Comprehensive immune profiling reveals that Orbivirus infection activates immune checkpoints during acute T cell immunosuppression.

Bluetongue virus (BTV) is an arbovirus transmitted by the bite of infected Culicoides midges that affects domestic and wild ruminants producing great economic losses. The infection induces an IFN response, followed by an adaptive immune response that is essential in disease clearance. BTV can nonetheless impair IFN and humoral responses. The main goal of this study was to gain a more detailed understanding of BTV pathogenesis and its effects on immune cell populations. To this end, we combined flow cytometry and transcriptomic analyses of several immune cells at different times post-infection (pi). Four sheep were infected with BTV serotype 8 and blood samples collected at days 0, 3, 7 and 15pi to perform transcriptomic analysis of B-cell marker+, CD4+, CD8+, and CD14+ sorted peripheral mononuclear cells. The maximum number of differentially expressed genes occurred at day 7pi, which coincided with the peak of infection. KEGG pathway enrichment analysis indicated that genes belonging to virus sensing and immune response initiation pathways were enriched at day 3 and 7 pi in all 4 cell population analyzed. Transcriptomic analysis also showed that at day 7pi T cell exhaustion pathway was enriched in CD4+ cells, while CD8+ cells downregulated immune response initiation pathways. T cell functional studies demonstrated that BTV produced an acute inhibition of CD4+ and CD8+ T cell activation at the peak of replication. This coincided with PD-L1 upregulation on the surface of CD4+ and CD8+ T cells as well as monocytes. Taken together, these data indicate that BTV could exploit the PD1/PD-L1 immune checkpoint to impair T cell responses. These findings identify several mechanisms in the interaction between host and BTV, which could help develop better tools to combat the disease.

Real-time detection of freezing of gait in Parkinson's disease using multi-head convolutional neural networks and a single inertial sensor.

BACKGROUND: Freezing of gait (FOG) is one of the most disabling symptoms of Parkinson's disease (PD), contributing to poor quality of life and increased risk of falls. Wearable sensors represent a valuable means for detecting FOG in the home environment. Moreover, real-time feedback has proven to help reduce the duration of FOG episodes. This work proposes a robust real-time FOG detection algorithm, which is easy to implement in stand-alone devices working in non-supervised conditions. METHOD: Data from three different data sets were used in this study, with two employed as independent test sets. Acceleration recordings from 118 PD patients and 21 healthy elderly subjects were collected while they performed simulated daily living activities. A single inertial sensor was attached to the waist of each subject. More than 17 h of valid data and a total number of 1110 FOG episodes were analyzed in this study. The implemented algorithm consisted of a multi-head convolutional neural network, which exploited different spatial resolutions in the analysis of inertial data. The architecture and the model parameters were designed to provide optimal performance while reducing computational complexity and testing time. RESULTS: The developed algorithm demonstrated good to excellent classification performance, with more than 50% (30%) of FOG episodes predicted on average 3.1 s (1.3 s) before the actual onset in the main (independent) data set. Around 50% of FOG was detected with an average delay of 0.8 s (1.1 s) in the main (independent) data set. Moreover, a specificity above 88% (93%) was obtained when testing the algorithm on the main (independent) test set, while 100% specificity was obtained on healthy elderly subjects. CONCLUSION: The algorithm proved robust, with low computational complexity and processing time, thus paving the way to a real-time implementation in a stand-alone device that can be used in non-supervised environments.

Non-replicative antibiotic resistance-free DNA vaccine encoding S and N proteins induces full protection in mice against SARS-CoV-2.

SARS-CoV-2 vaccines currently in use have contributed to controlling the COVID-19 pandemic. Notwithstanding, the high mutation rate, fundamentally in the spike glycoprotein (S), is causing the emergence of new variants. Solely utilizing this antigen is a drawback that may reduce the efficacy of these vaccines. Herein we present a DNA vaccine candidate that contains the genes encoding the S and the nucleocapsid (N) proteins implemented into the non-replicative mammalian expression plasmid vector, pPAL. This plasmid lacks antibiotic resistance genes and contains an alternative selectable marker for production. The S gene sequence was modified to avoid furin cleavage (Sfs). Potent humoral and cellular immune responses were observed in C57BL/6J mice vaccinated with pPAL-Sfs + pPAL-N following a prime/boost regimen by the intramuscular route applying in vivo electroporation. The immunogen fully protected K18-hACE2 mice against a lethal dose (105 PFU) of SARS-CoV-2. Viral replication was completely controlled in the lungs, brain, and heart of vaccinated mice. Therefore, pPAL-Sfs + pPAL-N is a promising DNA vaccine candidate for protection from COVID-19.

Adenoviral delivery of soluble ovine OX40L or CD70 costimulatory molecules improves adaptive immune responses to a model antigen in sheep.

The tumour necrosis factor superfamily OX40L and CD70 and their receptors are costimulatory signalling axes critical for adequate T and B cell activation in humans and mice. In this work we inoculated groups of sheep with human recombinant adenovirus type 5 (Ad) expressing Ovis aries (Oa)OX40L or OaCD70 or a control adenoviral vector to determine whether they could improve the immune response to the model antigen OVA. PBMCs and serum samples were obtained for analysis of the adaptive immune response to OVA at days 0, 15, 30 and 90 post-inoculation (pi). Recall responses to OVA were assessed at day 7 and 30 after the second antigen inoculation (pb) at day 90. Administration of these immunomodulatory molecules did not induce unspecific PBMC stimulation. While OaOX40L administration mainly increased TNF-α and IL-4 in PBMC at day 15 pi concomitantly with a slight increase in antibody titer and the number of IFN-γ producing cells, we detected greater effects on adaptive immunity after OaCD70 administration. AdOaCD70 inoculation improved antibody titers to OVA at days 30 and 90 pi, and increased anti-OVA-specific IgG-secreting B cell counts when compared to control. Moreover, higher IFN-γ production was detected on days 7 pi, 7 pb and 30 pb in PBMCs from this group. Phenotypic analysis of T cell activation showed an increase in effector CD8+ T cells (CD8+ CD62L- CD27-) at day 15 pi in AdOaCD70 group, concurrent with a decrease in early activated cells (CD8+ CD62L- CD27+). Moreover, recall anti-OVA CD8+ T cell responses were increased at 7 pb in the AdOaCD70 group. AdOaCD70 administration could therefore promote CD8+ T cell effector differentiation and long-term activity. In this work we characterized the in vivo adjuvant potential on the humoral and cellular immune response of OaOX40L and OaCD70 delivered by non-replicative adenovirus vectors using the model antigen OVA. We present data highlighting the potency of these molecules as veterinary vaccine adjuvant.

A Morbillivirus Infection Shifts DC Maturation Toward a Tolerogenic Phenotype to Suppress T Cell Activation.

Viruses have evolved numerous strategies to impair immunity so that they can replicate more efficiently. Among those, the immunosuppressive effects of morbillivirus infection can be particularly problematic, as they allow secondary infections to take hold in the host, worsening disease prognosis. In the present work, we hypothesized that the highly contagious morbillivirus peste des petits ruminants virus (PPRV) could target monocytes and dendritic cells (DC) to contribute to the immunosuppressive effects produced by the infection. Monocytes isolated from healthy sheep, a natural host of the disease, were able be infected by PPRV and this impaired the differentiation and phagocytic ability of immature monocyte-derived DC (MoDC). We also assessed PPRV capacity to infect differentiated MoDC. Ovine MoDC could be productively infected by PPRV, and this drastically reduced MoDC capacity to activate allogeneic T cell responses. Transcriptomic analysis of infected MoDC indicated that several tolerogenic DC signature genes were upregulated upon PPRV infection. Furthermore, PPRV-infected MoDC could impair the proliferative response of autologous CD4+ and CD8+ T cell to the mitogen concanavalin A (ConA), which indicated that DC targeting by the virus could promote immunosuppression. These results shed new light on the mechanisms employed by morbillivirus to suppress the host immune responses. IMPORTANCE Morbilliviruses pose a threat to global health given their high infectivity. The morbillivirus peste des petits ruminants virus (PPRV) severely affects small-ruminant-productivity and leads to important economic losses in communities that rely on these animals for subsistence. PPRV produces in the infected host a period of severe immunosuppression that opportunistic pathogens exploit, which worsens the course of the infection. The mechanisms of PPRV immunosuppression are not fully understood. In the present work, we demonstrate that PPRV can infect professional antigen-presenting cells called dendritic cells (DC) and disrupt their capacity to elicit an immune response. PPRV infection promoted a DC activation profile that favored the induction of tolerance instead of the activation of an antiviral immune response. These results shed new light on the mechanisms employed by morbilliviruses to suppress the immune responses.

A New Paradigm in Parkinson's Disease Evaluation With Wearable Medical Devices: A Review of STAT-ONTM.

In the past decade, the use of wearable medical devices has been a great breakthrough in clinical practice, trials, and research. In the Parkinson's disease field, clinical evaluation is time limited, and healthcare professionals need to rely on retrospective data collected through patients' self-filled diaries and administered questionnaires. As this often leads to inaccurate evaluations, a more objective system for symptom monitoring in a patient's daily life is claimed. In this regard, the use of wearable medical devices is crucial. This study aims at presenting a review on STAT-ONTM, a wearable medical device Class IIa, which provides objective information on the distribution and severity of PD motor symptoms in home environments. The sensor analyzes inertial signals, with a set of validated machine learning algorithms running in real time. The device was developed for 12 years, and this review aims at gathering all the results achieved within this time frame. First, a compendium of the complete journey of STAT-ONTM since 2009 is presented, encompassing different studies and developments in funded European and Spanish national projects. Subsequently, the methodology of database construction and machine learning algorithms design and development is described. Finally, clinical validation and external studies of STAT-ONTM are presented.

Arsenate and arsenite differential toxicity in Tetrahymena thermophila.

A comparative analysis of toxicities of both arsenic forms (arsenite and arsenate) in the model eukaryotic microorganism Tetrahymena thermophila (ciliate protozoa) has shown the presence of various detoxification mechanisms and cellular effects comparable to those of animal cells under arsenic stress. In the wild type strain SB1969 arsenate is almost 2.5 times more toxic than arsenite. According to the concentration addition model used in binary metallic mixtures their toxicities show an additive effect. Using fluorescent assays and flow cytometry, it has been detected that As(V) generates elevated levels of ROS/RNS compared to As(III). Both produce the same levels of superoxide anion, but As(V) also causes greater increases in hydrogen peroxide and peroxynitrite. The mitochondrial membrane potential is affected by both As(V) and As(III), and electron microscopy has also revealed that mitochondria are the main target of both arsenic ionic forms. Fusion/fission and swelling mitochondrial and mitophagy, together with macroautophagy, vacuolization and mucocyst extruction are mainly associated to As(V) toxicity, while As(III) induces an extensive lipid metabolism dysfunction (adipotropic effect). Quantitative RT-PCR analysis of some genes encoding antioxidant proteins or enzymes has shown that glutathione and thioredoxin metabolisms are involved in the response to arsenic stress. Likewise, the function of metallothioneins seems to be crucial in arsenic detoxification processes, after using both metallothionein knockout and knockdown strains and cells overexpressing metallothionein genes from this ciliate. The analysis of the differential toxicity of As(III) and As(V) shown in this study provides cytological and molecular tools to be used as biomarkers for each of the two arsenic ionic forms.

Interactions with Arsenic: Mechanisms of Toxicity and Cellular Resistance in Eukaryotic Microorganisms.

Arsenic (As) is quite an abundant metalloid, with ancient origin and ubiquitous distribution, which represents a severe environmental risk and a global problem for public health. Microbial exposure to As compounds in the environment has happened since the beginning of time. Selective pressure has induced the evolution of various genetic systems conferring useful capacities in many microorganisms to detoxify and even use arsenic, as an energy source. This review summarizes the microbial impact of the As biogeochemical cycle. Moreover, the poorly known adverse effects of this element on eukaryotic microbes, as well as the As uptake and detoxification mechanisms developed by yeast and protists, are discussed. Finally, an outlook of As microbial remediation makes evident the knowledge gaps and the necessity of new approaches to mitigate this environmental challenge.

Immunization With Bovine Herpesvirus-4-Based Vector Delivering PPRV-H Protein Protects Sheep From PPRV Challenge.

The Morbillivirus peste des petits ruminants virus (PPRV) is the causal agent of a highly contagious disease that mostly affects sheep and goats and produces considerable losses in developing countries. Current PPRV control strategies rely on live-attenuated vaccines, which are not ideal, as they cannot differentiate infected from vaccinated animals (DIVA). Recombinant vector-based vaccines expressing viral subunits can provide an alternative to conventional vaccines, as they can be easily paired with DIVA diagnostic tools. In the present work, we used the bovine herpesvirus-4-based vector (BoHV-4-A) to deliver PPRV hemagglutinin H antigen (BoHV-4-A-PPRV-H-ΔTK). Vaccination with BoHV-4-A-PPRV-H-ΔTK protected sheep from virulent PPRV challenge and prevented virus shedding. Protection correlated with anti-PPRV IgGs, neutralizing antibodies and IFN-γ-producing cells induced by the vaccine. Detection of antibodies exclusively against H-PPRV in animal sera and not against other PPRV viral proteins such as F or N could serve as a DIVA diagnostic test when using BoHV-4-A-PPRV-H-ΔTK as vaccine. Our data indicate that BoHV-4-A-PPRV-H-ΔTK could be a promising new approach for PPRV eradication programs.

The Interplay between Bluetongue Virus Infections and Adaptive Immunity.

Viral infections have long provided a platform to understand the workings of immunity. For instance, great strides towards defining basic immunology concepts, such as MHC restriction of antigen presentation or T-cell memory development and maintenance, have been achieved thanks to the study of lymphocytic choriomeningitis virus (LCMV) infections. These studies have also shaped our understanding of antiviral immunity, and in particular T-cell responses. In the present review, we discuss how bluetongue virus (BTV), an economically important arbovirus from the Reoviridae family that affects ruminants, affects adaptive immunity in the natural hosts. During the initial stages of infection, BTV triggers leucopenia in the hosts. The host then mounts an adaptive immune response that controls the disease. In this work, we discuss how BTV triggers CD8+ T-cell expansion and neutralizing antibody responses, yet in some individuals viremia remains detectable after these adaptive immune mechanisms are active. We present some unpublished data showing that BTV infection also affects other T cell populations such as CD4+ T-cells or γδ T-cells, as well as B-cell numbers in the periphery. This review also discusses how BTV evades these adaptive immune mechanisms so that it can be transmitted back to the arthropod host. Understanding the interaction of BTV with immunity could ultimately define the correlates of protection with immune mechanisms that would improve our knowledge of ruminant immunology.

Activation of OX40 and CD27 Costimulatory Signalling in Sheep through Recombinant Ovine Ligands.

Members of the tumour necrosis factor (TNF) superfamily OX40L and CD70 and their receptors are costimulating signalling axes critical for adequate T cell activation in humans and mice but characterisation of these molecules in other species including ruminants is lacking. Here we cloned and expressed the predicted ovine orthologues of the receptors OX40 and CD27, as well as soluble recombinant forms of their potential ovine ligands, OaOX40L and OaCD70. Using biochemical and immunofluorescence analyses, we show that both signalling axes are functional in sheep. We show that oligomeric recombinant ligand constructs are able to induce signalling through their receptors on transfected cells. Recombinant defective human adenoviruses were constructed to express the soluble forms of OaOX40L and OaCD70. Both proteins were detected in the supernatant of adenovirus-infected cells and shown to activate NF-κB signalling pathway through their cognate receptor. These adenovirus-secreted OaOX40L and OaCD70 forms could also activate ovine T cell proliferation and enhance IFN-γ production in CD4+ and CD8+ T cells. Altogether, this study provides the first characterisation of the ovine costimulatory OX40L-OX40 and CD70-CD27 signalling axes, and indicates that their activation in vivo may be useful to enhance vaccination-induced immune responses in sheep and other ruminants.

Estimating dyskinesia severity in Parkinson's disease by using a waist-worn sensor: concurrent validity study.

Our research team previously developed an accelerometry-based device, which can be worn on the waist during daily life activities and detects the occurrence of dyskinesia in patients with Parkinson's disease. The goal of this study was to analyze the magnitude of correlation between the numeric output of the device algorithm and the results of the Unified Dyskinesia Rating Scale (UDysRS), administered by a physician. In this study, 13 Parkinson's patients, who were symptomatic with dyskinesias, were monitored with the device at home, for an average period of 30 minutes, while performing normal daily life activities. Each patient's activity was simultaneously video-recorded. A physician was in charge of reviewing the recorded videos and determining the severity of dyskinesia through the UDysRS for every patient. The sensor device yielded only one value for dyskinesia severity, which was calculated by averaging the recorded device readings. Correlation between the results of physician's assessment and the sensor output was analyzed with the Spearman's correlation coefficient. The correlation coefficient between the sensor output and UDysRS result was 0.70 (CI 95%: 0.33-0.88; p = 0.01). Since the sensor was located on the waist, the correlation between the sensor output and the results of the trunk and legs scale sub-items was calculated: 0.91 (CI 95% 0.76-0.97: p < 0.001). The conclusion is that the magnitude of dyskinesia, as measured by the tested device, presented good correlation with that observed by a physician.

Diagnosing bluetongue virus in domestic ruminants: current perspectives.

This review provides an overview of current and potential new diagnostic techniques against bluetongue virus (BTV), an Orbivirus transmitted by arthropods that affects ruminants. Bluetongue is a disease currently notifiable to the World Organization for Animal Health (OIE), causing great economic losses due to decreased trade associated with bluetongue outbreaks and high mortality and morbidity. BTV cross-reacts with many antigenically related viruses including viruses that causes African Horse sickness and epizootic haemorrhagic disease of deer. Therefore, reliable diagnostic approaches to detect BTV among these other antigenically related viruses are used or being developed. The antigenic determinant for differentiation of virus species/serogroups among orbiviruses is the VP7 protein, meanwhile VP2 is serotype specific. Serologically, assays are established in many laboratories, based mainly on competitive ELISA or serum neutralization assay (virus neutralization assay [VNT]) although new techniques are being developed. Virus isolation from blood or semen is, additionally, another means of BTV diagnosis. Nevertheless, most of these techniques for viral isolation are time-consuming and expensive. Currently, reverse-transcription polymerase chain reaction (RT-PCR) panels or real-time RT-PCR are widely used methods although next-generation sequencing remains of interest for future virus diagnosis.

A Kinematic Sensor and Algorithm to Detect Motor Fluctuations in Parkinson Disease: Validation Study Under Real Conditions of Use.

BACKGROUND: A new algorithm has been developed, which combines information on gait bradykinesia and dyskinesia provided by a single kinematic sensor located on the waist of Parkinson disease (PD) patients to detect motor fluctuations (On- and Off-periods). OBJECTIVE: The goal of this study was to analyze the accuracy of this algorithm under real conditions of use. METHODS: This validation study of a motor-fluctuation detection algorithm was conducted on a sample of 23 patients with advanced PD. Patients were asked to wear the kinematic sensor for 1 to 3 days at home, while simultaneously keeping a diary of their On- and Off-periods. During this testing, researchers were not present, and patients continued to carry on their usual daily activities in their natural environment. The algorithm's outputs were compared with the patients' records, which were used as the gold standard. RESULTS: The algorithm produced 37% more results than the patients' records (671 vs 489). The positive predictive value of the algorithm to detect Off-periods, as compared with the patients' records, was 92% (95% CI 87.33%-97.3%) and the negative predictive value was 94% (95% CI 90.71%-97.1%); the overall classification accuracy was 92.20%. CONCLUSIONS: The kinematic sensor and the algorithm for detection of motor-fluctuations validated in this study are an accurate and useful tool for monitoring PD patients with difficult-to-control motor fluctuations in the outpatient setting.

Quantity of Movement as a Measure of Engagement for Dementia: The Influence of Motivational Disorders.

Engagement in activities is crucial to improve quality of life in dementia. Yet, its measurement relies exclusively on behavior observation and the influence that behavioral and psychological symptoms of dementia (BPSD) have on it is overlooked. This study investigated whether quantity of movement, gauged with a wrist-worn accelerometer, could be a sound measure of engagement and whether apathy and depression negatively affected engagement. Fourteen participants with dementia took part in 6 sessions of activities: 3 of cognitive games (eg, jigsaw puzzles) and 3 of robot play (Pleo). Results highlighted significant correlations between quantity of movement and observational scales of engagement and a strong negative influence of apathy and depression on engagement. Overall, these findings suggest that quantity of movement could be used as an ancillary measure of engagement and underline the need to profile people with dementia according to their concurrent BPSD to better understand their engagement in activities.

Peste des Petits Ruminants Virus Fusion and Hemagglutinin Proteins Trigger Antibody-Dependent Cell-Mediated Cytotoxicity in Infected Cells.

The adaptive immune system utilizes multiple effector mechanisms to clear viral infections. Among those antibody-dependent cell-mediated cytotoxicity (ADCC) can help recognize and clear virus-infected cells. In the present work we evaluated ADCC contribution to immunity in two economically important viral diseases that affect ruminants: bluetongue and peste des petits ruminants. Immune sera obtained from sheep experimentally infected with bluetongue virus (BTV) serotype 8 or peste des petits ruminant virus (PPRV) IC'89 were used for this study. PPRV immune sera could bind to the surface of PPRV-infected ovine B cells while BTV immune sera was unable to bind to the surface of BTV-infected sheep cells but could recognize intracellular BTV antigens. BTV and PPRV immune serum ADCC potency was established using an ovine autologous cytotoxicity assay that employed an NK cell-enriched fraction as effector cells and a virus-infected B cell-enriched fraction as target cells. In this system, immune sera triggered ADCC against PPRV-infected cells, but not against BTV-infected cells. PPRV immune sera could recognize PPRV fusion and hemagglutinin proteins on the surface of transfected cells, and enhanced lysis of these cells in ADCC assays. This indicated that these viral antigens are natural ADCC targets during PPRV infection. The present work describes a novel effector immune mechanism against PPRV in the natural host that could contribute to virus clearance highlighting the importance of studying protective immune mechanisms to improve current vaccines by invoking all effector arms of immunity.

Corrigendum: Analysis of Correlation between an Accelerometer-Based Algorithm for Detecting Parkinsonian Gait and UPDRS Subscales.

[This corrects the article on p. 431 in vol. 8, PMID: 28919877.].

Analysis of Correlation between an Accelerometer-Based Algorithm for Detecting Parkinsonian Gait and UPDRS Subscales.

BACKGROUND: Our group earlier developed a small monitoring device, which uses accelerometer measurements to accurately detect motor fluctuations in patients with Parkinson's (On and Off state) based on an algorithm that characterizes gait through the frequency content of strides. To further validate the algorithm, we studied the correlation of its outputs with the motor section of the Unified Parkinson's Disease Rating Scale part-III (UPDRS-III). METHOD: Seventy-five patients suffering from Parkinson's disease were asked to walk both in the Off and the On state while wearing the inertial sensor on the waist. Additionally, all patients were administered the motor section of the UPDRS in both motor phases. Tests were conducted at the patient's home. Convergence between the algorithm and the scale was evaluated by using the Spearman's correlation coefficient. RESULTS: Correlation with the UPDRS-III was moderate (rho -0.56; p < 0.001). Correlation between the algorithm outputs and the gait item in the UPDRS-III was good (rho -0.73; p < 0.001). The factorial analysis of the UPDRS-III has repeatedly shown that several of its items can be clustered under the so-called Factor 1: "axial function, balance, and gait." The correlation between the algorithm outputs and this factor of the UPDRS-III was -0.67 (p < 0.01). CONCLUSION: The correlation achieved by the algorithm with the UPDRS-III scale suggests that this algorithm might be a useful tool for monitoring patients with Parkinson's disease and motor fluctuations.

Reclassification of the Specialized Metabolite Producer Pseudomonas mesoacidophila ATCC 31433 as a Member of the Burkholderia cepacia Complex.

Pseudomonas mesoacidophila ATCC 31433 is a Gram-negative bacterium, first isolated from Japanese soil samples, that produces the monobactam isosulfazecin and the ß-lactam-potentiating bulgecins. To characterize the biosynthetic potential of P. mesoacidophila ATCC 31433, its complete genome was determined using single-molecule real-time DNA sequence analysis. The 7.8-Mb genome comprised four replicons, three chromosomal (each encoding rRNA) and one plasmid. Phylogenetic analysis demonstrated that P. mesoacidophila ATCC 31433 was misclassified at the time of its deposition and is a member of the Burkholderia cepacia complex, most closely related to Burkholderia ubonensis The sequenced genome shows considerable additional biosynthetic potential; known gene clusters for malleilactone, ornibactin, isosulfazecin, alkylhydroxyquinoline, and pyrrolnitrin biosynthesis and several uncharacterized biosynthetic gene clusters for polyketides, nonribosomal peptides, and other metabolites were identified. Furthermore, P. mesoacidophila ATCC 31433 harbors many genes associated with environmental resilience and antibiotic resistance and was resistant to a range of antibiotics and metal ions. In summary, this bioactive strain should be designated B. cepacia complex strain ATCC 31433, pending further detailed taxonomic characterization.IMPORTANCE This work reports the complete genome sequence of Pseudomonas mesoacidophila ATCC 31433, a known producer of bioactive compounds. Large numbers of both known and novel biosynthetic gene clusters were identified, indicating that P. mesoacidophila ATCC 31433 is an untapped resource for discovery of novel bioactive compounds. Phylogenetic analysis demonstrated that P. mesoacidophila ATCC 31433 is in fact a member of the Burkholderia cepacia complex, most closely related to the species Burkholderia ubonensis Further investigation of the classification and biosynthetic potential of P. mesoacidophila ATCC 31433 is warranted.

A Waist-Worn Inertial Measurement Unit for Long-Term Monitoring of Parkinson's Disease Patients.

Inertial measurement units (IMUs) are devices used, among other fields, in health applications, since they are light, small and effective. More concretely, IMUs have been demonstrated to be useful in the monitoring of motor symptoms of Parkinson's disease (PD). In this sense, most of previous works have attempted to assess PD symptoms in controlled environments or short tests. This paper presents the design of an IMU, called 9 × 3, that aims to assess PD symptoms, enabling the possibility to perform a map of patients' symptoms at their homes during long periods. The device is able to acquire and store raw inertial data for artificial intelligence algorithmic training purposes. Furthermore, the presented IMU enables the real-time execution of the developed and embedded learning models. Results show the great flexibility of the 9 × 3, storing inertial information and algorithm outputs, sending messages to external devices and being able to detect freezing of gait and bradykinetic gait. Results obtained in 12 patients exhibit a sensitivity and specificity over 80%. Additionally, the system enables working 23 days (at waking hours) with a 1200 mAh battery and a sampling rate of 50 Hz, opening up the possibility to be used for other applications like wellbeing and sports.