Region-specific myelin differences define behavioral consequences of chronic social defeat stress in mice.

Unlabelled: Exposure to stress increases the risk of developing mood disorders. While a subset of individuals displays vulnerability to stress, others remain resilient, but the molecular basis for these behavioral differences is not well understood. Using a model of chronic social defeat stress, we identified region-specific differences in myelination between mice that displayed social avoidance behavior ('susceptible') and those who escaped the deleterious effect to stress ('resilient').

A randomised, phase II study of nintedanib or sunitinib in previously untreated patients with advanced renal cell cancer: 3-year results.

Background: This exploratory study evaluated the safety/efficacy of nintedanib or sunitinib as first-line therapy in patients with advanced renal cell carcinoma (RCC).

Methods: Ninety-six patients were randomised (2:1) to either nintedanib (200 mg twice daily) or sunitinib (50 mg kg(-1) once daily (4 weeks on treatment; 2 weeks off)). Primary endpoint was progression-free survival (PFS) at 9 months.

Phase I study of nintedanib incorporating dynamic contrast-enhanced magnetic resonance imaging in patients with advanced solid tumors.

Background: This open-label phase I dose-escalation study investigated the safety, efficacy, pharmacokinetics (PK), and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) effects of the oral angiokinase inhibitor nintedanib in patients with advanced solid tumors.

Methods: Nintedanib was administered once daily continuously, starting at 100 mg and later amended to allow evaluation of 250 mg b.i.

Phase I Study to Assess the Combination of Afatinib with Trastuzumab in Patients with Advanced or Metastatic HER2-Positive Breast Cancer.

Purpose: The HER2 mAb, trastuzumab, is a standard therapy for patients with HER2-positive breast cancer before acquired resistance. Afatinib, an irreversible, oral, small-molecule ErbB family blocker, shows clinical activity in trastuzumab-refractory HER2-positive breast cancer.

Experimental Design: This phase I study used a 3+3 dose escalation to determine the MTD of oral once-daily afatinib in combination with the recommended dose of intravenous trastuzumab (4 mg/kg week 1; 2 mg/kg/wk thereafter).

Randomized Phase II trial of nintedanib, afatinib and sequential combination in castration-resistant prostate cancer.

Aims: The aim of this article was to evaluate afatinib (BIBW 2992), an ErbB family blocker, and nintedanib (BIBF 1120), a triple angiokinase inhibitor, in castration-resistant prostate cancer patients.

Patients & Methods: Patients were randomized to receive nintedanib (250 mg twice daily), afatinib (40 mg once daily [q.d.

Randomized phase II placebo-controlled trial of maintenance therapy using the oral triple angiokinase inhibitor BIBF 1120 after chemotherapy for relapsed ovarian cancer.

Purpose: Inhibiting angiogenesis is one of the most promising avenues for new therapies for ovarian cancer. We investigated the efficacy and safety of a novel agent, BIBF 1120, a triple angiokinase inhibitor, after chemotherapy for relapsed disease.

Patients And Methods: We conducted a randomized, double-blind, controlled phase II trial in 83 patients who had just completed chemotherapy for relapsed ovarian cancer, with evidence of response, but at high risk of further early recurrence.

Broader incorporation of bioinformatics in education: opportunities and challenges.

The major opportunities for broader incorporation of bioinformatics in education can be placed into three general categories: general applicability of bioinformatics in life science and related curricula; inherent fit of bioinformatics for promoting student learning in most biology programs; and the general experience and associated comfort students have with computers and technology. Conversely, the major challenges for broader incorporation of bioinformatics in education can be placed into three general categories: required infrastructure and logistics; instructor knowledge of bioinformatics and continuing education; and the breadth of bioinformatics, and the diversity of students and educational objectives. Broader incorporation of bioinformatics at all education levels requires overcoming the challenges to using transformative computer-requiring learning activities, assisting faculty in collecting assessment data on mastery of student learning outcomes, as well as creating more faculty development opportunities that span diverse skill levels, with an emphasis placed on providing resource materials that are kept up-to-date as the field and tools change.

Phase I trial of the irreversible EGFR and HER2 kinase inhibitor BIBW 2992 in patients with advanced solid tumors.

Purpose: Preclinical data have demonstrated that BIBW 2992 is a potent irreversible inhibitor of ErbB1 (EGFR/HER1) and mutated ErbB1 receptors including the T790M variant, as well as ErbB2 (HER2). A phase I study of continuous once-daily oral BIBW 2992 was conducted to determine safety, maximum-tolerated dose, pharmacokinetics (PK), food effect, and preliminary antitumor efficacy.

Patients And Methods: Patients with advanced solid tumors were treated.

The completion of the Mammalian Gene Collection (MGC).

Since its start, the Mammalian Gene Collection (MGC) has sought to provide at least one full-protein-coding sequence cDNA clone for every human and mouse gene with a RefSeq transcript, and at least 6200 rat genes. The MGC cloning effort initially relied on random expressed sequence tag screening of cDNA libraries. Here, we summarize our recent progress using directed RT-PCR cloning and DNA synthesis.

A generalizable strategy for imaging pre-mRNA levels in living subjects using spliceosome-mediated RNA trans-splicing.

Unlabelled: Molecular imaging of gene expression is currently hindered by the lack of a generalizable platform for probe design. For any gene of interest, a probe that targets protein levels must often be generated empirically. Targeting gene expression at the level of mRNA, however, would allow probes to be built on the basis of sequence information alone.

Targeted discovery of novel human exons by comparative genomics.

A complete and accurate set of human protein-coding gene annotations is perhaps the single most important resource for genomic research after the human-genome sequence itself, yet the major gene catalogs remain incomplete and imperfect. Here we describe a genome-wide effort, carried out as part of the Mammalian Gene Collection (MGC) project, to identify human genes not yet in the gene catalogs. Our approach was to produce gene predictions by algorithms that rely on comparative sequence data but do not require direct cDNA evidence, then to test predicted novel genes by RT-PCR.

Nitrogen fixation by white lupin under phosphorus deficiency.

Background And Aims: White lupin is highly adapted to growth in a low-P environment. The objective of the present study was to evaluate whether white lupin grown under P-stress has adaptations in nodulation and N2 fixation that facilitate continued functioning.

Methods: Nodulated plants were grown in silica sand supplied with N-free nutrient solution containing 0 to 0.

From genome to proteome: developing expression clone resources for the human genome.

cDNA clones have long been valuable reagents for studying the structure and function of proteins. With recent access to the entire human genome sequence, it has become possible and highly productive to compare the sequences of mRNAs to their genes, in order to validate the sequences and protein-coding annotations of each (1,2). Thus, well-characterized collections of human cDNAs are now playing an essential role in defining the structure and function of human genes and proteins.

Concerted assembly and cloning of multiple DNA segments using in vitro site-specific recombination: functional analysis of multi-segment expression clones.

The ability to clone and manipulate DNA segments is central to molecular methods that enable expression, screening, and functional characterization of genes, proteins, and regulatory elements. We previously described the development of a novel technology that utilizes in vitro site-specific recombination to provide a robust and flexible platform for high-throughput cloning and transfer of DNA segments. By using an expanded repertoire of recombination sites with unique specificities, we have extended the technology to enable the high-efficiency in vitro assembly and concerted cloning of multiple DNA segments into a vector backbone in a predefined order, orientation, and reading frame.

Application of combined immunofluorescence and fluorescence in situ hybridization on paraffin-embedded sections to characterize T-cell lymphoma with EBV-infected B-cell blasts.

Combined immunofluorescence (IF) and fluorescence in situ hybridization (FISH) on formalin-fixed, paraffin-embedded tissue sections were used to examine lymph node tissue from two patients diagnosed with T-cell lymphoma with Epstein-Barr virus (EBV)-infected B-cell blasts. The majority of cells within the samples comprised T-cells staining positively for CD3. In addition, both patients had a population of large pleiomorphic cells that were positive for the B-cell marker CD20 and for EBV LMP-1.

Expression of UDP-glucose dehydrogenase reduces cell-wall polysaccharide concentration and increases xylose content in alfalfa stems.

The primary cell-wall matrix of most higher plants is composed of large amounts of uronic acids, primarily D-galacturonic acid residues in the backbone of pectic polysaccharides. Uridine diphosphate (UDP)-glucose dehydrogenase is a key enzyme in the biosynthesis of uronic acids. We produced transgenic alfalfa (Medicago sativa) plants expressing a soybean UDP-glucose dehydrogenase cDNA under the control of two promoters active in alfalfa vascular tissues.

Whole genome sequence comparisons and "full-length" cDNA sequences: a combined approach to evaluate and improve Arabidopsis genome annotation.

To evaluate the existing annotation of the Arabidopsis genome further, we generated a collection of evolutionary conserved regions (ecores) between Arabidopsis and rice. The ecore analysis provides evidence that the gene catalog of Arabidopsis is not yet complete, and that a number of these annotations require re-examination. To improve the Arabidopsis genome annotation further, we used a novel "full-length" enriched cDNA collection prepared from several tissues.

Influence of transition diets on occurrence of subclinical laminitis in Holstein dairy cows.

Pre- and postpartum diets varying in energy and fiber were studied for effects on subclinical laminitis in Holstein cows. Also, ruminal acidosis was examined relative to sole hemorrhages and ulcers. Cows (n = 98) were assigned to a 2 x 2 factorial arrangement of treatments in a randomized complete block.

Using time-lapse video photography to assess dairy cattle lying behavior in a free-stall barn.

The objectives of this observational study were to use time-lapse video photography to document dairy cow behavioral patterns, examine factors affecting lying behavior, and to develop guidelines for visual assessment of free-stall usage during summer conditions in a high producing dairy. Four video cameras were placed in a free-stall pen containing 144 stalls and 129 high producing cows. The videos were recorded over a 6-d period in July 1999 and then were reviewed using 60-min scan sampling techniques.

Thermal plasticity of skeletal muscle phenotype in ectothermic vertebrates and its significance for locomotory behaviour.

Seasonal cooling can modify the thermal preferenda of ectothermic vertebrates and elicit a variety of physiological responses ranging from winter dormancy to an acclimation response that partially compensates for the effects of low temperature on activity. Partial compensation of activity levels is particularly common in aquatic species for which seasonal temperature changes provide a stable cue for initiating the response. Thermal plasticity of locomotory performance has evolved independently on numerous occasions, and there is considerable phylogenetic diversity with respect to the mechanisms at the physiological and molecular levels.

Purification, crystallization and preliminary structural studies of dTDP-4-keto-6-deoxy-glucose-5-epimerase (EvaD) from Amycolatopsis orientalis, the fourth enzyme in the dTDP-L-epivancosamine biosynthetic pathway.

The vancomycin class of antibiotics is regarded as the last line of defence against Gram-positive bacteria. The compounds used clinically are very complex organic molecules and are made by fermentation. The biosynthesis of these is complex and fascinating.

Determining patterns of motor recruitment during locomotion.

Motor units are the functional units of muscle contraction in vertebrates. Each motor unit comprises muscle fibres of a particular fibre type and can be considered as fast or slow depending on its fibre-type composition. Motor units are typically recruited in a set order, from slow to fast, in response to the force requirements from the muscle.

Embryonic temperature and the relative timing of muscle-specific genes during development in herring (Clupea harengus L.).

Temperature influences many aspects of muscle development in herring (Clupea harengus). In Clyde herring, myofibril synthesis occurred later with respect to somite stage in embryos reared at 5 degrees C compared with 12 degrees C. The aim of the present study was to test the hypothesis that the relative timing of expression of myogenic regulatory factors (MRFs) and myosin heavy chain (MyHC) transcripts changes with developmental temperature.

Use of phage antibodies to distinguish closely related species of protozoan parasites.

Acanthamoeba are typically identified in the laboratory using culture and microscopic observation. In this paper we describe the isolation and specificity of antibody fragments that can be used for the identification of Acanthamoeba. A phage library expressing a large repertoire (approx.