A phylogenetically-restricted essential cell cycle progression factor in the human pathogen Candida albicans

Chromosomal instability in fungal pathogens caused by cell division errors is associated with antifungal drug resistance. To identify mechanisms underlying such instability and to uncover new potential antifungal targets, we conducted an overexpression screen monitoring chromosomal stability in the human fungal pathogen Candida albicans. Analysis of ~1000 genes uncovered six chromosomal stability (CSA) genes, five of which are related to cell division genes in other organisms. The sixth gene, CSA6, is selectively present in the CUG-Ser clade species that includes C. albicans and other human fungal pathogens. The protein encoded by CSA6 localizes to the spindle pole bodies, is required for exit from mitosis, and induces a checkpoint-dependent metaphase arrest upon overexpression. Together, Csa6 defines an essential CUG-Ser fungal clade-specific cell cycle progression factor, highlighting the existence of phylogenetically-restricted cell division genes which may serve as potential unique therapeutic targets.

Mineralocorticoid Receptor Antagonists—Use in Chronic Kidney Disease

Mineralocorticoid receptor antagonists (MRA) are drugs with a potentially broad spectrum of action. They have been reported to have healing effects in many diseases, such as chronic heart failure, hypertension, or nephrotic syndrome. Numerous studies suggest that mineralocorticoid receptor activation is pathogenic and a progression factor of chronic kidney disease (CKD); however, results of studies on the use of MRA in the treatment of CKD are inconclusive. Current guidelines recommend against the use of MRA in patients with advanced CKD. Although, there is growing interest on their use in this population due to treatment benefits. In this review, we summarize studies which were purposed to evaluate the impact of MRA therapy on CKD patients. Despite many benefits of this treatment e.g., reducing cardiovascular mortality or alleviating proteinuria, steroidal MRA (such as spironolactone or eplerenone) have a low safety profile. They often lead to hyperkalemia complications which are dangerous in patients with CKD, and diabetic nephropathy, especially in hemodialysis patients. Studies on recently developed nonsteroidal MRA showed that they have fewer side effects. In our review, we discuss steroidal and nonsteroidal MRA treatment effects on the estimated glomerular filtration rate (eGFR), proteinuria, the cardiovascular system, and hyperkalemia in CKD patients. We present new content and recent publications in this field.

Epidemiology of Myopia in Children of the Russian Federation and Analysis of Its Control Methods

The increasing prevalence of myopia is observed all over the world, and Russia is no exception. In this regard, obtaining new data on its epidemiology among children and assessing methods of its control in real clinical practice are highly topical matters.Purpose. The purpose of this work was to assess the current issues of the epidemiology and treatment of progressive myopia in children in various regions of the Russian Federation.Materials and methods. We conducted a prospective multicenter epidemiological observational questionnaire study. This study involved 106 doctors from 53 regions of Russia and 2931 parents of myopic children.Results. 50% of the surveyed doctors noted that the manifestation of myopia is diagnosed in children aged 10–12 years, while 43% noted the same in children aged 7–9 years. According to 74.5% of doctors, the degree of the newly diagnosed myopia ranges from –1.25 to –3.00 diopters, 25.5% of doctors reported that it is below –1.0 diopters. The majority of doctors (73.6%) assess accommodation in myopic children, considering it one of the progression factors. 52.9% of ophthalmologists prescribe optical correction in cases when monocular distance visual acuity amounts to 0.6 (decimal scale) or lower values, while 29.2%, 16% and 1.9% of the surveyed ophthalmologists prescribe optical correction in cases when monocular distance visual acuity amounts to 0.7, 0.8 and 0.9 respectively.The following optical methods for juvenile myopia control are recommended by the doctors: orthokeratology contact lenses (53.8%), spectacles for full correction (51.9%), peripheral defocus-inducing (bifocal) soft contact lenses (18.9%), while 4.7% of the surveyed doctors utilized other methods of myopia control, which were not indicated in the questionnaire.Conclusion. In most cases, manifestation of myopia is diagnosed in children aged 7–12 years. Its degree ranges from –1.25 to –3.0 diopters, which indicates its late diagnosis; optical correction is prescribed mainly in cases when monocular distance visual acuity is 0.6 or lower; most ophthalmologists assess accommodation in myopic children, considering it a progression factor. As methods of myopia control, doctors utilize optical correction, device-assisted therapy and pharmacological treatment of accommodative disorders, while parents prefer methods that require minimum time expenditures.

Hepatitis B Virus X Protein Modulates Chemokine CCL15 Upregulation in Hepatocellular Carcinoma

Background: Hepatitis B virus X protein (HBx) is an indispensable progression factor in hepatocellular carcinoma (HCC). CCL15 could be a peculiar proteomic biomarker of HCC with tumorigenesis and tumor invasion. Objective: The aim of study was to explore the relationship between HBx and CCL15 expression in HCC. Methods: HBV–positive HCC pathological tissue samples and corresponding adjacent non-tumor liver tissues were clearly collected. The expression of HBx and CCL15 was analyzed by immunohistochemistry, real-time polymerase chain reaction (PCR) and western blot analysis in tissues or in vitro. Results: The levels of CCL15 mRNA and protein expression in HCC samples were observably higher than the ones of adjacent non-tumor liver tissues. The CCL15 was significantly associated with the expression of HBx in HBV-positive HCC samples. The up-regulation of HBx induced CCL15 expression in vitro. The high expression score of CCL15 was significant associated with the poor prognosis of HCC patients. Conclusions: The CCL15 expression was observably associated with HBx in HCC patients. The CCL15 may be considered as a indicator in clinical managment of HBV-associated HCC.

Isoform-specific functions of Numb in breast cancer progression, metastasis and proteome remodeling

ABSTRACTDeregulated alternative splicing of the endocytic adaptor NUMB resulting in high expression of Exon9in (exon 9-containing) isoforms has been reported in several cancer types. However, the role of Numb isoform expression in tumor progression and the underlying mechanisms remain elusive. Here, we report greater exon 9 inclusion in multiple cancer types including all subtypes of breast cancer, and correlation of higher exon 9 inclusion in patients with worse prognosis. Deletion of Exon9in in breast cancer cells leads to reduced cell growth and a significant decrease of lung metastasis in orthotopic xenograft experiments. Quantitative mass spectrometry revealed downregulation of proteins involved in EMT and ECM organization and remodeling of the endocytic protein network in cells lacking the Exon9in Numb isoforms. Exon 9 deletion also results in reduced surface levels of ITGβ5, and downstream signaling to ERK and SRC, consistent with enhance lysosomal targeting mediated by the remaining Exon9sk (exon 9 skipping) Numb isoforms.SIGNIFICANCEExpression of NUMB Exon9in protein isoforms correlate with worse progression free survival, particularly in breast cancer. Our findings also reveal that Exon9in isoforms promote breast cancer progression by relieving Numb mediated down regulation of integrins and implicate Numb alternative splicing as a progression factor in multiple cancer types.

Population ecology of Trigoniulus corallinus (Gervais) (Diplopoda: Spirobolida)

A population of Trigoniulus corallinus (Gervis) in an open land rich in organic matter is studied for a year. Population density and biomass ranged from 2.13 to 56.31per m2 and 1026.38 to 8494.38 per m2 respectively. Various indices showed that population of T. corallinus is aggregated in distribution in the peak period of their abundance and this is due to patchy distribution of food, soil moisture and sexual attraction. Monthly age structure showed adult and late stadia are abundant in June, October and November while August population covered all the stadia.In the developmental stages, length and width progression factor of T. corallinus ranged from 1.11 to 1.98 (mean 1.43) and 1.10 to 1.56 (mean 1.31) respectively. Weight progression factor in female is higher compared to that of male and this may due to more accumulation of egg forming tissue in female. Population density and biomass is significantly correlated with minimum temperature and rainfall.

Deviation of Dyar’s rule in the post-embryonic development in millipedes – a comprehensive analysis

Dyar’s value on the basis of length and width of nine polydesmid and 15 non-polydesmid millipede species were calculated. The value of polydesmid millipede ranged from 1.50 to 1.78 and that of non-polydesmid millipede ranged from 1.08 to 1.45. Weight progression factor was determined for nine species of millipede (two polydesmid and seven non-polydesmids). The result showed that the mean weight progression factor in polydesmid is 2.54 while that of non-polydesmid is 1.95. Both the results showed that Dyar’s value in polydesmida is significantly higher compared to that of non-polydesmida. In polydesmida, the number of stadium is only eight with higher Dyar’s value (mean 1.61) while in non-polydesmida, where number of stadium is more than eight have lower Dyar’s value (mean 1.23). As in other arthropods, Dyar’s value is inversely proportional to the number of stadium in millipede.The present study also affirmed Enders’ hypothesis in favour of adaptive importance of Dyar’s rule. Deviations from Dyar’s constant in these two group also support Crossby’s growth rule. The variation of Dyar’s value in these two groups of millipede is related to the development time and habitat utilization. The variation of weight progression factor in these two groups is also linked to the development time as observed in other arthropods.

Phosphorylation of Tyr sites of USP1 protein in K562 cell as a progression factor of chronic myeloid leukemia

Aim. To study the properties of Tyr phosphorylation of USP1 protein in K562 cells. Methods. The bioinformatics analysis of the USP1 protein sites of phosphorylayion using the Phosphosite software. Coimmunoprecipitation, Western blot. Immunofluorescence analysis and confocal microscopy. Results. Potential phosphorylation sites for USP1 protein for Tyr are provided. Phosphorylated form of USP1 protein detected in K562 cells. Using immunofluorescence analysis and confocal microscopy, we found that Tyr phosphorylated forms of USP1 protein are localized in the nucleus. Conclusions. We deem that Tyr phosphorylation of USP1 protein is the consequence of its interaction with Bcr-Abl oncoprotein, which has high kinase activity. USP1 phosphorylation can raise deubiquitinating activity of this protein, and as a result, avert the proteosomal degradation of Bcr-Abl in cell and facilitate the progress of the disease.Keywords: chronic myeloid leukemia, Bcr-Abl, USP1, Tyr site of phosphorylation.

An Improved Lock-Free Binary Search Tree

We investigated the binary search tree data structure proposed in the publication, Efficient Lock-Free Binary Search Trees by Bapi Chatterjee, Nhan Nguyen and Philipas Tsigas. We will explore its correctness, progression factor, and the linearizability of its operations and report our findings. With a lock-free algorithm, software engineers will be able to use a thread-safe binary search tree that is capable of the many different operations that are normally available on a binary search tree. This includes the basic, primitive operations of Add(), Contains(), and Remove(), without the performance loss of using a binary search tree that uses object locking. An implementation of a binary search tree that uses locks to promote thread-safety takes a performance loss due to the threads waiting when another thread holds the lock and causing contention. The approach outlined in the aforementioned paper claims to have several key fundamental improvements over existing lock-free binary search tree algorithms. This implementation of the binary search tree eliminates contention in Contains() operations where, if a node was modified while a Contains() operation took place, the program would restart any current operation from the root of the tree. This happens because the thread can no longer reliably confide in the traversal of the tree and must restart its search. This is taxing to the performance of a binary search tree and an inefficient design can underperform a sequential implementation. Among other improvements, the authors of this paper claim that their algorithm is linearizable and has improved disjoint-access parallelism compared to similar existing algorithms.