Brief Review of Models of Ectopic Bone Formation

Ectopic bone formation is a unique biologic entity?distinct from other areas of skeletal biology. Animal research models of ectopic bone formation most often employ rodent models and have unique advantages over orthotopic (bone) environments, including a relative lack of bone cytokine stimulation and cell-to-cell interaction with endogenous (host) bone-forming cells. This allows for relatively controlled in vivo experimental bone formation. A wide variety of ectopic locations have been used for experimentation, including subcutaneous, intramuscular, and kidney capsule transplantation. The method, benefits and detractions of each method are summarized in the following review. Briefly, subcutaneous implantation is the simplest method. However, the most pertinent concern is the relative paucity of bone formation in comparison to other models. Intramuscular implantation is also widely used and relatively simple, however intramuscular implants are exposed to skeletal muscle satellite progenitor cells. Thus, distinguishing host from donor osteogenesis becomes challenging without cell-tracking studies. The kidney capsule (perirenal or renal capsule) method is less widely used and more technically challenging. It allows for supraphysiologic blood and nutrient resource, promoting robust bone growth. In summary, ectopic bone models are extremely useful in the evaluation of bone-forming stem cells, new osteoinductive biomaterials, and growth factors; an appropriate choice of model, however, will greatly increase experimental success.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98476/1/scd%2E2011%2E0517.pd

Global Fluctuation Spectra in Big Crunch/Big Bang String Vacua

We study Big Crunch/Big Bang cosmologies that correspond to exact world-sheet superconformal field theories of type II strings. The string theory spacetime contains a Big Crunch and a Big Bang cosmology, as well as additional ``whisker'' asymptotic and intermediate regions. Within the context of free string theory, we compute, unambiguously, the scalar fluctuation spectrum in all regions of spacetime. Generically, the Big Crunch fluctuation spectrum is altered while passing through the bounce singularity. The change in the spectrum is characterized by a function $\Delta$, which is momentum and time-dependent. We compute $\Delta$ explicitly and demonstrate that it arises from the whisker regions. The whiskers are also shown to lead to ``entanglement'' entropy in the Big Bang region. Finally, in the Milne orbifold limit of our superconformal vacua, we show that $\Delta\to 1$ and, hence, the fluctuation spectrum is unaltered by the Big Crunch/Big Bang singularity. We comment on, but do not attempt to resolve, subtleties related to gravitational backreaction and light winding modes when interactions are taken into account.Comment: 68 pages, 1 figure; typos correcte

Entangled Stories: The Red Jews in Premodern Yiddish and German Apocalyptic Lore

“Far, far away from our areas, somewhere beyond the Mountains of Darkness, on the other side of the Sambatyon River…there lives a nation known as the Red Jews.” The Red Jews are best known from classic Yiddish writing, most notably from Mendele's Kitser masoes Binyomin hashlishi (The Brief Travels of Benjamin the Third). This novel, first published in 1878, represents the initial appearance of the Red Jews in modern Yiddish literature. This comical travelogue describes the adventures of Benjamin, who sets off in search of the legendary Red Jews. But who are these Red Jews or, in Yiddish, di royte yidelekh? The term denotes the Ten Lost Tribes of Israel, the ten tribes that in biblical times had composed the Northern Kingdom of Israel until they were exiled by the Assyrians in the eighth century BCE. Over time, the myth of their return emerged, and they were said to live in an uncharted location beyond the mysterious Sambatyon River, where they would remain until the Messiah's arrival at the end of time, when they would rejoin the rest of the Jewish people. This article is part of a broader study of the Red Jews in Jewish popular culture from the Middle Ages through modernity. It is partially based on a chapter from my book, Umstrittene Erlöser: Politik, Ideologie und jüdisch-christlicher Messianismus in Deutschland, 1500–1600 (Göttingen: Vandenhoeck & Ruprecht, 2011). Several postdoctoral fellowships have generously supported my research on the Red Jews: a Dr. Meyer-Struckmann-Fellowship of the German Academic Foundation, a Harry Starr Fellowship in Judaica/Alan M. Stroock Fellowship for Advanced Research in Judaica at Harvard University, a research fellowship from the Heinrich Hertz-Foundation, and a YIVO Dina Abramowicz Emerging Scholar Fellowship. I thank the organizers of and participants in the colloquia and conferences where I have presented this material in various forms as well as the editors and anonymous reviewers of AJS Review for their valuable comments and suggestions. I am especially grateful to Jeremy Dauber and Elisheva Carlebach of the Institute for Israel and Jewish Studies at Columbia University, where I was a Visiting Scholar in the fall of 2009, for their generous encouragement to write this article. Sue Oren considerably improved my English. The style employed for Romanization of Yiddish follows YIVO's transliteration standards. Unless otherwise noted, translations from the Yiddish, Hebrew, German, and Latin are my own. Quotations from the Bible follow the JPS translation, and those from the Babylonian Talmud are according to the Hebrew-English edition of the Soncino Talmud by Isidore Epstein

Metabolic networking in Brunfelsia calycina petals after flower opening

Brunfelsia calycina flowers change colour from purple to white due to anthocyanin degradation, parallel to an increase in fragrance and petal size. Here it was tested whether the production of the fragrant benzenoids is dependent on induction of the shikimate pathway, or if they are formed from the anthocyanin degradation products. An extensive characterization of the events taking place in Brunfelsia flowers is presented. Anthocyanin characterization was performed using ultraperfomance liquid chromatography–quadrupole time of flight–tandem mass specrometry (UPLC-QTOF-MS/MS). Volatiles emitted were identified by headspace solid phase microextraction–gas chromatography–mass spectrometry (HS-SPME-GC-MS). Accumulated proteins were identified by 2D gel electrophoresis. Transcription profiles were characterized by cross-species hybridization of Brunfelsia cDNAs to potato cDNA microarrays. Identification of accumulated metabolites was performed by UPLC-QTOF-MS non-targeted metabolite analysis. The results include characterization of the nine main anthocyanins in Brunfelsia flowers. In addition, 146 up-regulated genes, 19 volatiles, seven proteins, and 17 metabolites that increased during anthocyanin degradation were identified. A multilevel analysis suggests induction of the shikimate pathway. This pathway is the most probable source of the phenolic acids, which in turn are precursors of both the benzenoid and lignin production pathways. The knowledge obtained is valuable for future studies on degradation of anthocyanins, formation of volatiles, and the network of secondary metabolism in Brunfelsia and related species

Stabbing News: Articulating Crime Statistics in the Newsroom

There is a comprehensive body of scholarly work regarding the way media represent crime and how it is constructed in the media narrative as a news item. These works have often suggested that in many cases public anxieties in relation to crime levels are not justified by actual data. However, few works have examined the gathering and dissemination of crime statistics by non-specialist journalists and the way crime statistics are gathered and used in the newsroom. This article seeks to explore in a comparative manner how journalists in newsrooms access and interpret quantitative data when producing stories related to crime. In so doing, the article highlights the problems and limitations of journalists in dealing with crime statistics as a news source, while assessing statistics-related methodologies and skills used in the newsrooms across the United Kingdom when producing stories related to urban crime

Miscarriage rates after dehydroepiandrosterone (DHEA) supplementation in women with diminished ovarian reserve: a case control study

<p>Abstract</p> <p>Background</p> <p>Dehydroepinadrosterone (DHEA) supplementation improves pregnancy chances in women with diminished ovarian reserve (DOR), by possibly reducing aneuploidy. Since a large majority of spontaneous miscarriages are associated with aneuploidy, one can speculate that DHEA supplementation may also reduce miscarriage rates.</p> <p>Methods</p> <p>We retroactively compared, utilizing two independent statistical models, miscarriage rates in 73 DHEA supplemented pregnancies at two independent North American infertility centers, age-stratified, to miscarriages reported in a national U.S. in vitro fertilization (IVF) data base.</p> <p>Results</p> <p>After DHEA supplementation the miscarriage rate at both centers was 15.1% (15.0% and 15.2%, respectively). For DHEA supplementation Mantel-Hänszel common odds ratio (and 95% confidence interval), stratified by age, was significantly lower, relative to odds of miscarriage in the general IVF control population [0.49 (0.25-0.94; p = 0.04)]. Miscarriage rates after DHEA were significantly lower at all ages but most pronounced above age 35 years.</p> <p>Discussion</p> <p>Since DOR patients in the literature are reported to experience significantly higher miscarriage rates than average IVF patients, the here observed reduction in miscarriages after DHEA supplementation exceeds, however, all expectations. Miscarriage rates after DHEA not only were lower than in an average national IVF population but were comparable to rates reported in normally fertile populations. Low miscarriage rates, comparable to those of normal fertile women, are statistically impossible to achieve in DOR patients without assumption of a DHEA effect on embryo ploidy. Beyond further investigations in infertile populations, these data, therefore, also suggest the investigations of pre-conception DHEA supplementation in normal fertile populations above age 35 years.</p

Perceptual Learning in the Absence of Task or Stimulus Specificity

Performance on most sensory tasks improves with practice. When making particularly challenging sensory judgments, perceptual improvements in performance are tightly coupled to the trained task and stimulus configuration. The form of this specificity is believed to provide a strong indication of which neurons are solving the task or encoding the learned stimulus. Here we systematically decouple task- and stimulus-mediated components of trained improvements in perceptual performance and show that neither provides an adequate description of the learning process. Twenty-four human subjects trained on a unique combination of task (three-element alignment or bisection) and stimulus configuration (vertical or horizontal orientation). Before and after training, we measured subjects' performance on all four task-configuration combinations. What we demonstrate for the first time is that learning does actually transfer across both task and configuration provided there is a common spatial axis to the judgment. The critical factor underlying the transfer of learning effects is not the task or stimulus arrangements themselves, but rather the recruitment of commons sets of neurons most informative for making each perceptual judgment

Noncoding deletions reveal a gene that is critical for intestinal function.

Large-scale genome sequencing is poised to provide a substantial increase in the rate of discovery of disease-associated mutations, but the functional interpretation of such mutations remains challenging. Here we show that deletions of a sequence on human chromosome 16 that we term the intestine-critical region (ICR) cause intractable congenital diarrhoea in infants1,2. Reporter assays in transgenic mice show that the ICR contains a regulatory sequence that activates transcription during the development of the gastrointestinal system. Targeted deletion of the ICR in mice caused symptoms that recapitulated the human condition. Transcriptome analysis revealed that an unannotated open reading frame (Percc1) flanks the regulatory sequence, and the expression of this gene was lost in the developing gut of mice that lacked the ICR. Percc1-knockout mice displayed phenotypes similar to those observed upon ICR deletion in mice and patients, whereas an ICR-driven Percc1 transgene was sufficient to rescue the phenotypes found in mice that lacked the ICR. Together, our results identify a gene that is critical for intestinal function and underscore the need for targeted in vivo studies to interpret the growing number of clinical genetic findings that do not affect known protein-coding genes

Functional genomics reveals serine synthesis is essential in PHGDH-amplified breast cancer

Cancer cells adapt their metabolic processes to drive macromolecular biosynthesis for rapid cell growth and proliferation[superscript 1, 2]. RNA interference (RNAi)-based loss-of-function screening has proven powerful for the identification of new and interesting cancer targets, and recent studies have used this technology in vivo to identify novel tumour suppressor genes[superscript 3]. Here we developed a method for identifying novel cancer targets via negative-selection RNAi screening using a human breast cancer xenograft model at an orthotopic site in the mouse. Using this method, we screened a set of metabolic genes associated with aggressive breast cancer and stemness to identify those required for in vivo tumorigenesis. Among the genes identified, phosphoglycerate dehydrogenase (PHGDH) is in a genomic region of recurrent copy number gain in breast cancer and PHGDH protein levels are elevated in 70% of oestrogen receptor (ER)-negative breast cancers. PHGDH catalyses the first step in the serine biosynthesis pathway, and breast cancer cells with high PHGDH expression have increased serine synthesis flux. Suppression of PHGDH in cell lines with elevated PHGDH expression, but not in those without, causes a strong decrease in cell proliferation and a reduction in serine synthesis. We find that PHGDH suppression does not affect intracellular serine levels, but causes a drop in the levels of α-ketoglutarate, another output of the pathway and a tricarboxylic acid (TCA) cycle intermediate. In cells with high PHGDH expression, the serine synthesis pathway contributes approximately 50% of the total anaplerotic flux of glutamine into the TCA cycle. These results reveal that certain breast cancers are dependent upon increased serine pathway flux caused by PHGDH overexpression and demonstrate the utility of in vivo negative-selection RNAi screens for finding potential anticancer targets.Susan G. Komen Breast Cancer Foundation (Fellowship)Life Sciences Research Foundation (Fellowship)W. M. Keck FoundationDavid H. Koch Cancer Research FundAlexander and Margaret Stewart TrustNational Institutes of Health (U.S.) (Grant CA103866

Ghana 3D Telemedicine International MDT : A proof-of-concept study

A real-time 3D Telemedicine system – leveraging Microsoft's Holoportation™ communication technology – enabled an international multidisciplinary team meeting (MDT) to consult with complex reconstructive patients before, during, and after an overseas surgical collaboration. Methods: A proof-of-concept international 3D MDT clinic took place in November 2022, between the Canniesburn Plastic Surgery Unit, UK, and the National Reconstructive Plastic Surgery and Burns Centre, Korle Bu Teaching Hospital, Ghana. The 3D system was utilised 1) previsit to assess patients and enable logistical planning, 2) on-site in Ghana to further allow patients to see themselves and proposed operations in 3D, and 3) post visit to debrief the team and patients. Results: Four Ghana patients were followed through their patient journey (mandibular ameloblastoma, sarcoma thigh, maxillary tumour, sarcoma back). Thirteen participants (four patients, four Ghana clinicians, and five UK clinicians) completed feedback on the 3D MDT. Outcome measures were rated highly with satisfaction 84.31/100, perceived benefit 4.54/5, overall quality 127.3/147 (Telehealth Usability Questionnaire), and usability 83.2/100 (System Usability Scale). These data show close alignment with that previously published on high-income countries. Conclusions: This novel technology has the potential to enhance the delivery of overseas surgical visits to low-to-middle-income countries, by improving planning, informed discussion with patients, expert consensus on complex cases, and fostering engagement with professionals who may be thousands of miles away. This is the first demonstration that real-time 3D Telemedicine can both work, and enhance care within an international MDT clinic, and may thus enable change in the approach to overseas surgical collaborations