Mycobacterial panniculitis caused by Mycobacterium thermoresistibile in a cat.

Case summaryA domestic shorthair cat was evaluated for chronic, bilateral, ulcerative dermatitis affecting the inguinal region and lateral aspects of both pelvic limbs. Histopathologic examination of skin biopsies collected throughout the course of disease revealed chronic pyogranulomatous ulcerative dermatitis. Aerobic bacterial skin cultures yielded growth of a methicillin-resistant Staphylococcus aureus and Corynebacterium amycolatum. Upon referral the clinical findings were suggestive of a non-tuberculous Mycobacterium species infection. Previously obtained skin cultures failed to yield growth of mycobacterial organisms. A deep skin biopsy was collected and submitted for mycobacterial culture. At 5 weeks of incubation Mycobacterium thermoresistibile was isolated. In previous reports, M thermoresistibile has been isolated after 2-4 days of incubation, suggesting that this strain may have been a slower growing variant, or other factors (such as prior antimicrobial therapy) inhibited rapid growth of this isolate. The cat was hospitalized for intravenous antibiotic therapy, surgical debridement of wounds, vacuum-assisted wound closure therapy and reconstruction procedures. The wounds were ultimately primarily closed and the cat was discharged to the owner after 50 days of hospitalization. Seven months after hospitalization, the ulcerative skin lesions had healed.Relevance and novel informationTo our knowledge, only two cases of M thermoresistibile panniculitis have been reported in cats. In the only detailed report of feline M thermoresistibile panniculitis, treatment was not attempted. The second case only reported detection of M thermoresistibile by PCR without a clinical description of the case. In our case report, severe chronic skin infection with M thermoresistibile was addressed using prolonged specific antibiotic therapy, surgical debridement and reconstructions, and treatment of secondary bacterial infections

Peculiarities of left ventricular myocardial remodeling among pregnant women with chronic arterial hypertension complicated by preeclampsia

Objective: to evaluate the nature of LV myocardial remodeling among pregnant women with chronic arterial hypertension (CAH), complicated by preeclampsia (PE), and the effect of antihypertensive therapy start on the reversibility of cardiac changes.Materials and Methods: pregnant women with CAH (n = 376): group I - with isolated CAH (n = 172), group II - with the development of PE on its background. Depending on the time of antihypertensive therapy start: in the group with CAH - early (n = 58), delayed (n = 76), in the group with PE development on the CAH background - early (n = 114), delayed (n = 128). Clinical and statistical, echocardiography, tissue myocardial doppler echocardiography (TMDEchoCG).Results: the group of pregnant women with PE development on the CAH background was distinguished by large indicators of LV myocardium mass - by 15.5% in the second trimester of pregnancy, 12.1% - in the third one. The initial manifestations of diastolic dysfunction of the left ventricular (LV DD) were diagnosed according to the results of TMDEchoCG: among 28.9 % of pregnant women in the second trimester, 40.3% - in the third one. The frequency of abnormal LV remodeling on the CAH background was 76.3% in the II trimester, 85.4% in the III one, with an increase in LV hypertrophy of the concentric type by the III trimester from 28.2% to 38.6% .The absence of early antihypertensive therapy caused higher frequency of elevated (“> 128”) values of the disproportionality coefficient (DC): with PE development on the CAH background it increased by 1.3 times (60.9% vs 33.3%), with left ventricular hypertrophy (LVH) according to the concentric type - by 1.5 times in the second trimester (34.4% vs 18.8%) and by 2.5 times (59.4% vs 23.7%) - in the third one. The effectiveness of early CAH correction during pregnancy is proved by the lower occurrence of diastolic dysfunction (DD): in the second trimester 22.8% vs 38.3%, in the third one - 21.1% vs 61.7%.Conclusions: it is proved that the probability of LV myocardium damage development on the CAH background increases with the identification of a disproportionately high LV myocardium mass as a result of BP overload. The study of LV and DF geometry allows to clarify the degree of organ damage (myocardium) and the effectiveness of antihypertensive therapy. It is stated that in the absence of rational CAH correction, morphofunctional changes in the LV cardiac muscle progress with the course of pregnancy, to the greater extent - with PE complication

Transcription of a protein-coding gene on B chromosomes of the Siberian roe deer (Capreolus pygargus)

BACKGROUND: Most eukaryotic species represent stable karyotypes with a particular diploid number. B chromosomes are additional to standard karyotypes and may vary in size, number and morphology even between cells of the same individual. For many years it was generally believed that B chromosomes found in some plant, animal and fungi species lacked active genes. Recently, molecular cytogenetic studies showed the presence of additional copies of protein-coding genes on B chromosomes. However, the transcriptional activity of these genes remained elusive. We studied karyotypes of the Siberian roe deer (Capreolus pygargus) that possess up to 14 B chromosomes to investigate the presence and expression of genes on supernumerary chromosomes. RESULTS: Here, we describe a 2 Mbp region homologous to cattle chromosome 3 and containing TNNI3K (partial), FPGT, LRRIQ3 and a large gene-sparse segment on B chromosomes of the Siberian roe deer. The presence of the copy of the autosomal region was demonstrated by B-specific cDNA analysis, PCR assisted mapping, cattle bacterial artificial chromosome (BAC) clone localization and quantitative polymerase chain reaction (qPCR). By comparative analysis of B-specific and non-B chromosomal sequences we discovered some B chromosome-specific mutations in protein-coding genes, which further enabled the detection of a FPGT-TNNI3K transcript expressed from duplicated genes located on B chromosomes in roe deer fibroblasts. CONCLUSIONS: Discovery of a large autosomal segment in all B chromosomes of the Siberian roe deer further corroborates the view of an autosomal origin for these elements. Detection of a B-derived transcript in fibroblasts implies that the protein coding sequences located on Bs are not fully inactivated. The origin, evolution and effect on host of B chromosomal genes seem to be similar to autosomal segmental duplications, which reinforces the view that supernumerary chromosomal elements might play an important role in genome evolution

Depolarization of sperm membrane potential is a common feature of men with subfertility and is associated with low fertilization rate at IVF

STUDY QUESTION. Are significant abnormalities in outward (K+) conductance and resting membrane potential (Vm) present in the spermatozoa of patients undertaking IVF and ICSI and if so, what is their functional effect on fertilization success? SUMMARY ANSWER. Negligible outward conductance (≈5% of patients) or an enhanced inward conductance (≈4% of patients), both of which caused depolarization of Vm, were associated with a low rate of fertilization following IVF. WHAT IS KNOWN ALREADY. Sperm-specific potassium channel knockout mice are infertile with defects in sperm function, suggesting that these channels are essential for fertility. These observations suggest that malfunction of K+ channels in human spermatozoa might contribute significantly to the occurrence of subfertility in men. However, remarkably little is known of the nature of K+ channels in human spermatozoa or the incidence and functional consequences of K+ channel defects. STUDY DESIGN, SIZE AND DURATION. Spermatozoa were obtained from healthy volunteer research donors and subfertile IVF and ICSI patients attending a hospital assisted reproductive techniques clinic between May 2013 and December 2015. In total, 40 IVF patients, 41 ICSI patients and 26 normozoospermic donors took part in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS. Samples were examined using electrophysiology (whole-cell patch clamping). Where abnormal electrophysiological characteristics were identified, spermatozoa were further examined for Ca2+ influx induced by progesterone and penetration into viscous media if sufficient sample was available. Full exome sequencing was performed to specifically evaluate potassium calcium-activated channel subfamily M α 1 (KCNMA1), potassium calcium-activated channel subfamily U member 1 (KCNU1) and leucine-rich repeat containing 52 (LRRC52) genes and others associated with K+ signalling. In IVF patients, comparison with fertilization rates was done to assess the functional significance of the electrophysiological abnormalities. MAIN RESULTS AND THE ROLE OF CHANCE. Patch clamp electrophysiology was used to assess outward (K+) conductance and resting membrane potential (Vm) and signalling/motility assays were used to assess functional characteristics of sperm from IVF and ICSI patient samples. The mean Vm and outward membrane conductance in sperm from IVF and ICSI patients were not significantly different from those of control (donor) sperm prepared under the same conditions, but variation between individuals was significantly greater (P< 0.02) with a large number of outliers (>25%). In particular, in ≈10% of patients (7/81), we observed either a negligible outward conductance (4 patients) or an enhanced inward current (3 patients), both of which caused depolarization of Vm. Analysis of clinical data from the IVF patients showed significant association of depolarized Vm (≥0 mV) with low fertilization rate (P= 0.012). Spermatozoa with electrophysiological abnormities (conductance and Vm) responded normally to progesterone with elevation of [Ca2+]i and penetration of viscous medium, indicating retention of cation channel of sperm (CatSper) channel function. LIMITATIONS, REASONS FOR CAUTION. For practical, technical, ethical and logistical reasons, we could not obtain sufficient additional semen samples from men with conductance abnormalities to establish the cause of the conductance defects. Full exome sequencing was only available in two men with conductance defects. WIDER IMPLICATIONS OF THE FINDINGS. These data add significantly to the understanding of the role of ion channels in human sperm function and its impact on male fertility. Impaired potassium channel conductance (Gm) and/or Vm regulation is both common and complex in human spermatozoa and importantly is associated with impaired fertilization capacity when the Vm of cells is completely depolarized

Deletions of multidrug resistance gene loci in breast cancer leads to the down-regulation of its expression and predict tumor response to neoadjuvant chemotherapy

Neoadjuvant chemotherapy (NAC) is intensively used for the treatment of primary breast cancer. In our previous studies, we reported that clinical tumor response to NAC is associated with the change of multidrug resistance (MDR) gene expression in tumors after chemotherapy. In this study we performed a combined analysis of MDR gene locus deletions in tumor DNA, MDR gene expression and clinical response to NAC in 73 BC patients. Copy number variations (CNVs) in biopsy specimens were tested using high-density microarray platform CytoScanTM HD Array (Affymetrix, USA). 75%-100% persons having deletions of MDR gene loci demonstrated the down-regulation of MDR gene expression. Expression of MDR genes was 2-8 times lower in patients with deletion than in patients having no deletion only in post-NAC tumors samples but not in tumor tissue before chemotherapy. All patients with deletions of ABCB1 ABCB 3 ABCC5 gene loci--7q21.1, 6p21.32, 3q27 correspondingly, and most patients having deletions in ABCC1 (16p13.1), ABCC2 (10q24), ABCG1 (21q22.3), ABCG2 (4q22.1), responded favorably to NAC. The analysis of all CNVs, including both amplification and deletion showed that the frequency of 13q14.2 deletion was 85% among patients bearing tumor with the deletion at least in one MDR gene locus versus 9% in patients with no deletions. Differences in the frequency of 13q14.2 deletions between the two groups were statistically significant (p = 2.03 × 10(-11), Fisher test, Bonferroni-adjusted p = 1.73 × 10(-8)). In conclusion, our study for the first time demonstrates that deletion MDR gene loci can be used as predictive marker for tumor response to NAC

The lateral nasal wall abnormalities in rhinosinusal inflammatory recurrent and chronic pathology in children

Catedra Otorinolaringologie USMF “Nicolae Testemiţanu”Rhinosinusitis is frequently occurring pathology in otorhinolaringology. An important role in the pathogeny of these illnesses play the lateral nasal wall abnormalities. Contemporary diagnosis and surgery of the abnormalities of the lateral nasal wall is based on the endoscopic approach. The analysis of the received results has been debated in the comparative study and has established the anomalies of the lateral wall of the nose in 94,6 % of cases. Sinuzitele paranazale constituie o patologie frecventă în otorinolaringologie. Un rol important în patogenia acestor maladii joacă anomaliile peretelui lateral al foselor nazale. Diagnosticul contemporan şi chirurgia anomaliilor peretelui lateral nazal este fondat pe endoscopia nazală. Analiza rezultatelor obţinute într-un studiu comparat denotă prezenţa anomaliilor peretelui lateral nazal în 94,6% din cazuri

DNA polymerases ζ and Rev1 mediate error-prone bypass of non-B DNA structures

DNA polymerase ζ (Pol ζ) and Rev1 are key players in translesion DNA synthesis. The error-prone Pol ζ can also participate in replication of undamaged DNA when the normal replisome is impaired. Here we define the nature of the replication disturbances that trigger the recruitment of error-prone polymerases in the absence of DNA damage and describe the specific roles of Rev1 and Pol ζ in handling these disturbances. We show that Pol ζ/Rev1-dependent mutations occur at sites of replication stalling at short repeated sequences capable of forming hairpin structures. The Rev1 deoxycytidyl transferase can take over the stalled replicative polymerase and incorporate an additional ‘C’ at the hairpin base. Full hairpin bypass often involves template-switching DNA synthesis, subsequent realignment generating multiply mismatched primer termini and extension of these termini by Pol ζ. The postreplicative pathway dependent on polyubiquitylation of proliferating cell nuclear antigen provides a backup mechanism for accurate bypass of these sequences that is primarily used when the Pol ζ/Rev1-dependent pathway is inactive. The results emphasize the pivotal role of noncanonical DNA structures in mutagenesis and reveal the long-sought-after mechanism of complex mutations that represent a unique signature of Pol ζ

Controlling the topology of Fermi surfaces in metal nanofilms.

The properties of metal crystals are governed by the electrons of the highest occupied states at the Fermi level and determined by Fermi surfaces, the Fermi energy contours in momentum space. Topological regulation of the Fermi surface has been an important issue in synthesizing functional materials, which we found to be realized at room temperature in nanometer-thick films. Reducing the thickness of a metal thin film down to its electron wavelength scale induces the quantum size effect and the electronic system changes from three to two-dimensional, transforming the Fermi surface topology. Such an ultrathin film further changes its topology through one-dimensional (1D) structural deformation of the film when it is grown on a 1D substrate. In particular, when the interface has 1D metallic bands, the system is additionally stabilized by forming an electron energy gap by hybridization between 1D states of the film and substrate

Identification of an anti-CRISPR protein that inhibits the CRISPR-Cas type I-B system in Clostridioides difficile

CRISPR-Cas systems provide prokaryotic hosts with adaptive immunity against mobile genetic elements. Many bacteriophages encode anti-CRISPR (Acr) proteins that inhibit host defense. The identification of Acr proteins is challenging due to their small size and high sequence diversity, and only a limited number has been characterized to date. In this study, we report the discovery of a novel Acr protein, AcrIB2, encoded by the φCD38-2 Clostridioides difficile phage that efficiently inhibits interference by the type I-B CRISPR-Cas system of the host and likely acts as a DNA mimic. Most C. difficile strains contain two cas operons, one encoding a full set of interference and adaptation proteins and another encoding interference proteins only. Unexpectedly, we demonstrate that only the partial operon is required for interference and is subject to inhibition by AcrIB2.This work was supported by the Institut Universitaire de France (to O.S.), the Institute for Integrative Biology of the Cell, the University Paris-Saclay, Graduate School Life Sciences and Health, and OI MICROBES funding and Vernadski fellowship (to P.M.). This work was also supported by NIH grant R01 GM10407 (to K.S.), the Russian Science Foundation grant 19-14-00323, and the Ministry of Science and Higher Education of the Russian Science Federation agreement no. 075-10-2021-114

Tissue optical clearing as a diagnostic tool for tissue pathology differentiation

With the objective of developing a diagnostic tool