Cell Type-Specific Human APP Transgene Expression by Hippocampal Interneurons in the Tg2576 Mouse Model of Alzheimer's Disease

Amyloid precursor protein (APP) transgenic animal models of Alzheimer's disease have become versatile tools for basic and translational research. However, there is great heterogeneity of histological, biochemical, and functional data between transgenic mouse lines, which might be due to different transgene expression patterns. Here, the expression of human APP (hAPP) by GABAergic hippocampal interneurons immunoreactive for the calcium binding proteins parvalbumin, calbindin, calretinin, and for the peptide hormone somatostatin was analyzed in Tg2576 mice by double immunofluorescent microscopy. Overall, there was no GABAergic interneuron subpopulation that did not express the transgene. On the other hand, in no case all neurons of such a subpopulation expressed hAPP. In dentate gyrus molecular layer and in stratum lacunosum moleculare less than 10% of hAPP-positive interneurons co-express any of these interneuron markers, whereas in stratum oriens hAPP-expressing neurons frequently co-express these interneuron markers to different proportions. We conclude that these neurons differentially contribute to deficits in young Tg2576 mice before the onset of Abeta plaque pathology. The detailed analysis of distinct brain region and neuron type-specific APP transgene expression patterns is indispensable to understand particular pathological features and mouse line-specific differences in neuronal and systemic functions

Expression of Lineage Transcription Factors Identifies Differences in Transition States of Induced Human Oligodendrocyte Differentiation

Oligodendrocytes (OLs) are critical for myelination and are implicated in several brain disorders. Directed differentiation of human-induced OLs (iOLs) from pluripotent stem cells can be achieved by forced expression of different combinations of the transcription factors SOX10 (S), OLIG2 (O), and NKX6.2 (N). Here, we applied quantitative image analysis and single-cell transcriptomics to compare different transcription factor (TF) combinations for their efficacy towards robust OL lineage conversion. Compared with S alone, the combination of SON increases the number of iOLs and generates iOLs with a more complex morphology and higher expression levels of myelin-marker genes. RNA velocity analysis of individual cells reveals that S generates a population of oligodendrocyte-precursor cells (OPCs) that appear to be more immature than those generated by SON and to display distinct molecular properties. Our work highlights that TFs for generating iOPCs or iOLs should be chosen depending on the intended application or research question, and that SON might be beneficial to study more mature iOLs while S might be better suited to investigate iOPC biology

Angular anisotropy of the fusion-fission and quasifission fragments

The anisotropy in the angular distribution of the fusion-fission and quasifission fragments for the $^{16}$O+$^{238}$U, $^{19}$F+$^{208}$Pb and $^{32}$S+$^{208}$Pb reactions is studied by analyzing the angular momentum distributions of the dinuclear system and compound nucleus which are formed after capture and complete fusion, respectively. The orientation angles of axial symmetry axes of colliding nuclei to the beam direction are taken into account for the calculation of the variance of the projection of the total spin onto the fission axis. It is shown that the deviation of the experimental angular anisotropy from the statistical model picture is connected with the contribution of the quasifission fragments which is dominant in the $^{32}$S+$^{208}$Pb reaction. Enhancement of anisotropy at low energies in the $^{16}$O+$^{238}$U reaction is connected with quasifission of the dinuclear system having low temperature and effective moment of inertia.Comment: 17 pages 8 figures. Submitted to Euro. Phys. Jour.

Changes in body weight and food choice in those attempting smoking cessation: a cluster randomised controlled trial

<p><b>Background:</b> Fear of weight gain is a barrier to smoking cessation and significant cause of relapse for many people. The provision of nutritional advice as part of a smoking cessation programme may assist some in smoking cessation and perhaps limit weight gain. The aim of this study was to determine the effect of a structured programme of dietary advice on weight change and food choice, in adults attempting smoking cessation.</p> <p><b>Methods:</b> Cluster randomised controlled design. Classes randomised to intervention commenced a 24-week intervention, focussed on improving food choice and minimising weight gain. Classes randomised to control received "usual care".</p> <p><b>Results:</b> Twenty-seven classes in Greater Glasgow were randomised between January and August 2008. Analysis, including those who continued to smoke, showed that actual weight gain and percentage weight gain was similar in both groups. Examination of data for those successful at giving up smoking showed greater mean weight gain in intervention subjects (3.9 (SD 3.1) vs. 2.7 (SD 3.7) kg). Between group differences were not significant (p=0.23, 95% CI -0.9 to 3.5). In comparison to baseline improved consumption of fruit and vegetables and breakfast cereal were reported in the intervention group. A higher percentage of control participants continued smoking (74% vs. 66%).</p> <p><b>Conclusions:</b> The intervention was not successful at minimising weight gain in comparison to control but was successful in facilitating some sustained improvements in the dietary habits of intervention participants. Improved quit rates in the intervention group suggest that continued contact with advisors may have reduced anxieties regarding weight gain and encouraged cessation despite weight gain. Research should continue in this area as evidence suggests that the negative effects of obesity could outweigh the health benefits achieved through reductions in smoking prevalence.</p&gt

Nonequilibrium wetting

When a nonequilibrium growing interface in the presence of a wall is considered a nonequilibrium wetting transition may take place. This transition can be studied trough Langevin equations or discrete growth models. In the first case, the Kardar-Parisi-Zhang equation, which defines a very robust universality class for nonequilibrium moving interfaces, with a soft-wall potential is considered. While in the second, microscopic models, in the corresponding universality class, with evaporation and deposition of particles in the presence of hard-wall are studied. Equilibrium wetting is related to a particular case of the problem, it corresponds to the Edwards-Wilkinson equation with a potential in the continuum approach or to the fulfillment of detailed balance in the microscopic models. In this review we present the analytical and numerical methods used to investigate the problem and the very rich behavior that is observed with them.Comment: Review, 36 pages, 16 figure

Mitochondrial DNA Copy Number Is Associated with Breast Cancer Risk

Mitochondrial DNA (mtDNA) copy number in peripheral blood is associated with increased risk of several cancers. However, data from prospective studies on mtDNA copy number and breast cancer risk are lacking. We evaluated the association between mtDNA copy number in peripheral blood and breast cancer risk in a nested case-control study of 183 breast cancer cases with pre-diagnostic blood samples and 529 individually matched controls among participants of the Singapore Chinese Health Study. The mtDNA copy number was measured using real time PCR. Conditional logistic regression analyses showed that there was an overall positive association between mtDNA copy number and breast cancer risk (Ptrend = 0.01). The elevated risk for higher mtDNA copy numbers was primarily seen for women with <3 years between blood draw and cancer diagnosis; ORs (95% CIs) for 2nd, 3rd, 4th, and 5th quintile of mtDNA copy number were 1.52 (0.61, 3.82), 2.52 (1.03, 6.12), 3.12 (1.31, 7.43), and 3.06 (1.25, 7.47), respectively, compared with the 1st quintile (Ptrend = 0.004). There was no association between mtDNA copy number and breast cancer risk among women who donated a blood sample ≥3 years before breast cancer diagnosis (Ptrend = 0.41). This study supports a prospective association between increased mtDNA copy number and breast cancer risk that is dependent on the time interval between blood collection and breast cancer diagnosis. Future studies are warranted to confirm these findings and to elucidate the biological role of mtDNA copy number in breast cancer risk. © 2013 Thyagarajan et al

QUINT: Workflow for Quantification and Spatial Analysis of Features in Histological Images From Rodent Brain

Transgenic animal models are invaluable research tools for elucidating the pathways and mechanisms involved in the development of neurodegenerative diseases. Mechanistic clues can be revealed by applying labelling techniques such as immunohistochemistry or in situ hybridisation to brain tissue sections. Precision in both assigning anatomical location to the sections and quantifying labelled features is crucial for output validity, with a stereological approach or image-based feature extraction typically used. However, both approaches are restricted by the need to manually delineate anatomical regions. To circumvent this limitation, we present the QUINT workflow for quantification and spatial analysis of labelling in series of rodent brain section images based on available 3D reference atlases. The workflow is semi-automated, combining three open source software that can be operated without scripting knowledge, making it accessible to most researchers. As an example, a brain region-specific quantification of amyloid plaques across whole transgenic Tg2576 mouse brain series, immunohistochemically labelled for three amyloid-related antigens is demonstrated. First, the whole brain image series were registered to the Allen Mouse Brain Atlas to produce customised atlas maps adapted to match the cutting plan and proportions of the sections (QuickNII software). Second, the labelling was segmented from the original images by the Random Forest Algorithm for supervised classification (ilastik software). Finally, the segmented images and atlas maps were used to generate plaque quantifications for each region in the reference atlas (Nutil software). The method yielded comparable results to manual delineations and to the output of a stereological method. While the use case demonstrates the QUINT workflow for quantification of amyloid plaques only, the workflow is suited to all mouse or rat brain series with labelling that is visually distinct from the background, for example for the quantification of cells or labelled proteins

Disturbed Clockwork Resetting in Sharp-1 and Sharp-2 Single and Double Mutant Mice

BACKGROUND: The circadian system provides the basis to anticipate and cope with daily recurrent challenges to maintain the organisms' homeostasis. De-synchronization of circadian feedback oscillators in humans causes 'jet lag', likely contributes to sleep-, psychiatric-, metabolic disorders and even cancer. However, the molecular mechanisms leading to the disintegration of tissue-specific clocks are complex and not well understood. METHODOLOGY/PRINCIPAL FINDINGS: Based on their circadian expression and cell culture experiments, the basic Helix-Loop-Helix (bHLH) transcription factors SHARP-1(Dec2) and SHARP-2(Stra13/Dec1) were proposed as novel negative regulators of the molecular clock. To address their function in vivo, we generated Sharp-1 and Sharp-2 single and double mutant mice. Our experiments reveal critical roles for both factors in regulating period length, tissue-specific control of clock gene expression and entrainment to external cues. Light-pulse experiments and rapid delays of the light-dark cycle (experimental jet lag) unravel complementary functions for SHARP-1 and SHARP-2 in controlling activity phase resetting kinetics. Moreover, we show that SHARP-1 and 2 can serve dual functions as repressors and co-activators of mammalian clock gene expression in a context-specific manner. This correlates with increased amplitudes of Per2 expression in the cortex and liver and a decrease in the suprachiasmatic nucleus (SCN) of double mutant mice. CONCLUSIONS/SIGNIFICANCE: The existence of separate mechanisms regulating phase of entrainment, rhythm amplitude and period length has been postulated before. The differential effects of Sharp-deficiency on rhythmicity and behavioral re-entrainment, coupled to tissue-dependent regulatory functions, provide a new mechanistic basis to further understand the complex process of clock synchronizations

Propagación vegetativa de procedencias de Tithonia diversifolia (Hemsl) A. Gray en el Noreste de Argentina = Vegetative propagation of Tithonia diversifolia (Hemsl) A. Gray provenances in northeast Argentina

El objetivo del trabajo fue comparar sobrevivencia y crecimiento de tres procedencias y dos tipos de estaca de Botón de oro durante la etapa de propagación vegetativa en vivero. Se establecieron tres ensayos en red en la estación experimental de INTA Cerro Azul (Misiones), Campo Anexo Laharrague de INTA Montecarlo (Misiones) y en la Universidad del Salvador Sede Gdor. Virasoro, Corrientes. El diseño fue factorial con arreglo en BCA y cinco repeticiones. El factor procedencia con tres niveles: México, Brasil y Colombia y el factor tipo de estaca con dos niveles: basal y sub-apical. Los tratamientos fueron: CoA (Colombia apical), CoB (Colombia basal), BrA (Brasil apical), BrB (Brasil basal), MeA (México apical) y MeB (México basal). Se evaluó en las estacas (previo a la plantación): número de nudos, diámetro total (cm), diámetro de médula (cm) y peso (g), en vivero: sobrevivencia y prendimiento de brotes y altura máxima de planta a los 7, 15, 30 y 40 días y al finalizar el período se cosechó la biomasa aérea y subterránea. La menor sobrevivencia de plantas fue para MeA (84%) y MeB (90%). La mayor altura para BrB (70,16 cm) y el mayor número de brotes para BrB, BrA y CoA (2,2; 2,3 y 2,4). La biomasa total medida en Virasoro y Cerro Azul fue mayor para BrB (12,47 y 9,83 g MS planta-1 en ambos sitios). Las procedencias Brasil y Colombia presentaron los mayores valores de sobrevivencia, crecimiento en altura, número de brotes y producción de biomasa, por lo cual pueden ser consideradas más promisorias para la región de estudio.The aim of this work was to compare survival rate and growth of “Botón de oro” of three provenances and two cutting types in the vegetative propagation period in greenhouse. Three experiments were established at 216 INTA experimental station Cerro Azul (Misiones), INTA experimental field Laharrague (Montecarlo, Misiones) and Universidad Del Salvador, Gobernador Virasoro, Corrientes. The experimental design was factorial with CRB arrangement and five replicates. The origins were Mexico, Brazil and Colombia and cutting types were basal and sub-apical. The treatments results: CoA (Colombia apical, CoB (Colombia basal), BrA (Brazil apical), BrB (Brazil basal), MeA (Mexico apical) and MeB (Mexico basal). In cutting (before plantation): nodes number, total diameter (cm), marrow diameter (cm) and weight (g) were measured. In greenhouse: survival rate, sprout number and height at 7, 15, 30 and 40 days and at the end aerial and underground biomass were assessed. The lowest survival rate was for MeA (84%) and MeB (90%). The main height was for BrB (70,16cm) and the highest sprouts number were for BrB, BrA and CoA (2.2;2.3 and 2.4). The highest biomass was for BrB (12.47and 9.83g plant-1). Brazil and Colombia origins showed the best values for survival rate, height, sprouts number and biomass production, being the most adapted origins for the study region.EEA MontecarloFil: Rossner, Maria Belen. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Cerro Azul; ArgentinaFil: Ziegler, Ariana. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Cerro Azul. Agencia de Extensión Rural Apóstoles; ArgentinaFil: González, Paola. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Montecarlo; ArgentinaFil: Loto, Mauro. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Montecarlo; ArgentinaFil: Kimmich, Germán. Universidad del Salvador. Facultad de Ciencias Agrarias Virasoro; ArgentinaFil: Corró, Federico. Universidad del Salvador. Facultad de Ciencias Agrarias Virasoro; ArgentinaFil: Fernández, F. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Cerro Azul. Agencia de Extensión Rural Apóstoles; Argentin