Molecular, morphological, and phytochemical evidence for a broad species concept of Plagiochila bifaria (Hepaticae)

Debate over the synonymy of the European Plagiochila killarniensis and the Neotropical P bifaria of R sect. Arrectae has focused on differences in secondary metabolite composition. The broad morphological species concept of R bifaria proposed in recent papers has now been tested by comparing nrDNA ITS1 and ITS2 sequences of R bifaria populations encompassing several different morpho- and chemotypes from the British Isles, Tenerife, Costa Rica, Brazil, Ecuador, and Bolivia, with sequences of other species of R sects. Arrectae, Rutilantes, and Fuscoluteae. Phylogenetic analyses demonstrate that specimens of P. bifaria form a well supported clade within Plagiochila sect. Arrectae. Sequences of R bifaria from the British Isles, Tenerife, and Ecuador, representing the "methyl everninate" chemotype, form a well supported subclade within the P bifaria clade. Sequences of specimens from Costa Rica, Brazil, and Bolivia are placed in the basal part of the R bifaria clade. The data support a broad species concept of P bifaria. The different chemotypes do not warrant distinct taxonomic ranks. Plagiochila centrifuga and P. compressula are treated as new synonyms of R bifaria

Reserve Requirements Survey

Banks have a private motive to hold some level of cash and liquid reserves, but the negative externalities of bank runs create a public interest in setting a regulatory level higher than the privately optimal level. We can think of such reserve requirements (RRs) as the original form of liquidity regulation. In this paper, we focus on 14 cases in which central banks adjusted RRs after crises hit, typically to deal with liquidity shortages in the banking system. We observe that RR adjustments have several advantages in a crisis: (1) such changes require little process, and the change for banks can be quick; (2) stigma concerns may be much lower than with emergency lending operations; (3) RRs can be used to fine-tune incentives for holding various types and maturities of assets; and (4) RR easing can complement a central bank’s other liquidity support programs

Blanket Guarantees Survey

This paper surveys 10 blanket guarantee (BG) programs across 13 Key Design Decisions. The defining characteristics of these programs in terms of their inclusion in our BG series are (a) that they guaranteed a broader range of liabilities beyond deposit accounts and (b) that the guarantees covered existing liabilities in addition to newly issued ones. Each case represents an effort to eliminate creditors’ incentive to withdraw funding from institutions by guaranteeing that the funding will be paid back even if the institutions are unable to do so themselves. The main themes that emerge are: (a) the inability of blanket guarantees to address underlying problems without complementary liquidity support and restructuring measures; (b) the importance of credibility, particularly as related to the amount of liabilities guaranteed relative to fiscal resources; (c) the need to address the moral hazards that a blanket guarantee creates, by restricting banks’ behavior during the acute phase of a crisis—for example, through interest-rate caps or bans on aggressive marketing—and by promising to increase official supervisory oversight as the crisis extends into its chronic phase; (d) the importance of effective communication; and (e) the importance of clear political support for a program that represents potentially substantial fiscal costs, which authorities may be unable to quantify at the time of the announcement

Survey of Resolution and Restructuring in Europe: Pre- and Post-BRRD

This paper surveys 19 case studies of bank resolutions and restructurings across 15 Key Design Decisions. It focuses on interventions that occurred in Europe both in the years leading up to the adoption of the Bank Recovery and Resolution Directive (BRRD) in 2014 (when many jurisdictions were constrained by a lack of legal authority) and in the years after the BRRD was in place. The main themes that emerge are: (a) the need for resolution and restructuring to eliminate uncertainty about an institution’s solvency by closing it, recapitalizing it, or merging it with a healthier institution; (b) the importance of effective valuation in achieving this result; (c) the necessity of clarity in the treatment of creditors; and (d) the value of a credible bail-in tool to incentivize creditors to agree to solutions outside of resolution

The Effects of Serotonin Receptor Antagonists on Contraction and Relaxation Responses Induced by Electrical Stimulation in the Rat Small Intestine

Background: The main source of 5-HT in body is in enterchromafin cells of intestine, different studies mentioned different roles for endogenous 5-HT and receptors involved and it is not clearified the mechanism of action of endogenous 5-HT. Objectives: To study the role of endogenous 5-HT on modulation of contraction and relaxation responses induced by electrical field stimulation (EFS) in different regions of the rat intestine. Materials and Methods: Segments taken from the rat duodenum, jejunum, mid and terminal ileum were vertically mounted, connected to a transducer and exposed to EFS with different frequencies in the absence and presence of various inhibitors of enteric mediators i. e. specific 5-HT receptor antagonists. Results: EFS-induced responses were sensitive to TTX and partly to atropine, indicating a major neuronal involvement and a cholinergic system. Pre-treatment with WAY100635 (a 5-HT1A receptor antagonist) and granisetron up to 10.0 µM, GR113808 (a 5-HT4 receptor antagonist), methysergide and ritanserin up to 1.0 µM, failed to modify responses to EFS inall examined tissues. In the presence of SB258585 1.0 µM (a 5-HT6 receptor antagonist) there was a trend to enhance contraction in the proximal part of the intestine and reduce contraction in the distal part. Pre-treatment with SB269970A 1.0 µM (5-HT7 receptor antagonist) induced a greater contractile response to EFS at 0.4 Hz only in the duodenum. Conclusions: The application of 5-HT1A, 5-HT2, 5-HT3, 5-HT4, 5-HT6 and 5-HT7 receptor antagonists, applied at concentrations lower than 1.0 µM did not modify the EFS-induced contraction and relaxation responses, whichsuggests the unlikely involvement of endogenous 5-HT in mediating responses to EFS in the described test conditions. Keywords: Electric Stimulation Therapy; Serotonin 5-HT1 Receptor Antagonists; Intestine, Smal

l-Threonine Deaminase of Rhodospirillum rubrum

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65547/1/j.1432-1033.1971.tb01490.x.pd

Nintedanib targets KIT D816V neoplastic cells derived from induced pluripotent stem cells of systemic mastocytosis

The KIT D816V mutation is found in >80% of patients with systemic mastocytosis (SM) and is key to neoplastic mast cell (MC) expansion and accumulation in affected organs. Therefore, KIT D816V represents a prime therapeutic target for SM. Here, we generated a panel of patient-specific KIT D816V induced pluripotent stem cells (iPSCs) from patients with aggressive SM and mast cell leukemia to develop a patient-specific SM disease model for mechanistic and drug-discovery studies. KIT D816V iPSCs differentiated into neoplastic hematopoietic progenitor cells and MCs with patient-specific phenotypic features, thereby reflecting the heterogeneity of the disease. CRISPR/Cas9n-engineered KIT D816V human embryonic stem cells (ESCs), when differentiated into hematopoietic cells, recapitulated the phenotype observed for KIT D816V iPSC hematopoiesis. KIT D816V causes constitutive activation of the KIT tyrosine kinase receptor, and we exploited our iPSCs and ESCs to investigate new tyrosine kinase inhibitors targeting KIT D816V. Our study identified nintedanib, a US Food and Drug Administration-approved angiokinase inhibitor that targets vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and fibroblast growth factor receptor, as a novel KIT D816V inhibitor. Nintedanib selectively reduced the viability of iPSC-derived KIT D816V hematopoietic progenitor cells and MCs in the nanomolar range. Nintedanib was also active on primary samples of KIT D816V SM patients. Molecular docking studies show that nintedanib binds to the adenosine triphosphate binding pocket of inactive KIT D816V. Our results suggest nintedanib as a new drug candidate for KIT D816V-targeted therapy of advanced SM.Peer reviewe

A Burmese amber fossil of Radula (Porellales, Jungermanniopsida) provides insights into the Cretaceous evolution of epiphytic lineages of leafy liverworts

DNA-based divergence time estimates suggested major changes in the composition of epiphyte lineages of liverworts during the Cretaceous;however, evidence from the fossil record is scarce. We present the first Cretaceous fossil of the predominantly epiphytic leafy liverwort genus Radula in ca. 100 Myr old Burmese amber. The fossil's exquisite preservation allows first insights into the morphology of early crown group representatives of Radula occurring in gymnosperm-dominated forests. Ancestral character state reconstruction aligns the fossil with the crown group of Radula subg. Odontoradula;however, corresponding divergence time estimates using the software BEAST lead to unrealistically old age estimates. Alternatively, assignment of the fossil to the stem of subg. Odontoradula results in a stem age estimate of Radula of 227.8Ma (95% highest posterior density (HPD): 165.7-306.7) and a crown group estimate of 176.3Ma (135.1-227.4), in agreement with analyses employing standard substitution rates (stem age 235.6 Ma (142.9-368.5), crown group age 183.8 Ma (109.9-289.1)). The fossil likely belongs to the stem lineage of Radula subg. Odontoradula. The fossil's modern morphology suggests that switches from gymnosperm to angiosperm phorophytes occurred without changes in plant body plans in epiphytic liverworts. The fossil provides evidence for striking morphological homoplasy in time. Even conservative node assignments of the fossil support older rather than younger age estimates of the Radula crown group, involving origins for most extant subgenera by the end of the Cretaceous and diversification of their crown groups in the Cenozoic

Deficiency of FLCN in Mouse Kidney Led to Development of Polycystic Kidneys and Renal Neoplasia

The Birt–Hogg–Dubé (BHD) disease is a genetic cancer syndrome. The responsible gene, BHD, has been identified by positional cloning and thought to be a novel tumor suppressor gene. BHD mutations cause many types of diseases including renal cell carcinomas, fibrofolliculomas, spontaneous pneumothorax, lung cysts, and colonic polyps/cancers. By combining Gateway Technology with the Ksp-Cre gene knockout system, we have developed a kidney-specific BHD knockout mouse model. BHDflox/flox/Ksp-Cre mice developed enlarged kidneys characterized by polycystic kidneys, hyperplasia, and cystic renal cell carcinoma. The affected BHDflox/flox/Ksp-Cre mice died of renal failure at approximate three weeks of age, having blood urea nitrogen levels over tenfold higher than those of BHD flox/+/Ksp-Cre and wild-type littermate controls. We further demonstrated that these phenotypes were caused by inactivation of BHD and subsequent activation of the mTOR pathway. Application of rapamycin, which inhibits mTOR activity, to the affected mice led to extended survival and inhibited further progression of cystogenesis. These results provide a correlation of kidney-targeted gene inactivation with renal carcinoma, and they suggest that the BHD product FLCN, functioning as a cyst and tumor suppressor, like other hamartoma syndrome–related proteins such as PTEN, LKB1, and TSC1/2, is a component of the mTOR pathway, constituting a novel FLCN-mTOR signaling branch that regulates cell growth/proliferation

Polymer Composites Containing Gated Mesoporous Materials for On-Command Controlled Release

Polyamidic nanofibrous membranes containing gated silica mesoporous particles, acting as carriers, are described as novel hybrid composite materials for encapsulation and on-command delivery of garlic extracts. The carrier system consists of MCM-41 solids functionalized in the outer surface, with linear polyamines (solid P1) and with hydrolyzed starch (solid P2), both acting as molecular gates. Those particles were adsorbed on electospun nylon-6 nanofibrous membranes yielding to composite materials M1 and M2. FE-SEM analysis confirmed the presence of particles incorporated on the nylon nanofibers. The release of the entrapped molecules (garlic extract) from the P1, P2, M1, and M2 materials was evaluated using cyclic voltammetry measurements. Electrochemical studies showed that at acidic pH P1 and M1 were unable to release their entrapped cargo (closed gate), whereas at neutral pH both materials release their loading (open gate). Dealing with P2 and M2 materials, in the absence of pancreatin a negligible release is observed (closed gate), whereas in the presence of enzyme the load is freely to diffuse to the solution. These newly developed composite nanomaterials, provide a homogeneous easy-to-handle system with controlled delivery and bioactive-protective features, having potential applications on pharmacology, medical and engineering fields.The authors wish to express their gratitude to the Generalitat Valenciana (Grisolia scholarship 2011/012, project PROM-ETEO/2009/016), Spanish Government (MINECO Projects AGL2012-39597-C02-01, AGL2012-39597-C02-02 and MAT2012-38429-C04-01) and the CIBER-BBN for their support. IILA thanks DISTAM and Universita degli di Milano for a specialization scholarship. We would also like to thank the Institut de Ciencia dels Materials (ICMUV) and to the Microscopy Service of the Universitat Politecnica de Valencia for technical support. We thank Roquette for the Glucidex samples.Acosta Romero, C.; Pérez Esteve, E.; Fuenmayor, CA.; Benedetti, S.; Cosio, MS.; Soto Camino, J.; Sancenón Galarza, F.... (2014). Polymer Composites Containing Gated Mesoporous Materials for On-Command Controlled Release. ACS Applied Materials and Interfaces. 6(9):6453-6460. https://doi.org/10.1021/am405939y645364606