High-resolution neutron and X-ray diffraction room-temperature studies of an H-FABP-oleic acid complex: study of the internal water cluster and ligand binding by a transferred multipolar electron-density distribution

Crystal diffraction data of heart fatty acid binding protein (H-FABP) in complex with oleic acid were measured at room temperature with high-resolution X-ray and neutron protein crystallography (0.98 and 1.90 Å resolution, respectively). These data provided very detailed information about the cluster of water molecules and the bound oleic acid in the H-FABP large internal cavity. The jointly refined X-ray/neutron structure of H-FABP was complemented by a transferred multipolar electron-density distribution using the parameters of the ELMAMII library. The resulting electron density allowed a precise determination of the electrostatic potential in the fatty acid (FA) binding pocket. Bader's quantum theory of atoms in molecules was then used to study interactions involving the internal water molecules, the FA and the protein. This approach showed H···H contacts of the FA with highly conserved hydrophobic residues known to play a role in the stabilization of long-chain FAs in the binding cavity. The determination of water hydrogen (deuterium) positions allowed the analysis of the orientation and electrostatic properties of the water molecules in the very ordered cluster. As a result, a significant alignment of the permanent dipoles of the water molecules with the protein electrostatic field was observed. This can be related to the dielectric properties of hydration layers around proteins, where the shielding of electrostatic interactions depends directly on the rotational degrees of freedom of the water molecules in the interface.Facultad de Ciencias ExactasInstituto de Física de Líquidos y Sistemas Biológico

Verification of state and entanglement with incomplete tomography

There exists, in general, a convex set of quantum state estimators that maximize the likelihood for informationally incomplete data. We propose an estimation scheme, catered to measurement data of this kind, to search for the exact maximum-likelihood-maximum-entropy estimator using semidefinite programming and a standard multi-dimensional function optimization routine. This scheme can be used to infer the expectation values of a set of entanglement witnesses that can be used to verify the entanglement of the unknown quantum state for composite systems. Next, we establish an alternative numerical scheme that is more computationally robust for the sole purpose of maximizing the likelihood and entropy.Comment: 15 pages, 5 figure

Tracing PAH Emission in lambda-Orionis Using COBE/DIRBE Data

We use archival COBE/DIRBE data to construct a map of polycyclic aromatic hydrocarbon (PAH) emission in the &lambda;-Orionis region. The presence of the 3.3 &mu;m PAH feature within the DIRBE 3.5 &mu;m band and the corresponding lack of significant PAH spectral features in the adjacent DIRBE bands (1.25, 2.2, and 4.9 &mu;m) enable estimation of the PAH contribution to the 3.5 &mu;m data. Having the shortest wavelength of known PAH features, the 3.3 &mu;m feature probes the smallest PAHs, which are also the leading candidates for carriers of anomalous microwave emission (AME). We use this map to investigate the association between the AME and the emission from PAH molecules. We find that the spatial correlation in &lambda;-Orionis is higher between AME and far-infrared dust emission (as represented by the DIRBE 240 &mu;m map) than it is between our PAH map and AME. This finding, in agreement with previous studies using PAH features at longer wavelengths, is in tension with the hypothesis that AME is due to spinning PAHs. However, the expected correlation between mid-infrared and microwave emission could potentially be degraded by different sensitivities of each emission mechanism to local environmental conditions even if PAHs are the carriers of both. &nbsp;</p

Growth factor concentrations in platelet-rich plasma for androgenetic alopecia: an intra-subject, randomized, blinded, placebo-controlled, pilot study

YesBackground: Platelet rich plasma (PRP), processed from autologous peripheral blood, is used to treat androgenetic alopecia (AGA). Objective: To determine the efficacy of PRP for hair growth promotion in AGA patients in a randomized, blinded, placebo controlled, pilot clinical trial (NCT02074943). Methods: The efficacy of an 8 week, 5 session, PRP treatment course was determined by measuring hair density and hair caliber changes in 10 AGA affected patients. For each PRP sample, the concentrations of selected growth factors were determined using a multiplex assay system. The clinical results were then correlated to the growth factor concentrations in PRP. Results: At 16 weeks, 8 weeks after the last PRP injection, treated areas exhibited increased mean hair density (+12.76%) over baseline compared to placebo (+0.99%). Mean hair caliber decreased in both treated and placebo regions (-16.22% and -19.46% respectively). Serial analysis of PRP significant variability in concentrations between patients. Overall, there was a positive correlation between GDNF concentration and hair density (p= 0.004). Trends, though not statistically significant, were also observed for FGF2 and VEGF. Limitations: Small sample size and lack of comparative cohorts receiving protocol variations limit confidence in the study data. Conclusions: This small pilot clinical trial suggests PRP treatment may be beneficial for AGA. However, the variable hair growth responses between patients indicate there is a significant opportunity to improve PRP therapy protocols for hair growth promotion. The variability in growth factor concentration in PRP suggests standardization of growth factors post-processing might improve hair growth responses.RepliCel Life Sciences Inc. (Canada

Mutations in normal breast tissue and breast tumours

The accumulation of mutations is a feature of all normal cells. The probability of any individual gene in any cell acquiring a mutation is, however, low. Cancer is therefore a rare disease in comparison with the number of susceptible cells. Mutations in normal tissue are stochastic, vary widely among cells and are therefore difficult to detect using standard methods because each change is so rare. If, however, a tissue such as the breast undergoes considerable clonal expansion, particularly if relatively late in life, normal tissue may have accumulated many thousands of detectable mutations. Since breast cancers are clonal and have almost certainly undergone many more cell divisions than normal cells, each tumour may have many millions of mutations, most of which are entirely innocent and some of which have accumulated in the cell of origin prior to tumorigenesis. Despite some claims to the contrary, even at normal mutation rates, clonal expansion within a tumour is quite sufficient to account for the mutations of five or six genes that are generally supposed necessary for carcinogenesis to occur. Hypermutability does, however, contribute to the pathogenesis of many cancers and, although evidence is indirect in breast cancer, may take forms such as karyotypic instability via centrosome amplification

New developments in hair research

YesThis article is an editorial for the special focus theme issue on “hair research” published by the Experimental Dermatology journal. Here we introduce the articles from the special issue and pose a few questions. The full list of publications for the hair research special issue is available on the Journal’s web site. Many of the articles can be viewed free of charge on the web site. This is for; Experimental Dermatology, Volume 29, Number 3, published March 2020

High-resolution neutron and X-ray diffraction room-temperature studies of an H-FABP-oleic acid complex: study of the internal water cluster and ligand binding by a transferred multipolar electron-density distribution

Crystal diffraction data of heart fatty acid binding protein (H-FABP) in complex with oleic acid were measured at room temperature with high-resolution X-ray and neutron protein crystallography (0.98 and 1.90 Å resolution, respectively). These data provided very detailed information about the cluster of water molecules and the bound oleic acid in the H-FABP large internal cavity. The jointly refined X-ray/neutron structure of H-FABP was complemented by a transferred multipolar electron-density distribution using the parameters of the ELMAMII library. The resulting electron density allowed a precise determination of the electrostatic potential in the fatty acid (FA) binding pocket. Bader's quantum theory of atoms in molecules was then used to study interactions involving the internal water molecules, the FA and the protein. This approach showed H···H contacts of the FA with highly conserved hydrophobic residues known to play a role in the stabilization of long-chain FAs in the binding cavity. The determination of water hydrogen (deuterium) positions allowed the analysis of the orientation and electrostatic properties of the water molecules in the very ordered cluster. As a result, a significant alignment of the permanent dipoles of the water molecules with the protein electrostatic field was observed. This can be related to the dielectric properties of hydration layers around proteins, where the shielding of electrostatic interactions depends directly on the rotational degrees of freedom of the water molecules in the interface.Facultad de Ciencias ExactasInstituto de Física de Líquidos y Sistemas Biológico