Exposing the human nude phenotype [4]

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Suppression of innate and adaptive B cell activation pathways by antibody coengagement of FcgammaRIIb and CD19.

The Fc receptor (FcgammaRIIb) inhibits B cell responses when coengaged with B cell receptor (BCR), and has become a target for new autoimmune disease therapeutics. For example, BCR and FcgammaRIIb coengagement via the Fc-engineered anti-CD19 XmAb5871 suppresses humoral immune responses. We now assess effects of XmAb5871 on other activation pathways, including the pathogen-associated molecular pattern receptor, TLR9. Since TLR9 signaling is implicated in autoimmune diseases, we asked if XmAb5871 could inhibit TLR9 costimulation. We show that XmAb5871 decreases ERK and AKT activation, cell proliferation, cytokine, and IgG production induced by BCR and/or TLR9 signals. XmAb5871 also inhibited differentiation of citrullinated peptide-specific plasma cells from rheumatoid arthritis patients. XmAb5871 may therefore have potential to suppress pathogenic B cells in autoimmune diseases

Typing Late Prehistoric Cows and Bulls—Osteology and Genetics of Cattle at the Eketorp Ringfort on the Öland Island in Sweden

Human management of livestock and the presence of different breeds have been discussed in archaeozoology and animal breeding. Traditionally osteometrics has been the main tool in addressing these questions. We combine osteometrics with molecular sex identifications of 104 of 340 morphometrically analysed bones in order to investigate the use of cattle at the Eketorp ringfort on the Öland island in Sweden. The fort is dated to 300–1220/50 A.D., revealing three different building phases. In order to investigate specific patterns and shifts through time in the use of cattle the genetic data is evaluated in relation to osteometric patterns and occurrence of pathologies on cattle metapodia. Males were genotyped for a Y-chromosomal SNP in UTY19 that separates the two major haplogroups, Y1 and Y2, in taurine cattle. A subset of the samples were also genotyped for one SNP involved in coat coloration (MC1R), one SNP putatively involved in resistance to cattle plague (TLR4), and one SNP in intron 5 of the IGF-1 gene that has been associated to size and reproduction

Adding value to under-utilised Irish fish roe: a physico-chemical and sensory comparison of cured Irish pollock (Pollachius pollachius) roe with commercial mullet (Mugil cephalus) and cod (Gadus morhua) products

peer reviewedIrish marine fish roe is generally discarded at sea or processed as low value-added fishmeal and not utilised as nutritious seafood ingredients. Locally sourced pollock roes were salted, air-dried (Mediterranean-style) and compared to similar commercial mullet and cod products for: weight; moisture content; pH; instrumental texture and colour; and sensory attributes. Raw pollock roes averaged 105 g (n = 25). Roes lost on average 3.1% moisture (w/w) after a 2-h salting period and 48.8% weight reduction was observed after an average 105 h air-drying time. The moisture content of pollock was not significantly different to commercial products. Average pH for pollock, mullet and cod products was 5.9, 5.4 and 5.7, respectively (P < 0.05). Pollock and mullet had similar hardness, but cod was significantly harder than both, when measured instrumentally. Total colour difference (ΔE*) between the surface of pollock and cod, and that of pollock and mullet was 7.5 and 3.0, respectively. Sensory assessment of sliced and powdered products, using 9-point hedonic and 5-point just-about-right (JAR) scales, was conducted with 38 consumers. Pollock received the highest scores for overall liking and intention to purchase compared to commercial mullet and cod products, averaging 5.6, 5.6 and 4.9, respectively, for sliced roe products, and 6.3, 5.3 and 6.1 for powdered products. Penalty analysis of JAR showed “overall liking” was impacted by the flavour being “too fishy”. In conclusion, pollock had similar characteristics and acceptable sensory attributes compared to commercial products presenting opportunities to expand the range of value-added roe products (e.g., trout, salmon) available, while also contributing to waste reduction

Reduced costs with bisoprolol treatment for heart failure - An economic analysis of the second Cardiac Insufficiency Bisoprolol Study (CIBIS-II)

Background Beta-blockers, used as an adjunctive to diuretics, digoxin and angiotensin converting enzyme inhibitors, improve survival in chronic heart failure. We report a prospectively planned economic analysis of the cost of adjunctive beta-blocker therapy in the second Cardiac Insufficiency BIsoprolol Study (CIBIS II). Methods Resource utilization data (drug therapy, number of hospital admissions, length of hospital stay, ward type) were collected prospectively in all patients in CIBIS . These data were used to determine the additional direct costs incurred, and savings made, with bisoprolol therapy. As well as the cost of the drug, additional costs related to bisoprolol therapy were added to cover the supervision of treatment initiation and titration (four outpatient clinic/office visits). Per them (hospital bed day) costings were carried out for France, Germany and the U.K. Diagnosis related group costings were performed for France and the U.K. Our analyses took the perspective of a third party payer in France and Germany and the National Health Service in the U.K. Results Overall, fewer patients were hospitalized in the bisoprolol group, there were fewer hospital admissions perpatient hospitalized, fewer hospital admissions overall, fewer days spent in hospital and fewer days spent in the most expensive type of ward. As a consequence the cost of care in the bisoprolol group was 5-10% less in all three countries, in the per them analysis, even taking into account the cost of bisoprolol and the extra initiation/up-titration visits. The cost per patient treated in the placebo and bisoprolol groups was FF35 009 vs FF31 762 in France, DM11 563 vs DM10 784 in Germany and pound 4987 vs pound 4722 in the U.K. The diagnosis related group analysis gave similar results. Interpretation Not only did bisoprolol increase survival and reduce hospital admissions in CIBIS II, it also cut the cost of care in so doing. This `win-win' situation of positive health benefits associated with cost savings is Favourable from the point of view of both the patient and health care systems. These findings add further support for the use of beta-blockers in chronic heart failure

Maternal Germline Mosaicism in Dominant Dystrophic Epidermolysis Bullosa

3 páginas, 1 figura.Here, we report a family with one child affected by mild DEB. At birth, blistering and denuded areas were present together with the syndactyly of the second and third toes. By the age of 11 mo, blistering was significantly reduced but the blisters healed with hyperpigmented and hypopigmented scars and milia. Both parents and an older sibling were clinically unaffected, and there was no family history of consanguinity or of a blistering disorder or skin fragility.Peer reviewe