222,868 research outputs found
Weed Control with Straw Residues in Occasional Direct Seeding of Faba Bean (Vicia faba sp.) in Organic Agriculture
In order to gain momentum in the consolidation process of no-tillage systems in Europe’s Organic Agriculture, occasional direct seeding (DS) of faba bean (FAB) into a mulch layer of residues from precrop oats should be scrutinized. In contrast to non-legumes, grain legumes do not depend on soil-borne nitrogen due to their ability to fix nitrogen symbiotically. Concerning weed infestation, straw residues left by precrops may at least physically suppress weeds. In order to prove this hypothesis, two field experiments were carried out in 2009 at two sites in the lower Rhineland region, Germany. DS treatments were combined with 0, 4, and 6 t ha-1 of straw residues. Mouldboard ploughing (MP) combined with conventional seedbed preparation was used as control. Compared to the DS treatment without straw residue (0 t ha-1), DS treatments with straw residues (4 and 6 t ha-1, resp.) resulted in significantly lower weed density (70 and 84 % resp.). Neither differences were observed in both shoot dry matter of FAB and weeds for DS with straw residues compared with MP, nor for the grain yields of FAB. We conclude that occasional DS of FAB in OA is successful to reduce annual weeds sufficiently and may not lead to reduced FAB yields
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Prompting Fab Yeast Surface Display Efficiency by ER Retention and Molecular Chaperon Co-expression.
For antibody discovery and engineering, yeast surface display (YSD) of antigen-binding fragments (Fabs) and coupled fluorescence activated cell sorting (FACS) provide intact paratopic conformations and quantitative analysis at the monoclonal level, and thus holding great promises for numerous applications. Using anti-TNFα mAbs Infliximab, Adalimumab, and its variants as model Fabs, this study systematically characterized complementary approaches for the optimization of Fab YSD. Results suggested that by using divergent promoter GAL1-GAL10 and endoplasmic reticulum (ER) signal peptides for co-expression of light chain and heavy chain-Aga2 fusion, assembled Fabs were functionally displayed on yeast cell surface with sigmoidal binding responses toward TNFα. Co-expression of a Hsp70 family molecular chaperone Kar2p and/or protein-disulfide isomerase (Pdi1p) significantly improved efficiency of functional display (defined as the ratio of cells displaying functional Fab over cells displaying assembled Fab). Moreover, fusing ER retention sequences (ERSs) with light chain also enhanced Fab display quality at the expense of display quantity, and the degree of improvements was correlated with the strength of ERSs and was more significant for Infliximab than Adalimumab. The feasibility of affinity maturation was further demonstrated by isolating a high affinity Fab clone from 1:103 or 1:105 spiked libraries
Self-tuning and the derivation of the Fab Four
We have recently proposed a special class of scalar tensor theories known as
the Fab Four. These arose from attempts to analyse the cosmological constant
problem within the context of Horndeski's most general scalar tensor theory.
The Fab Four together give rise to a model of self-tuning, with the relevant
solutions evading Weinberg's no-go theorem by relaxing the condition of
Poincare invariance in the scalar sector. The Fab Four are made up of four
geometric terms in the action with each term containing a free potential
function of the scalar field. In this paper we rigorously derive this model
from the general model of Horndeski, proving that the Fab Four represents the
only classical scalar tensor theory of this type that has any hope of tackling
the cosmological constant problem. We present the full equations of motion for
this theory, and give an heuristic argument to suggest that one might be able
to keep radiative corrections under control. We also give the Fab Four in terms
of the potentials presented in Deffayet et al's version of Horndeski.Comment: 25 pages, 1 figur
Selective function-blocking monoclonal human antibody highlights the important role of membrane type-1 matrix metalloproteinase (MT1-MMP) in metastasis.
The invasion-promoting MT1-MMP is a cell surface-associated collagenase with a plethora of critical cellular functions. There is a consensus that MT1-MMP is a key protease in aberrant pericellular proteolysis in migrating cancer cells and, accordingly, a promising drug target. Because of high homology in the MMP family and a limited success in the design of selective small-molecule inhibitors, it became evident that the inhibitor specificity is required for selective and successful MT1-MMP therapies. Using the human Fab antibody library (over 1.25×109 individual variants) that exhibited the extended, 23-27 residue long, VH CDR-H3 segments, we isolated a panel of the inhibitory antibody fragments, from which the 3A2 Fab outperformed others as a specific and potent, low nanomolar range, inhibitor of MT1-MMP. Here, we report the in-depth characterization of the 3A2 antibody. Our multiple in vitro and cell-based tests and assays, and extensive structural modeling of the antibody/protease interactions suggest that the antibody epitope involves the residues proximal to the protease catalytic site and that, in contrast with tissue inhibitor-2 of MMPs (TIMP-2), the 3A2 Fab inactivates the protease functionality by binding to the catalytic domain outside the active site cavity. In agreement with the studies in metastasis by others, our animal studies in acute pulmonary melanoma metastasis support a key role of MT1-MMP in metastatic process. Conversely, the selective anti-MT1-MMP monotherapy significantly alleviated melanoma metastatic burden. It is likely that further affinity maturation of the 3A2 Fab will result in the lead inhibitor and a proof-of-concept for MT1-MMP targeting in metastatic cancers
Functional biodiversity to improve pest control in organic cropping systems
A sustainable use of functional agrobiodiversity (FAB) providing habitats with suitable floral resources is needed to conserve and improve pest control by natural enemies in organic cropping and other low-input systems. We present an overview on our activities identifying appropriate flowering plants in relation to the antagonists-pest complex and quantifying benefits and limits in lab- and field tests. We have focussed on the control of apple-aphids and cabbage lepidopterean pests in two organic cropping systems. We can show that tailoring the flowering strips to the needs of specific natural enemies within a cropping system is a key issue for successful application of FAB. We found plants as Fagopyrum esculentum, Centaurea cyanus and Vicia sativa enhancing target parasitoids in cabbage, and we found Daucus carota, Carvum carvi, Pastinca sativa, Vicia sepium as promising plants in apple orchards. A successful on-farm application of FAB using flowering strips and companion plants is challenging and needs further analyses of its impact on pest control, considering different scales as plot, farm and landscape
Crystal Structure of Human TWEAK in Complex with the Fab Fragment of a Neutralizing Antibody Reveals Insights into Receptor Binding.
The tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a multifunctional cytokine playing a key role in tissue regeneration and remodeling. Dysregulation of TWEAK signaling is involved in various pathological processes like autoimmune diseases and cancer. The unique interaction with its cognate receptor Fn14 makes both ligand and receptor promising targets for novel therapeutics. To gain insights into this important signaling pathway, we determined the structure of soluble human TWEAK in complex with the Fab fragment of an antibody selected for inhibition of receptor binding. In the crystallized complex TWEAK is bound by three Fab fragments of the neutralizing antibody. Homology modeling shows that Fab binding overlaps with the putative Fn14 binding site of TWEAK. Docking of the Fn14 cysteine rich domain (CRD) to that site generates a highly complementary interface with perfectly opposing charged and hydrophobic residues. Taken together the presented structure provides new insights into the biology of TWEAK and the TWEAK/Fn14 pathway, which will help to optimize the therapeutic strategy for treatment of related cancer types and autoimmune diseases
Association between depressive symptom clusters and food attentional bias
Background
The mechanisms underlying the depression-obesity relationship are unclear. Food attentional bias (FAB) represents one candidate mechanism that has not been examined. We evaluated the hypothesis that greater depressive symptoms are associated with increased FAB.
Method
Participants were 89 normal weight or overweight adults (mean age = 21.2 ± 4.0 years, 53% female, 33% non-white, mean body mass index in kg/m2 = 21.9 ± 1.8 for normal weight; 27.2 ± 1.5 for overweight). Total, somatic, and cognitive-affective depressive symptom scores were computed from the Patient Health Questionnaire-8 (PHQ-8). FAB scores were calculated using reaction times (RT) and eye-tracking (ET) direction and duration measures for a food visual probe task. Age, gender, race/ethnicity, and body fat percent were covariates.
Results
Only PHQ-8 somatic symptoms were positively associated with RT-measured FAB (β = 0.23, p = .04). The relationship between somatic symptoms and ET direction (β = 0.18, p = .17) and duration (β = 0.23, p = .08) FAB indices were of similar magnitude but were not significant. Somatic symptoms accounted for 5% of the variance in RT-measured FAB. PHQ-8 total and cognitive-affective symptoms were unrelated to all FAB indices (ps ≥ 0.09).
Conclusions
Only greater somatic symptoms of depression were linked to food attentional bias as measured using reaction time. Well-powered prospective studies should examine whether this bias replicates, particularly for eye-tracking measures, and whether it partially mediates the depression-to-obesity relationship
Spherical Cows in the Sky with Fab Four
We explore spherically symmetric static solutions in a subclass of unitary
scalar-tensor theories of gravity, called the `Fab Four' models. The weak field
large distance solutions may be phenomenologically viable, but only if the
Gauss-Bonnet term is negligible. Only in this limit will the Vainshtein
mechanism work consistently. Further, classical constraints and unitarity
bounds constrain the models quite tightly. Nevertheless, in the limits where
the range of individual terms at large scales is respectively Kinetic Braiding,
Horndeski, and Gauss-Bonnet, the horizon scale effects may occur while the
theory satisfies Solar system constraints and, marginally, unitarity bounds. On
the other hand, to bring the cutoff down to below a millimeter constrains all
the couplings scales such that `Fab Fours' can't be heard outside of the Solar
system.Comment: 15 pages, LaTe
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