Mcm10 proteolysis initiates before the onset of M-phase

<p>Abstract</p> <p>Background</p> <p>Mcm10 protein is essential for initiation and elongation phases of replication. Human cells proteolyze Mcm10 during mitosis, presumably to ensure a single round of replication. It has been proposed that anaphase promoting complex ubiquitinates Mcm10 in late M and early G₁phases.</p> <p>Results</p> <p>In contrast to the previous work, we report that the degradation of Mcm10 is initiated at the onset of mitosis. Immunoblotting and immunofluorescence assays display that Mcm10 levels are low in all phases of mitosis. We report that Mcm10 degradation is not dependent on anaphase promoting complex. Further, the proteolysis in M-phase can be independently mediated by non-overlapping regions of Mcm10, apparently employing a redundant mechanism to ensure downregulation.</p> <p>Conclusions</p> <p>It is believed that the proteolysis of Mcm10 during mitosis is a vital mechanism to prevent aberrant initiation of replication and the present study describes the regulation of Mcm10 during this phase of the cell-cycle.</p

On the Growths of Meromorphic Function Generated Wronskians from the View Point of Slowly Changing Functions

In the paper we extend and sometimes improve few results on comparative growth properties of composite entire or meromorphic functions using m-th generalized {p}L*-order and the m-th generalized {p}L*-lower order and wronskians generated by one of the factors where m and p are any two positive integers

Type-2 diabetic aldehyde dehydrogenase 2 mutant mice (ALDH 2*2) exhibiting heart failure with preserved ejection fraction phenotype can be determined by exercise stress echocardiography

E487K point mutation of aldehyde dehydrogenase (ALDH) 2 (ALDH2*2) in East Asians intrinsically lowers ALDH2 activity. ALDH2*2 is associated with diabetic cardiomyopathy. Diabetic patients exhibit heart failure of preserved ejection fraction (HFpEF) i.e. while the systolic heart function is preserved in them, they may exhibit diastolic dysfunction, implying a jeopardized myocardial health. Currently, it is challenging to detect cardiac functional deterioration in diabetic mice. Stress echocardiography (echo) in the clinical set-up is a procedure used to measure cardiac reserve and impaired cardiac function in coronary artery diseases. Therefore, we hypothesized that high-fat diet fed type-2 diabetic ALDH2*2 mutant mice exhibit HFpEF which can be measured by cardiac echo stress test methodology. We induced type-2 diabetes in 12-week-old male C57BL/6 and ALDH2*2 mice through a high-fat diet. At the end of 4 months of DM induction, we measured the cardiac function in diabetic and control mice of C57BL/6 and ALDH2*2 genotypes by conscious echo. Subsequently, we imposed exercise stress by allowing the mice to run on the treadmill until exhaustion. Post-stress, we measured their cardiac function again. Only after treadmill running, but not at rest, we found a significant decrease in % fractional shortening and % ejection fraction in ALDH2*2 mice with diabetes compared to C57BL/6 diabetic mice as well as non-diabetic (control) ALDH2*2 mice. The diabetic ALDH2*2 mice also exhibited poor maximal running speed and distance. Our data suggest that high-fat fed diabetic ALDH2*2 mice exhibit HFpEF and treadmill exercise stress echo test is able to determine this HFpEF in the diabetic ALDH2*2 mice

GROWTH OF MEROMORPHIC FUNCTIONS DEPENDING ON (p,q)-TH RELATIVE ORDER

In this paper for any two positive integers p and q, we wish to introduce an alternative definition of relative (p,q) th order of a meromorphic function with respect to another entire function which improves the earlier definition of relative (p,q) th order of meromorphic function introduced by Banerjee and Jana (2007). Also in this paper we discuss some growth rates of composite entire and meromorphic functions on the basis of the improved definition of relative (p,q) th order of meromorphic function

GC-MS ANALYSIS OF ESSENTIAL OIL OF SOME HIGH DRUG YIELDING GENOTYPES OF TURMERIC (CURCUMA LONGA L.)

Objective: The aim of this investigation was to carry out the qualitative evaluation of selected high drug yielding elite genotypes of turmeric to add to their eliteness.Methods: 131 turmeric genotypes collected from 10 different agroclimatic zones were analysed for curcumin content. Leaves and rhizomes of these plants were collected for extraction of essential oil. Curcumin percentage of the sample was estimated according to the ASTA method. Essential oil was extracted by hydro-distillation of fresh leaves and rhizomes following the method of Guenther (1972). Initial screening of elite genotypes was done on the basis of curcumin content (≥5%), rhizome oil content (≥1.5%) and leaf oil content (≥0.5%). Selected elite genotypes were subjected to qualitative evaluation of essential oil through GC-MS analysis.Results: The five high rhizome oil yielding genotypes, TR1, TR2, TR3 and TR5 containing high rhizome oil yield of 2.1%, 1.7%, 1.6% and 1.5% respectively were considered to be elite clones containing tumerone as the major constituent of rhizome essential oil along with all desirable constituents. On the basis of leaf oil yield, genotypes TL1 and TL2 with 1.9% and 1.1% leaf oil were proved as elite clones with α–phellandrene as the major constituent along with other desirable constituents. GC-MS analysis of 3 selected high curcumin yielding genotypes TC1, TC2 and TC3 with curcumin content 7.3, 7.2 and 7.0% respectively revealed TC1 and TC2 as elite genotypes containing high quality rhizome and leaf oil.Conclusion: The present investigation reveals that eight genotypes of turmeric selected with high drug yield and high quality essential oil would have enough significance for boosting the production and export of value added products in the national and international market.Â

Unraveling the relationship between the renin–angiotensin system and endometrial cancer: a comprehensive review

Endometrial cancer (EC), the most common adenocarcinoma, represents 90% of uterine cancer in women with an increased incidence of occurrence attributed to age, obesity, hypertension, and hypoestrogenism. Being the most common gynecological malignancy in women, it shows a relation with the activation of different components of the renin–angiotensin system (RAS), which is predominantly involved in maintaining blood pressure, salt, water, and aldosterone secretion, thereby playing a significant role in the etiology of hypertension. The components of the RAS, i.e., ACE-I, ACE-II, AT1R, AT2R, and Pro(renin) receptor, are widely expressed in both glandular and stromal cells of the endometrium, with varying levels throughout the different phases of the menstrual cycle. This causes the endometrial RAS to implicate angiogenesis, neovascularization, and cell proliferation. Thus, dysfunctioning of the endometrial RAS could predispose the growth and spread of EC. Interestingly, the increased expression of AngII, AGTR1, and AGTR2 showed advancement in the stages and progression of EC via the prorenin/ATP6AP2 and AngII/AGTR1 pathway. Therefore, this review corresponds to unraveling the relationship between the progression and development of endometrial cancer with the dysfunction in the expression of various components associated with RAS in maintaining blood pressure

CDK4/6 inhibitor-mediated cell overgrowth triggers osmotic and replication stress to promote senescence

Summary. Abnormal increases in cell size are associated with senescence and cell cycle exit. The mechanisms by which overgrowth primes cells to withdraw from the cell cycle remain unknown. We address this question using CDK4/6 inhibitors, which arrest cells in G0/G1 and are licensed to treat advanced HR+/HER2− breast cancer. We demonstrate that CDK4/6-inhibited cells overgrow during G0/G1, causing p38/p53/p21-dependent cell cycle withdrawal. Cell cycle withdrawal is triggered by biphasic p21 induction. The first p21 wave is caused by osmotic stress, leading to p38- and size-dependent accumulation of p21. CDK4/6 inhibitor washout results in some cells entering S-phase. Overgrown cells experience replication stress, resulting in a second p21 wave that promotes cell cycle withdrawal from G2 or the subsequent G1. We propose that the levels of p21 integrate signals from overgrowth-triggered stresses to determine cell fate. This model explains how hypertrophy can drive senescence and why CDK4/6 inhibitors have long-lasting effects in patients

Slowly changing function connected growth properties of wronskians generated by entire and meromorphic functions

In the paper we establish some new results depending on the comparative growth properties of composite entire or meromorphic functions using generalised pL*-type with rate pand generalised pL*-weak type with rate p and wronskians generated by one of the factors

Understanding normal development of adolescent sexuality: A bumpy ride

Adolescence, derived from the Latin word "adolescere" meaning "to grow up" is a critical developmental period. During adolescence, major biological as well as psychological developments take place. Development of sexuality is an important bio-psycho-social development, which takes an adult shape during this period. During adolescence, an individual′s thought, perception as well as response gets colored sexually. Puberty is an important landmark of sexuality development that occurs in the adolescence. The myriad of changes that occurs in adolescents puts them under enormous stress, which may have adverse physical, as well as psychological consequences. Understanding adolescent sexuality has important clinical, legal, social, cultural, as well as educational implications