Biology subjects

Rutkowski, J.

Publications and source records attributed to Rutkowski, J..

3 recordsLinked to original sources

bioRxiv2022

Increased severity of chronic kidney disease in response to high potassium intake is dependent on mineralocorticoid receptor activation

Dietary treatment is seminal for management of chronic kidney disease (CKD). The aim of our project was to assess the effects of potassium intake on the progression of CKD. We used 2 mouse CKD models to analyze the effects of potassium intake on CKD : the unilateral ureteral obstruction (UUO) and the POD-ATTAC models. POD-ATTAC mice display a podocyte-specific apoptosis after the administration of a chemical inducer. We also studied the effect of mineralocorticoid receptor (MR) using UUO in kidney tubule-specific MR knockout mice. In both UUO and POD-ATTAC mice, high potassium diet increased interstitial fibrosis. High potassium diet also increased the abundance of the extracellular matrix protein fibronectin and decreased the abundance of the epithelial marker Na+-K+ ATPase. Consistently, POD-ATTAC mice fed with high potassium diet displayed lower glomerular filtration rate. Spironolactone, a MR antagonist, decreased fibrosis induced by high potassium diet in POD-ATTAC mice. However, kidney tubule-specific MR knockout did not improve the fibrotic lesions induced by UUO under normal or high potassium diets. Macrophages from high potassium-fed POD-ATTAC mice displayed higher mRNA levels of the pro-inflammatory chemokine MCP1. This effect was decreased by spironolactone, suggesting a role of MR signaling in myeloid cells in the pro-fibrotic effect of potassium-rich diet. High potassium intake generates more fibrosis leading to decreased kidney function in experimental CKD. MR signaling plays a pivotal role in this potassium-induced fibrosis. The effect of reducing potassium intake on CKD progression should be assessed in future clinical trials. Translational statementDietetic approach is a cheap and effective therapy to slow down the development of chronic kidney diseases and kidney fibrosis. Potassium-rich diets are protective against renal and cardiovascular events in the general population, albeit some conflicting data were obtained in patients with chronic kidney disease. We showed that potassium-rich diet accelerates fibrosis development, by enhancing kidney inflammation in two mouse models of chronic kidney disease. These data suggest that potassium-rich diets should not be advised in patients with chronic kidney disease, unless future clinical trials demonstrate any beneficial effect in these patients.

physiology↗

bioRxiv2019

Metacontrast masking as a measure of change detection: Children with poor reading fluency show impaired change detection for both letters and shapes.

Developmental dyslexia, a specific learning difficulty in reading, manifests as effortful decoding of words and as such is commonly associated with reduced phonemic awareness. However, its underlying cause remains elusive, with magnocellular visual processing, temporal auditory processing, visual attentional deficits and cerebellar dysfunction all gaining some traction. More recent theories have concerned visual attention span, measuring the parallel attentive capacity of the sensory visual system. However the VA span task as implemented requires reports, both conscious recall and recognition of letters, that activate many cortical areas beyond sensory visual cortex. Change detection, in contrast, does not require the conscious recognition of items, but simply awareness that the stimulus has changed, or not, again testing visual attention in a parallel fashion, but avoiding the complications of higher order cognitive processes. Thus, we investigated change detection in 33 good and poor readers with ages of around 10 yr, using a gap paradigm. Groups of 4 letters or 4 shapes were presented for a fixed time (0.7 s), followed after a 0.25 s gap, by a second similar group, each item surrounded by an annular frame filled with dynamic random noise of variable contrast. Detection performance was manipulated by varying the contrast of these meta-contrast mask frames, yielding a threshold contrast of the frames at which participants could just detect change. In two separate experiments, letters and rectangular shapes were used as target items, in order to test whether previous findings of superior change detection in good compared with poor readers was a result of greater automaticity in letter recognition of the good readers. The results indicate that the good readers were able to detect change at higher levels of masking distraction for both the letter and shape targets, indicating that this difference is not specifically related to to the training of graphemic or lexical information but more likely reflects a difference in alerting or pre-recognition stages of visual processing. Together, the results provide further support of the notion that there is a low level attentional performance difference between dyslexic and normal reading children. Thus, the results further bring transient spatial attention directly into the spotlight as an ability critical for learning to read.

neuroscience↗

bioRxiv2019

Dyslexic children show altered temporal structure of the nonlinear VEP.

The neural basis of dyslexia remains unresolved, despite many theories relating dyslexia to dysfunction in visual magnocellular and auditory temporal processing, cerebellar dysfunction, attentional deficits, as well as excessive neural noise. Recent research identifies perceptual speed as a common factor, integrating several of these systems. Optimal perceptual speed invokes transient attention as a necessary component, and change detection in gap paradigm tasks is impaired in those with dyslexia. This research has also identified an overall better change detection for targets presented in the upper compared with lower visual fields. Despite the magnocellular visual pathway being implicated in the aetiology of dyslexia over 30 years ago, objective physiological measures have been lacking. Thus, we employed nonlinear visual evoked potential (VEP) techniques which generate second order kernel terms specific for magno and parvocellular processing as a means to assessing the physiological status of poor readers (PR, n=12) compared with good readers (GR, n=16) selected from children with a mean age of 10yr. The first and second order Wiener kernels using multifocal VEP were recorded from a 4{degrees} foveal stimulus patch as well as for upper and lower visual field peripheral arcs. Foveal responses showed little difference between GR and PR for low contrast stimulation, except for the second slice of the second order kernel where lower peak amplitudes were recorded for PR vs GR. At high contrast, there was a trend to smaller first order kernel amplitudes for short latency peaks of the PR vs GR. In addition, there were significant latency differences for the first negativity in the first two slices of the second order kernel. In terms of peripheral stimulation, lower visual field response amplitudes were larger compared with upper visual field responses, for both PR and GR. A trend to larger second/first order ratio for magnocellularly driven responses suggests the possibility of lesser neural efficiency in the periphery for the PR compared with the GR. Stronger lower field peripheral response may relate to better upper visual field change detection performance when target visibility is controlled through flicking masks. In conclusion, early cortical magnocellular processing at low contrast was normal in those with dyslexia, while cortical activity related to parvocellular afferents was reduced. In addition, the study demonstrated a physiological basis for upper versus lower visual field differences related to magnocellular function.

neuroscience↗