Brexit’s Effect on Citizens, Human Rights & Immigration

This report records the roundtable on “Brexit’s Effect on Citizens, Human Rights and Immigration” organised by Dr Adrienne Yong on 11 June 2019 at City, University of London funded by the Higher Education Innovation Fund (HEIF) 2018/19. Speakers included: • Hannah Wilkins (House of Commons Library) • Blanca Grey (Home Office)1 • Paul Erdunast (Immigration Law Practitioner’s Association - ILPA) • Christopher Desira (Seraphus Solicitors) • Nicole Masri (Rights of Women) • Ollie Persey (Public Law Project) • Katarzyna Zagrodniczek (East European Resource Centre) • Mihai Calin Bica (Roma Support Group) • Dr Adrienne Yong (City, University of London) • Dr Michaela Benson (Goldsmiths, University of London) • Madeleine Sumption (Migration Observatory) • Sheona York (Kent Law Clinic) A host of unique legal questions were raised in the aftermath of the UK’s referendum result where the electorate voted in favour of leaving the EU on the 23 June 2016. Opinion has been split as to whether the UK and EU have indeed struck a fair deal for citizens, with arguments that citizens have been used as bargaining chips throughout the process to achieve a deal. As negotiations progressed towards the original mandated date of withdrawal, 29 March 2019, various schemes emerged to handle post-Brexit immigration of EU citizens in the UK and reciprocal arrangements for British citizens in the EU. This is now reflected in the EU Settlement Scheme, the Immigration and Social Security Co-ordination Bill, and the reciprocity agreed with EU Member States as to British citizens in the EU. These issues and more were discussed at the roundtable

Mouse models for hereditary spastic paraplegia uncover a role of PI4K2A in autophagic lysosome reformation

Hereditary spastic paraplegia (HSP) denotes genetically heterogeneous disorders characterized by leg spasticity due to degeneration of corticospinal axons. SPG11 and SPG15 have a similar clinical course and together are the most prevalent autosomal recessive HSP entity. The respective proteins play a role for macroautophagy/autophagy and autophagic lysosome reformation (ALR). Here, we report that spg11 and zfyve26 KO mice developed motor impairments within the same course of time. This correlated with enhanced accumulation of autofluorescent material in neurons and progressive neuron loss. In agreement with defective ALR, tubulation events were diminished in starved KO mouse embryonic fibroblasts (MEFs) and lysosomes decreased in neurons of KO brain sections. Confirming that both proteins act in the same molecular pathway, the pathologies were not aggravated upon simultaneous disruption of both. We further show that PI4K2A (phosphatidylinositol 4-kinase type 2 alpha), which phosphorylates phosphatidylinositol to phosphatidylinositol-4-phosphate (PtdIns4P), accumulated in autofluorescent deposits isolated from KO but not WT brains. Elevated PI4K2A abundance was already found at autolysosomes of neurons of presymptomatic KO mice. Immunolabelings further suggested higher levels of PtdIns4P at LAMP1-positive structures in starved KO MEFs. An increased association with LAMP1-positive structures was also observed for clathrin and DNM2/dynamin 2, which are important effectors of ALR recruited by phospholipids. Because PI4K2A overexpression impaired ALR, while its knockdown increased tubulation, we conclude that PI4K2A modulates phosphoinositide levels at autolysosomes and thus the recruitment of downstream effectors of ALR. Therefore, PI4K2A may play an important role in the pathogenesis of SPG11 and SPG15. Abbreviations: ALR: autophagic lysosome reformation; AP-5: adaptor protein complex 5; BFP: blue fluorescent protein; dKO: double knockout; EBSS: Earle’s balanced salt solution; FBA: foot base angle; GFP: green fluorescent protein; HSP: hereditary spastic paraplegia; KO: knockout; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3 beta; MEF: mouse embryonic fibroblast; SQSTM1/p62: sequestosome 1; PI4K2A: phosphatidylinositol 4-kinase type 2 alpha; PtdIns3P: phosphatidylinositol-3-phosphate; PtdIns4P: phosphatidylinositol-4-phosphate; RFP: red fluorescent protein; SPG: spastic paraplegia gene; TGN: trans-Golgi network; WT: wild typ

ADAPT Identifies an ESCRT Complex Composition That Discriminates VCaP From LNCaP Prostate Cancer Cell Exosomes

Libraries of single-stranded oligodeoxynucleotides (ssODNs) can be enriched for sequences that specifically bind molecules on naïve complex biological samples like cells or tissues. Depending on the enrichment strategy, the ssODNs can identify molecules specifically associated with a defined biological condition, for example a pathological phenotype, and thus are potentially useful for biomarker discovery. We performed ADAPT, a variant of SELEX, on exosomes secreted by VCaP prostate cancer cells. A library of ∼1011 ssODNs was enriched for those that bind to VCaP exosomes and discriminate them from exosomes derived from LNCaP prostate cancer cells. Next-generation sequencing (NGS) identified the best discriminating ssODNs, nine of which were resynthesized and their discriminatory ability confirmed by qPCR. Affinity purification with one of the sequences (Sequence 7) combined with LC-MS/MS identified its molecular target complex, whereof most proteins are part of or associated with the multiprotein ESCRT complex participating in exosome biogenesis. Within this complex, YBX1 was identified as the directly-bound target protein. ADAPT thus is able to differentiate exosomes from cancer cell subtypes from the same lineage. The composition of ESCRT complexes in exosomes from VCaP versus LNCaP cells might constitute a discriminatory element between these prostate cancer subtypes

Factors considered by medical students when formulating their specialty preferences in Japan: findings from a qualitative study

<p>Abstract</p> <p>Background</p> <p>Little research addresses how medical students develop their choice of specialty training in Japan. The purpose of this research was to elucidate factors considered by Japanese medical students when formulating their specialty choice.</p> <p>Methods</p> <p>We conducted qualitative interviews with 25 Japanese medical students regarding factors influencing specialty preference and their views on roles of primary versus specialty care. We qualitatively analyzed the data to identify factors students consider when developing specialty preferences, to understand their views about primary and subspecialty care, and to construct models depicting the pathways to specialization.</p> <p>Results</p> <p>Students mention factors such as illness in self or close others, respect for family member in the profession, preclinical experiences in the curriculum such as labs and dissection, and aspects of patient care such as the clinical atmosphere, charismatic role models, and doctor-patient communication as influential on their specialty preferences. Participating students could generally distinguish between subspecialty care and primary care, but not primary care and family medicine. Our analysis yields a "Two Career" model depicting how medical graduates can first train for hospital-based specialty practice, and then switch to mixed primary/specialty care outpatient practice years later without any requirement for systematic training in principles of primary care practice.</p> <p>Conclusion</p> <p>Preclinical and clinical experiences as well as role models are reported by Japanese students as influential factors when formulating their specialty preferences. Student understanding of family medicine as a discipline is low in Japan. Students with ultimate aspirations to practice outpatient primary care medicine do not need to commit to systematic primary care training after graduation. The Two Career model of specialization leaves the door open for medical graduates to enter primary care practice at anytime regardless of post-graduate residency training choice.</p

Post-graduation migration intentions of students of Lebanese medical schools: a survey study

<p>Abstract</p> <p>Background</p> <p>The international migration of physicians is a global public health problem. Lebanon is a source country with the highest emigration factor in the Middle East and North Africa and the 7th highest in the World. Given that residency training abroad is a critical step in the migration of physicians, the objective of this study was to survey students of Lebanese medical schools about their intentions to train abroad and their post training plans.</p> <p>Methods</p> <p>Our target population consisted of all students of Lebanese medical schools in the pre-final and final years of medical school. We developed the survey questionnaire based on the results of a qualitative study assessing the intentions and motives for students of Lebanese medical schools to train abroad. The questionnaire inquired about student's demographic and educational characteristics, intention to train abroad, the chosen country of abroad training, and post-training intention of returning to Lebanon.</p> <p>Results</p> <p>Of 576 eligible students, 425 participated (73.8% response rate). 406 (95.5%) respondents intended to travel abroad either for specialty training (330 (77.6%)) or subspecialty training (76 (17.9%)). Intention to train abroad was associated with being single compared with being married. The top 4 destination countries were the US (301(74.1%)), France (49 (12.1%)), the United Kingdom (31 (7.6%)) and Canada (17 (4.2%)). One hundred and two (25.1%) respondents intended to return to Lebanon directly after finishing training abroad; 259 (63.8%) intended to return to Lebanon after working abroad temporarily for a varying number or years; 43 (10.6%) intended to never return to Lebanon. The intention to stay indefinitely abroad was associated male sex and having a 2^ndcitizenship. It was inversely associated with being a student of one of the French affiliated medical schools and a plan to train in a surgical specialty.</p> <p>Conclusion</p> <p>An alarming percentage of students of Lebanese medical schools intend to migrate for post graduate training, mainly to the US. A minority intends to return directly to Lebanon after finishing training abroad.</p

Investigating the Role of Islet Cytoarchitecture in Its Oscillation Using a New β-Cell Cluster Model

The oscillatory insulin release is fundamental to normal glycemic control. The basis of the oscillation is the intercellular coupling and bursting synchronization of β cells in each islet. The functional role of islet β cell mass organization with respect to its oscillatory bursting is not well understood. This is of special interest in view of the recent finding of islet cytoarchitectural differences between human and animal models. In this study we developed a new hexagonal closest packing (HCP) cell cluster model. The model captures more accurately the real islet cell organization than the simple cubic packing (SCP) cluster that is conventionally used. Using our new model we investigated the functional characteristics of β-cell clusters, including the fraction of cells able to burst fb, the synchronization index λ of the bursting β cells, the bursting period Tb, the plateau fraction pf, and the amplitude of intracellular calcium oscillation [Ca]. We determined their dependence on cluster architectural parameters including number of cells nβ, number of inter-β cell couplings of each β cell nc, and the coupling strength gc. We found that at low values of nβ, nc and gc, the oscillation regularity improves with their increasing values. This functional gain plateaus around their physiological values in real islets, at nβ∼100, nc∼6 and gc∼200 pS. In addition, normal β-cell clusters are robust against significant perturbation to their architecture, including the presence of non-β cells or dead β cells. In clusters with nβ>∼100, coordinated β-cell bursting can be maintained at up to 70% of β-cell loss, which is consistent with laboratory and clinical findings of islets. Our results suggest that the bursting characteristics of a β-cell cluster depend quantitatively on its architecture in a non-linear fashion. These findings are important to understand the islet bursting phenomenon and the regulation of insulin secretion, under both physiological and pathological conditions