Genome organization can regulate gene expression and promote cell fate transitions. The differentiation of germline stem cells (GSCs) to oocytes in Drosophila involves changes in genome organization mediated by heterochromatin and the nuclear pore complex (NPC). Heterochromatin represses germ cell genes during differentiation, and NPCs anchor these silenced genes to the nuclear periphery, maintaining silencing to allow for oocyte development. Surprisingly, we found that genome organization also contributes to NPC formation, mediated by the transcription factor Stonewall (Stwl). As GSCs differentiate, Stwl accumulates at boundaries between silenced and active gene compartments. Stwl at these boundaries plays a pivotal role in transitioning germ cell genes into a silenced state and activating a group of oocyte genes and nucleoporins (Nups). The upregulation of these Nups during differentiation is crucial for NPC formation and further genome organization. Thus, cross-talk between genome architecture and NPCs is essential for successful cell fate transitions.

The fourth universal definition of MI defines requires presence of j point elevation in two contiguous leads except v2-3 where the elevation should be equal to or >2 mm in men (2.5 mm in <40 years) and 1.5 mm in women.(1) We present two cases of patients who presented with electrocardiographic manifestations of occlusion of septal perforator of left anterior descending artery and discuss the salient feature of ECG in such patients. We also present the limitations of STEMI criteria given the dynamic nature of acute coronary occlusion and stress on early recognition of this MI.

Myocardial infarction (MI) in mice is a widely used surgical model in preclinical cardiac repair studies to recapitulate human cardiovascular ischemic disease. Induction of reproducible infarct size is crucial for quantitative and analytical purpose. Here we describe a quick and reliable method to induce consistent infarct size in mice in less than a minute.

BACKGROUND: The fact that during myocardial ischemia/reperfusion (I/R) injury, myosin light chain 1 (MLC1) and troponin I (TnI) are degraded by matrix metalloproteases activity has already been well established in both in vitro and ex vivo studies. However, I/R injury is a complex issue based on several overlapping mechanisms. Increased activity of myosin light chain kinase and nitric oxide synthase due to oxidative stress leads to post-translational modifications of MLC1, thus leading to the increased degradation of these proteins.
METHODS: Wistar rats were subjected to left anterior descending coronary artery occlusion. To measure the pharmacological effect of doxycycline, transthoracic echocardiography as well as biochemical tests, concentrations of TnI, LDH, MLC1, MMP-2 and MMP-9 were performed. Gelatinize activity and cytotoxicity level were also assessed; Results: I.p., administration of doxycycline before LAD occlusion surgery increased TnI and LDH content in the heart and decreased cytotoxicity. A reduction of MMP-2 and MMP-9 concentration and MMP-2 activity after administration of Doxy was also observed, as well as improvement in echocardiographic parameters just 7 days after surgery.
CONCLUSIONS: Inhibition of MMPs by doxycycline, in vivo, may serve as a protective agent in future therapy.

BACKGROUND: Oxidative stress is a pathological feature of acute coronary syndrome (ACS), a complex disease with varying clinical outcomes. Surrogate biomarkers of oxidative stress including, peroxiredoxin-2 (PRDX2), PRDX4, thioredoxin (TRX) and thioredoxin reductase (TRXR) were measured in ACS patients at presentation and follow-up, to assess their clinical utility in diagnosis and risk stratification.
METHODS: Plasma from 145 participants (80 ACS and 65 healthy) at diagnosis, 1-3 month (first) and 6-month follow-up (second) was analysed by ELISA. ACS patients were monitored for 12-months.
RESULTS: ACS patients at diagnosis had significantly higher concentrations of TRX (p < 0.05), TRXR (p < 0.01) and PRDX4 (p < 0.01), compared to healthy donors. This was increase was driven by non-ST elevated myocardial infarction for TRX (p < 0.01) and PRDX4 (p < 0.05). For TRXR, ACS females were significantly higher than males (p < 0.05). TRX was also higher in older females (>55 years) at diagnosis (p < 0.05). At first follow-up, TRX had lowered, whereas PRDX4 remained significantly high (p < 0.05). Stratification of ACS patients according to percutaneous coronary intervention (PCI) revealed that TRXR was significantly higher in patients receiving PCI to the right coronary artery (p < 0.05). Whereas both TRXR (p < 0.01) and PRDX4 (p < 0.01) were significantly higher in patients receiving PCI to the left anterior descending (LAD) artery. ACS patients who had plasma TRX >13.40 ng/ml at second follow-up were at high risk of readmission (p < 0.05), as were patients with TRXR of <1000 pg/ml at diagnosis having PCI to the LAD (p < 0.05).
CONCLUSIONS: This study indicates that TRX, TRXR and PRDX4 may have clinical utility for ACS stratification.

A comparison of the radiation exposure to the left anterior descending artery (LAD) and left ventricle (LV) was performed for twenty-three left breast cancer patients. For each participant, two tangential fields 3D-CRT, two- and seven-field IMRT and two and four partial arcs VMAT plans were created. Dose constraints for CTV, ipsilateral lung and heart were followed. The V40Gy, V30Gy, Dav of LAD and V23Gy, V5Gy, Dav of LV were calculated and extracted from the plans. Parametric and non-parametric tests were applied to compare the parameters derived from the five treatment techniques. All generated plans fulfilled the dose constraints. The Dav ranges of the LAD and LV from all examined techniques were 11.77-14.73 Gy and 5.37-6.40 Gy, respectively. The V40Gy and V30Gy ranges of the LAD were 2.90-12.91% and 10.80-18.51%, respectively. The V23Gy and V5Gy of the LV were 4.29-7.43% and 18.24-30.05%, respectively. The VMAT plans and seven-field IMRT significantly reduced the V40Gy, V30Gy of LAD and V23Gy of LV compared with the two-field treatments (p < 0.05). However, 3D-CRT plans provided statistically lower values for V5Gy of LV over the other techniques (p < 0.05). The presented results provide a detailed dataset of the radiation burden of two critical cardiac structures from five radiotherapy techniques.

Heterochromatin and euchromatin form different spatial compartments in the interphase nucleus, with heterochromatin being localized mainly at the nuclear periphery. The mechanisms responsible for peripheral localization of heterochromatin are still not fully understood. The nuclear lamina and nuclear pore complexes were obvious candidates for the role of heterochromatin binders. This review is focused on recent studies showing that heterochromatin interactions with the nuclear lamina and nuclear pore complexes maintain its peripheral localization. Differences in chromatin interactions with the nuclear envelope in cell populations and in individual cells are also discussed.

Functionally indispensable genes are likely to be retained and otherwise to be lost during evolution. This evolutionary fate of a gene can also be affected by factors independent of gene dispensability, including the mutability of genomic positions, but such features have not been examined well. To uncover the genomic features associated with gene loss, we investigated the characteristics of genomic regions where genes have been independently lost in multiple lineages. With a comprehensive scan of gene phylogenies of vertebrates with a careful inspection of evolutionary gene losses, we identified 813 human genes whose orthologs were lost in multiple mammalian lineages: designated \'elusive genes.\' These elusive genes were located in genomic regions with rapid nucleotide substitution, high GC content, and high gene density. A comparison of the orthologous regions of such elusive genes across vertebrates revealed that these features had been established before the radiation of the extant vertebrates approximately 500 million years ago. The association of human elusive genes with transcriptomic and epigenomic characteristics illuminated that the genomic regions containing such genes were subject to repressive transcriptional regulation. Thus, the heterogeneous genomic features driving gene fates toward loss have been in place and may sometimes have relaxed the functional indispensability of such genes. This study sheds light on the complex interplay between gene function and local genomic properties in shaping gene evolution that has persisted since the vertebrate ancestor.

Butyrate and propionate represent two of three main short-chain fatty acids produced by the intestinal microbiota. In healthy populations, their levels are reportedly equimolar, whereas a deviation in their ratio has been observed in various diseased cohorts. Monitoring such a ratio represents a valuable metric; however, it remains a challenge to adopt short-chain fatty acid detection techniques in clinical settings because of the volatile nature of these acids. Here we aimed to estimate short-chain fatty acid information indirectly through a novel, simple quantitative PCR-compatible assay (liquid array diagnostics) targeting a limited number of microbiome 16S markers. Utilizing 15 liquid array diagnostics probes to target microbiome markers selected by a model that combines partial least squares and linear discriminant analysis, the classes (normal vs high propionate-to-butyrate ratio) separated at a threshold of 2.6 with a prediction accuracy of 96%.

UNASSIGNED: To analyze whether deep inspiratory breath hold (DIBH) would be dosimetrically beneficial irrespective of radiotherapy planning techniques for patients with left breast cancers requiring adjuvant radiotherapy.
UNASSIGNED: Planning CT scans were taken in free-breathing (FB) as well as deep-inspiration breath hold (DIBH) for patients requiring adjuvant radiotherapy for left breast cancers. After registration, three radiotherapy plans - 3D-conformal radiotherapy (3DCRT), intensity modulated RT (IMRT), and volumetric modulated arc-therapy (VMAT) - were generated for both FB and DIBH scans for each patient. The dose-volume parameters were collected from the dose-volume histogram and analyzed. A paired t-test is used for statistical analysis of the parameters.
UNASSIGNED: The study was conducted on thirteen patients. The mean dose of the left lung was reduced with DIBH by 32%, 24%, and 6% (8.6 Gy, 6.6 Gy, and 6.4 Gy) with 3DCRT, IMRT, and VMAT, respectively. The mean heart dose was reduced by 3.3 Gy (2.2 vs 5.5 Gy), 2.2 Gy (7.5 vs 9.7 Gy), and 1.2 Gy (5.8 vs 7 Gy) with 3DCRT, IMRT, and VMAT with DIBH. Similarly, the left anterior descending artery (LAD) mean dose was relatively reduced by 80%, 34%, and 20% when compared with the FB scans for 3DCRT, IMRT, and VMAT respectively, with max dose in the 3DCRT plan.
UNASSIGNED: DIBH appears to have maximum benefit in achieving a better sparing of organs-at-risk for patients being considered for 3DCRT, and to a lesser extent with even IMRT and VMAT techniques.