Gene conversion and evolution of Xq28 duplicons involved in recurring inversions causing severe hemophilia A

Inversions breaking the 1041 bp int1h-1 or the 9.5-kb int22h-1 sequence of the F8 gene cause hemophilia A in 1/30,000 males. These inversions are due to homologous recombination between the above sequences and their inverted copies on the same DNA molecule, respectively, int1h-2 and int22h-2 or int22h-3. We find that (1) int1h and int22h duplicated more than 25 million years ago; (2) the identity of the copies (>99%) of these sequences in humans and other primates is due to gene conversion; (3) gene conversion is most frequent in the internal regions of int22h; (4) breakpoints of int22h-related inversions also tend to involve the internal regions of int22h; (5) sequence variations in a sample of human X chromosomes defined eight haplotypes of int22h-1 and 27 of int22h-2 plus int22h-3; (6) the latter two sequences, which lie, respectively, 500 and 600 kb telomeric to int22h-1 are five-fold more identical when in cis than when in trans, thus suggesting that gene conversion may be predominantly intrachromosomal; (7) int1h, int22h, and flanking sequences evolved at a rate of about 0.1% substitutions per million years during the divergence between humans and other primates, except for int1h during the human-chimpanzee divergence, when its rate of evolution was significantly lower. This is reminiscent of the slower evolution of palindrome arms in the male specific regions of the Y chromosome and we propose, as an explanation, that intrachromosomal gene conversion and cosegregation of the duplicated regions favors retention of the ancestral sequence and thus reduces the evolution rate.

Global climate change and tree nutrition: effects of elevated CO2 and temperature

Although tree nutrition has not been the primary focus of large climate change experiments on trees, we are beginning to understand its links to elevated atmospheric CO2 and temperature changes. This review focuses on the major nutrients, namely N and P, and deals with the effects of climate change on the processes that alter their cycling and availability. Current knowledge regarding biotic and abiotic agents of weathering, mobilization and immobilization of these elements will be discussed. To date, controlled environment studies have identified possible effects of climate change on tree nutrition. Only some of these findings, however, were verified in ecosystem scale experiments. Moreover, to be able to predict future effects of climate change on tree nutrition at this scale, we need to progress from studying effects of single factors to analysing interactions between factors such as elevated CO2, temperature or water availability.

Energetics of climate models: net energy balance and meridional enthalpy transport

We analyze the publicly released outputs of the simulations performed by climate models (CMs) in preindustrial (PI) and Special Report on Emissions Scenarios A1B (SRESA1B) conditions. In the PI simulations, most CMs feature biases of the order of 1 W m −2 for the net global and the net atmospheric, oceanic, and land energy balances. This does not result from transient effects but depends on the imperfect closure of the energy cycle in the fluid components and on inconsistencies over land. Thus, the planetary emission temperature is underestimated, which may explain the CMs' cold bias. In the PI scenario, CMs agree on the meridional atmospheric enthalpy transport's peak location (around 40°N/S), while discrepancies of ∼20% exist on the intensity. Disagreements on the oceanic transport peaks' location and intensity amount to ∼10° and ∼50%, respectively. In the SRESA1B runs, the atmospheric transport's peak shifts poleward, and its intensity increases up to ∼10% in both hemispheres. In most CMs, the Northern Hemispheric oceanic transport decreases, and the peaks shift equatorward in both hemispheres. The Bjerknes compensation mechanism is active both on climatological and interannual time scales. The total meridional transport peaks around 35° in both hemispheres and scenarios, whereas disagreements on the intensity reach ∼20%. With increased CO 2 concentration, the total transport increases up to ∼10%, thus contributing to polar amplification of global warming. Advances are needed for achieving a self-consistent representation of climate as a nonequilibrium thermodynamical system. This is crucial for improving the CMs' skill in representing past and future climate changes.

Spectro-electrochemical and DFT studies of a planar Cu(II)–phenolate complex active in the aerobic oxidation of primary alcohols

A square-planar compound [Cu(pyrimol)Cl] (pyrimol = 4-methyl-2-N-(2-pyridylmethylene)aminophenolate) abbreviated as CuL–Cl) is described as a biomimetic model of the enzyme galactose oxidase (GOase). This copper(II) compound is capable of stoichiometric aerobic oxidation of activated primary alcohols in acetonitrile/water to the corresponding aldehydes. It can be obtained either from Hpyrimol (HL) or its reduced/hydrogenated form Hpyramol (4-methyl-2-N-(2-pyridylmethyl)aminophenol; H2L) readily converting to pyrimol (L-) on coordination to the copper(II) ion. Crystalline CuL–Cl and its bromide derivative exhibit a perfect square-planar geometry with Cu–O(phenolate) bond lengths of 1.944(2) and 1.938(2) Å. The cyclic voltammogram of CuL–Cl exhibits an irreversible anodic wave at +0.50 and +0.57 V versus ferrocene/ferrocenium (Fc/Fc+) in dry dichloromethane and acetonitrile, respectively, corresponding to oxidation of the phenolate ligand to the corresponding phenoxyl radical. In the strongly donating acetonitrile the oxidation path involves reversible solvent coordination at the Cu(II) centre. The presence of the dominant CuII–L. chromophore in the electrochemically and chemically oxidised species is evident from a new fairly intense electronic absorption at 400–480 nm ascribed to a several electronic transitions having a mixed pi-pi(L.) intraligand and Cu–Cl -> L. charge transfer character. The EPR signal of CuL–Cl disappears on oxidation due to strong intramolecular antiferromagnetic exchange coupling between the phenoxyl radical ligand (L.) and the copper(II) centre, giving rise to a singlet ground state (S = 0). The key step in the mechanism of the primary alcohol oxidation by CuL–Cl is probably the alpha-hydrogen abstraction from the equatorially bound alcoholate by the phenoxyl moiety in the oxidised pyrimol ligand, Cu–L., through a five-membered cyclic transition state.

Epidemic K-Means clustering

The K-Means algorithm for cluster analysis is one of the most influential and popular data mining methods. Its straightforward parallel formulation is well suited for distributed memory systems with reliable interconnection networks. However, in large-scale geographically distributed systems the straightforward parallel algorithm can be rendered useless by a single communication failure or high latency in communication paths. This work proposes a fully decentralised algorithm (Epidemic K-Means) which does not require global communication and is intrinsically fault tolerant. The proposed distributed K-Means algorithm provides a clustering solution which can approximate the solution of an ideal centralised algorithm over the aggregated data as closely as desired. A comparative performance analysis is carried out against the state of the art distributed K-Means algorithms based on sampling methods. The experimental analysis confirms that the proposed algorithm is a practical and accurate distributed K-Means implementation for networked systems of very large and extreme scale.

Symmetric Push-Sum Protocol for decentralised aggregation

Gossip (or Epidemic) protocols have emerged as a communication and computation paradigm for large-scale networked systems. These protocols are based on randomised communication, which provides probabilistic guarantees on convergence speed and accuracy. They also provide robustness, scalability, computational and communication efficiency and high stability under disruption. This work presents a novel Gossip protocol named Symmetric Push-Sum Protocol for the computation of global aggregates (e.g., average) in decentralised and asynchronous systems. The proposed approach combines the simplicity of the push-based approach and the efficiency of the push-pull schemes. The push-pull schemes cannot be directly employed in asynchronous systems as they require synchronous paired communication operations to guarantee their accuracy. Although push schemes guarantee accuracy even with asynchronous communication, they suffer from a slower and unstable convergence. Symmetric Push- Sum Protocol does not require synchronous communication and achieves a convergence speed similar to the push-pull schemes, while keeping the accuracy stability of the push scheme. In the experimental analysis, we focus on computing the global average as an important class of node aggregation problems. The results have confirmed that the proposed method inherits the advantages of both other schemes and outperforms well-known state of the art protocols for decentralized Gossip-based aggregation.

New results on the thermodynamical properties of the climate system

In this paper the authors exploit two equivalent formulations of the average rate of material entropy production in the climate system to propose an approximate splitting between contributions due to vertical and eminently horizontal processes. This approach is based only on 2D radiative fields at the surface and at the top of atmosphere. Using 2D fields at the top of atmosphere alone, lower bounds to the rate of material entropy production and to the intensity of the Lorenz energy cycle are derived. By introducing a measure of the efficiency of the planetary system with respect to horizontal thermodynamic processes, it is possible to gain insight into a previous intuition on the possibility of defining a baroclinic heat engine extracting work from the meridional heat flux. The approximate formula of the material entropy production is verified and used for studying the global thermodynamic properties of climate models (CMs) included in the Program for Climate Model Diagnosis and Intercomparison (PCMDI)/phase 3 of the Coupled Model Intercomparison Project (CMIP3) dataset in preindustrial climate conditions. It is found that about 90% of the material entropy production is due to vertical processes such as convection, whereas the large-scale meridional heat transport contributes to only about 10% of the total. This suggests that the traditional two-box models used for providing a minimal representation of entropy production in planetary systems are not appropriate, whereas a basic—but conceptually correct—description can be framed in terms of a four-box model. The total material entropy production is typically 55 mW m−2 K−1, with discrepancies on the order of 5%, and CMs’ baroclinic efficiencies are clustered around 0.055. The lower bounds on the intensity of the Lorenz energy cycle featured by CMs are found to be around 1.0–1.5 W m−2, which implies that the derived inequality is rather stringent. When looking at the variability and covariability of the considered thermodynamic quantities, the agreement among CMs is worse, suggesting that the description of feedbacks is more uncertain. The contributions to material entropy production from vertical and horizontal processes are positively correlated, so that no compensation mechanism seems in place. Quite consistently among CMs, the variability of the efficiency of the system is a better proxy for variability of the entropy production due to horizontal processes than that of the large-scale heat flux. The possibility of providing constraints on the 3D dynamics of the fluid envelope based only on 2D observations of radiative fluxes seems promising for the observational study of planets and for testing numerical models.

Measurement of intrinsic properties of amyloid fibrils by the peak force QNM method

We report the investigation of the mechanical properties of different types of amyloid fibrils by the peak force quantitative nanomechanical (PF-QNM) technique. We demonstrate that this technique correctly measures the Young’s modulus independent of the polymorphic state and the cross-sectional structural details of the fibrils, and we show that values for amyloid fibrils assembled from heptapeptides, a-synuclein, Ab(1–42), insulin, b-lactoglobulin,lysozyme, ovalbumin, Tau protein and bovine serum albumin all fall in the range of 2–4 GPa.

The contribution of primary and secondary somatosensory cortices to the representation of body parts and body sides: an fMRI adaptation study

Although the somatosensory homunculus is a classically used description of the way somatosensory inputs are processed in the brain, the actual contributions of primary (SI) and secondary (SII) somatosensory cortices to the spatial coding of touch remain poorly understood. We studied adaptation of the fMRI BOLD response in the somatosensory cortex by delivering pairs of vibrotactile stimuli to the finger tips of the index and middle fingers. The first stimulus (adaptor) was delivered either to the index or to the middle finger of the right or left hand, whereas the second stimulus (test) was always administered to the left index finger. The overall BOLD response evoked by the stimulation was primarily contralateral in SI and was more bilateral in SII. However, our fMRI adaptation approach also revealed that both somatosensory cortices were sensitive to ipsilateral as well as to contralateral inputs. SI and SII adapted more after subsequent stimulation of homologous as compared with nonhomologous fingers, showing a distinction between different fingers. Most importantly, for both somatosensory cortices, this finger-specific adaptation occurred irrespective of whether the tactile stimulus was delivered to the same or to different hands. This result implies integration of contralateral and ipsilateral somatosensory inputs in SI as well as in SII. Our findings suggest that SI is more than a simple relay for sensory information and that both SI and SII contribute to the spatial coding of touch by discriminating between body parts (fingers) and by integrating the somatosensory input from the two sides of the body (hands).

Vision of the body and the differentiation of perceived body side in touch

Although tactile representations of the two body sides are initially segregated into opposite hemispheres of the brain, behavioural interactions between body sides exist and can be revealed under conditions of tactile double simultaneous stimulation (DSS) at the hands. Here we examined to what extent vision can affect body side segregation in touch. To this aim, we changed hand-related visual input while participants performed a go/no-go task to detect a tactile stimulus delivered to one target finger (e.g., right index), stimulated alone or with a concurrent non-target finger either on the same hand (e.g., right middle finger) or on the other hand (e.g., left index finger = homologous; left middle finger = non-homologous). Across experiments, the two hands were visible or occluded from view (Experiment 1), images of the two hands were either merged using a morphing technique (Experiment 2), or were shown in a compatible vs incompatible position with respect to the actual posture (Experiment 3). Overall, the results showed reliable interference effects of DSS, as compared to target-only stimulation. This interference varied as a function of which non-target finger was stimulated, and emerged both within and between hands. These results imply that the competition between tactile events is not clearly segregated across body sides. Crucially, non-informative vision of the hand affected overall tactile performance only when a visual/proprioceptive conflict was present, while neither congruent nor morphed hand vision affected tactile DSS interference. This suggests that DSS operates at a tactile processing stage in which interactions between body sides can occur regardless of the available visual input from the body.