Improved bone defect healing by a superagonistic GDF5 variant derived from a patient with multiple synostoses syndrome

Multiple synostoses syndrome 2 (SYNS2) is a rare genetic disease characterized by multiple fusions of the joints of the extremities, like phalangeal joints, carpal and tarsal joints or the knee and elbows. SYNS2 is caused by point mutations in the Growth and Differentiation Factor 5 (GDF5), which plays an essential role during skeletal development and regeneration. We selected one of the SYNS2-causing GDF5 mutations, p.N445T, which is known to destabilize the interaction with the Bone Morphogenetic Protein (BMP) antagonist NOGGIN (NOG), in order to generate the superagonistic GDF5 variant GDF5(N445T). In this study, we tested its capacity to support regeneration in a rat critical-sized defect model in vivo. MicroCT and histological analyses indicate that GDF5(N445T)-treated defects show faster and more efficient healing compared to GDF5 wild type (GDF5(wt))-treated defects. Microarray-based gene expression and quantitative PCR analyses from callus tissue point to a specific acceleration of the early phases of bone healing, comprising the inflammation and chondrogenesis phase. These results support the concept that disease-deduced growth factor variants are promising lead structures for novel therapeutics with improved clinical activities

Seasonal forage quality of rangelands across Kansas

The K-State Research and Extension Forage Task Force surveyed Kansas rangelands during the course of seasonal changes to enable producers and managers to better estimate the feed value of their pasture forage during particular times of the year. Kansas’ two distinct rangeland vegetation types, shortgrass and tallgrass prairie, were evaluated. Forage samples were collected monthly from two rangeland sites in each of 10 Kansas counties. Tallgrass vegetation was lowest in acid detergent fiber (ADF) and greatest in crude protein (CP) from May to July, and rapidly increased in ADF and declined in CP the rest of the season. Shortgrass vegetation was also lower in ADF and greater in CP from May to July, but changed less from early summer to the winter than did tallgrass vegetation. Degradable intake protein (DIP) was greatest for tallgrass vegetation in May. Otherwise DIP was similar between tallgrass and shortgrass except in February and March when shortgrass had greater DIP. DIP was greatest in May and June for both vegetation types and gradually declined from June to December. Undegradable intake protein (UIP) values were greater for tallgrass vegetation than for shortgrass vegetation from May through July, but all other months were similar. Seasonal forage quality is different between and within rangeland vegetation types, and identification of dominant vegetation is a key determinant in choosing appropriate animal nutritional management strategies

Discrete R-symmetries and Anomaly Universality in Heterotic Orbifolds

We study discrete R-symmetries, which appear in 4D low energy effective field theory derived from hetetoric orbifold models. We derive the R-symmetries directly from geometrical symmetries of orbifolds. In particular, we obtain the corresponding R-charges by requiring that the couplings be invariant under these symmetries. This allows for a more general treatment than the explicit computations of correlation functions made previously by the authors, including models with discrete Wilson lines, and orbifold symmetries beyond plane-by-plane rotational invariance. Surprisingly, for the cases covered by earlier explicit computations, the R-charges differ from the previous result. We study the anomalies associated with these R-symmetries, and comment on the results.Comment: 21 pages, 2 figures. Minor changes, typos corrected. Matches JHEP published versio

Forming conjectures within a spreadsheet environment

This paper is concerned with the use of spreadsheets within mathematical investigational tasks. Considering the learning of both children and pre-service teaching students, it examines how mathematical phenomena can be seen as a function of the pedagogical media through which they are encountered. In particular, it shows how pedagogical apparatus influence patterns of social interaction, and how this interaction shapes the mathematical ideas that are engaged with. Notions of conjecture, along with the particular faculty of the spreadsheet setting, are considered with regard to the facilitation of mathematical thinking. Employing an interpretive perspective, a key focus is on how alternative pedagogical media and associated discursive networks influence the way that students form and test informal conjectures