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Reversible Michael additions: Covalent inhibitors and prodrugs.

Covalent inhibition is an efficient molecular mechanism for inhibiting enzymes or modulating the function of proteins and is found in the action of many drugs and biologically active natural products. However, it is has been less appreciated that the formation of covalent bonds can be reversible or irreversible. This review focuses on biologically active compounds that are Michael acceptors and ho

A novel role for constitutively expressed epithelial-derived chemokines as antibacterial peptides in the intestinal mucosa.

Intestinal-derived chemokines have a central role in orchestrating immune cell influx into the normal and inflamed intestine. Here, we identify the chemokine CCL6 as one of the most abundant chemokines constitutively expressed by both murine small intestinal and colonic epithelial cells. CCL6 protein localized to crypt epithelial cells, was detected in the gut lumen and reached high concentrations

Exhaustion measured by the SF-36 vitality scale is associated with a flattened diurnal cortisol profile.

The possible association between stress-related exhaustion and reduced activity in the hypothalamo-pituitary-adrenal (HPA) axis is increasingly in focus. The aim of the present study was to examine whether exhaustion measured in a non-patient population is associated with alterations in diurnal cortisol profile. The study population included 78 working individuals. The study group was dichotomised

IgG glycan hydrolysis by a bacterial enzyme as a therapy against autoimmune conditions.

EndoS from Streptococcus pyogenes efficiently hydrolyzes the functionally important and conserved N-linked glycan of IgG in human blood. Repeated i.v. administration of EndoS in rabbits completely hydrolyzes the glycans of the whole IgG pool, despite the generation of anti-EndoS antibodies. EndoS administration had no apparent effects on the health of the animals. EndoS hydrolysis of the IgG glyca

Catheter-directed foam sclerotherapy treatment of saphenous vein incompetence.

Background: The aim of this study is to report the short-term results of catheter-directed foam sclerotherapy (CDFS) in the treatment of axial saphenous vein incompetence. Patients and methods: Data of all patients undergoing CDFS for symptomatic primary incompetence of the great or small saphenous vein were prospectively collected. Treatment results in terms of occlusion rate and patients grade

Diffractive Excitation in DIS and pp Collisions

We have in earlier papers presented an extension of Mueller's dipole cascade model, which includes subleading effects from energy conservation and running coupling as well as colour suppressed effects from pomeron loops via a ``dipole swing''. The model was applied to describe the total cross sections in pp and gamma*p collisions. In this paper we present a number of improvements of the model, in

Early-Pregnancy Cytokines in Mothers to Children Developing Multiple, Persistent Islet Autoantibodies, Type 1 Diabetes, or Both Before 7 Years of Age.

Citation Lindehammer SR, Fex M, Maziarz M, Hanson I, Marsal K, Lernmark Å on behalf of the Diabetes Prediction in Skåne (DiPiS) Study Group. Early-pregnancy cytokines in mothers to children developing multiple, persistent islet autoantibodies, type 1 diabetes, or both before 7 years of age. Am J Reprod Immunol 2011 Problem Increased levels of serum cytokines in early pregnancy may increase the ris

Harnessing immune alterations in neurodegenerative diseases.

Immune dysfunction, a well-established feature of neuroinflammatory disease, is increasingly recognized in neurodegenerative conditions. Its role is emerging as an early and active participant in neuropathology. Inflammation could be modified, with disease-slowing effects, by targeted interventions; it is also readily detectable and could serve as a source of valuable biomarkers.

The Bcl-xL inhibitor of apoptosis is preferentially expressed in cutaneous squamous cell carcinoma compared with that in keratoacanthoma.

Keratoacanthoma (KA) is difficult to histologically distinguish from squamous cell carcinoma (SCC). Therefore, although KA is a benign self-resolving skin lesion, KA is commonly treated as SCC. Biomarkers to distinguish KA and SCC would thus be desirable. In search for specific markers, paraffin-embedded tissue samples from 25 SCC and 64 KA were arranged in a tissue microarray (TMA) and stained fo

Distinct evolutionary mechanisms for genomic imbalances in high-risk and low-risk neuroblastomas

ABSTRACT: BACKGROUND: Neuroblastoma (NB) is the most common extracranial solid tumour of childhood. Several genomic imbalances correlate to prognosis in NB, with structural rearrangements, including gene amplification, in a near-diploid setting typically signifying high-risk tumours and numerical changes in a near-triploid setting signifying low-risk tumours. Little is known about the temporal seq

Phagosome dynamics during phagocytosis by neutrophils.

The neutrophil is a key player in immunity, and its activities are essential for the resolution of infections. Neutrophil-pathogen interactions usually trigger a large arsenal of antimicrobial measures that leads to the highly efficient killing of pathogens. In neutrophils, the phagocytic process, including the formation and maturation of the phagosome, is in many respects very different from that

Attosecond pulse trains using high-order harmonics

We demonstrate that high-order harmonics generated by an atom in intense laser field form trains of ultrashort pulses corresponding to different trajectories of electrons that tunnel out of the atom and recombine. Propagation in an atomic jet allows us to select one of these trajectories, leading to a train of pulses of extremely short duration.