Shotgun Sequencing Analysis of Trypanosoma cruzi I Sylvio X10/1 and Comparison with T. cruzi VI CL Brener

Trypanosoma cruzi is the causative agent of Chagas disease, which affects more than 9 million people in Latin America. We have generated a draft genome sequence of the TcI strain Sylvio X10/1 and compared it to the TcVI reference strain CL Brener to identify lineage-specific features. We found virtually no differences in the core gene content of CL Brener and Sylvio X10/1 by presence/absence analysis, but 6 open reading frames from CL Brener were missing in Sylvio X10/1. Several multicopy gene families, including DGF, mucin, MASP and GP63 were found to contain substantially fewer genes in Sylvio X10/1, based on sequence read estimations. 1,861 small insertion-deletion events and 77,349 nucleotide differences, 23% of which were non-synonymous and associated with radical amino acid changes, further distinguish these two genomes. There were 336 genes indicated as under positive selection, 145 unique to T. cruzi in comparison to T. brucei and Leishmania. This study provides a framework for further comparative analyses of two major T. cruzi lineages and also highlights the need for sequencing more strains to understand fully the genomic composition of this parasite

Twentieth-Century Jewish Émigrés and Medieval European Economic History

This essay discusses the intellectual contributions of five Jewish émigrés to the study of European economic history. In the midst of the war years, these intellectuals reconceptualized premodern European economic history and established the predominant postwar paradigms. The émigrés form three distinct groups defined by Jewish identity and by professional identity. The first two (Guido Kisch and Toni Oelsner) identified as Jews and worked as Jewish historians. The second two (Michal Postan and Robert Lopez) identified as Jews, but worked as European historians. The last (Karl Polanyi) was Jewish only by origin, identified as a Christian socialist, and worked first as an economic journalist, then in worker's education and late in life as a professor of economics. All five dealt with the origin of European capitalism, but in different veins: Kisch celebrated and Oelsner contested a hegemonic academic discourse that linked the birth of capitalism to Jews. Postan and Lopez contested the flip-side of this discourse, the presumption that medieval Europe was pre-capitalist par excellence. In doing so, they helped construct the current paradigm of a high medieval commercial revolution. Polanyi contested historical narratives that described the Free Market as the natural growth of economic life. This essay explores the grounding of these paradigms in the shared crucible of war and exile as Jewish émigrés. This shared context helps illuminate the significance of their intellectual contributions by uncovering the webs of meaning in which their work was suspended

Patient outcomes and costs associated with functional medicine-based care in a shared versus individual setting for patients with chronic conditions: a retrospective cohort study

Objective To compare outcomes and costs associated with functional medicine-based care delivered in a shared medical appointment (SMA) to those delivered through individual appointments.Design A retrospective cohort study was performed to assess outcomes and cost to deliver care to patients in SMAs and compared with Propensity Score (PS)-matched patients in individual appointments.Setting A single-centre study performed at Cleveland Clinic Center for Functional Medicine.Participants A total of 9778 patients were assessed for eligibility and 7323 excluded. The sample included 2455 patients (226 SMAs and 2229 individual appointments) aged ≥18 years who participated in in-person SMAs or individual appointments between 1 March 2017 and 31 December 2019. Patients had a baseline Patient-Reported Outcome Measurement Information System (PROMIS) Global Physical Health (GPH) score and follow-up score at 3 months. Patients were PS-matched 1:1 with 213 per group based on age, sex, race, marital status, income, weight, body mass index, blood pressure (BP), PROMIS score and functional medicine diagnostic category.Primary and secondary outcome measures The primary outcome was change in PROMIS GPH at 3 months. Secondary outcomes included change in PROMIS Global Mental Health (GMH), biometrics, and cost.Results Among 213 PS-matched pairs, patients in SMAs exhibited greater improvements at 3 months in PROMIS GPH T-scores (mean difference 1.18 (95% CI 0.14 to 2.22), p=0.03) and PROMIS GMH T-scores (mean difference 1.78 (95% CI 0.66 to 2.89), p=0.002) than patients in individual appointments. SMA patients also experienced greater weight loss (kg) than patients in individual appointments (mean difference −1.4 (95% CI −2.15 to −0.64), p<0.001). Both groups experienced a 5.5 mm Hg improvement in systolic BP. SMAs were also less costly to deliver than individual appointments.Conclusion SMAs deliver functional medicine-based care that improves outcomes more than care delivered in individual appointments and is less costly to deliver

Exploiting the enemy in the Orkneys : the employment of Italian prisoners of war on the Scapa Flow barriers during the Second World War

The British naval base at Scapa Flow in the Orkneys played a vital role during the Second World War for the Allied war effort. It housed the British Home Fleet and provided a strategic military base for Allied operations in the North Sea, Atlantic and the Arctic. Although Scapa Flow’s military history is well served, the barriers built by Italian prisoners of war (POWs) to strengthen its defences in the early war years have received little attention.1 Britain faced a peculiar dilemma in the Orkneys: defences needed to be fortified given Scapa Flow’s key location and military role, but manpower was extremely scarce. Civilians were reluctant to work on the islands due to harsh and dangerous working conditions. Since efforts to attract them via compulsion and bonus schemes, and to employ migrant workers were insufficient, the government employed 1,200 Italian POWs instead, despite the scheme’s doubtful legality under the Geneva Convention. This article examines the history and significance of the Italians’ employment in the Orkneys and demonstrates that their contribution was vital for the construction of the Churchill barriers. Previous studies have neglected the multiple strikes by the prisoners and their protests against illegal work and some wrongly assume that the prisoners were not participating in the construction of the barriers. This article explicitly examines the legality issue and the prisoners’ extensive employment. Although their employment violated the Geneva Convention, British authorities and neutral delegates deemed it legal, thus securing the barriers’ completion

Development of relaxin-3 agonists and antagonists based on grafted disulfide-stabilized scaffolds

Relaxin-3 is a neuropeptide with important roles in metabolism, arousal, learning and memory. Its cognate receptor is the relaxin family peptide-3 (RXFP3) receptor. Relaxin-3 agonist and antagonist analogs have been shown to be able to modulate food intake in rodent models. The relaxin-3 B-chain is sufficient for receptor interactions, however, in the absence of a structural support, linear relaxin-3 B-chain analogs are rapidly degraded and thus unsuitable as drug leads. In this study, two different disulfide-stabilized scaffolds were used for grafting of important relaxin-3 B-chain residues to improve structure and stability. The use of both Veronica hederifolia Trypsin inhibitor (VhTI) and apamin grafting resulted in agonist and antagonist analogs with improved helicity. VhTI grafted peptides showed poor binding and low potency at RXFP3, on the other hand, apamin variants retained significant activity. These variants also showed improved half-life in serum from ~5 min to >6 h, and thus are promising RXFP3 specific pharmacological tools and drug leads for neuropharmacological diseases