Kilohertz-driven Bose-Einstein condensates in optical lattices

We analyze time-of-flight absorption images obtained with dilute Bose-Einstein con-densates released from shaken optical lattices, both theoretically and experimentally. We argue that weakly interacting, ultracold quantum gases in kilohertz-driven optical potentials constitute equilibrium systems characterized by a steady-state distri-bution of Floquet-state occupation numbers. Our experimental results consistently indicate that a driven ultracold Bose gas tends to occupy a single Floquet state, just as it occupies a single energy eigenstate when there is no forcing. When the driving amplitude is sufficiently high, the Floquet state possessing the lowest mean energy does not necessarily coincide with the Floquet state connected to the ground state of the undriven system. We observe strongly driven Bose gases to condense into the former state under such conditions, thus providing nontrivial examples of dressed matter waves.Comment: 36 pages, 3 figures, Advance Atomic Molecular Physics in pres

Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice.

To gain insight into how mutant huntingtin (mHtt) CAG repeat length modifies Huntington's disease (HD) pathogenesis, we profiled mRNA in over 600 brain and peripheral tissue samples from HD knock-in mice with increasing CAG repeat lengths. We found repeat length-dependent transcriptional signatures to be prominent in the striatum, less so in cortex, and minimal in the liver. Coexpression network analyses revealed 13 striatal and 5 cortical modules that correlated highly with CAG length and age, and that were preserved in HD models and sometimes in patients. Top striatal modules implicated mHtt CAG length and age in graded impairment in the expression of identity genes for striatal medium spiny neurons and in dysregulation of cyclic AMP signaling, cell death and protocadherin genes. We used proteomics to confirm 790 genes and 5 striatal modules with CAG length-dependent dysregulation at the protein level, and validated 22 striatal module genes as modifiers of mHtt toxicities in vivo

Extensive Expression Analysis of Htt Transcripts in Brain Regions from the zQ175 HD Mouse Model Using a QuantiGene Multiplex Assay

Huntington’s disease (HD) is an inherited neurodegenerative disorder caused by a CAG repeat expansion within exon 1 of the huntingtin (HTT) gene. HTT mRNA contains 67 exons and does not always splice between exon 1 and exon 2 leading to the production of a small polyadenylated HTTexon1 transcript, and the full-length HTT mRNA has three 3′UTR isoforms. We have developed a QuantiGene multiplex panel for the simultaneous detection of all of these mouse Htt transcripts directly from tissue lysates and demonstrate that this can replace the more work-intensive Taqman qPCR assays. We have applied this to the analysis of brain regions from the zQ175 HD mouse model and wild type littermates at two months of age. We show that the incomplete splicing of Htt occurs throughout the brain and confirm that this originates from the mutant and not endogenous Htt allele. Given that HTTexon1 encodes the highly pathogenic exon 1 HTT protein, it is essential that the levels of all Htt transcripts can be monitored when evaluating HTT lowering approaches. Our QuantiGene panel will allow the rapid comparative assessment of all Htt transcripts in cell lysates and mouse tissues without the need to first extract RNA

Protocol for a home-based integrated physical therapy program to reduce falls and improve mobility in people with Parkinson’s disease

Background The high incidence of falls associated with Parkinson’s disease (PD) increases the risk of injuries and immobility and compromises quality of life. Although falls education and strengthening programs have shown some benefit in healthy older people, the ability of physical therapy interventions in home settings to reduce falls and improve mobility in people with Parkinson’s has not been convincingly demonstrated.Methods/design 180 community living people with PD will be randomly allocated to receive either a home-based integrated rehabilitation program (progressive resistance strength training, movement strategy training and falls education) or a home-based life skills program (control intervention). Both programs comprise one hour of treatment and one hour of structured homework per week over six weeks of home therapy. Blinded assessments occurring before therapy commences, the week after completion of therapy and 12 months following intervention will establish both the immediate and long-term benefits of home-based rehabilitation. The number of falls, number of repeat falls, falls rate and time to first fall will be the primary measures used to quantify outcome. The economic costs associated with injurious falls, and the costs of running the integrated rehabilitation program from a health system perspective will be established. The effects of intervention on motor and global disability and on quality of life will also be examined. Discussion This study will provide new evidence on the outcomes and cost effectiveness of home-based movement rehabilitation programs for people living with PD

Real-Time Imaging Reveals the Dynamics of Leukocyte Behaviour during Experimental Cerebral Malaria Pathogenesis

During experimental cerebral malaria (ECM) mice develop a lethal neuropathological syndrome associated with microcirculatory dysfunction and intravascular leukocyte sequestration. The precise spatio-temporal context in which the intravascular immune response unfolds is incompletely understood. We developed a 2-photon intravital microscopy (2P-IVM)-based brain-imaging model to monitor the real-time behaviour of leukocytes directly within the brain vasculature during ECM. Ly6Chi monocytes, but not neutrophils, started to accumulate in the blood vessels of Plasmodium berghei ANKA (PbA)-infected MacGreen mice, in which myeloid cells express GFP, one to two days prior to the onset of the neurological signs (NS). A decrease in the rolling speed of monocytes, a measure of endothelial cell activation, was associated with progressive worsening of clinical symptoms. Adoptive transfer experiments with defined immune cell subsets in recombinase activating gene (RAG)-1-deficient mice showed that these changes were mediated by Plasmodium-specific CD8+ T lymphocytes. A critical number of CD8+ T effectors was required to induce disease and monocyte adherence to the vasculature. Depletion of monocytes at the onset of disease symptoms resulted in decreased lymphocyte accumulation, suggesting reciprocal effects of monocytes and T cells on their recruitment within the brain. Together, our studies define the real-time kinetics of leukocyte behaviour in the central nervous system during ECM, and reveal a significant role for Plasmodium-specific CD8+ T lymphocytes in regulating vascular pathology in this disease. © 2014 Pai et al

Phenotype onset in Huntington's disease knock-in mice is correlated with the incomplete splicing of the mutant huntingtin gene

Huntington’s disease (HD) is a progressive neurodegenerative disorder caused by an expanded CAG repeat within the huntingtin (HTT) gene. The Q140 and HdhQ150 knock‐in HD mouse models were generated such that HdhQ150 mice have an expanded CAG repeat inserted into the mouse Htt gene, whereas in the Q140s, mouse exon 1 Htt was replaced with a mutated version of human exon 1. By standardizing mouse strain background, breeding to homozygosity and employing sensitive behavioral tests, we demonstrate that the onset of behavioral phenotypes occurs earlier in the Q140 than the HdhQ150 knock‐in mouse models and that huntingtin (HTT) aggregation appears earlier in the striata of Q140 mice. We have previously found that the incomplete splicing of mutant HTT from exon 1 to exon 2 results in the production of a small polyadenylated transcript that encodes the highly pathogenic mutant HTT exon 1 protein. In this report, we have identified a functional consequence of the sequence differences between these two models at the RNA level, in that the level of incomplete splicing, and of the mutant exon 1 HTT protein, are greater in the brains of Q140 mice. While differences in the human and mouse exon 1 HTT proteins (e.g., proline rich sequences) could also contribute to the phenotypic differences, our data indicate that the incomplete splicing of HTT and approaches to lower the levels of the exon 1 HTT transcript should be pursued as therapeutic targets

LDLR Expression and Localization Are Altered in Mouse and Human Cell Culture Models of Alzheimer's Disease

Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the most common form of dementia. The major molecular risk factor for late-onset AD is expression of the ε-4 allele of apolipoprotein E (apoE), the major cholesterol transporter in the brain. The low-density lipoprotein receptor (LDLR) has the highest affinity for apoE and plays an important role in brain cholesterol metabolism.Using RT-PCR and western blotting techniques we found that over-expression of APP caused increases in both LDLR mRNA and protein levels in APP transfected H4 neuroglioma cells compared to H4 controls. Furthermore, immunohistochemical experiments showed aberrant localization of LDLR in H4-APP neuroglioma cells, Aβ-treated primary neurons, and in the PSAPP transgenic mouse model of AD. Finally, immunofluorescent staining of LDLR and of γ- and α-tubulin showed a change in LDLR localization preferentially away from the plasma membrane that was paralleled by and likely the result of a disruption of the microtubule-organizing center and associated microtubule network.These data suggest that increased APP expression and Aβ exposure alters microtubule function, leading to reduced transport of LDLR to the plasma membrane. Consequent deleterious effects on apoE uptake and function will have implications for AD pathogenesis and/or progression

Psychometric properties of the IDS-SR30 for the assessment of depressive symptoms in spanish population

<p>Abstract</p> <p>Background</p> <p>Due to the high prevalence of depression, it is clinically relevant to improve the early identification and assessment of depressive episodes. The main objective of the present study was to examine the psychometric properties of the IDS-SR₃₀(Self-rated Inventory of Depressive Symptomatology) in a large Spanish sample of depressive patients.</p> <p>Methods</p> <p>This prospective, naturalistic, multicenter, nationwide epidemiological study conducted in Spain included 1595 adult patients (65.3% females) with a DSM-IV Major Depressive Disorder (MDD. IDS-SR₃₀and the Hamilton Depression Rating Scale (HDRS, 21 items)were administered to the sample. Data was collected during 2 routine visits. The second assessment was carried out after 10 ± 2 weeks after first assessment.</p> <p>Results</p> <p>The IDS-SR₃₀showed good internal consistency (α = 0.94) and high item total correlations (≥ 0.50) were found in 70% of the items. The convergent validity was 0.85. Results of the principal component analysis (PCA) and confirmatory factor analyses (CFA) showed that a three factor model (labelled mood/cognition, anxiety/somatic and sleep) is adequate for the current sample.</p> <p>Conclusions</p> <p>The Spanish version of the IDS-SR₃₀seems a reliable, valid and useful tool for measuring depression symptomatology in Spanish population.</p