Observation of magnetization reversal in epitaxial Gd0.67Ca0.33MnO3 thin films

High quality epitaxial thin films of Gd0.67Ca0.33MnO3 have been deposited onto (100) SrTiO3 substrates by pulsed-laser deposition. Enhanced properties in comparison with bulk samples were observed. The magnetic transition temperature (Tc) of the as-grown films is much higher than the corresponding bulk values. Most interestingly, magnetization measurements performed under small applied fields, exhibit magnetization reversals below Tc, no matter whether the film is field-cooled (FC) or zero-field-cooled (ZFC). A rapid magnetization reversal occurs at 7 K when field cooled, while as for the ZFC process the magnetization decreases gradually with increasing temperatures, taking negative values above 7 K and changing to positive values again, above 83 K. In higher magnetic fields the magnetization does not change sign. The reversal mechanism is discussed in terms of a negative exchange f-d interaction and magnetic anisotropy, this later enhanced by strain effects induced by the lattice mismatch between the film and the substrate.Comment: 16 pages, 4 figure

Physicochemical, functional and structural characterization of fibre from defatted Rosa rubiginosa and Gevuina avellana seeds

The composition, functional properties and structural features of the fiber from Rosa rubiginosa defatted seeds and from Gevuina avellana defatted and partially deproteinized seeds were evaluated. The effect of phosphate salts and temperature during the extraction of fibres and the influence of two drying technologies on the distribution of soluble and insoluble dietary fibre were assessed. The extraction of protein and monosaccharides was favoured by increasing temperature in the range studied. Water and oil absorption capacities higher than 10 g g¯¹ were observed for soluble and insoluble fibres from Gevuina avellana and for the soluble ones from Rosa rubiginosa. The insoluble fibre product from Rosa and Gevuina contained 650-810 g kgˉ¹ and 390-440 g kg¯¹ neutral detergent fibre respectively. The protein content in the insoluble fibre varied in the range 100-150 g kg¯¹ and 120-260 g kg¯¹ and in the soluble fibre between 200-550 g kg¯¹ and 180-370 g kg¯¹ for Rosa and Gevuina respectively.European Commission - INCO-DC. Xunta Galicia - University of Vigo - ERBIC 18 CT 970206, MEC (ALI98-1641-CE)

Crystal structures of I-SceI complexed to nicked DNA substrates: snapshots of intermediates along the DNA cleavage reaction pathway

I-SceI is a homing endonuclease that specifically cleaves an 18-bp double-stranded DNA. I-SceI exhibits a strong preference for cleaving the bottom strand DNA. The published structure of I-SceI bound to an uncleaved DNA substrate provided a mechanism for bottom strand cleavage but not for top strand cleavage. To more fully elucidate the I-SceI catalytic mechanism, we determined the X-ray structures of I-SceI in complex with DNA substrates that are nicked in either the top or bottom strands. The structures resemble intermediates along the DNA cleavage reaction. In a structure containing a nick in the top strand, the spatial arrangement of metal ions is similar to that observed in the structure that contains uncleaved DNA, suggesting that cleavage of the bottom strand occurs by a common mechanism regardless of whether this strand is cleaved first or second. In the structure containing a nick in the bottom strand, a new metal binding site is present in the active site that cleaves the top strand. This new metal and a candidate nucleophilic water molecule are correctly positioned to cleave the top strand following bottom strand cleavage, providing a plausible mechanism for top strand cleavage

Population Attributable Fraction of Early Age of Onset of Alcohol Use in Alcohol Abuse and Dependence: A 3-Year Follow-Up Study in University Students

Background: we aimed to determine the risk factors and associated population attributable fractions (PAFs) for the age of onset of alcohol use and also to identify protective factors. Methods: we analyzed follow-up data collected between autumn 2011 and spring 2016 (n = 5170) from the first two cohorts (2011, 2012) of the Spit for ScienceTM project. The dependent variables were alcohol abuse and dependence, and the independent variables were age of drinking onset, residence, ethnicity, religiosity, sexual orientation and work status. We determined the odds ratios (OR) using multilevel logistic regression for repeated measures in SPSSv.20. Results: the early onset of alcohol use was associated with an increased risk of alcohol abuse and dependence among females (OR = 14.98; OR = 11.83) and males (OR = 7.41; OR = 6.24). The PAFs for the early onset of alcohol use in alcohol abuse and dependence were respectively 80.9% and 71.7% in females and 71.0% and 63.5% in males. Among females, being white (OR = 1.58; OR = 1.51), living off-campus (OR = 1.73; OR = 2.76) and working full-time (OR = 1.69; OR = 1.78) were also risk factors. Strong religious beliefs were found to protect males from alcohol abuse (OR = 0.58), while same-gender sexual orientation increased the risk among females (OR = 2.09). Conclusion: delaying the age of onset by one year would reduce alcohol abuse among young adultsSpit for Science: The Student Survey was supported by the Virginia Commonwealth University, the NIAAA [P20 AA107828, R37AA011408, K02AA018755, and P50 AA022537] and the National Center for Research Resources and National Institutes of Health Roadmap for Medical Research [UL1RR031990]S

Binding-Folding Induced Regulation of AF1 Transactivation Domain of the Glucocorticoid Receptor by a Cofactor That Binds to Its DNA Binding Domain

Intrinsically disordered (ID) regions of proteins commonly exist within transcription factors, including the N-terminal domain (NTD) of steroid hormone receptors (SHRs) that possesses a powerful activation function, AF1 region. The mechanisms by which SHRs pass signals from a steroid hormone to control gene expression remain a central unresolved problem. The role of N-terminal activation function AF1, which exists in an intrinsically disordered (ID) conformation, in this process is of immense importance. It is hypothesized that under physiological conditions, ID AF1 undergoes disorder/order transition via inter- and intra-molecular communications, which allows AF1 surfaces to interact with specific co-regulatory proteins, critical for the final outcome of target gene expression regulated by SHRs. However, the means by which AF1 acquires functionally folded conformations is not well understood. In this study, we tested whether binding of jun dimerization protein 2 (JDP2) within the DNA binding domain (DBD) of the glucocorticoid receptor (GR) leads to acquisition of functionally active structure in its AF1/NTD. Our results show that signals mediated from GR DBD:JDP2 interactions in a two domain GR fragment, consisting of the entire NTD and little beyond DBD, significantly increased secondary/tertiary structure formation in the NTD/AF1. This increased structure formation facilitated AF1’s interaction with specific co-regulatory proteins and subsequent glucocorticoid response element-mediated AF1 promoter:reporter activity. These results support the hypothesis that inter- and intra-molecular signals give a functionally active structure(s) to the GR AF1, which is important for its transcriptional activity

SETD3 is an actin histidine methyltransferase that prevents primary dystocia.

For more than 50 years, the methylation of mammalian actin at histidine 73 has been known to occur1. Despite the pervasiveness of His73 methylation, which we find is conserved in several model animals and plants, its function remains unclear and the enzyme that generates this modification is unknown. Here we identify SET domain protein 3 (SETD3) as the physiological actin His73 methyltransferase. Structural studies reveal that an extensive network of interactions clamps the actin peptide onto the surface of SETD3 to orient His73 correctly within the catalytic pocket and to facilitate methyl transfer. His73 methylation reduces the nucleotide-exchange rate on actin monomers and modestly accelerates the assembly of actin filaments. Mice that lack SETD3 show complete loss of actin His73 methylation in several tissues, and quantitative proteomics analysis shows that actin His73 methylation is the only detectable physiological substrate of SETD3. SETD3-deficient female mice have severely decreased litter sizes owing to primary maternal dystocia that is refractory to ecbolic induction agents. Furthermore, depletion of SETD3 impairs signal-induced contraction in primary human uterine smooth muscle cells. Together, our results identify a mammalian histidine methyltransferase and uncover a pivotal role for SETD3 and actin His73 methylation in the regulation of smooth muscle contractility. Our data also support the broader hypothesis that protein histidine methylation acts as a common regulatory mechanism

Optical measurement of blood flow changes in spinal cord injury

Little is known about cell death in spinal cord tissue following compression injury, despite compression being a key component of spinal injuries. Currently models are used to mimic compression injury in animals and the effects of the compression evaluated by observing the extent and duration of recovery of normal motor function in the days and weeks following the injury. A fibreoptic photoplethysmography system was used to investigate whether pulsation of the small arteries in the spinal cord occurred before, during and after compressive loads were applied to the tissue. It was found that the signal amplitudes were reduced and this reduction persisted for at least five minutes after the compression ceased. It is hoped that results from this preliminary study may improve knowledge of the mechanism of spinal cord injury

Oncolytic viruses as therapeutic tools for pediatric brain tumors

In recent years, we have seen an important progress in our comprehension of the molecular basis of pediatric brain tumors (PBTs). However, they still represent the main cause of death by disease in children. Due to the poor prognosis of some types of PBTs and the long-term adverse effects associated with the traditional treatments, oncolytic viruses (OVs) have emerged as an interesting therapeutic option since they displayed safety and high tolerability in pre-clinical and clinical levels. In this review, we summarize the OVs evaluated in different types of PBTs, mostly in pre-clinical studies, and we discuss the possible future direction of research in this field. In this sense, one important aspect of OVs antitumoral effect is the stimulation of an immune response against the tumor which is necessary for a complete response in preclinical immunocompetent models and in the clinic. The role of the immune system in the response of OVs needs to be evaluated in PBTs and represents an experimental challenge due to the limited immunocompetent models of these diseases available for pre-clinical research