Measures for biomechanically correct positioning of knee joint endoprostheses]

Normal post-operative function, permanent stable fixation and long life for the implant material are determined mainly by the correct biomechanical positioning of the knee joint prosthesis. We have identified six measures within the surgical procedure that are of vital importance for achieving biomechanically correct positioning. Because of their great importance, we call these measures "The Golden Six", and describe their application using the ESKA Resurfacing Knee System (RKS). This system, which is so designed that it enables a maximal bone saving resection technique, makes use of a diagonal screw-fixation of the endoprosthetic elements, resulting in increased primary stability. For the safe and reliable implementation of our measures, we have developed a special set of instruments. Anatomical, kinematic and surgical studies have shown that with the aid of the above-mentioned six measures biomechanically correct positioning of all the implanted elements can be achieved, thus ensuring trouble-free post-operative function of the knee joint and the least possible mechanical stressing of the implanted materials.     

Airway epithelial cell migration and wound repair by ATP-mediated activation of dual oxidase 1

The airway epithelium is continuously subjected to environmental pollutants, airborne pathogens, and allergens and relies on several intrinsic mechanisms to maintain barrier integrity and to promote epithelial repair processes following injury. Here, we report a critical role for dual oxidase 1 (Duox1), a newly identified NADPH oxidase homolog within the tracheobronchial epithelium, in airway epithelial cell migration and repair following injury. Activation of Duox1 during epithelial injury is mediated by cellular release of ATP, which signals through purinergic receptors expressed on the epithelial cell surface. Purinergic receptor stimulation by extracellular ATP is a critical determinant of epithelial cell migration and repair following injury and is associated with activation of extracellular signal-regulated kinases (ERK1/2) and matrix metalloproteinase-9 (MMP-9). Stimulation of these integral features of epithelial cell migration and repair processes was found to require the activation of Duox1. Our findings demonstrate a novel role for Duox1 in the tracheobronchial epithelium, in addition to its proposed role in antimicrobial host defense, by participating in epithelial repair processes to maintain epithelial integrity and barrier function in the face of environmental stress.     

Apparent timing of density banding in the Caribbean coral Siderastrea siderea suggests complex role of key physiological variables

Coral Reefs - Skeletal growth bands in massive reef-building corals are increasingly used as proxies for environmental records despite an incomplete understanding of their formation. While the...     

Synthesis and SAR of 2-aryl pyrido[2,3-d]pyrimidines as potent mGlu5 receptor antagonists

A novel series of potent 2-aryl pyrido[2,3-d]pyrimidine mGlu5 receptor antagonists are described. The synthesis and pharmacological activities of these analogs are discussed.     

Mapping of the mucolipidosis type IV gene to chromosome 19p and definition of founder haplotypes.

Mucolipidosis type IV (MLIV) is a lysosomal storage disorder characterized by severe neurologic and ophthalmologic abnormalities. It is a rare autosomal recessive disease, and the majority of patients diagnosed, to date, are of Ashkenazi Jewish descent. We have mapped the MLIV gene to chromosome 19p13.2-13.3 by linkage analysis with 15 markers in 13 families. A maximum LOD score of 5.51 with no recombinants was observed with marker D19S873. Several markers in the linked interval also displayed significant linkage disequilibrium with the disorder. We constructed haplotypes in 26 Ashkenazi Jewish families and demonstrate the existence of two founder chromosomes in this population. The localization of MLIV to chromosome 19 will permit genetic prenatal diagnosis in affected families and will aid in the isolation of the disease gene.     

Discovery of a new class of triazole based inhibitors of acetyl transferase KAT2A

We have recently developed a new synthetic methodology that provided both N-aryl-5-hydroxytriazoles and N-pyridine-4-alkyl triazoles. A selection of these products was carried through virtual screening towards targets that are contemporary and validated for drug discovery and development. This study determined a number of potential structure target dyads of which N-pyridinium-4-carboxylic-5-alkyl triazole displayed the highest score specificity towards KAT2A. Binding affinity tests of abovementioned triazole and related analogs towards KAT2A confirmed the predictions of the in-silico assay. Finally, we have run in vitro inhibition assays of selected triazoles towards KAT2A; the ensemble of binding and inhibition assays delivered pyridyl-triazoles carboxylates as the prototype of a new class of inhibitors of KAT2A.     

Promoting inclusive metrics of success and impact to dismantle a discriminatory reward system in science

Success and impact metrics in science are based on a system that perpetuates sexist and racist “rewards” by prioritizing citations and impact factors. These metrics are flawed and biased against already marginalized groups and fail to accurately capture the breadth of individuals’ meaningful scientific impacts. We advocate shifting this outdated value system to advance science through principles of justice, equity, diversity, and inclusion. We outline pathways for a paradigm shift in scientific values based on multidimensional mentorship and promoting mentee well-being. These actions will require collective efforts supported by academic leaders and administrators to drive essential systemic change.

This Essay argues that success and impact metrics in science are based on a system that perpetuates sexist and racist ‘rewards’ by prioritizing citations and impact factors; the authors advocate shifting this outdated value system to advance science through principles of justice, equity, diversity, and inclusion.     

The Cerebellum Predicts the Temporal Consequences of Observed Motor Acts

It is increasingly clear that we extract patterns of temporal regularity between events to optimize information processing. The ability to extract temporal patterns and regularity of events is referred as temporal expectation. Temporal expectation activates the same cerebral network usually engaged in action selection, comprising cerebellum. However, it is unclear whether the cerebellum is directly involved in temporal expectation, when timing information is processed to make predictions on the outcome of a motor act. Healthy volunteers received one session of either active (inhibitory, 1Hz) or sham repetitive transcranial magnetic stimulation covering the right lateral cerebellum prior the execution of a temporal expectation task. Subjects were asked to predict the end of a visually perceived human body motion (right hand handwriting) and of an inanimate object motion (a moving circle reaching a target). Videos representing movements were shown in full; the actual tasks consisted of watching the same videos, but interrupted after a variable interval from its onset by a dark interval of variable duration. During the ‘dark’ interval, subjects were asked to indicate when the movement represented in the video reached its end by clicking on the spacebar of the keyboard. Performance on the timing task was analyzed measuring the absolute value of timing error, the coefficient of variability and the percentage of anticipation responses. The active group exhibited greater absolute timing error compared with the sham group only in the human body motion task. Our findings suggest that the cerebellum is engaged in cognitive and perceptual domains that are strictly connected to motor control.