Characterization of the structural and functional changes in the myocardium following focal ischemia-reperfusion injury

High-resolution (11.7 T) cardiac magnetic resonance imaging (MRI) and histological approaches have been employed in tandem to characterize the secondary damage suffered by the murine myocardium following the initial insult caused by ischemia-reperfusion (I/R). I/R-induced changes in the myocardium were examined in five separate groups at the following time points after I/R: 1 h, day 1, day 3, day 7, and day 14. The infarct volume increased from 1 h to day 1 post-I/R. Over time, the loss of myocardial function was observed to be associated with increased infarct volume and worsened regional wall motion. In the infarct region, I/R caused a decrease in end-systolic thickness coupled with small changes in end-diastolic thickness, leading to massive wall thickening abnormalities. In addition, compromised wall thickening was also observed in left ventricular regions adjacent to the infarct region. A tight correlation (r2 = 0.85) between measured MRI and triphenyltetrazolium chloride (TTC) infarct volumes was noted. Our observation that until day 3 post-I/R the infarct size as measured by TTC staining and MRI was much larger than that of the myocyte-silent regions in trichrome- or hematoxylin-eosin-stained sections is consistent with the literature and leads to the conclusion that at such an early phase, the infarct site contains structurally intact myocytes that are functionally compromised. Over time, such affected myocytes were noted to structurally disappear, resulting in consistent infarct sizes obtained from MRI and TTC as well as trichrome and hematoxylin-eosin analyses on day 7 following I/R. Myocardial remodeling following I/R includes secondary myocyte death followed by the loss of cardiac function over time.     

Decoding phage resistance by mpr and its role in survivability of Mycobacterium smegmatis

Bacteria and bacteriophages co-evolve in a constant arms race, wherein one tries and finds newer ways to overcome the other. Phage resistance poses a great threat to the development of phage therapy. Hence, it is both essential and important to understand the mechanism of phage resistance in bacteria. First identified in Mycobacterium smegmatis, the gene mpr, upon overexpression, confers resistance against D29 mycobacteriophage. Presently, the mechanism behind phage resistance by mpr is poorly understood. Here we show that Mpr is a membrane-bound DNA exonuclease, which digests DNA in a non-specific manner independent of the sequence, and shares no sequence or structural similarity with any known nuclease. Exonuclease activity of mpr provides resistance against phage infection, but the role of mpr may very well go beyond just phage resistance. Our experiments show that mpr plays a crucial role in the appearance of mutant colonies (phage resistant strains). However, the molecular mechanism behind the emergence of these mutant/resistant colonies is yet to be understood. Nevertheless, it appears that mpr is involved in the survival and evolution of M. smegmatis against phage. A similar mechanism may be present in other organisms, which requires further exploration.     

A neural circuit state change underlying skilled movements

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Structures of XH4 + and XH6 + (X = B, Al and Ga) Cations

Structures and energies of XH₄ ⁺ and XH₆ ⁺ (X = B, Al and Ga) have been calculated at the density functional theory (DFT) B3LYP/6-311++G(3df,2pd) level. Calculations indicate that although the structure with a three center two electron (3c-2e) bond is the global minimum for BH₄ ⁺, the global minima of AlH₄ ⁺ and GaH₄ ⁺ are not those with one 3c-2e bond, but those with two 3c-2e bonds. For calibration, both structures of AlH₄ ⁺ were also calculated at the ab initio CCSD(T)/cc-pVTZ level and results in agreement with the DFT results were found. Similar calculations also indicate that although the C_2v symmetrical structure with two 3c-2e bonds is the global minimum for BH₆ ⁺, the global minima of AlH₆ ⁺ and GaH₆ ⁺ are not the C_2v symmetrical structures with two 3c-2e bonds but the C₂ symmetrical structures with three 3c-2e bonds.Electronic Supplementary Material available.     

12/15-lipoxygenase inhibitors in diabetic nephropathy in the rat

The 12/15-lipoxygenase (12/15-LO) pathway is activated in diabetes mellitus (DM), increasing 12(S)-hydroxyeicosatetraenoic acid (12-HETE). We showed that a 12-LO inhibitor, cinnamyl-3,4-dihydroxy-alpha-cyanocinnamate (CDC) inhibited 12/15-LO activity in vivo and assessed the efficacy of another 12/15-LO inhibitor, N-benzyl-N-hydroxy-5-phenylpentamidine (BHPP), to diminish urinary 12-HETE and ameliorate diabetic nephropathy (DN) over 4 months. Rats studied were control (C, n=8), DM (n=6), and rats injected with BHPP (C+BHPP, n=4) and (DM+BHPP, n=5). BHPP 3 mg/kg/day decreased urinary (U) 12-HETE/creatinine (cr) by 30-50% after one injection and after 1 week of daily injections in DM rats. U 12-HETE/cr excretion increased paradoxically in controls given BHPP. There was a highly significant relationship between U 12-HETE/cr excretion and U alb/cr (r=0.79, P<10(-5)), demonstrating that renal 12/15-LO pathway activation is associated with albuminuria. BHPP did not inhibit glomerular collagen synthesis or improve histology. More sustained 12-LO inhibition may improve albuminuria in DN.     

Polycystins and mechanosensation in renal and nodal cilia

The external surfaces of the human body, as well as its internal organs, constantly experience different kinds of mechanical stimulations. For example, tubular epithelial cells of the kidney are continuously exposed to a variety of mechanical forces, such as fluid flow shear stress within the lumen of th nephron. The majority of epithelial cells along the nephron, except intercalated cells, possess a primary cilium, an organelle projecting from the cell's apical surface into the luminal space. Despite its discovery over 100 years ago, the primary cilium's function continued to elude researchers for many decades. However, recent studies indicate that renal cilia have a sensory function. Studies on polycystic kidney disease (PKD) have identified many of the molecular players, which should help solve the mystery of how the renal cilium senses fluid flow. In this review, we will summarize the recent breakthroughs in PKD research and discuss the role(s) of the polycystin signaling complex in mediating mechanosensory function by the primary cilium of renal epithelium as well as of the embryonic node.     

Fully Solution‐Processed TCO‐Free Semitransparent Perovskite Solar Cells for Tandem and Flexible Applications

Semitransparent perovskite solar cells (st‐PSCs) have received remarkable interest in recent years because of their great potential in applications for solar window, tandem solar cells, and flexible photovoltaics. However, all reported st‐PSCs require expensive transparent conducting oxides (TCOs) or metal‐based thin films made by vacuum deposition, which is not cost effective for large‐scale fabrication: the cost of TCOs is estimated to occupy ≈75% of the manufacturing cost of PSCs. To address this critical challenge, this study reports a low‐temperature and vacuum‐free strategy for the fabrication of highly efficient TCO‐free st‐PSCs. The TCO‐free st‐PSC on glass exhibits 13.9% power conversion efficiency (PCE), and the four‐terminal tandem cell made with the st‐PSC top cell and c‐Si bottom cell shows an overall PCE of 19.2%. Due to the low processing temperature, the fabrication of flexible st‐PSCs is demonstrated on polyethylene terephthalate and polyimide, which show excellent stability under repeated bending or even crumbing.     

Selective Targeting of Brain Tumors with Gold Nanoparticle-Induced Radiosensitization

Successful treatment of brain tumors such as glioblastoma multiforme (GBM) is limited in large part by the cumulative dose of Radiation Therapy (RT) that can be safely given and the blood-brain barrier (BBB), which limits the delivery of systemic anticancer agents into tumor tissue. Consequently, the overall prognosis remains grim. Herein, we report our pilot studies in cell culture experiments and in an animal model of GBM in which RT is complemented by PEGylated-gold nanoparticles (GNPs). GNPs significantly increased cellular DNA damage inflicted by ionizing radiation in human GBM-derived cell lines and resulted in reduced clonogenic survival (with dose-enhancement ratio of ∼1.3). Intriguingly, combined GNP and RT also resulted in markedly increased DNA damage to brain blood vessels. Follow-up in vitro experiments confirmed that the combination of GNP and RT resulted in considerably increased DNA damage in brain-derived endothelial cells. Finally, the combination of GNP and RT increased survival of mice with orthotopic GBM tumors. Prior treatment of mice with brain tumors resulted in increased extravasation and in-tumor deposition of GNP, suggesting that RT-induced BBB disruption can be leveraged to improve the tumor-tissue targeting of GNP and thus further optimize the radiosensitization of brain tumors by GNP. These exciting results together suggest that GNP may be usefully integrated into the RT treatment of brain tumors, with potential benefits resulting from increased tumor cell radiosensitization to preferential targeting of tumor-associated vasculature.     

Body measurements correlation and x-ray imaging of three Hystrix javanica fetuses in different fetal development stages

Hystrix javanica is endemic species in Indonesia. Study about fetal development of Hystrix javanica are very rare because of sample limitation. This study was carried out to describe the morphometrics and x-ray analysis of three fetuses in different stage to give basic information about fetal development of Hystrix javanica. Three fetus samples fixed in Bouin’s solution was used in this study. Observation was carried out to identify the characteristic of three fetus samples. This included the pattern of hair, body measurements, body volume, and body weight. X-ray analysis was carried out to know the ossification process in the fetal development. Statistical analysis was carried out using Microsoft 365® Excel program software. Three fetus samples had different specific hair pattern, that was hairless, smooth hairs, and smooth hairs with dense-non dense pattern. Body volume of 1^st, 2^nd, and 3^rd fetus were 23mL, 90mL, and 170mL, respectively. Body weight of 1^st, 2^nd, and 3^rd fetus were 19.5g, 79.22g, and 153.18g, respectively. Pearson’s correlation analysis shown strong relationship between total body length, front body length, back body length, horizontal body diameter, vertical body diameter, head length, and head diameter against body volume and body weight of three fetuses. Significant positive correlation was shown between horizontal body diameter, vertical body diameter, and head diameter against body volume and body length with P value < 0.05. Faint radiopaque images showed in the 2^nd fetus sample and strong radiopaque images showed in the 3^rd fetus sample. Radiopaque images were identified in the teeth, cranium, vertebrae, and extremities bones. In this study we concluded that there was a specific hair pattern in different fetal stage. All body measurements have positive correlation with body volume and body weight and x-ray analysis shown that the ossification of the bone was started to happen while the smooth hair was growth.