Vestibular contributions to lateral stabilization are bilaterally dependent during split belt walking

Vestibular information is critical for maintaining balance during locomotion, and is known to be attenuated with increasing locomotor velocity and cadence. This attenuation is muscle and phase dependent, and is thought to reflect the functional contribution of each muscle to balance control during each stride of the gait cycle. Bilaterally, the vestibular coupling is mirrored relative to the gait cycle as each leg undergoes similar modulation with variation in phase, velocity and cadence. Here, we asked whether the modulation of the vestibular contribution to each limb is bilaterally dependent. By using a split-belt treadmill with asymmetric belt speeds, we can control the locomotion properties of each leg and compare the vestibular modulation to symmetric conditions. We hypothesized that bilaterally symmetric vestibular modulation would indicate leg independent vestibular influence while bilaterally asymmetric vestibular modulation would indicate leg dependent vestibular influence. Subjects were exposed to binaural bipolar stochastic vestibular stimulation (0-25 Hz) during symmetric and asymmetric walking conditions. Symmetric trials were performed at belt speeds of 0.4 and 0.8 m/s and for 10 min. The asymmetric trial was performed at belt speeds of 0.4 and 0.8 m/s for 16 min. Subjects walked with a cadence of 78 steps/min which was easily maintained in both limbs. EMG of the bilateral medial gastrocnemii and three-dimensional ground reaction force and torques were collected. Only the last 340 strides (~ 9 min of data) were used in the analysis to avoid the adaptation that typically occurs within the first 250 strides (~ 6 min) of asymmetric walking. Significant muscle activity and lateral ground reaction forces (P < 0.01) were correlated to the input stimuli in all trials. Stimulus-EMG and -lateral ground reaction force correlations decreased at higher belt speeds during symmetric walking, as previously reported. During the split belt condition, the magnitude of correlations stimulus-EMG and -force were bilaterally asymmetric and different from their symmetric counterparts. During the asymmetric condition correlations decreased for the slow leg, but more closely resembled the responses observed during slow symmetric walking, and increased for the fast leg, but more closely resembled the responses observed during fast symmetric walking. These results indicate that the modulation of vestibular reflexes is dependent upon the specific kinematics of each leg but bilaterally linked to respond to the properties of the locomotion pattern

Molecular characterisation of viruses from Kiwifruit

In 2003 Apple stem grooving virus was discovered in Actinidia accessions from China, being held in quarantine in Auckland. Subsequent examination of kiwifruit germplasm from the same source has detected several additional viruses, including a ~300 nm rigid rod related to Ribgrass mosaic virus (Tobamovirus), a 700-750 nm flexuous virus related to Citrus leaf blotch virus (Flexiviridae) and a novel vitivirus. Currently these viruses have not been reported from commercial kiwifruit crops in New Zealand or elsewhere. The biological properties of the viruses from kiwifruit and their phylogenetic relationships with similar viruses from other plants will be described, and the possible implications for the international movement of Actinidia germplasm are discussed

Lack of the transcription factor hypoxia-inducible factor (HIF)-1α in macrophages accelerates the necrosis of Mycobacterium avium-induced granulomas

Accepted ManuscriptThe establishment of mycobacterial infection is characterized by the formation of granulomas, which are well-organized aggregates of immune cells, namely, infected macrophages. The granuloma's main function is to constrain and prevent dissemination of the mycobacteria while focusing the immune response to a limited area. In some cases these lesions can grow progressively into large granulomas which can undergo central necrosis, thereby leading to their caseation. Macrophages are the most abundant cells present in the granuloma and are known to adapt under hypoxic conditions in order to avoid cell death. Our laboratory has developed a granuloma necrosis model that mimics the human pathology of Mycobacterium tuberculosis, using C57BL/6 mice infected intravenously with a low dose of a highly virulent strain of Mycobacterium avium. In this work, a mouse strain deleted of the hypoxia inducible factor 1a (HIF-1a) under the Cre-lox system regulated by the lysozyme M gene promoter was used to determine the relevance of HIF-1a in the caseation of granulomas. The genetic ablation of HIF-1a in the myeloid lineage causes the earlier emergence of granuloma necrosis and clearly induces an impairment of the resistance against M. avium infection coincident with the emergence of necrosis. The data provide evidence that granulomas become hypoxic before undergoing necrosis through the analysis of vascularization and quantification of HIF-1a in a necrotizing mouse model. Our results show that interfering with macrophage adaptation to hypoxia, such as through HIF-1a inactivation, accelerates granuloma necrosis.Support from national funds through FCT/MEC (Fundação para a Ciência e a Tecnologia/Ministério da Educação e Ciência), when applicable cofunded by FEDER funds within the partnership agreement PT2020 related to the research unit number 4293; from “NORTE-07-0124-FEDER-000002-Host-Pathogen Interactions,” cofunded by Programa Operacional Regional do Norte (ON.2–O Novo Norte), under the Quadro de Referência Estratégico Nacional (QREN); and from HMSP-ICT/0024/2010. T.M.S. received postdoctoral grant ON2201310 from “NORTE-07-0124-FEDER-000002-Host-Pathogen Interactions,” cofunded by Programa Operacional Regional do Norte (ON.2–O Novo Norte), under the Quadro de Referência Estratégico Nacional (QREN). M.R. received Ph.D. grant SFRH/BD/89871/2012 from FCT, Portuga

Ne22 distillation and the cooling sequence of the old metal-rich open cluster NGC 6791

Recent Monte Carlo plasma simulations to study in crystallizing carbon-oxygen (CO) white dwarfs (WDs) the phase separation of Ne22 (the most abundant metal after carbon and oxygen) have shown that, under the right conditions, a distillation process that transports Ne22 toward the WD centre is efficient and releases a considerable amount of gravitational energy that can lead to cooling delays of up to several Gyr. Here we present the first CO WD stellar evolution models that self-consistently include the effect of neon distillation, and cover the full range of CO WD masses, for a progenitor metallicity twice-solar appropriate for the old open cluster NGC 6791. The old age (about 8.5 Gyr) and high metallicity of this cluster -- hence the high neon content (about 3% by mass) in the cores of its WDs -- maximize the effect of neon distillation in the models to be compared with the observed cooling sequence. We discuss the effect of distillation on the internal chemical stratification and cooling time of the models, confirming that distillation causes cooling delays up to several Gyr, that depend in a non-monotonic way on the mass. We also show how our models produce luminosity functions (LFs) that can match the faint end of the observed WD LF in NGC 6791, for ages consistent with the range determined from a sample of cluster's eclipsing binary stars, and the main sequence turn-off. Without the inclusion of distillation the theoretical WD cooling sequences reach too faint magnitudes compared to the observations. We also propose James Webb Space Telescope observations that can independently demonstrate the efficiency of neon distillation in the interiors of NGC 6791 WDs, and help resolve the current uncertainty on the treatment of the electron conduction opacities for the hydrogen-helium envelope of the WD models

Effects of Risedronate in Runx2 Overexpressing Mice, an Animal Model for Evaluation of Treatment Effects on Bone Quality and Fractures

Young mice overexpressing Runx2 specifically in cells of the osteoblastic lineage failed to gain bone mass and exhibited a dramatic increase in bone resorption, leading to severe osteopenia and spontaneous vertebral fractures. The objective of the current study was to determine whether treatment with a bisphosphonate (risedronate, Ris), which reduces fractures in postmenopausal as well as in juvenile osteoporosis, was able to improve bone quality and reduce vertebral fractures in mice overexpressing Runx2. Four-week-old female Runx2 mice received Ris at 2 and 10 μg/kg subcutaneously twice a week for 12 weeks. Runx2 and wild-type mice received vehicle (Veh) as control. We measured the number of new fractures by X-ray and bone mineral density (BMD) by DEXA. We evaluated bone quality by histomorphometry, micro-CT, and Fourier transform infrared imaging (FTIRI). Ris at 20 μg/kg weekly significantly reduced the average number of new vertebral fractures compared to controls. This was accompanied by significantly increased BMD, increased trabecular bone volume, and reduced bone remodeling (seen in indices of bone resorption and formation) in the vertebrae and femoral metaphysis compared to Runx2 Veh. At the femur, Ris also increased cortical thickness. Changes in collagen cross-linking seen on FTIRI confirmed that Runx2 mice have accelerated bone turnover and showed that Ris affects the collagen cross-link ratio at both forming and resorbing sites. In conclusion, young mice overexpressing Runx2 have high bone turnover-induced osteopenia and spontaneous fractures. Ris at 20 μg/kg weekly induced an increase in bone mass, changes in bone microarchitecture, and decreased vertebral fractures

Sensor Data Visualisation: A Composition-Based Approach to Support Domain Variability

International audienceIn the context of the Internet of Things, sensors are surrounding our environment. These small pieces of electronics are inserted in everyday life's elements (e.g., cars, doors, radiators, smartphones) and continuously collect information about their environment. One of the biggest challenges is to support the development of accurate monitoring dashboard to visualise such data. The one-size-fits-all paradigm does not apply in this context, as user's roles are variable and impact the way data should be visualised: a building manager does not need to work on the same data as classical users. This paper presents an approach based on model composition techniques to support the development of such monitoring dashboards, taking into account the domain variability. This variability is supported at both implementation and modelling levels. The results are validated on a case study named SmartCampus, involving sensors deployed in a real academic campus

A robust SNP barcode for typing Mycobacterium tuberculosis complex strains

Strain-specific genomic diversity in the Mycobacterium tuberculosis complex (MTBC) is an important factor in pathogenesis that may affect virulence, transmissibility, host response and emergence of drug resistance. Several systems have been proposed to classify MTBC strains into distinct lineages and families. Here, we investigate single-nucleotide polymorphisms (SNPs) as robust (stable) markers of genetic variation for phylogenetic analysis. We identify ~92k SNP across a global collection of 1,601 genomes. The SNP-based phylogeny is consistent with the gold-standard regions of difference (RD) classification system. Of the ~7k strain-specific SNPs identified, 62 markers are proposed to discriminate known circulating strains. This SNP-based barcode is the first to cover all main lineages, and classifies a greater number of sublineages than current alternatives. It may be used to classify clinical isolates to evaluate tools to control the disease, including therapeutics and vaccines whose effectiveness may vary by strain type