Developmental progression is driven by specific spatiotemporal domains of gene expression, which give rise to stereotypically patterned embryos even in the presence of environmental and genetic variation. Views of how transcription factors regulate gene expression are changing owing to recent genome-wide studies of transcription factor binding and RNA expression. Such studies reveal patterns that, at first glance, seem to contrast with the robustness of the developmental processes they encode. Here, we review our current knowledge of transcription factor function from genomic and genetic studies and discuss how different strategies, including extensive cooperative regulation (both direct and indirect), progressive priming of regulatory elements, and the integration of activities from multiple enhancers, confer specificity and robustness to transcriptional regulation during development.

http://materiais.dbio.uevora.pt/BD/Crescimento/TFs_2012.pdf

Transcription factors: from enhancer binding to developmental control.

INTRODUCTION: The copy number and in- tracellular localization of RNA are important regulators of gene expression. Measurement of these properties at the transcriptome scale in single cells will give answers to many ques- tions related to gene expression and regulation. Single-molecule RNA imaging approaches, such as single-molecule fluorescence in situ hybrid- ization(smFISH), are powerful toolsforcount- ing and mappingRNA; however, the number of RNA species that can be simultaneously im- aged in individual cells has been limited. This makes it challenging to perform transcriptomic analysis of single cells in a spatially resolved manner. Here, we report multiplexed error- robust FISH (MERFISH), a single-molecule im- aging method that allows thousands of RNA species to be imaged in single cells by using combinatorial FISH labeling with encoding schemes capable of detecting and/or correct- ing errors. RATIONALE: We labeled each cellular RNA with a set of encoding probes, which contain targeting sequences that bind the RNA and readout sequences that bind fluorescently la- beled readout probes. Each RNA species is encodedwithaparticular combinationofread- out sequences. We used successive rounds of hybridization and imaging, each with a differ- ent readout probe, to identify the readout se- quences bound to each RNA and to decode the RNA. In principle, combinatorial labeling al- lows the number of detectable RNA species to

http://science.sciencemag.org/content/sci/348/6233/aaa6090.full.pdf

Spatially resolved, highly multiplexed RNA profiling in single cells

eMedicine创建于1996年，由近万名临床医师作为作者或编辑参与此临床医学知识库的建设，其中编辑均是来自美国哈佛、耶鲁、斯坦福、芝加哥、德克萨斯、加州大学等各分校医学院的教授或副教授。

eMedicine

Cis-regulatory sequences, such as enhancers and promoters, control development and physiology by regulating gene expression. Mutations that affect the function of these sequences contribute to phenotypic diversity within and between species. With many case studies implicating divergent cis-regulatory activity in phenotypic evolution, researchers have recently begun to elucidate the genetic and molecular mechanisms that are responsible for cis-regulatory divergence. Approaches include detailed functional analysis of individual cis-regulatory elements and comparing mechanisms of gene regulation among species using the latest genomic tools. Despite the limited number of mechanistic studies published to date, this work shows how cis-regulatory activity can diverge and how studies of cis-regulatory divergence can address long-standing questions about the genetic mechanisms of phenotypic evolution.

Cis-regulatory elements: molecular mechanisms and evolutionary processes underlying divergence

Genomic enhancers are important regulators of gene expression, but their identification is a challenge, and methods depend on indirect measures of activity. We developed a method termed STARR-seq to directly and quantitatively assess enhancer activity for millions of candidates from arbitrary sources of DNA, which enables screens across entire genomes. When applied to the Drosophila genome, STARR-seq identifies thousands of cell type–specific enhancers across a broad continuum of strengths, links differential gene expression to differences in enhancer activity, and creates a genome-wide quantitative enhancer map. This map reveals the highly complex regulation of transcription, with several independent enhancers for both developmental regulators and ubiquitously expressed genes. STARR-seq can be used to identify and quantify enhancer activity in other eukaryotes, including humans.

Genome-wide quantitative enhancer activity maps identified by STARR-seq.

Advances in our understanding of pathophysiology and tissue healing and developments in trauma care and biomaterials have undoubtedly improved outcomes in high energy and other complex fractures. However, controversy still exists. In this article some of these developments will be discussed, based on a literature review of current topics and key papers which have shaped the management of the facial trauma over the last 10–20 years.

Developments and controversies in maxillofacial trauma: initial considerations in getting the patient to theatre

Oral melanoacanthomas are benign lesions that can grow quickly, and malignancy must be excluded by biopsy. They can occur at any age with the mean being 35. Females are affected more than males. The lesion is seen more commonly in darker skinned patients, followed by non-Hispanic Whites and then Hispanics. 

157. Case report on an Oral Melanoacanthoma – A diagnostic dilemma

1 Removal of devices used for osteosynthesis can be difficult t times, particularly when there is a degree of osseointegraion, the wrong kit is used, or the head of the screw has become amaged.1 During one such procedure we were attempting to remove miniplate from the infraorbital margin in a patient having secondary operation after repair abroad. Initial attempts to emove the screws using our “universal screwdriver kit” were ot successful, and eventually damage to the heads of two crews prevented the screwdriver being engaged securely. As an alternative we decided to drill the bone circumferntially, and use a clip to grasp the head – a commonly used, nd a tried and tested technique, although others have been escribed.2 However, unknown to us the drill motor was set in everse and when applied, the Toller fissure burr engaged the rst screw with enough frictional torque to remove it easily Fig. 1). The second screw was removed in a similar way by placing he burr directly over it to maximise grip. It also came out ith relative ease. The technique has now worked on several ccasions and is a conservative way of removing problem

Alternative approach for the removal of problem miniscrews--a serendipitous finding.

Background Vancouver B2 periprosthetic femur fractures have traditionally been treated with revision arthroplasty. However, there is increasing evidence that open reduction and internal fixation (ORIF) may be a valid alternative treatment strategy. The purpose of this study was to compare the outcomes of ORIF versus revision arthroplasty for the treatment of Vancouver B2 fractures and evaluate the influence of the treating surgeon’s fellowship training on treatment selection. Methodology This was a retrospective cohort study of 31 patients treated for Vancouver B2 periprosthetic fractures (16 ORIF and 15 revision arthroplasty) at a single academic Level 1 trauma center. Outcome measures included one-year mortality, revision, reoperation, infection, and blood loss. Results There were no statistically significant differences in revision, reoperation, or infection at an average follow-up of 65 weeks. Median estimated blood loss was higher in the arthroplasty group (700 cc versus 400 cc; P = 0.04). There were five deaths in the ORIF group versus one in the revision group (P = 0.18). Cases treated by surgeons with fellowship training in arthroplasty were more likely to be treated with revision arthroplasty (10/11, 90.9%) than those treated by surgeons with fellowship training in trauma (5/15, 33.3%; P < 0.01). Conclusions There was no difference in outcomes between the two treatment strategies, but revision was associated with higher blood loss. The appropriate treatment method should be based on surgeon familiarity and patients' characteristics.

/pdf/treatment-of-vancouver-b2-femur-fractures-with-open-1v5jcx4f.pdf

Michael Perry

Papers

Developments and controversies in maxillofacial trauma: initial considerations in getting the patient to theatre

157. Case report on an Oral Melanoacanthoma – A diagnostic dilemma

Alternative approach for the removal of problem miniscrews--a serendipitous finding.

Treatment of Vancouver B2 Femur Fractures With Open Reduction Internal Fixation Versus Revision Arthroplasty

How often and how long should we follow up adult maxillofacial trauma? – A preliminary study