The Ursinus Weekly, February 27, 1961

Student-faculty show to climax charity drive • ICG holds banquet at Immaculata • Dr. Elmer H. Funk addresses students • Power lines snap, disrupt campus • YM-YWCA plans fireside chats, first will be held on March 1 • Jun Kawashima addresses PSEA on Japan\u27s education • WSGA plans two demonstrations • Meistersingers open season at Faith Church • Frosh girls, reps receive colors on February 23 • U.C. students dine with Republicans • AF recruiter offers ACPP applications • International Relations Club to hear speaker on Finland • Joan Meszaros elected Spring Festival queen • Jazz festival in Fla. over recess • Placement Office posts job listing • Newman Club to hold next meeting on March 6 • Editorial: Apathy again • Eichmann: Perhaps a case of injustice • Northbound • From the continent to the cottage • Book review: The same door • Chestnut Hill falls to badminton team • Girls\u27 swimming team defeats Beaver 44-21 • Thinclads have practice meet with Delaware • Intramural corner • Lassies cop two during past week; Crosley stars • Basketball team split; End with 6-11 season • Grapplers win 2, down Drexel, PMC • Greek gleanings • Letters to the editor • Like I went to a work camphttps://digitalcommons.ursinus.edu/weekly/1334/thumbnail.jp

The Ursinus Weekly, March 20, 1961

Peiffer is prom queen; Cub & Key taps 5 men • Men urged to take April SSCQ tests • A pair of lunatics, Curtain Club offering • YWCA worker to speak Monday in Paisley Hall • French Club attends Comedie Francaise • Brownback-Anders hears Ben Hauser, Jeff med student • Bogel wins two posts at meeting • Carolyn Boyer elected into Stars and Players • Ed Myers wins SPSEA regional presidential post • Festival concessions encouraged by WSGA • Students sought for jobs in amusement parks • John Swinton is named as new Weekly editor • Holl to address Young Republicans • Campus Chest figures released • Four seniors placed as high school teachers • Officer nominations invited by YM-YWCA • Father Conran to address Newman Club tonight at 6:30 • Editorial: Thank you • Letters to the editor • Eccentric circles • What does organized labor want? • Chapel commentary • Archaeology and the Bible • Intramural corner • Cindermen boast greater depth • Mermaids lose to Swarthmore, 45-30 • Girl basketballers chalk up 2 more • Norm Bramall to present tennis clinic on Thurs. • Greek gleaningshttps://digitalcommons.ursinus.edu/weekly/1337/thumbnail.jp

Plasticity of fimbrial genotype and serotype within populations of <em>Bordetella pertussis</em>:analysis by paired flow cytometry and genome sequencing

The fimbriae of Bordetella pertussis are required for colonization of the human respiratory tract. Two serologically distinct fimbrial subunits, Fim2 and Fim3, considered important vaccine components for many years, are included in the Sanofi Pasteur 5-component acellular pertussis vaccine, and the World Health Organization recommends the inclusion of strains expressing both fimbrial serotypes in whole-cell pertussis vaccines. Each of the fimbrial major subunit genes, fim2, fim3, and fimX, has a promoter poly(C) tract upstream of its −10 box. Such monotonic DNA elements are susceptible to changes in length via slipped-strand mispairing in vitro and in vivo, which potentially causes on/off switching of genes at every cell division. Here, we have described intra-culture variability in poly(C) tract lengths and the resulting fimbrial phenotypes in 22 recent UK B. pertussis isolates. Owing to the highly plastic nature of fimbrial promoters, we used the same cultures for both genome sequencing and flow cytometry. Individual cultures of B. pertussis contained multiple fimbrial serotypes and multiple different fimbrial promoter poly(C) tract lengths, which supports earlier serological evidence that B. pertussis expresses both serotypes during infection.</jats:p

Controlled overexpression of Pax6 in vivo negatively autoregulates the Pax6 locus, causing cell-autonomous defects of late cortical progenitor proliferation with little effect on cortical arealization

Levels of expression of the transcription factor Pax6 vary throughout corticogenesis in a rostro-lateral(high) to caudo-medial(low) gradient across the cortical proliferative zone. Previous loss-of-function studies have indicated that Pax6 is required for normal cortical progenitor proliferation, neuronal differentiation, cortical lamination and cortical arealization, but whether and how its level of expression affects its function is unclear. We studied the developing cortex of PAX77 YAC transgenic mice carrying several copies of the human PAX6 locus with its full complement of regulatory regions. We found that PAX77 embryos express Pax6 in a normal spatial pattern, with levels up to three times higher than wild type. By crossing PAX77 mice with a new YAC transgenic line that reports Pax6 expression (DTy54), we showed that increased expression is limited by negative autoregulation. Increased expression reduces proliferation of late cortical progenitors specifically, and analysis of PAX77↔wild-type chimeras indicates that the defect is cell autonomous. We analyzed cortical arealization in PAX77 mice and found that, whereas the loss of Pax6 shifts caudal cortical areas rostrally, Pax6 overexpression at levels predicted to shift rostral areas caudally has very little effect. These findings indicate that Pax6 levels are stabilized by autoregulation, that the proliferation of cortical progenitors is sensitive to altered Pax6 levels and that cortical arealization is not

Genomic characterisation of human monkeypox virus in Nigeria

Monkeypox virus (MPXV) is a large, double-stranded DNA virus belonging to the Orthopox genus in the family Poxviridae. First identified in 1958, MPXV has caused sporadic human outbreaks in central and west Africa, with a mortality rate between 1% and 10%.1 Viral genomes from west Africa and the Congo Basin separate into two clades, the latter being more virulent.2 Recently, MPXV outbreaks have occurred in Sudan (2005), the Republic of the Congo and Democratic Republic of the Congo (2009), and the Central African Republic (2016).3 A suspected outbreak of human MPXV was reported to WHO on Sept 26, 2017, by the Nigeria Centre for Disease Control (NCDC) after a cluster of suspected cases had occurred in Yenagoa Local Government Area, Bayelsa State, Nigeria.4 Since the onset of the outbreak, 155 cases have been reported by the NCDC, of which 56 were confirmed.4 A subset of these samples was sent to the WHO Collaborating Center at the Institut Pasteur de Dakar (IPD) in Senegal for confirmation by PCR

Optimal functional outcome measures for assessing treatment for Dupuytren's disease: A systematic review and recommendations for future practice

This article is available through the Brunel Open Access Publishing Fund. Copyright © 2013 Ball et al.; licensee BioMed Central Ltd.Background: Dupuytren's disease of the hand is a common condition affecting the palmar fascia, resulting in progressive flexion deformities of the digits and hence limitation of hand function. The optimal treatment remains unclear as outcomes studies have used a variety of measures for assessment. Methods: A literature search was performed for all publications describing surgical treatment, percutaneous needle aponeurotomy or collagenase injection for primary or recurrent Dupuytren’s disease where outcomes had been monitored using functional measures. Results: Ninety-one studies met the inclusion criteria. Twenty-two studies reported outcomes using patient reported outcome measures (PROMs) ranging from validated questionnaires to self-reported measures for return to work and self-rated disability. The Disability of Arm, Shoulder and Hand (DASH) score was the most utilised patient-reported function measure (n=11). Patient satisfaction was reported by eighteen studies but no single method was used consistently. Range of movement was the most frequent physical measure and was reported in all 91 studies. However, the methods of measurement and reporting varied, with seventeen different techniques being used. Other physical measures included grip and pinch strength and sensibility, again with variations in measurement protocols. The mean follow-up time ranged from 2 weeks to 17 years. Conclusions: There is little consistency in the reporting of outcomes for interventions in patients with Dupuytren’s disease, making it impossible to compare the efficacy of different treatment modalities. Although there are limitations to the existing generic patient reported outcomes measures, a combination of these together with a disease-specific questionnaire, and physical measures of active and passive individual joint Range of movement (ROM), grip and sensibility using standardised protocols should be used for future outcomes studies. As Dupuytren’s disease tends to recur following treatment as well as extend to involve other areas of the hand, follow-up times should be standardised and designed to capture both short and long term outcomes

Long-range downstream enhancers are essential for Pax6 expression

AbstractPax6 is a developmental control gene with an essential role in development of the eye, brain and pancreas. Pax6, as many other developmental regulators, depends on a substantial number of cis-regulatory elements in addition to its promoters for correct spatiotemporal and quantitative expression. Here we report on our analysis of a set of mice transgenic for a modified yeast artificial chromosome carrying the human PAX6 locus. In this 420 kb YAC a tauGFP-IRES-Neomycin reporter cassette has been inserted into the PAX6 translational start site in exon 4. The YAC has been further engineered to insert LoxP sites flanking a 35 kb long, distant downstream regulatory region (DRR) containing previously described DNaseI hypersensitive sites, to allow direct comparison between the presence or absence of this region in the same genomic context. Five independent transgenic lines were obtained that vary in the extent of downstream PAX6 locus that has integrated. Analysis of transgenic embryos carrying full-length and truncated versions of the YAC indicates the location and putative function of several novel tissue-specific enhancers. Absence of these distal regulatory elements abolishes expression in specific tissues despite the presence of more proximal enhancers with overlapping specificity, strongly suggesting interaction between these control elements. Using plasmid-based reporter transgenic analysis we provide detailed characterization of one of these enhancers in isolation. Furthermore, we show that overexpression of a short PAX6 isoform derived from an internal promoter in a multicopy YAC transgenic line results in a microphthalmia phenotype. Finally, direct comparison of a single-copy line with the floxed DRR before and after Cre-mediated deletion demonstrates unequivocally the essential role of these long-range control elements for PAX6 expression

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Gluttony, excess, and the fall of the planter class in the British Caribbean

Food and rituals around eating are a fundamental part of human existence. They can also be heavily politicized and socially significant. In the British Caribbean, white slaveholders were renowned for their hospitality towards one another and towards white visitors. This was no simple quirk of local character. Hospitality and sociability played a crucial role in binding the white minority together. This solidarity helped a small number of whites to dominate and control the enslaved majority. By the end of the eighteenth century, British metropolitan observers had an entrenched opinion of Caribbean whites as gluttons. Travelers reported on the sumptuous meals and excessive drinking of the planter class. Abolitionists associated these features of local society with the corrupting influences of slavery. Excessive consumption and lack of self-control were seen as symptoms of white creole failure. This article explores how local cuisine and white creole eating rituals developed as part of slave societies and examines the ways in which ideas about hospitality and gluttony fed into the debates over slavery that led to the dismantling of slavery and the fall of the planter class

Advancing schizophrenia drug discovery : optimizing rodent models to bridge the translational gap

Although our knowledge of the pathophysiology of schizophrenia has increased, treatments for this devastating illness remain inadequate. Here, we critically assess rodent models and behavioural end points used in schizophrenia drug discovery and discuss why these have not led to improved treatments. We provide a perspective on how new models, based on recent advances in the understanding of the genetics and neural circuitry underlying schizophrenia, can bridge the translational gap and lead to the development of more effective drugs. We conclude that previous serendipitous approaches should be replaced with rational strategies for drug discovery in integrated preclinical and clinical programmes. Validation of drug targets in disease-based models that are integrated with translationally relevant end point assessments will reduce the current attrition rate in schizophrenia drug discovery and ultimately lead to therapies that tackle the disease process