A Minimal, Unstrained S-Allyl Handle for Pre-Targeting Diels-Alder Bioorthogonal Labeling in Live Cells

The unstrained S-allyl cysteine amino acid was site-specifically installed on apoptosis protein biomarkers and was further used as a chemical handle and ligation partner for 1,2,4,5-tetrazines by means of an inverse-electron-demand Diels-Alder reaction. We demonstrate the utility of this minimal handle for the efficient labeling of apoptotic cells using a fluorogenic tetrazine dye in a pre-targeting approach. The small size, easy chemical installation, and selective reactivity of the S-allyl handle towards tetrazines should be readily extendable to other proteins and biomolecules, which could facilitate their labeling within live cells.China Scholarship Council, FCT Portugal, European Union (Marie-Sklodowska Curie ITN Protein Conjugates; Marie-Sklodowska Curie IEF), MINECO (CTQ2015-70524-R and RYC-2013-14706), Engineering and Physical Sciences Research Council, BiFi (Memento cluster), Royal Society, European Research Counci

The human gC1qR/p32 gene, C1qBP. Genomic organization and promoter analysis

gC1qR is an ubiquitously expressed cell protein that interacts with the globular heads of C1q (gC1q) and many other ligands. In this study, the 7.8-kilobase pair (kb) human gC1qPJp32 (C1qBP) gene was cloned and found to consist of 6 exons and 5 introns. Analysis of a 1.3-kb DNA fragment at the 5′-flanking region of this gene revealed the presence of multiple TATA, CCAAT, and Sp1 binding sites. Luciferase reporter assays performed in different human cell lines demonstrated that the reporter gene was ubiquitously driven by this 1.3-kb fragment. Subsequent 5′ and 3′ deletion of this fragment confined promoter elements to within 400 base pairs (bp) upstream of the translational start site. Because the removal of the 8-bp consensus TATATATA at -399 to -406 and CCAAT at -410 to -414 did not significantly affect the transcription efficiency of the promoter, GC-rich sequences between this TATA box and the translation start site may be very important for the promoter activity of the C1qBP gene. One of seven GC-rich sequences in this region binds specifically to PANC-1 nuclear extracts, and the transcription factor Sp1 was shown to bind to this GC-rich sequence by the supershift assay. Primer extension analysis mapped three major transcription start regions. The farthest transcription start site is 49 bp upstream of the ATG translation initiation codon and is in close proximity of the specific SP1 binding site.postprin

Global existence theory for the two-dimensional derivative Ginzburg-Landau equation

The generalized derivative Ginzburg-Landau equation in two spatial dimensions is discussed. The existence and uniqueness of global solution are obtained by Galerkin method and by a priori estimates on the solution in H-1-norm and H-2-norm

Living between languages: The politics of translation in Leila Aboulela’s Minaret and Xiaolu Guo’s A Concise Chinese-English Dictionary for Lovers

This is the author's final draft post-refereeing as published in The Journal of Commonwealth Literature 2012 47: 207 DOI:10.1177/0021989412440433. The online version of this article can be found at: http://jcl.sagepub.com/content/47/2/20

Turing instabilities in a mathematical model for signaling networks

GTPase molecules are important regulators in cells that continuously run through an activation/deactivation and membrane-attachment/membrane-detachment cycle. Activated GTPase is able to localize in parts of the membranes and to induce cell polarity. As feedback loops contribute to the GTPase cycle and as the coupling between membrane-bound and cytoplasmic processes introduces different diffusion coefficients a Turing mechanism is a natural candidate for this symmetry breaking. We formulate a mathematical model that couples a reaction-diffusion system in the inner volume to a reaction-diffusion system on the membrane via a flux condition and an attachment/detachment law at the membrane. We present a reduction to a simpler non-local reaction-diffusion model and perform a stability analysis and numerical simulations for this reduction. Our model in principle does support Turing instabilities but only if the lateral diffusion of inactivated GTPase is much faster than the diffusion of activated GTPase.Comment: 23 pages, 5 figures; The final publication is available at http://www.springerlink.com http://dx.doi.org/10.1007/s00285-011-0495-

A direct examination of the dynamics of dipolarization fronts using MMS

Energy conversion on the dipolarization fronts (DFs) has attracted much research attention through the suggestion that intense current densities associated with DFs can modify the more global magnetotail current system. The current structures associated with a DF are at the scale of one to a few ion gyroradii, and their duration is comparable to a spacecraft's spin period. Hence, it is crucial to understand the physical mechanisms of DFs with measurements at a timescale shorter than a spin period. We present a case study whereby we use measurements from the Magnetospheric Multiscale (MMS) Mission, which provides full 3-D particle distributions with a cadence much shorter than a spin period. We provide a cross validation amongst the current density calculations and examine the assumptions that have been adopted in previous literature using the advantages of MMS mission (i.e., small-scale tetrahedron and high temporal resolution). We also provide a cross validation on the terms in the generalized Ohm's law using these advantageous measurements. Our results clearly show that the majority of the currents on the DF are contributed by both ion and electron diamagnetic drifts. Our analysis also implies that the ion frozen-in condition does not hold on the DF, while electron frozen-in condition likely holds. The new experimental capabilities allow us to accurately calculate Joule heating within the DF, which shows that plasma energy is being converted to magnetic energy in our event

Reading faces: differential lateral gaze bias in processing canine and human facial expressions in dogs and 4-year-old children

Sensitivity to the emotions of others provides clear biological advantages. However, in the case of heterospecific relationships, such as that existing between dogs and humans, there are additional challenges since some elements of the expression of emotions are species-specific. Given that faces provide important visual cues for communicating emotional state in both humans and dogs, and that processing of emotions is subject to brain lateralisation, we investigated lateral gaze bias in adult dogs when presented with pictures of expressive human and dog faces. Our analysis revealed clear differences in laterality of eye movements in dogs towards conspecific faces according to the emotional valence of the expressions. Differences were also found towards human faces, but to a lesser extent. For comparative purpose, a similar experiment was also run with 4-year-old children and it was observed that they showed differential processing of facial expressions compared to dogs, suggesting a species-dependent engagement of the right or left hemisphere in processing emotions

Using LASSO regression to detect predictive aggregate effects in genetic studies

We use least absolute shrinkage and selection operator (LASSO) regression to select genetic markers and phenotypic features that are most informative with respect to a trait of interest. We compare several strategies for applying LASSO methods in risk prediction models, using the Genetic Analysis Workshop 17 exome simulation data consisting of 697 individuals with information on genotypic and phenotypic features (smoking, age, sex) in 5-fold cross-validated fashion. The cross-validated averages of the area under the receiver operating curve range from 0.45 to 0.63 for different strategies using only genotypic markers. The same values are improved to 0.69–0.87 when both genotypic and phenotypic information are used. The ability of the LASSO method to find true causal markers is limited, but the method was able to discover several common variants (e.g., FLT1) under certain conditions

Primary extraskeletal osteosarcoma of omentum majus

Extraskeletal osteosarcoma is a rare malignant soft tissue tumor. Here we present a case of a primary extraskeletal osteosarcoma arising from omentum majus in a 40-year-old Chinese woman. Ultrasonography of the pelvic cavity showed a large soft tissue mass with marked calcification. Complete surgical resection of the primary tumor was performed and the histopathological diagnosis was extraskeletal osteosarcoma of omentum majus. She was followed up without adjuvant radiotherapy and chemotherapy, and died from widespread intra-abdominal, lung and liver metastases 7 months postoperatively

Associations of vitamin D pathway genes with circulating 25-hydroxyvitamin-D, 1,25-dihydroxyvitamin-D, and prostate cancer:a nested case-control study

Vitamin D pathway single nucleotide polymorphisms (SNPs) are potentially useful proxies for investigating whether circulating vitamin D metabolites [total 25-hydroxyvitamin-D, 25(OH)D; 1,25-dihydroxyvitamin, 1,25(OH)2D] are causally related to prostate cancer. We investigated associations of sixteen SNPs across seven genes with prostate-specific antigen-detected prostate cancer