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Objectives: The objective was to evaluate the efficacy of a required emergency medicine (EM) experience embedded in a new community‐based longitudinal integrated clerkship (LIC) for participating students and faculty. Methods: We developed and implemented a community‐based LIC EM experience. The experience included 10 clinical shifts, one emergency medical services prehospital care shift, four didactic sessions, one reflection, and an emergency medicine simulation session. Students' outcomes were assessed using end‐of‐year surveys, focus groups, an emergency medicine subject examination, simulation performance, and clinical evaluations of the students by faculty. Faculty were recruited, underwent faculty development, and were evaluated by students. Faculty perceptions were gathered from a focus group and faculty retention rates were collected. Results: Three cohorts of LIC students (total N = 61) have completed their core emergency medicine experience in our community‐based LIC. Among students, 76% to 95% rated the overall quality of teaching as very good or excellent and 66% to 100% rated the quality of learning in their community‐based setting as very good or excellent. All students who passed the EM subject examination achieved the clinical competencies of the experience based on clinical evaluations. Among faculty, we have retained greater than 95% each year and they have reflected positively on their precepting experience. Conclusions: Implementing a required EM experience within a community‐based LIC model can be an effective learning experience for students and perceived positively by community‐based faculty. This model may offer an opportunity to expand clinical learning experiences in EM. [ABSTRACT FROM AUTHOR]

Mismatch repair prevents the accumulation of erroneous insertions/deletions and non-Watson-Crick base pairs in the genome. Pathogenic mutations in the MLH1 gene are associated with a predisposition to Lynch and Turcot's syndromes. Although genetic testing for these mutations is available, robust classification of variants requires strong clinical and functional support. Here, the first structure of the N-terminus of human MLH1, determined by X-ray crystallography, is described. The structure shares a high degree of similarity with previously determined prokaryotic MLH1 homologs; however, this structure affords a more accurate platform for the classification of MLH1 variants. [ABSTRACT FROM AUTHOR]

The poly(ADP-ribose) polymerase (PARP) family represents a new class of therapeutic targets with diverse potential disease indications. PARP1 and PARP2 inhibitors have been developed for breast and ovarian tumors manifesting double-stranded DNA-repair defects, whereas tankyrase 1 and 2 (TNKS1 and TNKS2, also known as PARP5a and PARP5b, respectively) inhibitors have been developed for tumors with elevated β-catenin activity. As the clinical relevance of PARP inhibitors continues to be actively explored, there is heightened interest in the design of selective inhibitors based on the detailed structural features of how small-molecule inhibitors bind to each of the PARP family members. Here, the high-resolution crystal structures of the human TNKS2 PARP domain in complex with 16 various PARP inhibitors are reported, including the compounds BSI-201, AZD-2281 and ABT-888, which are currently in Phase 2 or 3 clinical trials. These structures provide insight into the inhibitor-binding modes for the tankyrase PARP domain and valuable information to guide the rational design of future tankyrase-specific inhibitors. [ABSTRACT FROM AUTHOR]

Highlights: [•] We report the first crystal structures of SUV420H1 and SUV420H2. [•] SUV420H1 and SUV420H2 exhibit unique N-terminal and Zn-binding post-SET domains. [•] We developed the first in vitro assay for characterizing and screening SUV420H1 and SUV420H2 in a 384-well format. [Copyright &y& Elsevier]

The versatility of nanodiamonds (NDs) as a polymer-embedded therapeutic vehicle was demonstrated by the development of a hybrid material consisting of a poly(ethylene glycol) diacrylate (PEGDA) hydrogel embedded with ND-drug complexes. A wide range of PEGDA structures, including single and multiple drug reservoirs, exhibited high loading capabilities and stable slow-release, augmented with the addition of ND conjugates. ND-PEGDA hydrogels were compared to unmodified, drug-embedded PEGDA hydrogels to demonstrate their robust drug sequestering capacity in vitro. Remarkably, ND-embedded hydrogels were capable of mitigating the harmful effects of burst-release by displaying slow and controlled administration of therapeutic compounds, an improvement over standard diffusion-based release profiles. The tunable customization of PEGDA hydrogel, both in structure and content, as well as its facile methods of synthesis, make this material an effective multi-therapeutic complement to the drug delivery abilities of NDs. A hybrid material that utilizes the synergy of PEGDA and ND components has the potential for applications toward a diverse array of biomedical challenges. [ABSTRACT FROM AUTHOR]

Abstract: The human PHD finger protein 20 (PHF20) is a putative transcription factor. While little is known about its cognate cellular role, antibodies against PHF20 are present in sera from patients with hepatocellular carcinoma, glioblastoma and childhood medulloblastula. PHF20 comprises two N-terminal Tudor domains, a central C2H2-link zinc finger domain and a C-terminal zinc-binding PHD domain, and is a component of some MLL methyltransferase complexes. Here, we report the crystal structures of the N-terminal Tudor domains of PHF20 and highlight the novel structural features of each domain. We also confirm previous studies suggesting that the second Tudor domain of PHF20 exhibits preference for dimethylated histone substrates. [Copyright &y& Elsevier]

Abstract: We present here the crystal structures of human lamin B1 globular tail domain and coiled 2B domain, which adopt similar folds to Ig-like domain and coiled-coil domain of lamin A, respectively. Despite the overall similarity, we found an extra intermolecular disulfide bond in the lamin B1 coil 2B domain, which does not exist in lamin A/C. In addition, the structural analysis indicates that interactions at the lamin B1 homodimer interface are quite different from those of lamin A/C. Thus our research not only reveals the diversely formed homodimers among lamin family members, but also sheds light on understanding the important roles of lamin B1 in forming the nuclear lamina matrix. Structured summary of protein interactions: Lamin-B and Lamin-B bind by x-ray crystallography (View interaction) [Copyright &y& Elsevier]

The article offers a design of the X-CHIP device and the accompanying tools for setting up crystallization trials and mounting the chip for data collection and the benefits, limitations and implications inherent to this platform. The protein kinase domain of human ephrin receptor tyrosine kinase and the Pseudomonas aeruginosa alkylhydroperoxidase D protein were chosen as model proteins to show the feasibility of crystal growth using X-CHIP. It concludes that X-CHIP increases efficiency and offers the opportunity for full automation.

The rational design of novel antibiotics for bacteria involves the identification of inhibitors for enzymes involved in essential biochemical pathways in cells. In this study, the cloning, expression, purification, crystallization and structure of the enzyme peptidyl-tRNA hydrolase from Francisella tularensis, the causative agent of tularemia, was performed. The structure of F. tularensis peptidyl-tRNA hydrolase is comparable to those of other bacterial peptidyl-tRNA hydrolases, with most residues in the active site conserved amongst the family. The resultant reagents, structural data and analyses provide essential information for the structure-based design of novel inhibitors for this class of proteins. [ABSTRACT FROM AUTHOR]

Urease plays a central role in the pathogenesis of Helicobacter pylori in humans. Maturation of this nickel metalloenzyme in bacteria requires the participation of the accessory proteins UreD (termed UreH in H. pylori), UreF, and UreG, which form sequential complexes with the urease apoprotein as well as UreE, a metallochaperone. Here, we describe the crystal structure of C-terminal truncated UreF from H. pylori (residues 1-233), the first UreF structure to be determined, at 1.55 Å resolution using SAD methods. UreF forms a dimer in vitro and adopts an all-helical fold congruent with secondary structure prediction. On the basis of evolutionary conservation analysis, the structure reveals a probable binding surface for interaction with other urease components as well as key conserved residues of potential functional relevance. Proteins 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The article presents a study, which attempts to determine whether the Wechsler Intelligence Scale for Children (WISC) is useful in this respect. The subjects for this study were examined with psychological tests and consisted of 104 children between the ages of 6-0 and 15-11 years. Thirty-one of forty-two children with intelligence quotients below 80 who because of test data were suspected of suffering from organic brain disease were found to have confirmatory signs on neurological examinations. Organics tend to score lower on the WISC Full Scale than non-organics. Organics tend to do more poorly on the WISC Performance and Full Scales than on the WISC Verbal Scale. The possibility of organicity increases considerably as the emotional quotient drops below the borderline feeble-minded range.

TiGeSb adopts the PbFCl- or ZrSiS-type structure, with Ti atoms (4mm symmetry) centred within monocapped square anti-prisms generated by the stacking of denser square nets of Ge atoms (m2 symmetry) alternating with less dense square nets of Sb atoms (4mm symmetry).