Structural requirement of leucine for activation of p70 S6 kinase

AbstractThe addition of leucine induced activation of p70S6k in amino acid-depleted H4IIE cells. Whereas the activation of p70S6k by leucine was transient, the complete amino acid stimulated p70S6k more persistently. The effect of leucine on p70S6k was sensitive to rapamycin, but less sensitive to wortmannin. Using various amino acids and derivatives of leucine, we found that the chirality, the structure of the four branched hydrocarbons, and the primary amine are required for the ability of leucine to stimulate p70S6k, indicating that the structural requirement of leucine to induce p70S6k activation is very strict and precise. In addition, some leucine derivatives exhibited the ability to stimulate p70S6k and the other derivatives acted as inhibitors against the leucine-induced activation of p70S6k

Biodegradable polymer with collagen microsponge serves as a new bioengineered cardiovascular prosthesis

AbstractObjectiveBiodegradable materials with autologous cell seeding have attracted much interest as potential cardiovascular grafts. However, pretreatment of these materials requires a complicated and invasive procedure that carries the risk of infection. To avoid these problems, we sought to develop a biodegradable graft material containing collagen microsponge that would permit the regeneration of autologous vessel tissue. The ability of this material to accelerate in situ cellularization with autologous endothelial and smooth muscle cells was tested with and without precellularization.MethodsPoly(lactic-co-glycolic acid) as a biodegradable scaffold was compounded with collagen microsponge to form a vascular patch material. These poly(lactic-co-glycolic acid)–collagen patches with (n = 10) or without (n = 10) autologous vessel cellularization were used to patch the canine pulmonary artery trunk. Histologic and biochemical assessments were performed 2 and 6 months after the implantation.ResultsThere was no thrombus formation in either group, and the poly(lactic-co-glycolic acid) scaffold was almost completely absorbed in both groups. Histologic results showed the formation of an endothelial cell monolayer, a parallel alignment of smooth muscle cells, and reconstructed vessel wall with elastin and collagen fibers. The cellular and extracellular components in the patch had increased to levels similar to those in native tissue at 6 months.ConclusionsThe poly(lactic-co-glycolic acid)–collagen microsponge patch with and without precellularization showed good histologic findings and durability. This patch shows promise as a bioengineered material for promoting in situ cellularization and the regeneration of autologous tissue in cardiovascular surgery

Metastatic Breast Cancer to the Stomach Resembling Early Gastric Cancer

Breast cancer metastases to the stomach are very rare. As characteristics of breast cancer metastases to the stomach, metastases of lobular carcinoma, mainly with signet ring cells, are frequently observed, and they are often difficult to distinguish from a primary gastric cancer with signet ring cells. Moreover, because no characteristic symptoms are shown and they involve a submucosal lesion, it is difficult to make a radiographic diagnosis. However, if a gastric lesion is observed after breast carcinoma surgery, differentiation between a gastric primary lesion and a metastatic lesion is very important in order to determine treatment. We encountered a case that was diagnosed as early gastric cancer discovered using an endoscope 2 years after surgery and which was found to be breast cancer metastasis to the stomach by gross cystic disease fluid protein (GCDFP) and cytokeratin (CK) 7/20 immunostaining of the biopsy tissue. Here, we report our findings of this unique case

Endometrial Metastasis from Breast Cancer during Adjuvant Endocrine Therapy

It is well-known that tamoxifen increases the risk of endometrial cancer. Although metastasis to the uterus from breast cancer is uncommon, there have been some case reports on uterine metastasis. If an endometrial abnormality is detected, the differential diagnosis of whether the uterine tumor is metastatic or primary is very important to determine the course of treatment. We herein report a case in which we detected a uterine tumor during follow-up after treatment with tamoxifen, and demonstrate that GCDFP-15 is useful in diagnosing metastatic uterine tumors arising from breast cancer

Cardiosphere-derived exosomal microRNAs for myocardial repair in pediatric dilated cardiomyopathy

Although cardiosphere-derived cells (CDCs) improve cardiac function and outcomes in patients with single ventricle physiology, little is known about their safety and therapeutic benefit in children with dilated cardiomyopathy (DCM). We aimed to determine the safety and efficacy of CDCs in a porcine model of DCM and translate the preclinical results into this patient population. A swine model of DCM using intracoronary injection of microspheres created cardiac dysfunction. Forty pigs were randomized as preclinical validation of the delivery method and CDC doses, and CDC-secreted exosome (CDCex)–mediated cardiac repair was analyzed. A phase 1 safety cohort enrolled five pediatric patients with DCM and reduced ejection fraction to receive CDC infusion. The primary endpoint was to assess safety, and the secondary outcome measure was change in cardiac function. Improved cardiac function and reduced myocardial fibrosis were noted in animals treated with CDCs compared with placebo. These functional benefits were mediated via CDCex that were highly enriched with proangiogenic and cardioprotective microRNAs (miRNAs), whereas isolated CDCex did not recapitulate these reparative effects. One-year follow-up of safety lead-in stage was completed with favorable profile and preliminary efficacy outcomes. Increased CDCex-derived miR-146a-5p expression was associated with the reduction in myocardial fibrosis via suppression of proinflammatory cytokines and transcripts. Collectively, intracoronary CDC administration is safe and improves cardiac function through CDCex in a porcine model of DCM. The safety lead-in results in patients provide a translational framework for further studies of randomized trials and CDCex-derived miRNAs as potential paracrine mediators underlying this therapeutic strategy

The Belle II Physics Book

We present the physics program of the Belle II experiment, located on the intensity frontier SuperKEKB $e^+e^-$ collider. Belle II collected its first collisions in 2018, and is expected to operate for the next decade. It is anticipated to collect 50/ab of collision data over its lifetime. This book is the outcome of a joint effort of Belle II collaborators and theorists through the Belle II theory interface platform (B2TiP), an effort that commenced in 2014. The aim of B2TiP was to elucidate the potential impacts of the Belle II program, which includes a wide scope of physics topics: B physics, charm, tau, quarkonium, electroweak precision measurements and dark sector searches. It is composed of nine working groups (WGs), which are coordinated by teams of theorist and experimentalists conveners: Semileptonic and leptonic B decays, Radiative and Electroweak penguins, phi_1 and phi_2 (time-dependent CP violation) measurements, phi_3 measurements, Charmless hadronic B decay, Charm, Quarkonium(like), tau and low-multiplicity processes, new physics and global fit analyses. This book highlights "golden- and silver-channels", i.e. those that would have the highest potential impact in the field. Theorists scrutinised the role of those measurements and estimated the respective theoretical uncertainties, achievable now as well as prospects for the future. Experimentalists investigated the expected improvements with the large dataset expected from Belle II, taking into account improved performance from the upgraded detector.Comment: 689 page

Choanoflagellates in the Antarctic Ocean, with special reference to Parvicorbicula socialis (Meunier) Deflandre

Distribution and morphology of choanoflagellates, collared heterotrophic flagellates bearing an extracellular siliceous lorica, were reviewed. Eleven species were reported from the Antarctic Ocean. Three of the eleven species were originally described from the Antarctic and are known to be endemic to the Antarctic. The other eight were found in various oceanic areas. Choanoflagellates had been found in both ice and water, which suggested their wide and abundant distribution in the Antarctic. Ecological significance of the choanoflagellate, Parvicorbicula socialis (MEUNIER) DEFLANDRE, most common species in the Antarctic, was stressed as the food of the Antarctic krill, Euphausia superba DANA. Morphological variation of the lorica structure of P. socialis, caused by water temperature, was discussed on specimens collected in various oceanic areas from polar to equatorial