Kroghovgaard6822

Optical intrinsic signal imaging (OISi) method is an optical technique to evaluate the functional connectivity (FC) of the cortex in animals. Already, using OISi, the FC of the cortex has been measured in time or frequency domain separately, and at frequencies below 0.08 Hz, which is not in the frequency range of hemodynamic oscillations which are able to track fast cortical events, including neurogenic, myogenic, cardiac and respiratory activities. In the current work, we calculated the wavelet coherence (WC) transform of the OISi time series to evaluate the cerebral response changes in the stroke rats. Utilizing WC, we measured FC at frequencies up to 4.5 Hz, and could monitor the time and frequency dependency of the FC simultaneously. The results showed that the WC of the brain diminished significantly in ischemic motor and somatosensory cortices. According to the statistical results, the signal amplitude, responsive area size, correlation, and wavelet coherence of the motor and the somatosensory cortices for stroke hemisphere were found to be significantly lower compared to the healthy hemisphere. The obtained results confirm that the OISi-based WC analysis is an efficient method to diagnose the relative severity of infarction and the size of the infarcted region after ischemic stroke.The topology concept in the condensed physics and acoustics is introduced into the elastic wave metamaterial plate, which can show the topological property of the flexural wave. The elastic wave metamaterial plate consists of the hexagonal array which is connected by the piezoelectric shunting circuits. The Dirac point is found by adjusting the size of the unit cell and numerical simulations are illustrated to show the topological immunity. Then the closing and breaking of the Dirac point can be generated by the negative capacitance circuits. These investigations denote that the topological immunity can be achieved for flexural wave in mechanical metamaterial plate. The experiments with the active control action are finally carried out to support the numerical design.Drug sensitivity prediction constitutes one of the main challenges in personalized medicine. Critically, the sensitivity of cancer cells to treatment depends on an unknown subset of a large number of biological features. Here, we compare standard, data-driven feature selection approaches to feature selection driven by prior knowledge of drug targets, target pathways, and gene expression signatures. We asses these methodologies on Genomics of Drug Sensitivity in Cancer (GDSC) dataset, evaluating 2484 unique models. For 23 drugs, better predictive performance is achieved when the features are selected according to prior knowledge of drug targets and pathways. The best correlation of observed and predicted response using the test set is achieved for Linifanib (r = 0.75). Extending the drug-dependent features with gene expression signatures yields the most predictive models for 60 drugs, with the best performing example of Dabrafenib. For many compounds, even a very small subset of drug-related features is highly predictive of drug sensitivity. Small feature sets selected using prior knowledge are more predictive for drugs targeting specific genes and pathways, while models with wider feature sets perform better for drugs affecting general cellular mechanisms. Appropriate feature selection strategies facilitate the development of interpretable models that are indicative for therapy design.Naturally occurring autopolyploid species, such as the autotetraploid potato Solanum tuberosum, face a variety of challenges during meiosis. These include proper pairing, recombination and correct segregation of multiple homologous chromosomes, which can form complex multivalent configurations at metaphase I, and in turn alter allelic segregation ratios through double reduction. Here, we present a reference map of meiotic stages in diploid and tetraploid S. tuberosum using fluorescence in situ hybridisation (FISH) to differentiate individual meiotic chromosomes 1 and 2. A diploid-like behaviour at metaphase I involving bivalent configurations was predominant in all three tetraploid varieties. The crossover frequency per bivalent was significantly reduced in the tetraploids compared with a diploid variety, which likely indicates meiotic adaptation to the autotetraploid state. Nevertheless, bivalents were accompanied by a substantial frequency of multivalents, which varied by variety and by chromosome (7-48%). We identified possible sites of synaptic partner switching, leading to multivalent formation, and found potential defects in the polymerisation and/or maintenance of the synaptonemal complex in tetraploids. These findings demonstrate the rise of S. tuberosum as a model for autotetraploid meiotic recombination research and highlight constraints on meiotic chromosome configurations and chiasma frequencies as an important feature of an evolved autotetraploid meiosis.Purpose Cerebrotendinous xanthomatosis (CTX) is a treatable hereditary disorder caused by the deficiency of sterol 27-hydroxylase, which is encoded by the CYP27A1 gene. Different newborn screening biomarkers for CTX have been described, including 7α,12α-dihydroxy-4-cholesten-3-one (7α12αC4), 5β-cholestane-3α,7α,12α,25-tetrol glucuronide (GlcA-tetrol), the ratio of GlcA-tetrol to tauro-chenodeoxycholic acid (t-CDCA) (GlcA-tetrol/t-CDCA), and the ratio of tauro-trihydroxycholestanoic acid (t-THCA) to GlcA-tetrol (t-THCA/GlcA-tetrol). We set out to evaluate these screening methods in a research study using over 32,000 newborn dried blood spots (DBS). Methods Metabolites were extracted from DBS with methanol containing internal standard, which was then quantified by ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Results The measurement of 7α12αC4 was complicated by isobaric interferences and was discontinued. A total of 32,737 newborns were screened based on the GlcA-tetrol concentration in DBS. GlcA-tetrol/t-CDCA and t-THCA/GlcA-tetrol ratios were also calculated. Newborns displaying both elevated GlcA-tetrol and GlcA-tetrol/t-CDCA ratio were considered to be screen positives. The t-THCA/GlcA-tetrol ratio was used to further distinguish CTX screen positives from Zellweger Spectrum Disorder (ZSD) screen positives. Only one newborn displayed both elevated GlcA-tetrol concentration in DBS and a typical CTX biochemical profile. This newborn was interpreted as a CTX-affected patient as CYP27A1 gene sequencing identified two known pathogenic variants. Conclusion The results indicate that both GlcA-tetrol and the GlcA-tetrol/t-CDCA ratio are excellent CTX biomarkers suitable for newborn screening. By characterizing the relationship of GlcA-tetrol, t-CDCA, and t-THCA as secondary markers, 100% assay specificity can be achieved.There is an increased pressure to return results from research studies. In Iceland, deCODE Genetics has emphasised the importance of returning results to research participants, particularly the founder pathogenic BRCA2 variant; NM_000059.3c.771_775del. To do so, they opened the website www.arfgerd.is. Individuals who received positive results via the website were offered genetic counselling (GC) at Landspitali in Reykjavik. At the end of May 2019, over 46.000 (19% of adults of Icelandic origin) had registered at the website and 352 (0.77%) received text message informing them about their positive results. Of those, 195 (55%) contacted the GC unit. Additionally, 129 relatives asked for GC and confirmatory testing, a total of 324 individuals. Various information such as gender and age, prior knowledge of the variant and perceived emotional impact, was collected. Of the BRCA2 positive individuals from the website, 74 (38%) had prior knowledge of the pathogenic variant (PV) in the family. The majority initially stated worries, anxiety or other negative emotion but later in the process many communicated gratitude for the knowledge gained. Males represented 41% of counsellees as opposed to less than 30% in the regular hereditary breast and ovarian (HBOC) clinic. It appears that counselling in clinical settings was more reassuring for worried counsellees. In this article, we describe one-year experience of the GC service to those who received positive results via the website. this website This experience offers a unique opportunity to study the public response of a successful method of the return of genetic results from research.Dominant and recessive mutations in podocalyxin (PODXL) are associated with human kidney disease. Interestingly, some PODXL mutations manifest as anuria while others are associated with proteinuric kidney disease. PODXL heterozygosity is associated with adult-onset kidney disease and podocalyxin shedding into the urine is a common biomarker of a variety nephrotic syndromes. It is unknown, however, how various lesions in PODXL contribute to these disparate disease pathologies. Here we generated two mouse stains one that deletes Podxl in developmentally mature podocytes (Podxl∆Pod) and a second that is heterozygous for podocalyxin in all tissues (Podxl+/-). We used histologic and ultrastructural analyses, as well as clinical chemistry assays to evaluate kidney development and function in these strains. In contrast to null knockout mice (Podxl-/-), which die shortly after birth from anuria and hypertension, Podxl∆Pod mice develop an acute congenital nephrotic syndrome characterized by focal segmental glomerulosclerosis (FSGS) and proteinuria. Podxl+/- mice, in contrast, have a normal lifespan, and fail to develop kidney disease under normal conditions. Intriguingly, although wild-type C57Bl/6 mice are resistant to puromycin aminonucleoside (PA)-induced nephrosis (PAN), Podxl+/- mice are highly sensitive and PA induces severe proteinuria and collapsing FSGS. In summary, we find that the developmental timepoint at which podocalyxin is ablated (immature vs. mature podocytes) has a profound effect on the urinary phenotype due to its critical roles in both the formation and the maintenance of podocyte ultrastructure. In addition, Podxl∆Pod and Podxl+/- mice offer powerful new mouse models to evaluate early biomarkers of proteinuric kidney disease and to test novel therapeutics.Aging is characterized by a chronic, low-grade inflammation, which is a major risk factor for cardiovascular diseases. It remains poorly understood whether pro-inflammatory factors released from non-cardiac tissues contribute to the non-autonomous regulation of age-related cardiac dysfunction. Here, we report that age-dependent induction of cytokine unpaired 3 (upd3) in Drosophila oenocytes (hepatocyte-like cells) is the primary non-autonomous mechanism for cardiac aging. We show that upd3 is significantly up-regulated in aged oenocytes. Oenocyte-specific knockdown of upd3 is sufficient to block aging-induced cardiac arrhythmia. We further show that the age-dependent induction of upd3 is triggered by impaired peroxisomal import and elevated JNK signaling in aged oenocytes. We term hormonal factors induced by peroxisome dysfunction as peroxikines. Intriguingly, oenocyte-specific overexpression of Pex5, the key peroxisomal import receptor, blocks age-related upd3 induction and alleviates cardiac arrhythmicity. Thus, our studies identify an important role of hepatocyte-specific peroxisomal import in mediating non-autonomous regulation of cardiac aging.