Germinal Center B Cells Regulate Their Capability to Present Antigen by Modulation of HLA-DO

Peptide acquisition by MHC class II molecules is catalyzed by HLA-DM (DM). In B cells, HLA-DO (DO) inhibits or modifies the peptide exchange activity of DM. We show here that DO protein levels are modulated during B cell differentiation. Remarkably, germinal center (GC) B cells, which have low levels of DO relative to naive and memory B cells, are shown to have enhanced antigen presentation capabilities. DM protein levels also were somewhat reduced in GC B cells; however, the ratio of DM to DO in GC B cells was substantially increased, resulting in more free DM in GC B cells. We conclude that modulation of DM and DO in distinct stages of B cell differentiation represents a mechanism by which B cells regulate their capacity to function as antigen-presenting cells. Efficient antigen presentation in GC B cells would promote GC B cell–T cell interactions that are essential for B cells to survive positive selection in the GC

Production of tocotrienols in seeds of cotton (Gossypium hirsutum L.) enhances oxidative stability and offers nutraceutical potential

Upland cotton (Gossypium hirsutum L.) is an economically important multi-purpose crop cultivated globally for fibre, seed oil and protein. Cottonseed oil also is naturally rich in vitamin E components (collectively known as tocochromanols), with a- and c-tocopherols comprising nearly all of the vitamin E components. By contrast, cottonseeds have little or no tocotrienols, tocochromanols with a wide range of health benefits. Here, we generated transgenic cotton lines expressing the barley (Hordeum vulgare) homogentisate geranylgeranyl transferase coding sequence under the control of the Brassica napus seed-specific promoter, napin. Transgenic cottonseeds had ~twofold to threefold increases in the accumulation of total vitamin E (tocopherols + tocotrienols), with more than 60% c-tocotrienol. Matrix assisted laser desorption ionization-mass spectrometry imaging showed that c-tocotrienol was localized throughout the transgenic embryos. In contrast, the native tocopherols were distributed unequally in both transgenic and non-transgenic embryos. a- Tocopherol was restricted mostly to cotyledon tissues and c-tocopherol was more enriched in the embryonic axis tissues. Production of tocotrienols in cotton embryos had no negative impact on plant performance or yield of other important seed constituents including fibre, oil and protein. Advanced generations of two transgenic events were field grown, and extracts of transgenic seeds showed increased antioxidant activity relative to extracts from non-transgenic seeds. Furthermore, refined cottonseed oil from the two transgenic events showed 30% improvement in oxidative stability relative to the non-transgenic cottonseed oil. Taken together, these materials may provide new opportunities for cottonseed co-products with enhanced vitamin E profile for improved shelf life and nutrition

Alzheimer’s disease progression by geographical region in a clinical trial setting

INTRODUCTION: To facilitate enrollment and meet local registration requirements, sponsors have increasingly implemented multi-national Alzheimer's disease (AD) studies. Geographic regions vary on many dimensions that may affect disease progression or its measurement. To aid researchers designing and implementing Phase 3 AD trials, we assessed disease progression across geographic regions using placebo data from four large, multi-national clinical trials of investigational compounds developed to target AD pathophysiology. METHODS: Four similarly-designed 76 to 80 week, randomized, double-blind placebo-controlled trials with nearly identical entry criteria enrolled patients aged ≥55 years with mild or moderate NINCDS/ADRDA probable AD. Descriptive analyses were performed for observed mean score and observed mean change in score from baseline at each scheduled visit. Data included in the analyses were pooled from the intent-to-treat placebo-assigned overall (mild and moderate) AD dementia populations from all four studies. Disease progression was assessed as change from baseline for each of 5 scales - the AD Assessment Scale-cognitive subscale (ADAS-cog11), the AD Cooperative Study- Activities of Daily Living Scale (ADCS-ADL), Mini-Mental State Examination (MMSE), the Clinical Dementia Rating scored by the sum of boxes method (CDR-SB), and the Neuropsychiatric Inventory (NPI). RESULTS: Regions were heterogeneous at baseline. At baseline, disease severity as measured by ADAS-cog11, ADCS-ADL, and CDR-SB was numerically worse for Eastern Europe/Russia compared with other regions. Of all regional populations, Eastern Europe/Russia showed the greatest cognitive and functional decline from baseline; Japan, Asia and/or S. America/Mexico showed the least cognitive and functional decline. CONCLUSIONS: These data suggest that in multi-national clinical trials, AD progression or its measurement may differ across geographic regions; this may be in part due to heterogeneity across populations at baseline. The observed differences in AD progression between outcome measures across geographic regions may generalize to 'real-world' clinic populations, where heterogeneity is the norm

Superconductivity in Cu_xTiSe_2

Charge density waves (CDWs) are periodic modulations of the conduction electron density in solids. They are collective states that arise from intrinsic instabilities often present in low dimensional electronic systems. The layered dichalcogenides are the most well-studied examples, with TiSe_2 one of the first CDW-bearing materials known. The competition between CDW and superconducting collective electronic states at low temperatures has long been held and explored, and yet no chemical system has been previously reported where finely controlled chemical tuning allows this competition to be studied in detail. Here we report how, upon controlled intercalation of TiSe_2 with Cu to yield Cu_xTiSe_2, the CDW transition is continuously suppressed, and a new superconducting state emerges near x = 0.04, with a maximum T_c of 4.15 K found at x = 0.08. Cu_xTiSe_2 thus provides the first opportunity to study the CDW to Superconductivity transition in detail through an easily-controllable chemical parameter, and will provide new insights into the behavior of correlated electron systems.Comment: Accepted to Nature Physic

Analyses of zebrafish and Xenopus oocyte maturation reveal conserved and diverged features of translational regulation of maternal cyclin B1 mRNA

<p>Abstract</p> <p>Background</p> <p>Vertebrate development relies on the regulated translation of stored maternal mRNAs, but how these regulatory mechanisms may have evolved to control translational efficiency of individual mRNAs is poorly understood. We compared the translational regulation and polyadenylation of the cyclin B1 mRNA during zebrafish and <it>Xenopus </it>oocyte maturation. Polyadenylation and translational activation of cyclin B1 mRNA is well characterized during <it>Xenopus </it>oocyte maturation. Specifically, <it>Xenopus </it>cyclin B1 mRNA is polyadenylated and translationally activated during oocyte maturation by proteins that recognize the conserved AAUAAA hexanucleotide and U-rich Cytoplasmic Polyadenylation Elements (CPEs) within cyclin B1 mRNA's 3'<b>U</b>n<b>T</b>ranslated <b>R</b>egion (3'<b>UTR</b>).</p> <p>Results</p> <p>The zebrafish cyclin B1 mRNA was polyadenylated during zebrafish oocyte maturation. Furthermore, the zebrafish cyclin B1 mRNA's 3'UTR was sufficient to stimulate translation of a reporter mRNA during zebrafish oocyte maturation. This stimulation required both AAUAAA and U-rich CPE-like sequences. However, in contrast to AAUAAA, the positions and sequences of the functionally defined CPEs were poorly conserved between <it>Xenopus </it>and zebrafish cyclin B1 mRNA 3'UTRs. To determine whether these differences were relevant to translation efficiency, we analyzed the translational activity of reporter mRNAs containing either the zebrafish or <it>Xenopus </it>cyclin B1 mRNA 3'UTRs during both zebrafish and <it>Xenopus </it>oocyte maturation. The zebrafish cyclin B1 3'UTR was quantitatively less effective at stimulating polyadenylation and translation compared to the <it>Xenopus </it>cyclin B1 3'UTR during both zebrafish and <it>Xenopus </it>oocyte maturation.</p> <p>Conclusion</p> <p>Although the factors that regulate translation of maternal mRNAs are highly conserved, the target sequences and overall sequence architecture within the 3'UTR of the cyclin B1 mRNA have diverged to affect translational efficiency, perhaps to optimize levels of cyclin B1 protein required by these different species during their earliest embryonic cell divisions.</p

Learn before Lecture: A Strategy That Improves Learning Outcomes in a Large Introductory Biology Class

Actively engaging students in lecture has been shown to increase learning gains. To create time for active learning without displacing content we used two strategies for introducing material before class in a large introductory biology course. Four to five slides from 2007/8 were removed from each of three lectures in 2009 and the information introduced in preclass worksheets or narrated PowerPoint videos. In class, time created by shifting lecture material to learn before lecture (LBL) assignments was used to engage students in application of their new knowledge. Learning was evaluated by comparing student performance in 2009 versus 2007/8 on LBL-related question pairs, matched by level and format. The percentage of students who correctly answered five of six LBL-related exam questions was significantly higher (p < 0.001) in 2009 versus 2007/8. The mean increase in performance was 21% across the six LBL-related questions compared with <3% on all non-LBL exam questions. The worksheet and video LBL formats were equally effective based on a cross-over experimental design. These results demonstrate that LBLs combined with interactive exercises can be implemented incrementally and result in significant increases in learning gains in large introductory biology classes

Learning physics in context: a study of student learning about electricity and magnetism

This paper re-centres the discussion of student learning in physics to focus on context. In order to do so, a theoretically-motivated understanding of context is developed. Given a well-defined notion of context, data from a novel university class in electricity and magnetism are analyzed to demonstrate the central and inextricable role of context in student learning. This work sits within a broader effort to create and analyze environments which support student learning in the sciencesComment: 36 pages, 4 Figure

Evolution of the grass leaf by primordium extension and petiole-lamina remodeling

The sheathing leaf found in grasses and other monocots is an evolutionary innovation, yet its origin has been a subject of long-standing debate. Here, we revisit the problem in the light of developmental genetics and computational modeling. We show that the sheathing leaf likely arose through WOX-gene-dependent extension of a primordial zone straddling concentric domains around the shoot apex. Patterned growth within this zone, oriented by two polarity fields, accounts for wild-type, mutant and mosaic grass leaf development, whereas zone contraction and growth remodeling accounts for eudicot leaf development. In contrast to the prevailing view, our results suggest that the sheath derives from petiole, whereas the blade derives from the lamina of the eudicot leaf, consistent with homologies proposed in the 19th century

Non-Centrosymmetric Heavy-Fermion Superconductors

In this chapter we discuss the physical properties of a particular family of non-centrosymmetric superconductors belonging to the class heavy-fermion compounds. This group includes the ferromagnet UIr and the antiferromagnets CeRhSi3, CeIrSi3, CeCoGe3, CeIrGe3 and CePt3Si, of which all but CePt3Si become superconducting only under pressure. Each of these superconductors has intriguing and interesting properties. We first analyze CePt3Si, then review CeRhSi3, CeIrSi3, CeCoGe3 and CeIrGe3, which are very similar to each other in their magnetic and electrical properties, and finally discuss UIr. For each material we discuss the crystal structure, magnetic order, occurrence of superconductivity, phase diagram, characteristic parameters, superconducting properties and pairing states. We present an overview of the similarities and differences between all these six compounds at the end.Comment: To appear in "Non-Centrosymmetric Superconductors: Introduction and Overview", Lecture Notes in Physics 847, edited by E. Bauer and M. Sigrist (Springer-Verlag, Berlin Heidelberg, 2012) Chap. 2, pp. 35-7