609 research outputs found
Bispecific Tau Antibodies with Additional Binding to C1q or Alpha-Synuclein
BACKGROUND:
Alzheimerâs disease (AD) and other tauopathies are neurodegenerative disorders characterized by cellular accumulation of aggregated tau protein. Tau pathology within these disorders is accompanied by chronic neuroinflammation, such as activation of the classical complement pathway by complement initiation factor C1q. Additionally, about half of the AD cases present with inclusions composed of aggregated alpha-synuclein called Lewy bodies. Lewy bodies in disorders such as Parkinsonâs disease and Lewy body dementia also frequently occur together with tau pathology.
OBJECTIVE:
Immunotherapy is currently the most promising treatment strategy for tauopathies. However, the presence of multiple pathological processes within tauopathies makes it desirable to simultaneously target more than one disease pathway.
METHODS:
Herein, we have developed three bispecific antibodies based on published antibody binding region sequences. One bispecific antibody binds to tau plus alpha-synuclein and two bispecific antibodies bind to tau plus C1q.
RESULTS:
Affinity of the bispecific antibodies to their targets compared to their monospecific counterparts ranged from nearly identical to one order of magnitude lower. All bispecific antibodies retained binding to aggregated protein in patient-derived brain sections. The bispecific antibodies also retained their ability to inhibit aggregation of recombinant tau, regardless of whether the tau binding sites were in IgG or scFv format. Mono- and bispecific antibodies inhibited cellular seeding induced by AD-derived pathological tau with similar efficacy. Finally, both Tau-C1q bispecific antibodies completely inhibited the classical complement pathway.
CONCLUSIONS:
Bispecific antibodies that bind to multiple pathological targets may therefore present a promising approach to treat tauopathies and other neurodegenerative disorders
Control of an atom laser using feedback
A generalised method of using feedback to control Bose-Einstein condensates
is introduced. The condensates are modelled by the Gross-Pitaevskii equation,
so only semiclassical fluctations can be suppressed, and back-action from the
measurement is ignored. We show that for any available control, a feedback
scheme can be found to reduce the energy while the appropriate moment is still
dynamic. We demonstrate these schemes by considering a condensate trapped in a
harmonic potential that can be modulated in strength and position. The
formalism of our feedback scheme also allows the inclusion of certain types of
non-linear controls. If the non-linear interaction between the atoms can be
controlled via a Feshbach resonance, we show that the feedback process can
operate with a much higher efficiency.Comment: 6 pages, 7 figure
Sequencing SARS-CoV-2 Genomes From Saliva
Genomic sequencing is crucial to understanding the epidemiology and evolution of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Often, genomic studies rely on remnant diagnostic material, typically nasopharyngeal (NP) swabs, as input into whole-genome SARS-CoV-2 next-generation sequencing pipelines. Saliva has proven to be a safe and stable specimen for the detection of SARS-CoV-2 RNA via traditional diagnostic assays; however, saliva is not commonly used for SARS-CoV-2 sequencing. Using the ARTIC Network amplicon-generation approach with sequencing on the Oxford Nanopore MinION, we demonstrate that sequencing SARS-CoV-2 from saliva produces genomes comparable to those from NP swabs, and that RNA extraction is necessary to generate complete genomes from saliva. In this study, we show that saliva is a useful specimen type for genomic studies of SARS-CoV-2
The dynamics of component separation in a binary mixture of Bose-Einstein condensates
We present studies of the time-evolution of a two-component system of
Bose-Einstein condensates (BEC) in the |F=1, mf=-1> and |2,1> spin states of
Rb-87. The two condensates are created with a well-defined relative phase and
complete spatial overlap. In subsequent evolution they undergo complex relative
motions which tend to preserve the total density profile. the motions quickly
damp out, leaving the condensates in a steady state with a nonnegligible (and
adjustable) overlap region.Comment: 4 pages, 5 figure
Nonsystematic Reporting Biases of the SARS-CoV-2 Variant Mu Could Impact Our Understanding of the Epidemiological Dynamics of Emerging Variants
Developing a timely and effective response to emerging SARS-CoV-2 variants of concern (VOCs) is of paramount public health importance. Global health surveillance does not rely on genomic data alone to identify concerning variants when they emerge. Instead, methods that utilize genomic data to estimate the epidemiological dynamics of emerging lineages have the potential to serve as an early warning system. However, these methods assume that genomic data are uniformly reported across circulating lineages. In this study, we analyze differences in reporting delays among SARS-CoV-2 VOCs as a plausible explanation for the timing of the global response to the former VOC Mu. Mu likely emerged in South America in mid-2020, where its circulation was largely confined. In this study, we demonstrate that Mu was designated as a VOC âŒ1 year after it emerged and find that the reporting of genomic data for Mu differed significantly than that of other VOCs within countries, states, and individual laboratories. Our findings suggest that nonsystematic biases in the reporting of genomic data may have delayed the global response to Mu. Until they are resolved, the surveillance gaps that affected the global response to Mu could impede the rapid and accurate assessment of future emerging variants
Realization of Bose-Einstein condensates in lower dimensions
Bose-Einstein condensates of sodium atoms have been prepared in optical and
magnetic traps in which the energy-level spacing in one or two dimensions
exceeds the interaction energy between atoms, realizing condensates of lower
dimensionality. The cross-over into two-dimensional and one-dimensional
condensates was observed by a change in aspect ratio and saturation of the
release energy when the number of trapped atoms was reduced
Red light represses the photophysiology of the scleractinian coral Stylophora pistillata
Light spectrum plays a key role in the biology of symbiotic corals, with blue light resulting in higher coral growth, zooxanthellae density, chlorophyll a content and photosynthesis rates as compared to red light. However, it is still unclear whether these physiological processes are blue-enhanced or red-repressed. This study investigated the individual and combined effects of blue and red light on the health, zooxanthellae density, photophysiology and colouration of the scleractinian coral Stylophora pistillata over 6 weeks. Coral fragments were exposed to blue, red, and combined 50/50% blue red light, at two irradiance levels (128 and 256 ÎŒmol mâ2 sâ1). Light spectrum affected the health/survival, zooxanthellae density, and NDVI (a proxy for chlorophyll a content) of S. pistillata. Blue light resulted in highest survival rates, whereas red light resulted in low survival at 256 ÎŒmol mâ2 sâ1. Blue light also resulted in higher zooxanthellae densities compared to red light at 256 ÎŒmol mâ2 sâ1, and a higher NDVI compared to red and combined blue red light. Overall, our results suggest that red light negatively affects the health, survival, symbiont density and NDVI of S. pistillata, with a dominance of red over blue light for NDVI
Quantum dynamics in ultra-cold atomic physics
We review recent developments in the theory of quantum dynamics in ultra-cold
atomic physics, including exact techniques, but focusing on methods based on
phase-space mappings that are appli- cable when the complexity becomes
exponentially large. These phase-space representations include the truncated
Wigner, positive-P and general Gaussian operator representations which can
treat both bosons and fermions. These phase-space methods include both
traditional approaches using a phase-space of classical dimension, and more
recent methods that use a non-classical phase-space of increased
dimensionality. Examples used include quantum EPR entanglement of a four-mode
BEC, time-reversal tests of dephasing in single-mode traps, BEC quantum
collisions with up to 106 modes and 105 interacting particles, quantum
interferometry in a multi-mode trap with nonlinear absorp- tion, and the theory
of quantum entropy in phase-space. We also treat the approach of variational
optimization of the sampling error, giving an elementary example of a nonlinear
oscillator
Effectiveness of a parenting programme in a public health setting: a randomised controlled trial of the positive parenting programme (Triple P) level 3 versus care as usual provided by the preventive child healthcare (PCH)
BACKGROUND: Considering the high burden of disease of psychosocial problems in children and adolescents, early intervention regarding problem behaviour of young children is very important. The Preventive Child Healthcare (PCH) offers a good setting to detect such problem behaviour and to provide parenting support to the parents concerned. This paper aims to describe the design of an effectiveness study of a parenting programme for parents of children with mild psychosocial problems after an initial, evidence based screening in routine PCH. METHODS/DESIGN: The effects of the intervention will be studied in a randomised controlled trial. Prior to a routine PCH health examination, parents complete a screening questionnaire on psychosocial problems. Parents of children with increased but still subclinical levels of psychosocial problems will be assigned at random to the experimental group (Triple P, level 3) or to the control group (care as usual). Outcome measures, such as problem behaviour in the child and parenting behaviour, will be assessed before, directly after and 6 and 12 months after the intervention. DISCUSSION: Parenting support may be an effective intervention to reduce psychosocial problems in children but evidence-based parenting programmes that fit the needs of the PCH are not available as yet. Although the Triple P programme seems promising and suitable for a universal population approach, evidence on its effectiveness in routine PCH still lacks. TRIAL REGISTRATION: NTR1338
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