Malassezia is a unique lipophilic genus in class Malasseziomycetes in Ustilaginomycotina, (Basidiomycota, fungi) that otherwise consists almost exclusively of plant pathogens. Malassezia are typically isolated from warm-blooded animals, are dominant members of the human skin mycobiome and are associated with common skin disorders. To characterize the genetic basis of the unique phenotypes of Malassezia spp., we sequenced the genomes of all 14 accepted species and used comparative genomics against a broad panel of fungal genomes to comprehensively identify distinct features that define the Malassezia gene repertoire: gene gain and loss; selection signatures; and lineage-specific gene family expansions. Our analysis revealed key gene gain events (64) with a single gene conserved across all Malassezia but absent in all other sequenced Basidiomycota. These likely horizontally transferred genes provide intriguing gain-of-function events and prime candidates to explain the emergence of Malassezia. A larger set of genes (741) were lost, with enrichment for glycosyl hydrolases and carbohydrate metabolism, concordant with adaptation to skin’s carbohydrate-deficient environment. Gene family analysis revealed extensive turnover and underlined the importance of secretory lipases, phospholipases, aspartyl proteases, and other peptidases. Combining genomic analysis with a re-evaluation of culture characteristics, we establish the likely lipid-dependence of all Malassezia. Our phylogenetic analysis sheds new light on the relationship between Malassezia and other members of Ustilaginomycotina, as well as phylogenetic lineages within the genus. Overall, our study provides a unique genomic resource for understanding Malassezia niche-specificity and potential virulence, as well as their abundance and distribution in the environment and on human skin.

Heart rate variability (HRV), extracted from an electrocardiogram, is known to be a noninvasive indicator reflecting the dynamic interplay between perturbations to cardiovascular function and the dynamic response of the cardiovascular regulatory system. Photoplethysmography (PPG) is a noninvasive method to monitor arterial oxygen saturation on a continuous basis. Given the rich cardiovascular information in the PPG signal, and the ubiquity and simplicity of pulse oximetry, we are investigating the feasibility of acquiring dynamics pertaining to the autonomic nervous system from PPG waveforms. To do this, we are quantifying PPG variability (PPGV). Detailed algorithmic approaches for extracting accurate PPGV signals are presented. We compare PPGV to HRV by computing time and frequency domain parameters often associated with HRV measurements, as well as approximate entropy calculations. Our results demonstrate that the parameters of PPGV are highly correlated with the parameters of HRV. Thus, our results indicate that PPGV could be used as an alternative measurement of HRV.

The discovery that endoplasmic reticulum (ER) luminal chaperones such as GRP78/BiP can escape to the cell surface upon ER stress where they regulate cell signaling, proliferation, apoptosis, and immunity represents a paradigm shift. Toward deciphering the mechanisms, we report here that, upon ER stress, IRE1α binds to and triggers tyrosine kinase SRC activation, leading to ASAP1 phosphorylation and Golgi accumulation of ASAP1 and Arf1-GTP, resulting in KDEL receptor dispersion from the Golgi and suppression of retrograde transport. At the cell surface, GRP78 binds to and acts in concert with a glycosylphosphatidylinositol-anchored protein, CD109, in blocking TGF-β signaling by promoting the routing of the TGF-β receptor to the caveolae, thereby disrupting its binding to and activation of Smad2. Collectively, we uncover a SRC-mediated signaling cascade that leads to the relocalization of ER chaperones to the cell surface and a mechanism whereby GRP78 counteracts the tumor-suppressor effect of TGF-β.

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BackgroundIt has been verified that taurine has some preventive effects on diabetes and its complications when used alone or together with other drugs, but there are few reports about taurine on the prevention of diabetic nephropathy, the mechanisms of which are still unknown.MethodsTaurine was administered to type Ⅱ diabetic rats induced by high fat high sugar diet combined with STZ injection. The preventive effect of taurine on diabetic nephropathy was investigated by detecting blood glucose, lipid metabolism, kidney function and glomerular basement membrane metabolism.ResultsTaurine could lower blood glucose, TG, TC, BUN, Scr, NAG, U-PRO, the expression of laminin B1( LBN1) mRNA, and increase HDL-C of diabetic rats.ConclusionsThe results indicated that taurine could prevent the occurrence and development of diabetic nephropathy by decreasing blood glucose, improving lipid metabolism, glomerular basement membrane metabolism, and kidney function.

M agnetic resonance imaging (MRI) is a widely used diagnostic tool for breast imaging in daily practice, with its high sensitivity to detect primary, recurrent, and residual breast cancer. Breast MRI serves as a reliable problem-solving tool in case of inconclusive mammography and ultrasonography (US) findings. It can be used to monitor the results of neoadjuvant chemotherapy and it may also contribute to preoperative evaluation of known lesions. With increasing use of MRI, number of breast lesions visible only on MRI and need for MRI-guided breast biopsy have increased (1). Second-look US can also be used for re-evaluation of these lesions; because US-guided biopsy is an easier, cheaper, and faster method if these lesions are visible on second-look US. According to a recently published meta-analysis, lesion detection rates with second-look US are variable in the literature (22.6%-82.1%). Mass lesions and malignant lesions were more likely to be detected at second-look US; average detection rates were 66% for masses, 29% for non-mass-like enhancement (NME) (2, 3). However, focal or NME lesions, which are less detectable than masses on second-look US, require MRI-guided biopsy in the majority of cases. According to the MRI-guided biopsy series in the literature, approximately 25%-35% of these lesions are diagnosed as malignant (4-9).Within this context, the aim of the present study is to assess the effectiveness of MRI-guided 10 Gauge (G) vacuum-assisted breast biopsies (VABB) performed at our institution and to examine the relationship between lesion characteristics and histopathologic results. B R E A S T I MAG I N G O R I G I N A L A R T I C L E PURPOSEWe aimed to assess the effectiveness of magnetic resonance imaging (MRI)-guided vacuum-assisted breast biopsy (VABB), evaluate and compare the characteristics and histopathologic findings of lesions, and overview the follow-up results of benign lesions. METHODSMRI findings and histopathologic results of breast lesions biopsied by MRI-guided VABB between 2013 and 2016 were retrospectively analyzed. MRI findings closely related with malignancy were investigated in particular. Follow-up results of benign lesions were evaluated. RESULTSMRI-guided VABB was applied to 116 lesions of 112 women. Of the lesions, 75 (65%) were benign, while 41 (35%) were malignant. Segmental (94%), clustered (89%), and clustered ring (67%) nonmass-like enhancement patterns were found to be more related with malignancy. False-negative rate of MRI-guided VABB was 12%, underestimation rate was 21%. One of the 54 followed-up benign lesions had a malignant result. CONCLUSION MRI-guided VABB is a reliable method for the diagnosis of breast lesions that are positive only on MRI. Follow-up results show that cancer detection rate is low for radio-pathologically concordant lesions. Further multicenter studies with larger patient population are needed to elucidate these results.You may cite this article as: Taşkın F, Soyder A, Tanyeri A, Öztürk VS, Ünsal A. Lesion characteristics, histopathologic r...

Pulmonary transit time derived from pulmonary angiography is useful for diagnosing HPS, especially for patients with intracardiac shunts and inadequate echocardiographic windows.

We propose a method to extend to time-varying (TV) systems the procedure for generating typical surrogate time series, in order to test the presence of nonlinear dynamics in potentially nonstationary signals. The method is based on fitting a TV autoregressive (AR) model to the original series and then regressing the model coefficients with random replacements of the model residuals to generate TV AR surrogate series. The proposed surrogate series were used in combination with a TV sample entropy (SE) discriminating statistic to assess nonlinearity in both simulated and experimental time series, in comparison with traditional time-invariant (TIV) surrogates combined with the TIV SE discriminating statistic. Analysis of simulated time series showed that using TIV surrogates, linear nonstationary time series may be erroneously regarded as nonlinear and weak TV nonlinearities may remain unrevealed, while the use of TV AR surrogates markedly increases the probability of a correct interpretation. Application to short (500 beats) heart rate variability (HRV) time series recorded at rest (R), after head-up tilt (T), and during paced breathing (PB) showed: 1) modifications of the SE statistic that were well interpretable with the known cardiovascular physiology; 2) significant contribution of nonlinear dynamics to HRV in all conditions, with significant increase during PB at 0.2 Hz respiration rate; and 3) a disagreement between TV AR surrogates and TIV surrogates in about a quarter of the series, suggesting that nonstationarity may affect HRV recordings and bias the outcome of the traditional surrogate-based nonlinearity test.