Syndecan-4 regulates ADAMTS-5 activation and cartilage breakdown in osteoarthritis

Echtermeyer, Frank,Bertrand, Jessica,Dreier, Rita,Meinecke, Ingmar,Neugebauer, Katja,Fuerst, Martin,Lee, Yun Jong,Song, Yeong Wook,Herzog, Christine,Theilmeier, Gregor,Pap, Thomas Nature Publishing Group 2009 Nature medicine Vol.15 No.9

Aggrecan cleavage by a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 5 (ADAMTS-5) is crucial for the breakdown of cartilage matrix during osteoarthritis, a degenerative joint disease that leads to the progressive destruction of articular structures. The mechanisms of ADAMTS-5 activation and their links to the pathogenesis of osteoarthritis remain poorly understood, but syndecans have been shown to be involved in the activation of ADAMTS-4 (ref. 3). Here we show that syndecan-4 is specifically induced in type X collagen–producing chondrocytes both in human osteoarthritis and in murine models of the disease. The loss of syndecan-4 in genetically modified mice and intra-articular injections of syndecan-4–specific antibodies into wild-type mice protect from proteoglycan loss and thereby prevent osteoarthritic cartilage damage in a surgically induced model of osteoarthritis. The occurrence of less severe osteoarthritis-like cartilage destruction in both syndecan-4–deficient mice and syndecan-4–specific antibody–treated wild-type mice results from a marked decrease in ADAMTS-5 activity. Syndecan-4 controls the activation of ADAMTS-5 through direct interaction with the protease and through regulating mitogen-activated protein kinase (MAPK)-dependent synthesis of matrix metalloproteinase-3 (MMP-3). Our data suggest that strategies aimed at the inhibition of syndecan-4 will be of great value for the treatment of cartilage damage in osteoarthritis.

EEG-based usability assessment of 3D shutter glasses

Wenzel, Markus A,Schultze-Kraft, Rafael,Meinecke, Frank C,Fabien Cardinaux,Kemp, Thomas,Klaus-Robert Mü,ller,Gabriel Curio,Benjamin Blankertz IOP 2016 Journal of neural engineering Vol.13 No.1

<P> <I>Objective.</I> Neurotechnology can contribute to the usability assessment of products by providing objective measures of neural workload and can uncover usability impediments that are not consciously perceived by test persons. In this study, the neural processing effort imposed on the viewer of 3D television by shutter glasses was quantified as a function of shutter frequency. In particular, we sought to determine the critical shutter frequency at which the ‘neural flicker’ vanishes, such that visual fatigue due to this additional neural effort can be prevented by increasing the frequency of the system. <I>Approach.</I> Twenty-three participants viewed an image through 3D shutter glasses, while multichannel electroencephalogram (EEG) was recorded. In total ten shutter frequencies were employed, selected individually for each participant to cover the range below, at and above the threshold of flicker perception. The source of the neural flicker correlate was extracted using independent component analysis and the flicker impact on the visual cortex was quantified by decoding the state of the shutter from the EEG. <I>Main Result.</I> Effects of the shutter glasses were traced in the EEG up to around 67?Hz—about 20?Hz over the flicker perception threshold—and vanished at the subsequent frequency level of 77?Hz. <I>Significance.</I> The impact of the shutter glasses on the visual cortex can be detected by neurotechnology even when a flicker is not reported by the participants. <I>Potential impact.</I> Increasing the shutter frequency from the usual 50?Hz or 60?Hz to 77?Hz reduces the risk of visual fatigue and thus improves shutter-glass-based 3D usability.</P>

Fatty Acid Modulation of Atherosclerosis by Peroxisome Proliferator- Activated Receptors

Erickson, Kent L.,Hubbard, Neil E.,Meinecke, Lynette M. The Korean Society of Food Science and Nutrition 2002 Preventive Nutrition and Food Science Vol.7 No.4

While atherosclerosis is a major killer, there is now concern that mortality from the disease will increase due to the rising incidence of type II diabetes. Because diet can potentially influence both diseases, it is important to elucidate the role of diet in the progression of atherosclerosis. In addition, the mechanisms involved in dietary-related alterations of the disease need to be defined to guide public health recommendations to reduce athero-sclerosis incidence and limiting unwanted side effects. Since diet is thought to play a role in atherosclerosis even without added complications due to type II diabetes, reducing the incidence of that metabolic disease will not be enough. While evidence is increasing that high intake of carbohydrate can lead to type II diabetes and atherosclerosis, the preponderance of existing evidence indicates that intake of specific fats as a major dietary causal factor. It has recently been hypothesized that a dietary fat link to atherosclerosis may depend partly on the activity of a transcriptional regulator, the peroxisome proliferator activated receptors (PPAR). Thusfar, PPAR $\alpha$, $\beta$/$\delta$ and ${\gamma}$, have been shown to play a major role in metabolism, inflammation, and cancer. Furthermore, PPAR may regulate specific processes associated with atherosclerosis such as triglyceride and low density lipoprotein (LDL) metabolism; the reverse cholesterol transport pathway; lipid accumulation within plaques; the local inflammatory response and plaque stability. Synthetic ligands for PPAR have been developed; however, natural ligands include specific fatty acids and their metabolites. Though the role of PPAR in atherosclerosis has been reported with respect to synthetic ligands, additional studies need to be done with established and possible natural ligands. In this review, we will focus on the relation of dietary fat to PPAR alteration of atherosclerosis.

A mathematical model for the two-learners problem

Mü,ller, Jan Saputra,Vidaurre, Carmen,Schreuder, Martijn,Meinecke, Frank C,von Bü,nau, Paul,Mü,ller, Klaus-Robert IOP 2017 Journal of neural engineering Vol.14 No.3

<P> <I>Objective</I>. We present the first generic theoretical formulation of the co-adaptive learning problem and give a simple example of two interacting linear learning systems, a human and a machine. <I>Approach</I>. After the description of the training protocol of the two learning systems, we define a simple linear model where the two learning agents are coupled by a joint loss function. The simplicity of the model allows us to find learning rules for both human and machine that permit computing theoretical simulations. <I>Main results</I>. As seen in simulations, an astonishingly rich structure is found for this eco-system of learners. While the co-adaptive learners are shown to easily stall or get out of sync for some parameter settings, we can find a broad sweet spot of parameters where the learning system can converge quickly. It is defined by mid-range learning rates on the side of the learning machine, quite independent of the human in the loop. Despite its simplistic assumptions the theoretical study could be confirmed by a real-world experimental study where human and machine co-adapt to perform cursor control under distortion. Also in this practical setting the mid-range learning rates yield the best performance and behavioral ratings. <I>Significance</I>. The results presented in this mathematical study allow the computation of simple theoretical simulations and performance of real experimental paradigms. Additionally, they are nicely in line with previous results in the BCI literature.</P>

Fatty Acid Modulation of Atherosclerosis by Peroxisome Proliferator - Activated Receptors

Kent L. Erickson,Neil E. Hubbard,Lynette M. Meinecke 한국식품영양과학회 2002 Preventive Nutrition and Food Science Vol.7 No.4

While atherosclerosis is a major killer, there is now concern that mortality from the disease will increase due to the rising incidence of type II diabetes. Because diet can potentially influence both diseases, it is important to elucidate the role of diet in the progression of atherosclerosis. In addition, the mechanisms involved in dietaryrelated alterations of the disease need to be defined to guide public health recommendations to reduce atherosclerosis incidence and limiting unwanted side effects. Since diet is thought to play a role in atherosclerosis even without added complications due to type II diabetes, reducing the incidence of that metabolic disease will not be enough. While evidence is increasing that high intake of carbohydrate can lead to type II diabetes and atherosclerosis, the preponderance of existing evidence indicates that intake of specific fats as a major dietary causal factor. It has recently been hypothesized that a dietary fat link to atherosclerosis may depend partly on the activity of a transcriptional regulator, the peroxisome proliferator activated receptors (PPAR). Thusfar, PPAR α, β/δ andγ, have been shown to play a major role in metabolism, inflammation, and cancer. Furthermore, PPAR may regulate specific processes associated with atherosclerosis such as triglyceride and low density lipoprotein (LDL) metabolism; the reverse cholesterol transport pathway; lipid accumulation within plaques; the local inflammatory response and plaque stability. Synthetic ligands for PPAR have been developed; however, natural ligands include specific fatty acids and their metabolites. Though the role of PPAR in atherosclerosis has been reported with respect to synthetic ligands, additional studies need to be done with established and possible natural ligands. In this review, we will focus on the relation of dietary fat to PPAR alteration of atherosclerosis.

A variant of Desbuquois dysplasia characterized by advanced carpal bone age, short metacarpals, and elongated phalanges: Report of seven cases

Kim, Ok-Hwa,Nishimura, Gen,Song, Hae-Ryong,Matsui, Yoshito,Sakazume, Satoru,Yamada, Masanobu,Narumi, Yoko,Alanay, Yasemin,Unger, Sheila,Cho, Tae-Joon,Park, Sung Sup,Ikegawa, Shiro,Meinecke, Peter,Supe Wiley Subscription Services, Inc., A Wiley Company 2010 AMERICAN JOURNAL OF MEDICAL GENETICS PART A Vol.a152 No.4

<P>We present the clinical and radiological findings of seven patients with a seemingly new variant of Desbuquois dysplasia (DBQD) and emphasize the radiographic findings in the hand. All cases showed remarkably accelerated carpal bone ages in childhood, but none of the patients had an accessory ossification center distal to the second metacarpal, or thumb anomalies, instead, there was shortness of one or all metacarpals, with elongated appearance of phalanges, resulting in nearly equal length of the second to fifth fingers. The two sibs followed for 20 years showed narrowing and fusion of the intercarpal joints with age and ultimately, precocious degenerative arthritis. The changes in the feet were similar to those of the hands, with advanced tarsal bone ages, shortness of the metatarsals and elongation of the second and third toes. Other radiographic findings were narrowness of the intervertebral disc spaces resulting in precocious degenerative spondylosis and progressive scoliosis. The femoral neck was short and thick and showed a persistent enlargement of the lesser trochanter with a high-riding, bulbous greater trochanter that became more prominent with age. Molecular testing of the diastrophic dysplasia sulfate transporter (DTDST) gene was performed on six patients and no mutations were detected. This radiographic and clinical observation further adds to the evidence that there may be subtypes of DBQD. Long-term follow-up showed that severe precocious osteoarthritis of the hand and spine is a major manifestation of this specific variant. © 2010 Wiley-Liss, Inc.</P>