Blueprint for a high-performance biomaterial: full-length spider dragline silk genes.

Spider dragline (major ampullate) silk outperforms virtually all other natural and manmade materials in terms of tensile strength and toughness. For this reason, the mass-production of artificial spider silks through transgenic technologies has been a major goal of biomimetics research. Although all known arthropod silk proteins are extremely large (>200 kiloDaltons), recombinant spider silks have been designed from short and incomplete cDNAs, the only available sequences. Here we describe the first full-length spider silk gene sequences and their flanking regions. These genes encode the MaSp1 and MaSp2 proteins that compose the black widow's high-performance dragline silk. Each gene includes a single enormous exon (>9000 base pairs) that translates into a highly repetitive polypeptide. Patterns of variation among sequence repeats at the amino acid and nucleotide levels indicate that the interaction of selection, intergenic recombination, and intragenic recombination governs the evolution of these highly unusual, modular proteins. Phylogenetic footprinting revealed putative regulatory elements in non-coding flanking sequences. Conservation of both upstream and downstream flanking sequences was especially striking between the two paralogous black widow major ampullate silk genes. Because these genes are co-expressed within the same silk gland, there may have been selection for similarity in regulatory regions. Our new data provide complete templates for synthesis of recombinant silk proteins that significantly improve the degree to which artificial silks mimic natural spider dragline fibers

MEK Inhibitor-Based Combination Strategies in Selected Molecular Subsets of Non-Small Cell Lung Cancer (NSCLC): rationale for the Design of Phase I Clinical Trials

Lung cancer is the leading cause of both cancer and cancer-related mortality in the United States. Targeting different receptor tyrosine kinase pathways has proven to be a potent therapeutic strategy for such cancers

Premolar root and canal variation in South African Plio-Pleistocene specimens attributed to Australopithecus africanus and Paranthropus robustus

South African hominin fossils attributed to Australopithecus africanus derive from the cave sites of Makapansgat, Sterkfontein, and Taung, from deposits dated between about 2 and 3 million years ago (Ma), while Paranthropus robustus is known from Drimolen, Kromdraai, and Swartkrans, from deposits dated between about 1 and 2 Ma. Although variation in the premolar root complex has informed taxonomic and phylogenetic hypotheses for these fossil hominin species, traditionally there has been a focus on external root form, number, and position. In this study, we use microtomography to undertake the first comprehensive study of maxillary and mandibular premolar root and canal variation in Australopithecus africanus and Paranthropus robustus (n = 166 teeth) within and between the species. We also test for correlations between premolar size and root morphology as predicted under the ‘size/number continuum’ (SNC) model, which correlates increasing root number with tooth size. Our results demonstrate previously undocumented variation in these two fossil hominin species and highlight taxonomic differences in the presence and frequency of particular root types, qualitative root traits, and tooth size (measured as cervix cross-sectional area). Patterns of tooth size and canal/root number are broadly consistent with the SNC model, however statistically significant support is limited. The implications for hominin taxonomy in light of the increased variation in root morphology documented in this study are discussed

Transcriptional profiling reveals extraordinary diversity among skeletal muscle tissues

Skeletal muscle comprises a family of diverse tissues with highly specialized functions. Many acquired diseases, including HIV and COPD, affect specific muscles while sparing others. Even monogenic muscular dystrophies selectively affect certain muscle groups. These observations suggest that factors intrinsic to muscle tissues influence their resistance to disease. Nevertheless, most studies have not addressed transcriptional diversity among skeletal muscles. Here we use RNAseq to profile mRNA expression in skeletal, smooth, and cardiac muscle tissues from mice and rats. Our data set, MuscleDB, reveals extensive transcriptional diversity, with greater than 50% of transcripts differentially expressed among skeletal muscle tissues. We detect mRNA expression of hundreds of putative myokines that may underlie the endocrine functions of skeletal muscle. We identify candidate genes that may drive tissue specialization, including Smarca4, Vegfa, and Myostatin. By demonstrating the intrinsic diversity of skeletal muscles, these data provide a resource for studying the mechanisms of tissue specialization

COVID-19 randomised trial protocols : Rapid publication without barriers

Peer reviewedPublisher PD

The PyCBC search for gravitational waves from compact binary coalescence

We describe the PyCBC search for gravitational waves from compact-object binary coalescences in advanced gravitational-wave detector data. The search was used in the first Advanced LIGO observing run and unambiguously identified two black hole binary mergers, GW150914 and GW151226. At its core, the PyCBC search performs a matched-filter search for binary merger signals using a bank of gravitational-wave template waveforms. We provide a complete description of the search pipeline including the steps used to mitigate the effects of noise transients in the data, identify candidate events and measure their statistical significance. The analysis is able to measure false-alarm rates as low as one per million years, required for confident detection of signals. Using data from initial LIGO's sixth science run, we show that the new analysis reduces the background noise in the search, giving a 30% increase in sensitive volume for binary neutron star systems over previous searches.Comment: 29 pages, 7 figures, accepted by Classical and Quantum Gravit

Differential MicroRNA Expression Levels in Cutaneous Acute Graft-versus Host Disease

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for numerous haematological malignancies. However, acute graft-versus-host disease (aGvHD) is a major complication affecting 40-70% of all transplant patients, whereby the earliest and most frequent presentation is in the skin. MicroRNAs play a role in varied biological process and have been reported as potential biomarkers for aGvHD. More recently, microRNAs have received added attention as circulatory biomarkers that can be detected in biofluids. In the present study we performed global microRNA expression profiling using a discovery cohort of diagnostic cutaneous aGvHD biopsies (n=5, stage 1-3) and healthy volunteers (n=4), in order to identify a signature list of microRNAs that could be used as diagnostic biomarkers for cutaneous aGvHD. Candidate microRNAs (n=8) were then further investigated in a validation cohort of post-HSCT skin biopsies (n=17) for their association with aGvHD. Expression of miR-34a-5p (p<0.001), miR-34a-3p (p=0.013), miR-503-5p (p=0.021) and let-7c-5p (p=0.037) was elevated in cutaneous aGvHD and significantly associated with survival outcome (miR-34a-3p ROC AUC=0.93, p=0.003, Log Rank p=0.004; miR-503-5p ROC AUC=0.83 p=0.021, Log Rank p=0.003). There was no association with relapse. A statistical interaction between miR-34a-3p and miR-503-5p (p=0.016) was diagnostic for aGvHD. Expression levels of the miR-34a-5p protein target p53 were assessed in the epidermis of the skin, and an inverse correlation was identified (r2=0.44, p=0.039). Expression of the validated candidate microRNAs was also assessed at day 28 post-HSCT in the sera of transplant recipients, in order to investigate their potential as circulatory microRNA biomarkers. Expression of miR-503-5p (p=0.001), miR-34a-5p (p=0.005) and miR-34a-3p (p=0.004) were significantly elevated in the sera of patients who developed aGvHD vs. no-aGvHD (n=30) and miR-503-5p was associated with overall survival (ROC AUC=0.80, p=0.04, Log Rank p=0.041). In conclusion, this investigation reports that microRNA expression levels in clinical skin biopsies, obtained at the time of cutaneous aGvHD onset, show potential as diagnostic biomarkers for aGvHD and as predictive biomarkers for overall survival. Additionally, the same microRNAs can be detected in the circulation and show predictive association with post-HSCT outcomes

Software for Spatial Statistics

We give an overview of the papers published in this special issue on spatial statistics, of the Journal of Statistical Software. 21 papers address issues covering visualization (micromaps, links to Google Maps or Google Earth), point pattern analysis, geostatistics, analysis of areal aggregated or lattice data, spatio-temporal statistics, Bayesian spatial statistics, and Laplace approximations. We also point to earlier publications in this journal on the same topic

PENGARUH ATOPI TERHADAP TIMBULNYA DERMATITIS KONTAK PADA MAHASISWIRNPENDIDIKAN DOKTER FAKULTAS KEDOKTERAN UNIVERSITAS SYIAH KUALA RNBANDA ACEH

Dermatitis kontak adalah inflamasi non infeksi pada kulit yang disebabkan karena pemaparan dengan suatu zat tertentu yang dapat mengiritasi kulit atau menyebabkan reaksi alergi. Perempuan lebih sering mengalami dermatitis kontak dibandingkan laki-laki. Atopi merupakan salah satu faktor predisposisi timbulnya dermatitis kontak. Penelitian ini bertujuan untuk mengetahui pengaruh atopi terhadap timbulnya dermatitis kontak pada mahasiswi Pendidikan Dokter Fakultas Kedokteran Universitas Syiah Kuala Banda Aceh. Penelitian ini bersifat analitik dengan pendekatan cross sectional. Data yang digunakan adalah data primer yang diperoleh dengan wawancara langsung pada responden. Uji statistik dengan menggunakan Chi Square diperoleh nilai p yang signifikan sebesar 0,00, ini berarti p < 0,05 maka secara statistik didapatkan hubungan antara atopi dengan dermatitis kontak dengan rasio prevalensi 2,17, artinya seseorang yang menderita atopi memiliki peluang sebesar 2,17 kali untuk mengalami dermatitis kontak dibandingkan dengan orang yang tidak menderita atopi. Bahan yang paling sering menyebabkan dermatitis kontak pada mahasiswi adalah deterjen dan kosmetik. Hasil penelitian yang diperoleh ada pengaruh atopi terhadap timbulnya dermatitis kontak pada mahasiswi Pendidikan Dokter FK Unsyiah Banda Aceh, dimana mahasiswi yang menderita atopi cenderung mengalami dermatitis kontak.Kata kunci: Atopi, Dermatitis kontak Alergi, Dermatitis kontak iritanBanda Ace