Lectures on the Statutes of the Sacred Order of St. John of Jerusalem : at the University (of Studies) of Malta 1792

The Statutes of the Order of Malta were compiled anew in 1776; they are still valid as subsidiary. Micallef, a Maltese Conventual Chaplain of the Order and professor at the Order\u27s University of Malta, delivered lectures on the Statutes which were printed in a very limited number in 1791. Edited in English is included with the lectures\u27 text .a brief history of the Order and of the University together with a short biography on Micallef; in appendix: the present Constitution and Code of the Order

Lectures on the Statutes of the Sacred Order of St. John of Jerusalem : at the University (of Studies) of Malta 1792

The Statutes of the Order of Malta were compiled anew in 1776; they are still valid as subsidiary. Micallef, a Maltese Conventual Chaplain of the Order and professor at the Order's University of Malta, delivered lectures on the Statutes which were printed in a very limited number in 1791.Edited in English is included with the lectures' text .a brief history of the Order and of the University together with a short biography on Micallef; in appendix: the present Constitution and Code of the Order

Polymorphism of the flap endonuclease 1 gene in keratoconus and Fuchs endothelial corneal dystrophy

Oxidative stress is implicated in the pathogenesis of many diseases, including serious ocular diseases, keratoconus (KC) and Fuchs endothelial corneal dystrophy (FECD). Flap endonuclease 1 (FEN1) plays an important role in the repair of oxidative DNA damage in the base excision repair pathway. We determined the association between two single nucleotide polymorphisms (SNPs), c.-441G>A (rs174538) and g.61564299G>T (rs4246215), in the FEN1 gene and the occurrence of KC and FECD. This study involved 279 patients with KC, 225 patients with FECD and 322 control individuals. Polymerase chain reaction (PCR) and length polymorphism restriction fragment analysis (RFLP) were applied. The T/T genotype of the g.61564299G>T polymorphism was associated with an increased occurrence of KC and FECD. There was no association between the c.-441G>A polymorphism and either disease. However, the GG haplotype of both polymorphisms was observed more frequently and the GT haplotype less frequently in the KC group than the control. The AG haplotype was associated with increased FECD occurrence. Our findings suggest that the g.61564299G>T and c.-441G>A polymorphisms in the FEN1 gene may modulate the risk of keratoconus and Fuchs endothelial corneal dystrophy.peer-reviewe

Exploiting and assessing multi-source data for supervised biomedical named entity recognition

Motivation: Recognition of biomedical entities from scientific text is a critica l component of natural language processing and automated information extraction platfo rms. Modern named entity recognition approaches rely heavily on supervised machine learning tech niques, which are critically dependent on annotated training corpora. These approaches have been shown to perform well when trained and tested on the same source. However, in such scenario, the performance and evaluation of these models may be optimistic, as such models may not necessarily generalize to in dependent corpora, resulting in potential non-optimal entity recognition for large-scale tagging of widel y diverse articles in databases such as PubMed. Results: Here we aggregated published corpora for the recognition of bio molecular entities (such as genes, RNA, proteins, variants, drugs, and metabolites), identi fied entity class overlap and performed leave-corpus-out cross validation strategy to test the efficiency o f existing models. We demonstrate that accuracies of models trained on individual corpora decre ase substantially for recognition of the same biomolecular entity classes in independent corpora. Thi s behavior is possibly due to limited generalizability of entity-class-related features captured by i ndividual corpora (model “overtraining”) which we investigated further at the orthographic level, as well as potenti al annotation standard differences. We show that the combined use of multi-source training corpora re sults in overall more generalizable models for named entity recognition, while achieving comparab le individual performance. By performing learning-curve-based power analysis we further identified that performance is often not limited by the quantity of the annotated data

Septins Recognize and Entrap Dividing Bacterial Cells for Delivery to Lysosomes.

The cytoskeleton occupies a central role in cellular immunity by promoting bacterial sensing and antibacterial functions. Septins are cytoskeletal proteins implicated in various cellular processes, including cell division. Septins also assemble into cage-like structures that entrap cytosolic Shigella, yet how septins recognize bacteria is poorly understood. Here, we discover that septins are recruited to regions of micron-scale membrane curvature upon invasion and division by a variety of bacterial species. Cardiolipin, a curvature-specific phospholipid, promotes septin recruitment to highly curved membranes of Shigella, and bacterial mutants lacking cardiolipin exhibit less septin cage entrapment. Chemically inhibiting cell separation to prolong membrane curvature or reducing Shigella cell growth respectively increases and decreases septin cage formation. Once formed, septin cages inhibit Shigella cell division upon recruitment of autophagic and lysosomal machinery. Thus, recognition of dividing bacterial cells by the septin cytoskeleton is a powerful mechanism to restrict the proliferation of intracellular bacterial pathogens

Mitochondria mediate septin cage assembly to promote autophagy of Shigella.

Septins, cytoskeletal proteins with well-characterised roles in cytokinesis, form cage-like structures around cytosolic Shigella flexneri and promote their targeting to autophagosomes. However, the processes underlying septin cage assembly, and whether they influence S. flexneri proliferation, remain to be established. Using single-cell analysis, we show that the septin cages inhibit S. flexneri proliferation. To study mechanisms of septin cage assembly, we used proteomics and found mitochondrial proteins associate with septins in S. flexneri-infected cells. Strikingly, mitochondria associated with S. flexneri promote septin assembly into cages that entrap bacteria for autophagy. We demonstrate that the cytosolic GTPase dynamin-related protein 1 (Drp1) interacts with septins to enhance mitochondrial fission. To avoid autophagy, actin-polymerising Shigella fragment mitochondria to escape from septin caging. Our results demonstrate a role for mitochondria in anti-Shigella autophagy and uncover a fundamental link between septin assembly and mitochondria