Plac8 is required for white adipocyte differentiation in vitro and cell number control in vivo.

Plac8 belongs to an evolutionary conserved family of proteins, mostly abundant in plants where they control fruit weight through regulation of cell number. In mice, Plac8 is expressed both in white and brown adipose tissues and we previously showed that Plac8(-/-) mice develop late-onset obesity, with abnormal brown fat differentiation and reduced thermogenic capacity. We also showed that in brown adipocytes, Plac8 is an upstream regulator of C/EBPβ expression. Here, we first assessed the role of Plac8 in white adipogenesis in vitro. We show that Plac8 is induced early after induction of 3T3-L1 adipocytes differentiation, a process that is prevented by Plac8 knockdown; similarly, embryonic fibroblasts obtained from Plac8 knockout mice failed to form adipocytes upon stimulation of differentiation. Knockdown of Plac8 in 3T3-L1 was associated with reduced expression of C/EBPβ, Krox20, and Klf4, early regulators of the white adipogenic program, and we show that Plac8 could transactivate the C/EBPβ promoter. In vivo, we show that absence of Plac8 led to increased white fat mass with enlarged adipocytes but reduced total number of adipocytes. Finally, even though Plac8(-/-) mice showed impaired thermogenesis due to brown fat dysfunction, this was not associated with changes in glycemia or plasma free fatty acid and triglyceride levels. Collectively, these data indicate that Plac8 is an upstream regulator of C/EBPβ required for adipogenesis in vitro. However, in vivo, Plac8 is dispensable for the differentiation of white adipocytes with preserved fat storage capacity but is required for normal fat cell number regulation.

Linear prediction application for modelling the relationships between a large number of stand characteristics of Norway spruce stands

Abstract

Copy number variation modifies expression time courses.

A preliminary understanding into the phenotypic effect of DNA segment copy number variation (CNV) is emerging. These rearrangements were demonstrated to influence, in a somewhat dose-dependent manner, the expression of genes that map within them. They were also shown to modify the expression of genes located on their flanks and sometimes those at a great distance from their boundary. Here we demonstrate, by monitoring these effects at multiple life stages, that these controls over expression are effective throughout mouse development. Similarly, we observe that the more specific spatial expression patterns of CNV genes are maintained through life. However, we find that some brain-expressed genes mapping within CNVs appear to be under compensatory loops only at specific time points, indicating that the effect of CNVs on these genes is modulated during development. Notably, we also observe that CNV genes are significantly enriched within transcripts that show variable time courses of expression between strains. Thus, modifying the copy number of a gene may potentially alter not only its expression level, but also the timing of its expression.

KCTD13 is a major driver of mirrored neuroanatomical phenotypes of the 16p11.2 copy number variant.

Copy number variants (CNVs) are major contributors to genetic disorders. We have dissected a region of the 16p11.2 chromosome--which encompasses 29 genes--that confers susceptibility to neurocognitive defects when deleted or duplicated. Overexpression of each human transcript in zebrafish embryos identified KCTD13 as the sole message capable of inducing the microcephaly phenotype associated with the 16p11.2 duplication, whereas suppression of the same locus yielded the macrocephalic phenotype associated with the 16p11.2 deletion, capturing the mirror phenotypes of humans. Analyses of zebrafish and mouse embryos suggest that microcephaly is caused by decreased proliferation of neuronal progenitors with concomitant increase in apoptosis in the developing brain, whereas macrocephaly arises by increased proliferation and no changes in apoptosis. A role for KCTD13 dosage changes is consistent with autism in both a recently reported family with a reduced 16p11.2 deletion and a subject reported here with a complex 16p11.2 rearrangement involving de novo structural alteration of KCTD13. Our data suggest that KCTD13 is a major driver for the neurodevelopmental phenotypes associated with the 16p11.2 CNV, reinforce the idea that one or a small number of transcripts within a CNV can underpin clinical phenotypes, and offer an efficient route to identifying dosage-sensitive loci.

Fractional slot permanent magnet synchronous motors for low speed applications

This study compares different rotor structures of permanent magnet motors with fractional slot windings. The surface mounted magnet and the embedded magnet rotor structures are studied. This thesis analyses the characteristics of a concentrated two-layer winding, each coil of which is wound around one tooth and which has a number of slots per pole and per phase less than one (q < 1). Compared to the integer slot winding, the fractional winding (q < 1) has shorter end windings and this, thereby, makes space as well as manufacturing cost saving possible. Several possible ways of winding a fractional slot machine with slots per pole and per phase lessthan one are examined. The winding factor and the winding harmonic components are calculated. The benefits attainable from a machine with concentrated windingsare considered. Rotor structures with surface magnets, radially embedded magnets and embedded magnets in V-position are discussed. The finite element method isused to solve the main values of the motors. The waveform of the induced electro motive force, the no-load and rated load torque ripple as well as the dynamic behavior of the current driven and voltage driven motor are solved. The results obtained from different finite element analyses are given. A simple analytic method to calculate fractional slot machines is introduced and the values are compared to the values obtained with the finite element analysis. Several different fractional slot machines are first designed by using the simple analytical methodand then computed by using the finite element method. All the motors are of thesame 225-frame size, and have an approximately same amount of magnet material, a same rated torque demand and a 400 - 420 rpm speed. An analysis of the computation results gives new information on the character of fractional slot machines.A fractional slot prototype machine with number 0.4 for the slots per pole and per phase, 45 kW output power and 420 rpm speed is constructed to verify the calculations. The measurement and the finite element method results are found to beequal.

Influence of "historic" photoperiod during stem elongation on the number of fertile florets in wheat

Extending the duration of the late reproductive phase in wheat has been proposed as a possible avenue to improve spike fertility. There is a positive correlation between the number of fertile florets and the duration of the stem elongation phase when this phase is varied by extended photoperiod. Photoperiod treatments imposed during the vegetative period also influence the duration of stem elongation. The present study analysed the effect of long photoperiod (19 h) of different duration (10, 12, 14, 18 or 22 d) imposed before the onset of stem elongation on floret fertility in wheat. It was found that the length of the stem elongation phase was modified by earlier ‘historic ’ photoperiod treatments imposed during previous phases. However, neither the number of fertile florets per spike nor the spikelet fertility was affected significantly by these historic treatments. The results of the study therefore showed that an increased duration of the late reproductive phase was ineffective in increasing the number of fertile florets, unless the length of that phase was directly altered by current photoperiod.

Copy number variation in the porcine genome inferred from a 60 k SNP BeadChip

Background: Recent studies in pigs have detected copy number variants (CNVs) using the Comparative Genomic Hybridization technique in arrays designed to cover specific porcine chromosomes. The goal of this study was to identify CNV regions (CNVRs) in swine species based on whole genome SNP genotyping chips. Results: We used predictions from three different programs (cnvPartition, PennCNV and GADA) to analyze data from the Porcine SNP60 BeadChip. A total of 49 CNVRs were identified in 55 animals from an Iberian x Landrace cross (IBMAP) according to three criteria: detected in at least two animals, contained three or more consecutive SNPs and recalled by at least two programs. Mendelian inheritance of CNVRs was confirmed in animals belonging to several generations of the IBMAP cross. Subsequently, a segregation analysis of these CNVRs was performed in 372 additional animals from the IBMAP cross and its distribution was studied in 133 unrelated pig samples from different geographical origins. Five out of seven analyzed CNVRs were validated by real time quantitative PCR, some of which coincide with well known examples of CNVs conserved across mammalian species. Conclusions: Our results illustrate the usefulness of Porcine SNP60 BeadChip to detect CNVRs and show that structural variants can not be neglected when studying the genetic variability in this species.

Complexation to macromolecules with a large number of sites

This paper presents an approach based on the saddle-point approximation to study the equilibrium interactions between small molecules and macromolecules with a large number of sites. For this case, the application of the Darwin–Fowler method results in very simple expressions for the stoichiometric equilibrium constants and their corresponding free energies in terms of integrals of the binding curve plus a correction term which depends on the first derivatives of the binding curve in the points corresponding to an integer value of the mean occupation number. These expressions are simplified when the number of sites tends to infinity, providing an interpretation of the binding curve in terms of the stoichiometric stability constants. The formalism presented is applied to some simple complexation models, obtaining good values for the free energies involved. When heterogeneous complexation is assumed, simple expressions are obtained to relate the macroscopic description of the binding, given by the stoichiomeric constants, with the microscopic description in terms of the intrinsic stability constants or the affinity spectrum. © 1999 American Institute of Physics.

Female major histocompatibility complex type affects male testosterone levels and sperm number in the horse (Equus caballus).

Odours of vertebrates often contain information about the major histocompatibility complex (MHC), and are used in kin recognition, mate choice or female investment in pregnancy. It is, however, still unclear whether MHC-linked signals can also affect male reproductive strategies. We used horses (Equus caballus) to study this question under experimental conditions. Twelve stallions were individually exposed either to an unfamiliar MHC-similar mare and then to an unfamiliar MHC-dissimilar mare, or vice versa. Each exposure lasted over a period of four weeks. Peripheral blood testosterone levels were determined weekly. Three ejaculates each were collected in the week after exposure to both mares (i.e. in the ninth week) to determine mean sperm number and sperm velocity. We found high testosterone levels when stallions were kept close to MHC-dissimilar mares and significantly lower ones when kept close to MHC-similar mares. Mean sperm number per ejaculate (but not sperm velocity) was positively correlated to mean testosterone levels and also affected by the order of presentation of mares: sperm numbers were higher if MHC-dissimilar mares were presented last than if MHC-similar mares were presented last. We conclude that MHC-linked signals influence testosterone secretion and semen characteristics, two indicators of male reproductive strategies.

Copy number variations and cognitive phenotypes in unselected populations

IMPORTANCE: The association of copy number variations (CNVs), differing numbers of copies of genetic sequence at locations in the genome, with phenotypes such as intellectual disability has been almost exclusively evaluated using clinically ascertained cohorts. The contribution of these genetic variants to cognitive phenotypes in the general population remains unclear. OBJECTIVE: To investigate the clinical features conferred by CNVs associated with known syndromes in adult carriers without clinical preselection and to assess the genome-wide consequences of rare CNVs (frequency ≤0.05%; size ≥250 kilobase pairs [kb]) on carriers' educational attainment and intellectual disability prevalence in the general population. DESIGN, SETTING, AND PARTICIPANTS: The population biobank of Estonia contains 52,000 participants enrolled from 2002 through 2010. General practitioners examined participants and filled out a questionnaire of health- and lifestyle-related questions, as well as reported diagnoses. Copy number variant analysis was conducted on a random sample of 7877 individuals and genotype-phenotype associations with education and disease traits were evaluated. Our results were replicated on a high-functioning group of 993 Estonians and 3 geographically distinct populations in the United Kingdom, the United States, and Italy. MAIN OUTCOMES AND MEASURES: Phenotypes of genomic disorders in the general population, prevalence of autosomal CNVs, and association of these variants with educational attainment (from less than primary school through scientific degree) and prevalence of intellectual disability. RESULTS: Of the 7877 in the Estonian cohort, we identified 56 carriers of CNVs associated with known syndromes. Their phenotypes, including cognitive and psychiatric problems, epilepsy, neuropathies, obesity, and congenital malformations are similar to those described for carriers of identical rearrangements ascertained in clinical cohorts. A genome-wide evaluation of rare autosomal CNVs (frequency, ≤0.05%; ≥250 kb) identified 831 carriers (10.5%) of the screened general population. Eleven of 216 (5.1%) carriers of a deletion of at least 250 kb (odds ratio [OR], 3.16; 95% CI, 1.51-5.98; P = 1.5e-03) and 6 of 102 (5.9%) carriers of a duplication of at least 1 Mb (OR, 3.67; 95% CI, 1.29-8.54; P = .008) had an intellectual disability compared with 114 of 6819 (1.7%) in the Estonian cohort. The mean education attainment was 3.81 (P = 1.06e-04) among 248 (≥250 kb) deletion carriers and 3.69 (P = 5.024e-05) among 115 duplication carriers (≥1 Mb). Of the deletion carriers, 33.5% did not graduate from high school (OR, 1.48; 95% CI, 1.12-1.95; P = .005) and 39.1% of duplication carriers did not graduate high school (OR, 1.89; 95% CI, 1.27-2.8; P = 1.6e-03). Evidence for an association between rare CNVs and lower educational attainment was supported by analyses of cohorts of adults from Italy and the United States and adolescents from the United Kingdom. CONCLUSIONS AND RELEVANCE: Known pathogenic CNVs in unselected, but assumed to be healthy, adult populations may be associated with unrecognized clinical sequelae. Additionally, individually rare but collectively common intermediate-size CNVs may be negatively associated with educational attainment. Replication of these findings in additional population groups is warranted given the potential implications of this observation for genomics research, clinical care, and public health.

ZnO nanorods for efficient third harmonic UV generation.

ZnO nanorods grown by both high temperature vapour phase transport and low temperature chemical bath deposition are very promising sources for UV third harmonic generation. Material grown by both methods show comparable efficiencies, in both cases an order of magnitude higher than surface third harmonic generation at the quartz-air interface of a bare quartz substrate. This result is in stark contrast to the linear optical properties of ZnO nanorods grown by these two methods, which show vastly different PL efficiencies. The third harmonic generated signal is analysed using intensity dependent measurements and interferometric frequency resolved optical gating, allowing extraction of the laser pulse parameters. The comparable levels of efficiency of ZnO grown by these very different methods as sources for third harmonic UV generation provides a broad suite of possible growth methods to suit various substrates, coverage and scalability requirements. Potential application areas range from interferometric frequency resolved optical gating characterization of few cycle fs pulses to single cell UV irradiation for biophysical studies.

Thomas-Fermi theory for atomic nuclei revisited

The recently developed semiclassical variational Wigner-Kirkwood (VWK) approach is applied to finite nuclei using external potentials and self-consistent mean fields derived from Skyrme inter-actions and from relativistic mean field theory. VWK consist s of the Thomas-Fermi part plus a pure, perturbative h 2 correction. In external potentials, VWK passes through the average of the quantal values of the accumulated level density and total en energy as a function of the Fermi energy. However, there is a problem of overbinding when the energy per particle is displayed as a function of the particle number. The situation is analyzed comparing spherical and deformed harmonic oscillator potentials. In the self-consistent case, we show for Skyrme forces that VWK binding energies are very close to those obtained from extended Thomas-Fermi functionals of h 4 order, pointing to the rapid convergence of the VWK theory. This satisfying result, however, does not cure the overbinding problem, i.e., the semiclassical energies show more binding than they should. This feature is more pronounced in the case of Skyrme forces than with the relativistic mean field approach. However, even in the latter case the shell correction energy for e.g.208 Pb turns out to be only ∼ −6 MeV what is about a factor two or three off the generally accepted value. As an adhoc remedy, increasing the kinetic energy by 2.5%, leads to shell correction energies well acceptable throughout the periodic table. The general importance of the present studies for other finite Fermi systems, self-bound or in external potentials, is pointed out.

The univalent Bloch-Landau constant, harmonic symmetry and conformal glueing

By modifying a domain first suggested by Ruth Goodman in 1935 and by exploiting the explicit solution by Fedorov of the Polyá-Chebotarev problem in the case of four symmetrically placed points, an improved upper bound for the univalent Bloch-Landau constant is obtained. The domain that leads to this improved bound takes the form of a disk from which some arcs are removed in such a way that the resulting simply connected domain is harmonically symmetric in each arc with respect to the origin. The existence of domains of this type is established, using techniques from conformal welding, and some general properties of harmonically symmetric arcs in this setting are established.

Päällystyskoneiden runkojen värähtelyiden FE-analysoinnin kehittäminen

Työssä kehitettiin päällystyskoneen runkojen FE-analysointia erityisesti vastelaskennan kannalta, joskin myös ominaistaajuuslaskennan tarkentamiseksi esitettiin parannuksia. Työssä rajoitutaan harmonisten telaherätteiden aiheuttamien vasteiden analysointiin. . Työssä käsitellään värähtelyjen teoriaa ja tarkastellaan Abaqus-ohjelmiston (versio 5.8) laskentamenetelmiä vakiotilan värähtelyvasteen laskemiseksi. FEM-mallin rakenteeseen liittyen käsitellään perustuksien ja maaperän, konepalkin ja telaherätteiden mallintamista ja mallinnuksen laajuutta. Telaherätteitä käsitellään yksittäisen telan ja telojen samanvaiheisuuden kannalta. Samanvaiheisuutta tutkitaan työssä kehitetyllä summafunktiolla. Värähtelyjen mittaukseen FEM-mallien verifioimiseksi esitetään parannuksia. Nykyinen mallinnustapa käsitellään lyhyesti. Parannusehdotuksia kokeiltiin mallintamalla Rauma 400-päällystyskone ja vertaamalla tuloksia mitattuihin. Laskennan tulokset vastasivat vaihtelevasti mittaustuloksia, mittaustulosten puutteellisuus vaikeutti vertailua. Tulosten perusteella herätetiedon parantaminen on perusteltua ja mallin laajennus lisää todenmukaisuutta. Maaperän huomiointi vaikuttaa ennen kaikkea ominaistaajuuksiin ja muotoihin ja suora ratkaisutapa on käyttökelpoinen vasteen laskentamenetelmä otettaessa maaperä huomioon.

Priming psychic and conjuring abilities of a magic demonstration influences event interpretation and random number generation biases

Magical ideation and belief in the paranormal is considered to represent a trait-like character; people either believe in it or not. Yet, anecdotes indicate that exposure to an anomalous event can turn skeptics into believers. This transformation is likely to be accompanied by altered cognitive functioning such as impaired judgments of event likelihood. Here, we investigated whether the exposure to an anomalous event changes individuals' explicit traditional (religious) and non-traditional (e.g., paranormal) beliefs as well as cognitive biases that have previously been associated with non-traditional beliefs, e.g., repetition avoidance when producing random numbers in a mental dice task. In a classroom, 91 students saw a magic demonstration after their psychology lecture. Before the demonstration, half of the students were told that the performance was done respectively by a conjuror (magician group) or a psychic (psychic group). The instruction influenced participants' explanations of the anomalous event. Participants in the magician, as compared to the psychic group, were more likely to explain the event through conjuring abilities while the reverse was true for psychic abilities. Moreover, these explanations correlated positively with their prior traditional and non-traditional beliefs. Finally, we observed that the psychic group showed more repetition avoidance than the magician group, and this effect remained the same regardless of whether assessed before or after the magic demonstration. We conclude that pre-existing beliefs and contextual suggestions both influence people's interpretations of anomalous events and associated cognitive biases. Beliefs and associated cognitive biases are likely flexible well into adulthood and change with actual life events.