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The cellular prion protein, PrPC, is a copper‐binding protein abundantly expressed in the brain, particularly by neurons, and its conformational conversion into the amyloidogenic isoform, PrPSc, plays a key pathogenic role in prion diseases. However, the role of copper binding to PrPC in prion diseases remains unclear. Here, we fed mice with a low‐copper or regular diet and intracerebrally inoculated them with two different mouse‐adapted RML scrapie and BSE prions. Mice with a low‐copper diet developed disease significantly but only slightly later than those with a regular diet after inoculation with BSE prions, but not with RML prions, suggesting that copper could play a minor role in BSE prion pathogenesis, but not in RML prion pathogenesis. We then generated two lines of transgenic mice expressing mouse PrP with copper‐binding histidine (His) residues in the N‐terminal domain replaced with alanine residues, termed TgPrP(5H > A)‐7342/Prnp0/0 and TgPrP(5H > A)‐7524/Prnp0/0 mice, and similarly inoculated RML and BSE prions into them. Due to 2‐fold higher expression of PrP(5H > A) than PrPC in wild‐type (WT) mice, TgPrP(5H > A)‐7524/Prnp0/0 mice were highly susceptible to these prions, compared to WT mice. However, TgPrP(5H > A)‐7342/Prnp0/0 mice, which express PrP(5H > A) 1.2‐fold as high as PrPC in WT mice, succumbed to disease slightly, but not significantly, later than WT mice after inoculation with RML prions, but significantly so after inoculation with BSE prions. Subsequent secondary inoculation experiments revealed that amino acid sequence differences between PrP(5H > A) and WT PrPSc created no prion transmission barrier to BSE prions. These results suggest that copper‐binding His residues in PrPC are dispensable for RML prion pathogenesis but have a minor effect on BSE prion pathogenesis. Taken together, our current results suggest that copper could have a minor effect on prion pathogenesis in a strain‐dependent manner through binding to His residues in the N‐terminal domain of PrPC. [ABSTRACT FROM AUTHOR]

The photochemical conversion of 1,8a‐dihydroazulene‐1,1‐dicarbonitrile (DHA) to vinylheptafulvene (VHF) is a positive T‐type photoswitch that is well understood in solution, but has not been explored in the solid state. Upon excitation with UV light, DHA is converted into VHF in the solid state, with a distinct color change from yellow to deep‐red, and retention of crystallinity. The structure of the ring‐opened product was assigned to syn‐VHF using variable‐temperature infrared spectroscopy, and determined by X‐ray photodiffraction in a crystal enriched with the product by two‐photon excitation. A radical pathway becomes an observable photoreaction channel at low temperatures, and includes a strongly colored, short‐lived diradical intermediate. True colors: Crystals of dihydroazulene can be reversibly switched between closed and open forms with a distinct color change from yellow to deep‐red. In addition to the closed‐shell ring‐opening reaction, a radical pathway becomes dominant at low temperatures, and includes a strongly colored, short‐lived diradical intermediate. [ABSTRACT FROM AUTHOR]

One of the most inevitable limitations of any material that is exposed to mechanical impact is that they are inexorably prone to mechanical damage, such as cracking, denting, gouging, or wearing. To confront this challenge, the field of polymers has developed materials that are capable of autonomous self-healing and recover their macroscopic integrity similar to biological organisms. However, the study of this phenomenon has mostly remained within the soft materials community and has not been explored by solid-state organic chemists. The first evidence of self-healing in a molecular crystal is now presented using crystals of dipyrazolethiuram disulfide. The crystals were mildly compressed and the degree of healing was found to be 6.7 %. These findings show that the self-healing properties can be extended beyond mesophasic materials and applied towards the realm of ordered solid-state compounds. [ABSTRACT FROM AUTHOR]

The peroxisome proliferator-activated receptor (PPAR)α is mainly expressed in the liver and plays an important role in the regulation of lipid metabolism. It has been reported that PPARα activation enhances fatty acid oxidation and reduces fat storage. Therefore, PPARα agonists are used to treat dyslipidemia. In the present study, we found that 9-oxo-10( E),12( Z),15( Z)-octadecatrienoic acid (9-oxo-OTA), which is a α-linolenic acid (ALA) derivative, is present in tomato ( Solanum lycopersicum) extract. We showed that 9-oxo-OTA activated PPARα and induced the mRNA expression of PPARα target genes in murine primary hepatocytes. These effects promoted fatty acid uptake and the secretion of β-hydroxybutyrate, which is one of the endogenous ketone bodies. We also demonstrated that these effects of 9-oxo-OTA were not observed in PPARα-knockout (KO) primary hepatocytes. To our knowledge, this is the first study to report that 9-oxo-OTA promotes fatty acid metabolism via PPARα activation and discuss its potential as a valuable food-derived compound for use in the management of dyslipidemia. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor (PPAR)γ is expressed in adipose tissue and plays a key role in the regulation of adipogenesis. PPARγ activators are known to have potent antihyperglycemic activity and are used to treat insulin resistance associated with diabetes. Therefore, many natural and synthetic agonists of PPARγ are used in the treatment of glucose disorders. In the present study, we found that 13-oxo-9( Z),11( E),15( Z)-octadecatrienoic acid (13-oxo-OTA), a linolenic acid derivative, is present in the extract of tomato ( Solanum lycopersicum), Mandarin orange ( Citrus reticulata), and bitter gourd ( Momordica charantia). We also found that 13-oxo-OTA activated PPARγ and induced the mRNA expression of PPARγ target genes in adipocytes, thereby promoting differentiation. Furthermore, 13-oxo-OTA induced secretion of adiponectin and stimulated glucose uptake in adipocytes. To our knowledge, this is the first study to report that 13-oxo-OTA induces adipogenesis through PPARγ activation and to present 13-oxo-OTA as a valuable food-derived compound that may be applied in the management of glucose metabolism disorders. [ABSTRACT FROM AUTHOR]

Introduction: Ventricular repolarization abnormalities are thought to contribute to lethal ventricular arrhythmias in patients with idiopathic dilated cardiomyopathy (DCM). The purpose of this study was to evaluate exercise-induced T wave changes in DCM patients before and after beta-blocker therapy to investigate repolarization abnormalities. Methods and Results: Treadmill exercise testing was performed in 20 DCM patients and 50 normal subjects. T wave amplitude (TA: baseline to T wave apex; mV) and recovery time (RT: QRS onset to the maximum dV/dt point of the T wave; msec) were measured before and 1 minute after peak exercise. TA was averaged in the right and left precordial leads (TAV1–3, TAV4–6). RT was normalized to the maximum QT interval in the 12-lead ECG and expressed as the %RT (%RT). %RT was also averaged in the precordial leads (%RTV1–3, %RTV4–6). After exercise, TA increased and %RT decreased in both groups. In DCM patients, TAV1–3 was greater and TAV4–6 was less than in normal subjects before and after exercise. There was no difference in %RTV1–3 between the groups, but %RTV4–6 was greater in DCM patients both before and after exercise. DCM patients repeated the same evaluation after 6 months of oral beta-blocker therapy. Compared with measurements before beta-blocker therapy, TAV1–3 and %RTV1–3 did not change. However, TAV4–6 increased and %RTV4–6 decreased significantly both before and after exercise. Conclusion: DCM patients showed small TA and large %RT in the left precordial leads at rest as well as after exercise. Chronic beta-blocker therapy in DCM patients normalized these ventricular repolarization abnormalities. [ABSTRACT FROM AUTHOR]

The yeast [ PSI+] factor is transmitted by a prion mechanism involving self-propagating Sup35 aggregates. As with mammalian prions, a species barrier prevents prion transmission between yeast species. The N-terminal of Sup35 of Saccharomyces cerevisiae, necessary for [ PSI+], contains two species-signature elements—a Gln/Asn-rich region (residues 1–41; designated NQ) that is followed by oligopeptide repeats (designated NR). In this study, we show that S. cerevisiae[ PSI+] is transmissible through plasmid shuffling and cytoplasmic transfer to heterotypic Sup35s whose NQ is replaced with the S. cerevisiae NQ. In addition to homology, the N-terminal location is essential for NQ mediated susceptibility to [ PSI+] transmission amongst heterotypic Sup35s. In vitro, a swap of NQ of S. cerevisiae Sup35 led to cross seeding of amyloid formation. These findings suggest that NQ discriminates self from non-self, and is sufficient to initiate [ PSI+] transmission irrespective of whether NR is heterotypic. NR as well as NQ alone coalesces into existing [ PSI+] aggregates, showing their independent potentials to interact with the identical sequence in the [ PSI+] conformer. The role of NQ and NR in [ PSI+] prion formation is discussed. [ABSTRACT FROM AUTHOR]

Presents a study which reported Bepridil, a multiple ion-channel blocker, to prevent paroxysmal atrial fibrillation. Patient population and methods; Results and discussion; Conclusion.