Genetic epidemiological studies have demonstrated a significant genetic basis to both psoriasis and psoriatic arthritis (PsA). Although candidate gene association studies had identified genes for ...disease susceptibility, recent genome-wide association studies have demonstrated robust associations both within and outside the major histocompatibility region on chromosome 6p. The susceptibility genes identified include
HLA-C
,
IL13
,
IL4, TNFAIP3
,
IL23A
,
IL23R
,
IL28RA
,
REL
,
IFIH1
,
ERAP
,
TRAF3IP2
,
NFKBIA
,
TYK2
,
ZNF313
,
NOS2
,
FBXL19
and
NFKBIA
in subjects of European ethnicity and
HLA-C
,
IL12B
,
LCE3D
,
ERAP1
,
TNIP1
,
PTTG1
,
CSMD1
,
GJB2
,
SERPINB8
and
ZNF816A
in subjects of Chinese ethnicity. These associations provide us with a model for the pathogenesis of psoriasis involving skin barrier function, innate and adaptive immunity. Gene–gene and gene–environmental interaction effects have also been demonstrated. However, loci identified to date do not fully account for the high heritability of psoriasis and PsA, and therefore many genetic as well as environmental factors and interaction effects remain to be determined. This article reviews the current status of genetic studies in psoriasis and PsA.
Ankylosing spondylitis (AS) was first identified in the late 17th century. 250 years later, inflammatory spine disease was recognized to be one of the patterns of psoriatic arthritis (PsA). Isolated ...spondylitis is rare among patients with PsA, occurring in less than 5% of patients; however, many patients with PsA have axial disease that is concurrent with peripheral arthritis. At the other end of the spondyloarthritis spectrum, psoriasis is observed in 10% of patients with AS. Although axial involvement in PsA can be indistinguishable from axial disease in AS, it can also differ in several respects, raising the question of whether axial PsA and AS (with or without psoriasis) are different clinical presentations of the same disease, or whether they are separate diseases that have overlapping features. In this Review, the clinical presentation, metrology, radiographic characteristics, genetic factors, treatment options and axial prognosis of the two diseases are addressed. The aim of this Review is to capture all available comparisons made to date, to highlight the similarities and differences between AS and axial PsA and to propose a research agenda.
This perspective outlines recent developments in the field of NMR spectroscopy, enabling new opportunities for in situ studies on bulk and confined clathrate hydrates. These hydrates are crystalline ...ice-like materials, built up from hydrogen-bonded water molecules, forming cages occluding non-polar gaseous guest molecules, including CH4, CO2 and even H2 and He gas. In nature, they are found in low-temperature and high-pressure conditions. Synthetic confined versions hold immense potential for energy storage and transportation, as well as for carbon capture and storage. Using previous studies, this report highlights static and magic angle spinning NMR hardware and strategies enabling the study of clathrate hydrate formation in situ, in bulk and in nano-confinement. The information obtained from such studies includes phase identification, dynamics, gas exchange processes, mechanistic studies and the molecular-level elucidation of the interactions between water, guest molecules and confining interfaces.
Psoriatic arthritis (PsA) is a complex inflammatory disease with heterogeneous clinical features, which complicates psoriasis in 30% of patients. There are no diagnostic criteria or tests available. ...Diagnosis is most commonly made by identifying inflammatory musculoskeletal features in joints, entheses or the spine in the presence of skin and/or nail psoriasis and in the usual absence of rheumatoid factor and anti-cyclic citrullinated peptide. The evolution of psoriasis to PsA may occur in stages, although the mechanisms are unclear. In many patients, there may be little or no relationship between severity of musculoskeletal inflammation and severity of skin or nail psoriasis. The reason for this disease heterogeneity may be explained by differences in genotype, especially in the HLA region. New targeted therapies for PsA have been approved with additional therapies in development. These developments have substantially improved both short-term and long-term outcomes including a reduction in musculoskeletal and skin manifestations and in radiographic damage. With efforts underway aimed at improving our understanding of the molecular basis for the heterogeneity of PsA, a personalized approach to treating PsA may become possible.
Selective catalytic reduction (SCR) of NOx by ammonia is one of the dominant pollution abatement technologies for near-zero NOx emission diesel engines. A crucial step in the reduction of NOx to N2 ...with Cu zeolite NH3-SCR catalysts is the generation of a multi-electron donating active site, implying the permanent or transient dimerization of Cu ions. Cu atom mobility has been implicated by computational chemistry as a key factor in this process. This report demonstrates how variable temperature 1H NMR reveals the Cu induced generation of sharp 1H resonances associated with a low concentration of sites on the zeolite. The onset temperature of the appearance of these signals was found to strongly correlate with the NH3-SCR activity and was observed for a range of catalysts covering multiple frameworks (CHA, AEI, AFX, ERI, ERI-CHA, ERI-OFF, *BEA), with different Si/Al ratios and different Cu contents. The results point towards universal applicability of variable temperature NMR to predict the activity of a Cu-zeolite SCR catalyst. The unique relationship of a spectroscopic feature with catalytic behavior for zeolites with different structures and chemical compositions is exceptional in heterogeneous catalysis.
Greatly Increased Toughness of Infiltrated Spider Silk Lee, Seung-Mo; Pippel, Eckhard; Gösele, Ulrich ...
Science (American Association for the Advancement of Science),
04/2009, Volume:
324, Issue:
5926
Journal Article
Peer reviewed
In nature, tiny amounts of inorganic impurities, such as metals, are incorporated in the protein structures of some biomaterials and lead to unusual mechanical properties of those materials. A desire ...to produce these biomimicking new materials has stimulated materials scientists, and diverse approaches have been attempted. In contrast, research to improve the mechanical properties of biomaterials themselves by direct metal incorporation into inner protein structures has rarely been tried because of the difficulty of developing a method that can infiltrate metals into biomaterials, resulting in a metal-incorporated protein matrix. We demonstrated that metals can be intentionally infiltrated into inner protein structures of biomaterials through multiple pulsed vapor-phase infiltration performed with equipment conventionally used for atomic layer deposition (ALD). We infiltrated zinc (Zn), titanium (Ti), or aluminum (Al), combined with water from corresponding ALD precursors, into spider dragline silks and observed greatly improved toughness of the resulting silks. The presence of the infiltrated metals such as Al or Ti was verified by energy-dispersive x-ray (EDX) and nuclear magnetic resonance spectra measured inside the treated silks. This result of enhanced toughness of spider silk could potentially serve as a model for a more general approach to enhance the strength and toughness of other biomaterials.
To examine the association between sonographic enthesitis and the severity of radiographic features of damage in the peripheral and axial joints in psoriatic arthritis (PsA).
A cross-sectional ...analysis was conducted in patients with PsA. The MAdrid Sonography Enthesitis Index (MASEI) scoring system was used to quantify the extent of sonographic entheseal abnormalities. Radiographic damage in the peripheral joints and spine was assessed by the modified Steinbrocker score (mSS), Modified New York Criteria for sacroiliitis, and the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). The association between MASEI and the extent of radiographic damage was assessed using negative binomial and logistic regression. The results were expressed in terms of the regression coefficient estimates and their exponentiated values (e
) or odds ratios (OR), and 95% confidence intervals (CI).
Two hundred and twenty three patients were analyzed; 58% were males, with mean ± SD age of 55.9 ± 12.9 years and PsA duration of 16.7 ± 12.4 years. Regression analyses yielded an association between higher MASEI scores (10 units increase) and peripheral joint damage including mSS (e
= 1.42, 95% CI: 1.15, 1.72), joint ankylosis (OR = 1.93, 95% CI: 1.37, 2.72), arthritis mutilans (OR = 1.77, 95% CI: 1.23, 2.54), and periostitis (OR = 1.41, 95% CI: 1.08, 1.84). Similarly, an association was found between higher MASEI scores and axial damage as measured by mSASSS (e
= 2.18, 95% CI: 1.16, 4.09) and sacroiliitis (OR = 1.33, 95% CI: 1.03, 1.72).
The severity of sonographic enthesitis is a potential marker of radiographic peripheral and axial joint damage in PsA.
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