Editor’s Note: Introducing the University of New Hampshire Law Review

Note from the Editor introducing the University of New Hampshire Law Review

Causalities of war: The connection between type VI secretion system and microbiota

Cellular Microbiology published by John Wiley & Sons Ltd Microbiota niches have space and/or nutrient restrictions, which has led to the coevolution of cooperation, specialisation, and competition within the population. Different animal and environmental niches contain defined resident microbiota that tend to be stable over time and offer protection against undesired intruders. Yet fluxes can occur, which alter the composition of a bacterial population. In humans, the microbiota are now considered a key contributor to maintenance of health and homeostasis, and its alteration leads to dysbiosis. The bacterial type VI secretion system (T6SS) transports proteins into the environment, directly into host cells or can function as an antibacterial weapon by killing surrounding competitors. Upon contact with neighbouring cells, the T6SS fires, delivering a payload of effector proteins. In the absence of an immunity protein, this results in growth inhibition or death of prey leading to a competitive advantage for the attacker. It is becoming apparent that the T6SS has a role in modulating and shaping the microbiota at multiple levels, which is the focus of this review. Discussed here is the T6SS, its role in competition, key examples of its effect upon the microbiota, and future avenues of researc

Refining pathological evaluation of neoadjuvant therapy for adenocarcinoma of the esophagus

AIM: To assess tumour regression grade (TRG) and lymph node downstaging to help define patients who benefit from neoadjuvant chemotherapy.METHODS: Two hundred and eighteen consecutive patients with adenocarcinoma of the esophagus or gastro-esophageal junction treated with surgery alone or neoadjuvant chemotherapy and surgery between 2005 and 2011 at a single institution were reviewed. Triplet neoadjuvant chemotherapy consisting of platinum, fluoropyrimidine and anthracycline was considered for operable patients (World Health Organization performance status ? 2) with clinical stage T2-4 N0-1. Response to neoadjuvant chemotherapy (NAC) was assessed using TRG, as described by Mandard et al. In addition lymph node downstaging was also assessed. Lymph node downstaging was defined by cN1 at diagnosis: assessed radiologically (computed tomography, positron emission tomography, endoscopic ultrasonography), then pathologically recorded as N0 after surgery; ypN0 if NAC given prior to surgery, or pN0 if surgery alone. Patients were followed up for 5 years post surgery. Recurrence was defined radiologically, with or without pathological confirmation. An association was examined between t TRG and lymph node downstaging with disease free survival (DFS) and a comprehensive range of clinicopathological characteristics.RESULTS: Two hundred and eighteen patients underwent esophageal resection during the study interval with a mean follow up of 3 years (median follow up: 2.552, 95%CI: 2.022-3.081). There was a 1.8% (n = 4) inpatient mortality rate. One hundred and thirty-six (62.4%) patients received NAC, with 74.3% (n = 101) of patients demonstrating some signs of pathological tumour regression (TRG 1-4) and 5.9% (n = 8) having a complete pathological response. Forty four point one percent (n = 60) had downstaging of their nodal disease (cN1 to ypN0), compared to only 15.9% (n = 13) that underwent surgery alone (pre-operatively overstaged: cN1 to pN0), (P < 0.0001). Response to NAC was associated with significantly increased DFS (mean DFS; TRG 1-2: 5.1 years, 95%CI: 4.6-5.6 vs TRG 3-5: 2.8 years, 95%CI: 2.2-3.3, P < 0.0001). Nodal down-staging conferred a significant DFS advantage for those patients with a poor primary tumour response to NAC (median DFS; TRG 3-5 and nodal down-staging: 5.533 years, 95%CI: 3.558-7.531 vs TRG 3-5 and no nodal down-staging: 1.114 years, 95%CI: 0.961-1.267, P < 0.0001).CONCLUSION: Response to NAC in the primary tumour and in the lymph nodes are both independently associated with improved DFS

Editor’s Note: Inaugural Symposium Issue on Social Justice

Note from the Editor on the Inaugural Symposium Issue on Social Justice

An Investigative Analysis of Fernando Sor’s Introduction and Variations on “O Cara Armonia” From Mozart’s \u3ci\u3eThe Magic Flute\u3c/i\u3e

Fernando Sor provides directions for fingering his Introduction and Variations on “O Cara Armonia” in the specific beaming and notation of the work. Although there are numerous publications of Sor’s Op. 9, most fail to provide elegant fingerings for his difficult passages. In these editions, the editor either failed to understand Sor’s intentions rendered in the notation, or disregarded Sor’s technical practices in favor of modern technical practices. Both avenues will lead to a disastrous reproduction of the work. While the piece may offer a challenge for the guitarist, the technical difficulties of Sor’s Op. 9 should not be readily apparent to the audience. This document will provide a comprehensive guide to Sor’s idiomatic intentions for the piece

The effectiveness of early lens extraction with intraocular lens implantation for the treatment of primary angle-closure glaucoma (EAGLE): Study protocol for a randomized controlled trial

BACKGROUND: Glaucoma is the leading cause of irreversible blindness. Although primary open-angle glaucoma is more common, primary angle-closure glaucoma (PACG) is more likely to result in irreversible blindness. By 2020, 5·3 million people worldwide will be blind because of PACG. The current standard care for PACG is a stepped approach of a combination of laser iridotomy surgery (to open the drainage angle) and medical treatment (to reduce intraocular pressure). If these treatments fail, glaucoma surgery (eg, trabeculectomy) is indicated. It has been proposed that, because the lens of the eye plays a major role in the mechanisms leading to PACG, early clear lens extraction will improve glaucoma control by opening the drainage angle. This procedure might reduce the need for drugs and glaucoma surgery, maintain good visual acuity, and improve quality of life compared with standard care.EAGLE aims to evaluate whether early lens extraction improves patient-reported, clinical outcomes, and cost-effectiveness, compared with standard care.METHODS/DESIGN: EAGLE is a multicentre pragmatic randomized trial. All people presenting to the recruitment centres in the UK and east Asia with newly diagnosed PACG and who are at least 50 years old are eligible.The primary outcomes are EQ-5D, intraocular pressure, and incremental cost per quality adjusted life year (QALY) gained. Other outcomes are: vision and glaucoma-specific patient-reported outcomes, visual acuity, visual field, angle closure, number of medications, additional surgery (e.g., trabeculectomy), costs to the health services and patients, and adverse events.A single main analysis will be done at the end of the trial, after three years of follow-up. The analysis will be based on all participants as randomized (intention to treat). 400 participants (200 in each group) will be recruited, to have 90% power at 5% significance level to detect a difference in EQ-5D score between the two groups of 0·05, and a mean difference in intraocular pressure of 1·75 mm Hg. The study will have 80% power to detect a difference of 15% in the glaucoma surgery rate.TRIAL REGISTRATION: ISRCTN44464607.</p

Genomic analysis of oceanic cyanobacterial myoviruses compared with T4-like myoviruses from diverse hosts and environments

T4-like myoviruses are ubiquitous, and their genes are among the most abundant documented in ocean systems. Here we compare 26 T4-like genomes, including 10 from non-cyanobacterial myoviruses, and 16 from marine cyanobacterial myoviruses (cyanophages) isolated on diverse Prochlorococcus or Synechococcus hosts. A core genome of 38 virion construction and DNA replication genes was observed in all 26 genomes, with 32 and 25 additional genes shared among the non-cyanophage and cyanophage subsets, respectively. These hierarchical cores are highly syntenic across the genomes, and sampled to saturation. The 25 cyanophage core genes include six previously described genes with putative functions (psbA,mazG, phoH, hsp20, hli03, cobS), a hypothetical protein with a potential phytanoyl-CoA dioxygenase domain, two virion structural genes, and 16 hypothetical genes. Beyond previously described cyanophageencoded photosynthesis and phosphate stress genes, we observed core genes that may play a role in nitrogen metabolism during infection through modulation of 2-oxoglutarate. Patterns among non-core genes that may drive niche diversification revealed that phosphorus-related gene content reflects source waters rather than host strain used for isolation, and that carbon metabolism genes appear associated with putative mobile elements. As well, phages isolated on Synechococcus had higher genome-wide %G+C and often contained different gene subsets (e.g. petE, zwf, gnd, prnA, cpeT) than those isolated on Prochlorococcus. However, no clear diagnostic genes emerged to distinguish these phage groups, suggesting blurred boundaries possibly due to cross-infection. Finally, genome-wide comparisons of both diverse and closely related, co-isolated genomes provide a locus-to-locus variability metric that will prove valuable forinterpreting metagenomic data sets.Gordon and Betty Moore FoundationNational Science Foundation (U.S.)Massachusetts Institute of Technology. Undergraduate Research Opportunities ProgramUnited States. Dept. of Energy. Genomics:GTLNational Science Foundation (U.S.) (DBI-0850105)University of Arizona (Fulbright Scholarship)University of Arizona (BIO5 and Biosphere 2 funds)National Institute of Environmental Health Sciences (1-P50-ES012742)National Science Foundation (U.S.) (OCE-0430724

Neuromodulation of the feedforward dentate gyrus-CA3 microcircuit

The feedforward dentate gyrus-CA3 microcircuit in the hippocampus is thought to activate ensembles of CA3 pyramidal cells and interneurons to encode and retrieve episodic memories. The creation of these CA3 ensembles depends on neuromodulatory input and synaptic plasticity within this microcircuit. Here we review the mechanisms by which the neuromodulators aceylcholine, noradrenaline, dopamine, and serotonin reconfigure this microcircuit and thereby infer the net effect of these modulators on the processes of episodic memory encoding and retrieval