's status, including her/his perception of the living environment. Its potential is huge, also in terms of support to the healthcare system and ageing people; however, there are several engineering challenges to consider, especially in terms of sensors integrability, connectivity, and metrological performance, in order to obtain reliable and accurate measurement systems

Heartbeat detection by laser doppler vibrometry and machine learning

Background: Heartbeat detection is a crucial step in several clinical fields. Laser Doppler Vibrometer (LDV) is a promising non-contact measurement for heartbeat detection. The aim of this work is to assess whether machine learning can be used for detecting heartbeat from the carotid LDV signal. Methods: The performances of Support Vector Machine (SVM), Decision Tree (DT), Random Forest (RF) and K-Nearest Neighbor (KNN) were compared using the leave-one-subject-out cross-validation as the testing protocol in an LDV dataset collected from 28 subjects. The classification was conducted on LDV signal windows, which were labeled as beat, if containing a beat, or no-beat, otherwise. The labeling procedure was performed using electrocardiography as the gold standard. Results: For the beat class, the f1-score (f 1) values were 0.93, 0.93, 0.95, 0.96 for RF, DT, KNN and SVM, respectively. No statistical differences were found between the classifiers. When testing the SVM on the full-length (10 min long) LDV signals, to simulate a real-world application, we achieved a median macro-f 1 of 0.76. Conclusions: Using machine learning for heartbeat detection from carotid LDV signals showed encouraging results, representing a promising step in the field of contactless cardiovascular signal analysis

Efficient Remyelination Requires DNA Methylation

Oligodendrocyte progenitor cells (OPCs) are the principal source of new myelin in the central nervous system. A better understanding of how they mature into myelin-forming cells is of high relevance for remyelination. It has recently been demonstrated that during developmental myelination, the DNA methyltransferase 1 (DNMT1), but not DNMT3A, is critical for regulating proliferation and differentiation of OPCs into myelinating oligodendrocytes (OLs). However, it remains to be determined whether DNA methylation is also critical for the differentiation of adult OPCs during remyelination. After lysolecithin-induced demyelination in the ventrolateral spinal cord white matter of adult mice of either sex, we detected increased levels of DNA methylation and higher expression levels of the DNA methyltransferase DNMT3A and lower levels of DNMT1 in differentiating adult OLs. To functionally assess the role of DNMT1 and DNMT3 in adult OPCs, we used mice with inducible and lineage-specific ablation of $\small \textit{Dnmt3a}$ and/or $\small \textit{Dnmt1}$ (i.e., $\small \textit{Plp-creER(t);Dnmt3a-flox, Plp-creER(t);Dnmt1-flox, Plp-creER(t);Dnmt1-flox;Dnmt3aflox}$). Upon lysolecithin injection in the spinal cord of these transgenic mice, we detected defective OPC differentiation and inefficient remyelination in the $\small \textit{Dnmt3a}$ null and $\small \textit{Dnmt1/Dnmt3a}$ null mice, but not in the $\small \textit{Dnmt1}$ null mice. Taken together with previous results in the developing spinal cord, these data suggest an age-dependent role of distinct DNA methyltransferases in the oligodendrocyte lineage, with a dominant role for DNMT1 in neonatal OPCs and for DNMT3A in adult OPCs.This work was supported by NIH-R37NS42925-14 to P.C., NIH-F31NS077504 Fellowship to J.L.H., postdoctoral fellowships from the Paralyzed Veterans of America (3061) and National Multiple Sclerosis Society (FG-1507-04996) to S.M., a program grant from the UK Multiple Sclerosis Society (R.J.M.F., C.Z.) and a core support grant from the Wellcome Trust and MRC to the Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute (R.J.M.F.)

Hypoxia Alters Cell Cycle Regulatory Protein Expression and Induces Premature Maturation of Oligodendrocyte Precursor Cells

Periventricular white matter injury (PWMI) is a common form of brain injury sustained by preterm infants. A major factor that predisposes to PWMI is hypoxia. Because oligodendrocytes (OLs) are responsible for myelination of axons, abnormal OL development or function may affect brain myelination. At present our understanding of the influences of hypoxia on OL development is limited. To examine isolated effects of hypoxia on OLs, we examined the influences of hypoxia on OL development in vitro.Cultures of oligodendrocyte precursor cells (OPCs) were prepared from mixed glial cultures and were 99% pure. OPCs were maintained at 21% O(2) or hypoxia (1% or 4% O(2)) for up to 7 days. We observed that 1% O(2) lead to an increase in the proportion of myelin basic protein (MBP)-positive OLs after 1 week in culture, and a decrease in the proportion of platelet-derived growth factor receptor alpha (PDGFRalpha)-positive cells suggesting premature OL maturation. Increased expression of the cell cycle regulatory proteins p27(Kip1) and phospho-cdc2, which play a role in OL differentiation, was seen as well.These results show that hypoxia interferes with the normal process of OL differentiation by inducing premature OPC maturation

Conserved chromosome 2q31 conformations are associated with transcriptional regulation of GAD1 GABA synthesis enzyme and altered in prefrontal cortex of subjects with schizophrenia

Little is known about chromosomal loopings involving proximal promoter and distal enhancer elements regulating GABAergic gene expression, including changes in schizophrenia and other psychiatric conditions linked to altered inhibition. Here, we map in human chromosome 2q31 the 3D configuration of 200 kb of linear sequence encompassing the GAD1 GABA synthesis enzyme gene locus, and we describe a loop formation involving the GAD1 transcription start site and intergenic noncoding DNA elements facilitating reporter gene expression. The GAD1-TSS(-50kbLoop) was enriched with nucleosomes epigenetically decorated with the transcriptional mark, histone H3 trimethylated at lysine 4, and was weak or absent in skin fibroblasts and pluripotent stem cells compared with neuronal cultures differentiated from them. In the prefrontal cortex of subjects with schizophrenia, GAD1-TSS(-50kbLoop) was decreased compared with controls, in conjunction with downregulated GAD1 expression. We generated transgenic mice expressing Gad2 promoter-driven green fluorescent protein-conjugated histone H2B and confirmed that Gad1-TSS(-55kbLoop), the murine homolog to GAD1-TSS(-50kbLoop), is a chromosomal conformation specific for GABAergic neurons. In primary neuronal culture, Gad1-TSS(-55kbLoop) and Gad1 expression became upregulated when neuronal activity was increased. We conclude that 3D genome architectures, including chromosomal loopings for promoter-enhancer interactions involved in the regulation of GABAergic gene expression, are conserved between the rodent and primate brain, and subject to developmental and activity-dependent regulation, and disordered in some cases with schizophrenia. More broadly, the findings presented here draw a connection between noncoding DNA, spatial genome architecture, and neuronal plasticity in development and disease

Functional Characterization of DNA Methylation in the Oligodendrocyte Lineage

Oligodendrocytes derive from progenitors (OPCs) through the interplay of epigenomic and transcriptional events. By integrating high-resolution methylomics, RNA-sequencing, and multiple transgenic lines, this study defines the role of DNMT1 in developmental myelination. We detected hypermethylation of genes related to cell cycle and neurogenesis during differentiation of OPCs, yet genetic ablation of Dnmt1 resulted in inefficient OPC expansion and severe hypomyelination associated with ataxia and tremors in mice. This phenotype was not caused by lineage switch or massive apoptosis but was characterized by a profound defect of differentiation associated with changes in exon-skipping and intron-retention splicing events and by the activation of an endoplasmic reticulum stress response. Therefore, loss of Dnmt1 in OPCs is not sufficient to induce a lineage switch but acts as an important determinant of the coordination between RNA splicing and protein synthesis necessary for myelin formation.This work was supported by NIH-NINDS grants R37NS042925 and NS-R0152738 (P.C.) and F31NS077504 (J.L.H.), the UK Multiple Sclerosis Society (R.J.M.F.), and NIH-NIMH grant R01MH090948 (J.Z.)

PKCη promotes a proliferation to differentiation switch in keratinocytes via upregulation of p27Kip1 mRNA through suppression of JNK/c-Jun signaling under stress conditions

To maintain epidermal homeostasis, the balance between keratinocyte proliferation and differentiation is tightly controlled. However, the molecular mechanisms underlying this balance remain unclear. In 3D organotypic coculture with mouse keratinocytes and fibroblasts, the thickness of stratified cell layers was prolonged, and growth arrest and terminal differentiation were delayed when PKCη-null keratinocytes were used. Re-expression of PKCη in PKCη-null keratinocytes restored stratified cell layer thickness, growth arrest and terminal differentiation. We show that in 3D cocultured PKCη-null keratinocytes, p27Kip1 mRNA was downregulated, whereas JNK/c-Jun signaling was enhanced. Furthermore, inhibition of JNK/c-Jun signaling in PKCη-null keratinocytes led to upregulation of p27Kip1 mRNA, and to thinner stratified cell layers. Collectively, our findings indicate that PKCη upregulates p27Kip1 mRNA through suppression of JNK/c-Jun signaling. This results in promoting a proliferation to differentiation switch in keratinocytes