Early handling and repeated cross-fostering have opposite effect on mouse emotionality

Early life events have a crucial role in programming the individual phenotype and exposure to traumatic experiences during infancy can increase later risk for a variety of neuropsychiatric conditions, including mood and anxiety disorders. Animal models of postnatal stress have been developed in rodents to explore molecular mechanisms responsible for the observed short and long lasting neurobiological effects of such manipulations. The main aim of this study was to compare the behavioral and hormonal phenotype of young and adult animals exposed to different postnatal treatments. Outbred mice were exposed to (i) the classical Handling protocol (H: 15 min-day of separation from the mother from day 1 to 14 of life) or to (ii) a Repeated Cross-Fostering protocol (RCF: adoption of litters from day 1 to 4 of life by different dams). Handled mice received more maternal care in infancy and showed the already described reduced emotionality at adulthood. Repeated cross fostered animals did not differ for maternal care received, but showed enhanced sensitivity to separation from the mother in infancy and altered respiratory response to 6% CO2 in breathing air in comparison with controls. Abnormal respiratory responses to hypercapnia are commonly found among humans with panic disorders (PD), and point to RCF-induced instability of the early environment as a valid developmental model for PD. The comparisons between short-and long-term effects of postnatal handling vs. RCF indicate that different types of early adversities are associated with different behavioral profiles, and evoke psychopathologies that can be distinguished according to the neurobiological systems disrupted by early-life manipulation

Time-approximation trade-offs for inapproximable problems

In this paper we focus on problems which do not admit a constant-factor approximation in polynomial time and explore how quickly their approximability improves as the allowed running time is gradually increased from polynomial to (sub-)exponential. We tackle a number of problems: For Min Independent Dominating Set, Max Induced Path, Forest and Tree, for any r(n), a simple, known scheme gives an approximation ratio of r in time roughly rn/r. We show that, for most values of r, if this running time could be significantly improved the ETH would fail. For Max Minimal Vertex Cover we give a nontrivial √r-approximation in time 2n/r. We match this with a similarly tight result. We also give a log r-approximation for Min ATSP in time 2n/r and an r-approximation for Max Grundy Coloring in time rn/r. Furthermore, we show that Min Set Cover exhibits a curious behavior in this superpolynomial setting: for any δ > 0 it admits an mδ-approximation, where m is the number of sets, in just quasi-polynomial time. We observe that if such ratios could be achieved in polynomial time, the ETH or the Projection Games Conjecture would fail. © Édouard Bonnet, Michael Lampis and Vangelis Th. Paschos; licensed under Creative Commons License CC-BY

Psychiatric, behavioral, and cognitive disorders in patients with extracranial cancers

Patients with cancer may report neuropsychiatric abnormalities including cognitive impairment, behavioral disturbances, and psychiatric disorders that potentially worsen their quality of life, reduce their treatment response, and aggravate their overall prognosis. Neuropsychiatric disturbances have a different pathophysiology, including immuno-inflammatory and neuroendocrine mechanisms, as a consequence of oncologic treatments (chemo- and radio-therapy). Among clinicians involved in the management of such patients, psychiatrists need to pay particular attention in recognizing behavioral disturbances that arise in oncologic patients, and determining those that may be effectively treated with psychotropic medications, psychotherapeutic interventions, and an integration of them. Through the contribution of different clinicians actively involved in the management of oncological patients, the present review is ultimately aimed at updating psychiatrists in relation to the pathophysiological mechanisms responsible for the onset of cognitive, affective, and behavioral syndromes in these patients, along with epidemiologic and clinical considerations and therapeutic perspectives

Postnatal Aversive Experience Impairs Sensitivity to Natural Rewards and Increases Susceptibility to Negative Events in Adult Life

Evidence shows that maternal care and postnatal traumatic events can exert powerful effects on brain circuitry development but little is known about the impact of early postnatal experiences on processing of rewarding and aversive stimuli related to the medial prefrontal cortex (mpFC) function in adult life. In this study, the unstable maternal environment induced by repeated cross-fostering (RCF) impaired palatable food conditioned place preference and disrupted the natural preference for sweetened fluids in the saccharin preference test. By contrast, RCF increased sensitivity to conditioned place aversion (CPA) and enhanced immobility in the forced swimming test. Intracerebral microdialysis data showed that the RCF prevents mpFC dopamine (DA) outflow regardless of exposure to rewarding or aversive stimuli, whereas it induces a strong and sustained prefrontal norepinephrine (NE) release in response to different aversive experiences. Moreover, the selective mpFC NE depletion abolished CPA, thus indicating that prefrontal NE is required for motivational salience attribution to aversionrelated stimuli. These findings demonstrate that an unstable maternal environment impairs the natural propensity to seek pleasurable sources of reward, enhances sensitivity to negative events in adult life, blunts prefrontal DA outflow, and modulates NE release in the reverse manner depending on the exposure to rewarding or aversive stimuli

On the (parameterized) complexity of recognizing well-covered (r,l)-graphs.

An (r,ℓ)(r,ℓ)-partition of a graph G is a partition of its vertex set into r independent sets and ℓℓ cliques. A graph is (r,ℓ)(r,ℓ) if it admits an (r,ℓ)(r,ℓ)-partition. A graph is well-covered if every maximal independent set is also maximum. A graph is (r,ℓ)(r,ℓ)-well-covered if it is both (r,ℓ)(r,ℓ) and well-covered. In this paper we consider two different decision problems. In the (r,ℓ)(r,ℓ)-Well-Covered Graph problem ((r,ℓ)(r,ℓ) wcg for short), we are given a graph G, and the question is whether G is an (r,ℓ)(r,ℓ)-well-covered graph. In the Well-Covered (r,ℓ)(r,ℓ)-Graph problem (wc (r,ℓ)(r,ℓ) g for short), we are given an (r,ℓ)(r,ℓ)-graph G together with an (r,ℓ)(r,ℓ)-partition of V(G) into r independent sets and ℓℓ cliques, and the question is whether G is well-covered. We classify most of these problems into P, coNP-complete, NP-complete, NP-hard, or coNP-hard. Only the cases wc(r, 0)g for r≥3r≥3 remain open. In addition, we consider the parameterized complexity of these problems for several choices of parameters, such as the size αα of a maximum independent set of the input graph, its neighborhood diversity, or the number ℓℓ of cliques in an (r,ℓ)(r,ℓ)-partition. In particular, we show that the parameterized problem of deciding whether a general graph is well-covered parameterized by αα can be reduced to the wc (0,ℓ)(0,ℓ) g problem parameterized by ℓℓ, and we prove that this latter problem is in XP but does not admit polynomial kernels unless coNP⊆NP/polycoNP⊆NP/poly

A tetragonal-to-monoclinic phase transition in a ferroelectric perovskite: the structure of PbZr(0.52)Ti(0.48)O3

The perovskite-like ferroelectric system PbZr(1-x)Ti(x)O3 (PZT) has a nearly vertical morphotropic phase boundary (MPB) around x=0.45-0.50. Recent synchrotron x-ray powder diffraction measurements by Noheda et al. [Appl. Phys. Lett. 74, 2059 (1999)] have revealed a new monoclinic phase between the previously-established tetragonal and rhombohedral regions. In the present work we describe a Rietveld analysis of the detailed structure of the tetragonal and monoclinic PZT phases on a sample with x= 0.48 for which the lattice parameters are respectively: at= 4.044 A, ct= 4.138 A, at 325 K, and am= 5.721 A, bm= 5.708 A, cm= 4.138 A, beta= 90.496 deg., at 20K. In the tetragonal phase the shifts of the atoms along the polar [001] direction are similar to those in PbTiO3 but the refinement indicates that there are, in addition, local disordered shifts of the Pb atoms of ~0.2 A perpendicular to the polar axis.. The monoclinic structure can be viewed as a condensation along one of the directions of the local displacements present in the tetragonal phase. It equally well corresponds to a freezing-out of the local displacements along one of the directions recently reported by Corker et al.[J. Phys. Condens. Matter 10, 6251 (1998)] for rhombohedral PZT. The monoclinic structure therefore provides a microscopic picture of the MPB region in which one of the "locally" monoclinic phases in the "average" rhombohedral or tetragonal structures freezes out, and thus represents a bridge between these two phases.Comment: REVTeX, 7 figures. Modifications after referee's suggestion: new figure (figure 5), comments in 2nd para. (Sect.III) and in 2nd & 3rd para. (Sect. IV-a), in the abstract: "...of ~0.2 A perpendicular to the polar axis.

Bromodomain and extra-terminal domain inhibition modulates the expression of pathologically relevant microRNAs in diffuse large B-cell lymphoma.

Aberrant changes in microRNA expression contribute to lymphomagenesis. Bromodomain and extra-terminal domain inhibitors such as OTX015 (MK-8628, birabresib) have demonstrated preclinical and clinical activity in hematologic tumors. MicroRNA profiling of diffuse large B-cell lymphoma cells treated with OTX015 revealed changes in the expression levels of a limited number of microRNAs, including miR-92a-1-5p, miR-21-3p, miR-155-5p and miR-96-5p. Analysis of publicly available chromatin immunoprecipitation sequencing data of diffuse large B-cell lymphoma cells treated with bromodomain and extra-terminal domain (BET) inhibitors showed that the BET family member BRD4 bound to the upstream regulatory regions of multiple microRNA genes and that this binding decreased following BET inhibition. Alignment of our microRNA profiling data with the BRD4 chromatin immunoprecipitation sequencing data revealed that microRNAs downregulated by OTX015 also exhibited reduced BRD4 binding in their promoter regions following treatment with another bromodomain and extra-terminal domain inhibitor, JQ1, indicating that BRD4 contributes directly to microRNA expression in lymphoma. Treatment with bromodomain and extra-terminal domain inhibitors also decreased the expression of the arginine methyltransferase PRMT5, which plays a crucial role in B-cell transformation and negatively modulates the transcription of miR-96-5p. The data presented here indicate that in addition to previously observed effects on the expression of coding genes, bromodomain and extra-terminal domain inhibitors also modulate the expression of microRNAs involved in lymphomagenesis

High Differentiation among Eight Villages in a Secluded Area of Sardinia Revealed by Genome-Wide High Density SNPs Analysis

To better design association studies for complex traits in isolated populations it's important to understand how history and isolation moulded the genetic features of different communities. Population isolates should not “a priori” be considered homogeneous, even if the communities are not distant and part of a small region. We studied a particular area of Sardinia called Ogliastra, characterized by the presence of several distinct villages that display different history, immigration events and population size. Cultural and geographic isolation characterized the history of these communities. We determined LD parameters in 8 villages and defined population structure through high density SNPs (about 360 K) on 360 unrelated people (45 selected samples from each village). These isolates showed differences in LD values and LD map length. Five of these villages show high LD values probably due to their reduced population size and extreme isolation. High genetic differentiation among villages was detected. Moreover population structure analysis revealed a high correlation between genetic and geographic distances. Our study indicates that history, geography and biodemography have influenced the genetic features of Ogliastra communities producing differences in LD and population structure. All these data demonstrate that we can consider each village an isolate with specific characteristics. We suggest that, in order to optimize the study design of complex traits, a thorough characterization of genetic features is useful to identify the presence of sub-populations and stratification within genetic isolates

Observation of the Decay Λ0b→Λ+cτ−¯ν

The first observation of the semileptonic b-baryon decay Λb0→Λc+τ-ν¯τ, with a significance of 6.1σ, is reported using a data sample corresponding to 3 fb-1 of integrated luminosity, collected by the LHCb experiment at center-of-mass energies of 7 and 8 TeV at the LHC. The τ- lepton is reconstructed in the hadronic decay to three charged pions. The ratio K=B(Λb0→Λc+τ-ν¯τ)/B(Λb0→Λc+π-π+π-) is measured to be 2.46±0.27±0.40, where the first uncertainty is statistical and the second systematic. The branching fraction B(Λb0→Λc+τ-ν¯τ)=(1.50±0.16±0.25±0.23)% is obtained, where the third uncertainty is from the external branching fraction of the normalization channel Λb0→Λc+π-π+π-. The ratio of semileptonic branching fractions R(Λc+)B(Λb0→Λc+τ-ν¯τ)/B(Λb0→Λc+μ-ν¯μ) is derived to be 0.242±0.026±0.040±0.059, where the external branching fraction uncertainty from the channel Λb0→Λc+μ-ν¯μ contributes to the last term. This result is in agreement with the standard model prediction