Journal of Cardiovascular Magnetic Resonance ® , 3(4), 349–360 (2001) Mechanisms of the Effects of Nicorandil in the Isolated Rat Heart During Ischemia and Reperfusion: A 31 P-Nuclear Magnetic Resonance Study

Nicorandil (SG75) is a potent K �-channel activator with an additional nitro moiety. In the present study we investigated the potential mechanisms (K �-channel activation and nitric oxide [NO] release) for the effects of nicorandil on isolated perfused rat hearts during total global ischemia using 31 P-nuclear magnetic resonance. After a 10-min control perfusion, hearts were subjected to treatment with nicorandilcontaining (100, 300, or 1000 µM) buffer for 10 min, 15 min of total global ischemia, and 30 min of reperfusion. At high dose (10 �3 M), nicorandil reduced ATP depletion during ischemia by 26 % compared with untreated hearts. Blockade of K � channels by glibenclamide prevented this protective effect. At all doses (10 �4 to 10 �3 M), nicorandil reduced the accumulation of protons during ischemia compared with untreated hearts (pH 6.22 � 0.03 vs. 6.02 � 0.05 in untreated hearts at the end of ischemia). This effect was preserved after blockade of K � channels by glibenclamide. Hearts treated with nitroglycerine before ischemia also showed reduced proton accumulation. Therefore, NO release accompanied by increased coronary flow before ischemia, which is caused by the nitro moiety of nicorandil and nitroglycerine treatment, results in reduced proton accumulation. During reperfusion, a pro-arrhythmic effect was observed in hearts treated with the nonpharmacologically high dose of nicorandil (1000 µM). Thus, we conclude that the effects of nicorandil are caused Address correspondence and reprint requests to Michael Horn

Criteria for flatness and injectivity

Let $R$ be a commutative Noetherian ring. We give criteria for flatness of $R$-modules in terms of associated primes and torsion-freeness of certain tensor products. This allows us to develop a criterion for regularity if $R$ has characteristic $p$, or more generally if it has a locally contracting endomorphism. Dualizing, we give criteria for injectivity of $R$-modules in terms of coassociated primes and (h-)divisibility of certain \Hom-modules. Along the way, we develop tools to achieve such a dual result. These include a careful analysis of the notions of divisibility and h-divisibility (including a localization result), a theorem on coassociated primes across a \Hom-module base change, and a local criterion for injectivity.Comment: 19 page

Auslander-Buchweitz approximation theory for triangulated categories

We introduce and develop an analogous of the Auslander-Buchweitz approximation theory (see \cite{AB}) in the context of triangulated categories, by using a version of relative homology in this setting. We also prove several results concerning relative homological algebra in a triangulated category \T, which are based on the behavior of certain subcategories under finiteness of resolutions and vanishing of Hom-spaces. For example: we establish the existence of preenvelopes (and precovers) in certain triangulated subcategories of \T. The results resemble various constructions and results of Auslander and Buchweitz, and are concentrated in exploring the structure of a triangulated category \T equipped with a pair (\X,\omega), where \X is closed under extensions and $\omega$ is a weak-cogenerator in \X, usually under additional conditions. This reduces, among other things, to the existence of distinguished triangles enjoying special properties, and the behavior of (suitably defined) (co)resolutions, projective or injective dimension of objects of \T and the formation of orthogonal subcategories. Finally, some relationships with the Rouquier's dimension in triangulated categories is discussed.Comment: To appear at: Appl. Categor. Struct. (2011); 22 page

Importin α7 Is Essential for Zygotic Genome Activation and Early Mouse Development

Importin α is involved in the nuclear import of proteins. It also contributes to spindle assembly and nuclear membrane formation, however, the underlying mechanisms are poorly understood. Here, we studied the function of importin α7 by gene targeting in mice and show that it is essential for early embryonic development. Embryos lacking importin α7 display a reduced ability for the first cleavage and arrest completely at the two-cell stage. We show that the zygotic genome activation is severely disturbed in these embryos. Our findings indicate that importin α7 is a new member of the small group of maternal effect genes

Clinical relevance of genetic instability in prostatic cells obtained by prostatic massage in early prostate cancer

We investigated whether genetic lesions such as loss of heterozygosity (LOH) are detected in prostatic cells obtained by prostatic massage during early diagnosis of prostate cancer (CaP) and discussed their clinical relevance. Blood and first urine voided after prostatic massage were collected in 99 patients with total prostate-specific antigen (PSA) between 4 and 10 ng ml−1, prior to prostate biopsies. Presence of prostatic cells was confirmed by quantitative RT–PCR analysis of PSA mRNA. Genomic DNA was analysed for LOH on six chromosomal regions. One or more allelic deletions were found in prostatic fluid from 57 patients analysed, of whom 33 (58%) had CaP. Sensitivity and specificity of LOH detection and PSA free to total ratio <15% for positive biopsy were respectively 86.7 and 44% (P=0.002) for LOH, and 55 and 74% (P=0.006) for PSA ratio <15%. Analysis of LOH obtained from prostatic tumours revealed similar patterns compared to prostatic fluid cells in 86% of cases, confirming its accuracy. The presence of LOH of urinary prostatic cells obtained after prostatic massage is significantly associated with CaP on biopsy and may potentially help to identify a set of patients who are candidates for further prostate biopsies

Loss of heterozygosity (LOH), malignancy grade and clonality in microdissected prostate cancer

The aim of the present study was to find out whether increasing malignancy of prostate carcinoma correlates with an overall increase of loss of heterozygosity (LOH), and whether LOH typing of microdissected tumour areas can help to distinguish between multifocal or clonal tumour development. In 47 carcinomas analysed at 25 chromosomal loci, the overall LOH rate was found to be significantly lower in grade 1 areas (2.2%) compared with grade 2 (9.4%) and grade 3 areas (8.3%, P = 0.007). A similar tendency was found for the mean fractional allele loss (FAL, 0.043 for grade 1, 0.2 for grade 2 and 0.23 for grade 3, P = 0.0004). Of 20 tumours (65%) with LOH in several microdissected areas, 13 had identical losses at 1–4 loci within two or three areas, suggesting clonal development of these areas. Markers near RB, DCC, BBC1, TP53 and at D13S325 (13q21–22) showed higher loss rates in grades 2 and 3 (between 25% and 44.4%) compared with grade 1 (0–6.6%). Tumour-suppressor genes (TSGs) near these loci might, thus, be important for tumour progression. TP53 mutations were detected in 27%, but BBC1 mutations in only 7%, of samples with LOH. Evaluation of all 25 loci in every tumour made evident that each prostate cancer has its own pattern of allelic losses. © 1999 Cancer Research Campaig

Magnetic crystals and helical liquids in alkaline-earth fermionic gases

The joint action of a synthetic gauge potential and of atomic contact repulsion in a one-dimensional alkaline-earth(-like) fermionic gas with nuclear spin I leads to the existence of a hierarchy of fractional insulating and conducting states with intriguing properties. We unveil the existence and the features of those phases by means of both analytical bosonization techniques and numerical methods based on the density-matrix renormalization group algorithm. In particular, we show that the gapless phases can support helical modes, whereas the gapped states, which appear under certain conditions, are characterised both by density and magnetic order. Several distinct features emerge solely for spin I larger than 1/2, thus making their study with cold-atoms unique. We will finally argue that these states are related to the properties of an unconventional fractional quantum Hall effect in the thin-torus limit. The properties of this hierarchy of states can be experimentally studied in state-of-the-art cold-atom laboratories

Discrete derived categories I: homomorphisms, autoequivalences and t-structures

Discrete derived categories were studied initially by Vossieck (J Algebra 243:168–176, 2001) and later by Bobiński et al. (Cent Eur J Math 2:19–49, 2004). In this article, we describe the homomorphism hammocks and autoequivalences on these categories. We classify silting objects and bounded t-structures