•Full genome characterization of a PRRSV-2 strain causing significant clinical disease in the field.•Examination of the field isolate in an experimental infection study in growing pigs.•Investigation ...of the prophylactic effect of a current MLV PRRS-2 vaccine against the field isolate.
Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is the cause of severe reproductive and respiratory disease in swine worldwide. In Denmark, both PRRSV-1 and PRRSV-2 are circulating and approximately 35% of pig herds are seropositive for PRRSV.
In November 2010, a pig herd in the Northern part of Denmark experienced an infection with PRRSV-2 with clinical signs that were much more severe than normally reported from current Danish PRRSV-2 affected herds. Due to the clinical observations of reproductive failure in sows and high mortality in piglets, it was speculated that a new, more pathogenic or vaccine evading PRRSV strain had emerged in Denmark. The overall aim of the present study was to perform a genetic and biological characterization of the virus isolated from the diseased herd. Complete genome sequencing of isolates from this herd revealed that although the case strain had some unique genetic features including a deduced 3 amino acid deletion, it was in overall very similar to the other PRRS-2 viruses circulating in Denmark. In an experimental trial in growing pigs, no overt clinical signs or pathology were observed following intranasal inoculation with the new virus isolate. Virus shedding, acute phase protein responses and serological responses were comparable to those seen after experimental challenge with a Danish PRRSV-2 reference strain isolated in 1997. Vaccination with a commercial modified live PRRSV-2 vaccine had a clear reducing effect on virus shedding, magnitude, and duration of viremia and viral load in the lungs. Overall, the results indicate that the severe disease observed in the field was contributed by additional factors in combination with the PRRS virus infection.
The intestinal microbiome has been associated with response to immune checkpoint inhibitors (ICIs) in humans and causally implicated in ICI responsiveness in animal models. Two recent human trials ...demonstrated that fecal microbiota transplant (FMT) from ICI responders can rescue ICI responses in refractory melanoma, but FMT has specific limitations to scaled use.
We conducted an early-phase clinical trial of a cultivated, orally delivered 30-species microbial consortium (Microbial Ecosystem Therapeutic 4, MET4) designed for co-administration with ICIs as an alternative to FMT and assessed safety, tolerability and ecological responses in patients with advanced solid tumors.
The trial achieved its primary safety and tolerability outcomes. There were no statistically significant differences in the primary ecological outcomes; however, differences in MET4 species relative abundance were evident after randomization that varied by patient and species. Increases in the relative abundance of several MET4 taxa, including Enterococcus and Bifidobacterium, taxa previously associated with ICI responsiveness, were observed and MET4 engraftment was associated with decreases in plasma and stool primary bile acids.
This trial is the first report of the use of a microbial consortium as an alternative to FMT in advanced cancer patients receiving ICI and the results justify the further development of microbial consortia as a therapeutic co-intervention for ICI treatment in cancer.
•MET4-IO is a first-in-class oral multi-strain microbiome therapeutic in advanced cancer patients receiving immunotherapy.•The trial achieved its primary safety and tolerability outcomes.•No differences in the primary ecological outcomes were observed.•Differences in MET4 species relative abundance were evident after randomization that varied by patient and species.•The efficacy of MET4 with anti-PD1 will be explored in a phase II study in advanced head and neck cancer patients.
The production cost of materials for hydrogen storage is one of the major issues to be addressed in order to consider them suitable for large scale applications. In the last decades several authors ...reported on the hydrogen sorption properties of Mg and Mg-based systems. In this work magnesium industrial wastes of AZ91 alloy and Mg-10 wt.% Gd alloy are used for the production of hydrogen storage materials. The hydrogen sorption properties of the alloys were investigated by means of volumetric technique, in situ synchrotron radiation powder X-ray diffraction (SR-PXD) and calorimetric methods. The measured reversible hydrogen storage capacity for the alloys AZ91 and Mg-10 wt.% Gd are 4.2 and 5.8 wt.%, respectively. For the Mg-10 wt.% Gd alloy, the hydrogenated product was also successfully used as starting reactant for the synthesis of Mg(NH2)2 and as MgH2 substitute in the Reactive Hydride Composite (RHC) 2LiBH4 + MgH2. The results of this work demonstrate the concrete possibility to use Mg alloy wastes for hydrogen storage purposes.
•Mg based wastes can be used for H2 storage purposes.•The hydrogenated alloys show a H2 capacity of ∼6 wt.%.•The conversion process is possible and easily achievable.
In this tutorial review we give an introduction into the field of stimulus responsive peptide based materials illustrated by some recent and current developments. We have tried to categorize them ...according to the stimulus the materials are responsive to, being pH, temperature, metal ions, enzymes and light. Because we have focused on the structural changes that these stimuli effect we have further classified the topics according to the secondary structures that are involved. These changes in molecular structure in turn cause a change in the macroscopic properties of the material they constitute. It is believed that these materials, often referred to as smart materials, have a great potential being applicable in areas like drug delivery, tissue engineering and bio-sensors.
A trio of genome-wide association studies recently reported sequence variants at three loci to be significantly associated with schizophrenia. No sequence polymorphism had been unequivocally (P<5 × ...10(-8)) associated with schizophrenia earlier. However, one variant, rs1344706T, had come very close. This polymorphism, located in an intron of ZNF804A, was reported to associate with schizophrenia with a P-value of 1.6 × 10(-7), and with psychosis (schizophrenia plus bipolar disorder) with a P-value of 1.0 × 10(-8). In this study, using 5164 schizophrenia cases and 20,709 controls, we replicated the association with schizophrenia (odds ratio OR = 1.08, P = 0.0029) and, by adding bipolar disorder patients, we also confirmed the association with psychosis (added N = 609, OR = 1.09, P = 0.00065). Furthermore, as it has been proposed that variants such as rs1344706T-common and with low relative risk-may also serve to identify regions harboring less common, higher-risk susceptibility alleles, we searched ZNF804A for large copy number variants (CNVs) in 4235 psychosis patients, 1173 patients with other psychiatric disorders and 39,481 controls. We identified two CNVs including at least part of ZNF804A in psychosis patients and no ZNF804A CNVs in controls (P = 0.013 for association with psychosis). In addition, we found a ZNF804A CNV in an anxiety patient (P = 0.0016 for association with the larger set of psychiatric disorders).
RATIONALE:There are several methods to measure cardiomyocyte and muscle contraction, but these require customized hardware, expensive apparatus, and advanced informatics or can only be used in single ...experimental models. Consequently, data and techniques have been difficult to reproduce across models and laboratories, analysis is time consuming, and only specialist researchers can quantify data.
OBJECTIVE:Here, we describe and validate an automated, open-source software tool (MUSCLEMOTION) adaptable for use with standard laboratory and clinical imaging equipment that enables quantitative analysis of normal cardiac contraction, disease phenotypes, and pharmacological responses.
METHODS AND RESULTS:MUSCLEMOTION allowed rapid and easy measurement of movement from high-speed movies in (1) 1-dimensional in vitro models, such as isolated adult and human pluripotent stem cell-derived cardiomyocytes; (2) 2-dimensional in vitro models, such as beating cardiomyocyte monolayers or small clusters of human pluripotent stem cell-derived cardiomyocytes; (3) 3-dimensional multicellular in vitro or in vivo contractile tissues, such as cardiac “organoids,” engineered heart tissues, and zebrafish and human hearts. MUSCLEMOTION was effective under different recording conditions (bright-field microscopy with simultaneous patch-clamp recording, phase contrast microscopy, and traction force microscopy). Outcomes were virtually identical to the current gold standards for contraction measurement, such as optical flow, post deflection, edge-detection systems, or manual analyses. Finally, we used the algorithm to quantify contraction in in vitro and in vivo arrhythmia models and to measure pharmacological responses.
CONCLUSIONS:Using a single open-source method for processing video recordings, we obtained reliable pharmacological data and measures of cardiac disease phenotype in experimental cell, animal, and human models.
Stimulus responsive peptide based materials Löwik, Dennis W. P. M.; Leunissen, E. H. P.; van den Heuvel, M. ...
Chemical Society reviews,
2010, Letnik:
39, Številka:
9
Journal Article
Atomic-Scale Visualization of Inertial Dynamics Lindenberg, A. M; Larsson, J; Sokolowski-Tinten, K ...
Science (American Association for the Advancement of Science),
04/2005, Letnik:
308, Številka:
5720
Journal Article
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The motion of atoms on interatomic potential energy surfaces is fundamental to the dynamics of liquids and solids. An accelerator-based source of femtosecond x-ray pulses allowed us to follow ...directly atomic displacements on an optically modified energy landscape, leading eventually to the transition from crystalline solid to disordered liquid. We show that, to first order in time, the dynamics are inertial, and we place constraints on the shape and curvature of the transition-state potential energy surface. Our measurements point toward analogies between this nonequilibrium phase transition and the short-time dynamics intrinsic to equilibrium liquids.
The motor control resolution of any animal behavior is limited to the minimal force step available when activating muscles, which is set by the number and size distribution of motor units (MUs) and ...muscle-specific force. Birdsong is an excellent model system for understanding acquisition and maintenance of complex fine motor skills, but we know surprisingly little about how the motor pool controlling the syrinx is organized and how MU recruitment drives changes in vocal output. Here we developed an experimental paradigm to measure MU size distribution using spatiotemporal imaging of intracellular calcium concentration in cross-sections of living intact syrinx muscles. We combined these measurements with muscle stress and an in vitro syrinx preparation to determine the control resolution of fundamental frequency (fo), a key vocal parameter, in zebra finches. We show that syringeal muscles have extremely small MUs, with 40%–50% innervating ≤3 and 13%–17% innervating a single muscle fiber. Combined with the lowest specific stress (5 mN/mm2) known to skeletal vertebrate muscle, small force steps by the major fo controlling muscle provide control of 50-mHz to 7.3-Hz steps per MU. We show that the song system has the highest motor control resolution possible in the vertebrate nervous system and suggest this evolved due to strong selection on fine gradation of vocal output. Furthermore, we propose that high-resolution motor control was a key feature contributing to the radiation of songbirds that allowed diversification of song and speciation by vocal space expansion.
•Motor neurons in the zebra finch vocal motor pool innervate single muscle fibers•Zebra finch vocal muscles have the lowest measured isometric stress•Small motor unit size and low muscle stress provide sub-hertz pitch control resolution•High-resolution control is key to vocal space expansion and songbird radiation
Adam et al. show that the zebra finch vocal motor pool has extremely small motor units, with 13%–17% of motor neurons innervating single syringeal muscle fibers. Together with very low muscle stress, this high-resolution motor control allows for fine control of vocal output, including sub-hertz pitch control, leading to vocal space expansion.
While higher intake of fish and lower consumption of red/processed meats have been suggested to play a protective role in the etiology of several cancers, prospective evidence for hepatocellular ...carcinoma (HCC) is limited, particularly in Western European populations.
The associations of fish and meats with HCC risk were analyzed in the EPIC cohort. Between 1992 and 2010, 191 incident HCC were identified among 477 206 participants. Baseline diet was assessed using validated dietary questionnaires. A single 24-h diet recall from a cohort subsample was used for calibration. Multivariable proportional hazard regression was utilized to estimate hazard ratios (HR) and 95% confidence intervals (CI). In a nested case–control subset (HCC = 122), HBV/HCV status and liver function biomarkers were measured.
HCC risk was inversely associated with intake of total fish (per 20 g/day increase, HR = 0.83, 95% CI 0.74–0.95 and HR = 0.80, 95% CI 0.69–0.97 before and after calibration, respectively). This inverse association was also suggested after adjusting for HBV/HCV status and liver function score (per 20-g/day increase, RR = 0.86, 95% CI 0.66–1.11 and RR = 0.74, 95% CI 0.50–1.09, respectively) in a nested case–control subset. Intakes of total meats or subgroups of red/processed meats, and poultry were not associated with HCC risk.
In this large European cohort, total fish intake is associated with lower HCC risk.
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