Ab initio investigation of monoclinic phase stability and martensitic transformation in crystalline polyethylene

We study the phase stability and martensitic transformation of orthorhombic and monoclimic polyethylene by means of density functional theory using the nonempirical consistent-exchange vdW-DF-cx functional [Phys. Rev. B 89, 035412 (2014)]. The results show that the orthorhombic phase is the most stable of the two. Owing to the occurrence of soft librational phonon modes, the monoclimic phase is predicted not to be stable at zero pressure and temperature, but becomes stable when subjected to compressive transverse deformations that pin the chains and prevent them from wiggling freely. This theoretical characterization, or prediction, is consistent with the fact that the monoclimic phase is only observed experimentally when the material is subjected to mechanical loading. Also, the estimated threshold energy for the combination of lattice deformation associated with the T1 and T2 transformation paths (between the orthorhombic and monoclimic phases) and chain shuffling is found to be sufficiently low for thermally activated back transformations to occur. Thus, our prediction is that the crystalline part can transform back from the monoclimc to the orthorhombic phase upon unloading and/or annealing, which is consistent with experimental observations. Finally, we observe how a combination of such phase transformations can lead to a fold-plane reorientation from {110} to {100} type in a single orthorhombic crystal

Lactadherin binds to elastin - a starting point for medin amyloid formation?

Medin amyloid is found in the medial layer of the aorta in almost 100% of the Caucasian population over 50 years of age. The medin fragment is 5.5 kDa and derives from the C2-like domain of the precursor protein lactadherin. We have previously reported immunohistochemical findings showing that medin amyloid co-localizes with elastic fibers of arteries and herein we show that lactadherin also is associated with elastic structures of human aortic material. In addition, results from in vitro binding assays demonstrate that both medin and lactadherin bind to tropoelastin in a concentration-dependent fashion, suggesting that the lactadherin-tropoelastin interaction is mediated via the medin domain. It is possible that lactadherin, which is a cell adhesion protein, in this way connects smooth muscle cells to the elastic fibers of arteries. Given that both medin and lactadherin interact with elastic fibers, elastin is probably an important component in the formation of medin amyloid

LRIG1 and the liar paradox in prostate cancer: a study of the expression and clinical significance of LRIG1 in prostate cancer

The course of prostate cancer varies greatly, and additional prognostic markers are needed. Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) is an endogenous inhibitor of growth factor signaling and a proposed tumor suppressor. Publicly available gene expression datasets indicate that LRIG1 may be overexpressed in prostate cancer. In our study, the expression of LRIG1 protein in prostate cancer was evaluated for the first time. Immunohistochemistry was performed on tissue microarrays from two different patient series: 355 Swedish patients diagnosed by transurethral resection and 293 American patients who underwent radical prostatectomy. In the Swedish series, high expression of LRIG1 correlated with Gleason score, T-stage, tumor cell proliferation, vascular density and epidermal growth factor receptor (EGFR) phosphorylation. Among the 256 Swedish patients, followed by watchful waiting, high LRIG1 expression was significantly associated with short overall and prostate cancer-specific survival. In contrast, in the US series, high LRIG1 expression was significantly associated with long overall survival. In vitro cell experiments showed that LRIG1 was induced by androgen stimulation, and its expression inhibited prostate cancer cell proliferation. Thus, LRIG1 expression was an independent marker for poor survival in the untreated patient series, perhaps as a secondary marker of androgen receptor and/or EGFR activation. On the contrary, LRIG1 was a marker for good prognosis after prostatectomy, which might be due to its growth inhibiting properties. We propose that LRIG1 is an important determinant of prostate cancer growth, and the implications of its expression on patient outcome depend on the clinical and biological circumstances

Dual relationships of xylitol and alcohol dehydrogenases in families of two protein types

AbstractXylitol dehydrogenase encoded by gene XYL2 from Pichia stipitis is a member of the medium-chain alcohol dehydrogenase family, as evidenced by the domain organization and a distant homology (24% residue identity with the human class Iγ1 alcohol dehydrogenase). Much of a loop structure is missing, like in mammalian sorbitol and prokaryotic threonine dehydrogenases, many additional differences occur, and relationships are closest with the sorbitol dehydrogenase, the equivalence of which in P. stipitis may actually be the xylitol dehydrogenase. A second P. stipitis gene, also cloned and corresponding to a xylitol dehydrogenase, is highly different from XYL2, but encodes an enzyme with structural properties typical of the short-chain dehydrogenase family, which also contains an alcohol dehydrogenase (from Drosophila). Thus, yeast xylitol dehydrogenases, like alcohol and polyol dehydrogenases from other sources, have dual derivations, combining similar enzyme activities in separate protein families. In contrast to the situation with the other enzymes, both forms of xylitol dehydrogenase are present in one organism