No abstract

Telomere attachment to the nuclear envelope (NE) is a prerequisite for chromosome movement during meiotic prophase I that is required for pairing of homologous chromosomes, synapsis, and homologous recombination. Here we show that Speedy A, a noncanonical activator of cyclin-dependent kinases (Cdks), is specifically localized to telomeres in prophase I male and female germ cells in mice, and plays an essential role in the telomere-NE attachment. Deletion of Spdya in mice disrupts telomere-NE attachment, and this impairs homologous pairing and synapsis and leads to zygotene arrest in male and female germ cells. In addition, we have identified a telomere localization domain on Speedy A covering the distal N terminus and the Cdk2-binding Ringo domain, and this domain is essential for the localization of Speedy A to telomeres. Furthermore, we found that the binding of Cdk2 to Speedy A is indispensable for Cdk2's localization on telomeres, suggesting that Speedy A and Cdk2 might be the initial components that are recruited to the NE for forming the meiotic telomere complex. However, Speedy A-Cdk2-mediated telomere-NE attachment is independent of Cdk2 activation. Our results thus indicate that Speedy A and Cdk2 might mediate the initial telomere-NE attachment for the efficient assembly of the telomere complex that is essential for meiotic prophase I progression. meiosis | telomere | Speedy A | Cdk2 | germ cells

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Recent progress in the field of zwitterionic polyelectrolytes is reviewed. This class of polyelectrolytes is only five decades old, since the first synthesis was in 1952. Polycarboxybetaines, polysulfobetaines, polyphosphobetaines and a few more zwitterionic materials compose this class of polymers. In the current search for ‘biomimicking’ materials, this class is particularly important. The responsive properties of polyzwitterions are specific, sensitive and instantaneous to a wide variety of external stimuli, which has been reviewed in this article. The synthesis of polyampholytes and polybetaines (homopolymers, copolymers, block polymers) are reviewed. The exploitation of such materials in solid state conducting materials, chromatographic materials and other applications has been incorporated. The extensive discussion on solution properties, antipolyelectrolytic characteristics and influence of varying class of electrolytes has been qualitative as well as quantitative providing an insight into the importance and relevance of such materials, the block polymers form reversible ‘schizophrenic’ micelles also.

A unique feature of female germ cell development in mammals is their remarkably long arrest at the prophase of meiosis I, which lasts up to 50 years in humans. Both dormant and growing oocytes are arrested at prophase I and completely lack the ability to resume meiosis. Here, we show that the prolonged meiotic arrest of female germ cells is largely achieved via the inhibitory phosphorylation of Cdk1 (cyclin-dependent kinase 1). In two mouse models where we have introduced mutant Cdk1T14AY15F which cannot be inhibited by phosphorylation (Cdk1AF) in small meiotically incompetent oocytes, the prophase I arrest is interrupted, leading to a premature loss of female germ cells. We show that in growing oocytes, Cdk1AF leads to premature resumption of meiosis with condensed chromosomes and germinal vesicle breakdown followed by oocyte death, whereas in dormant oocytes, Cdk1AF leads to oocyte death directly, and both situations damage the ovarian reserve that maintains the female reproductive lifespan, which should be around 1 year in mice. Furthermore, interruption of the inhibitory phosphorylation of Cdk1 results in DNA damage, which is accompanied by induction of the Chk2 (checkpoint kinase 2)-p53/p63-dependent cell death pathway, which eventually causes global oocyte death. Together, our data demonstrate that the phosphorylation-mediated suppression of Cdk1 activity is one of the crucial factors that maintain the lengthy prophase arrest in mammalian female germ cells, which is essential for preserving the germ cell pool and reproductive lifespan in female mammals.

Schematic outline of the most potent compound, benzothiazole bearing amide moiety A07, showing antibacterial activity and its mode of action.

Heterocyclic compounds, analogs and derivatives have attracted attention due to their diverse biological and pharmacological properties. Benzoheterocycles such as benzothiazoles, benzimidazoles and benzoxazoles are constituents of many bioactive heterocyclic compounds, having wider range of applications. They have been extensively studied for their biological activities, and can serve as unique and versatile scaffolds for drug design. The benzothiazole, in the family of heterocyclic compounds has assumed special significance in synthetic chemistry, pharmaceutical chemistry as well as in clinical applications because of its anti-tumor properties. This review is organized in the following ways. It begins with brief introduction on the chemical diversity of synthetic analogs of benzothiazole. After this, drug design strategy and mechanisms of action through its diverse biological targets in which benzothiazole and its derivatives display their anticancer activity are discussed. It ends with the metabolism pattern of benzothiazole and its analogs. Analysis of the structure-activity relationships (SAR), quantitative structure-activity relationships (QSAR) as well as on docking studies of this family of compounds highlights the potential that may lead to the development of novel anticancer agents. Such relationships will definitely create lot of interest among the researchers to synthesize optimized variety of benzothiazole derivatives and to screen them for their anticancer activity.

The current study describes the effect of the concentration of Span 60 (gelator) on the properties of oleogels. Mustard oil was chosen as the representative vegetable oil. Microscopy showed that an increase in the gelator concentration resulted in the increase in the gelator network density. Thermal studies (crystallization kinetics and differential scanning calorimetry) indicated a 2-stage crystallization process. An increase in the gelator proportion resulted in the increase in the compatibility amongst the oleogel components. The formation of gelator network was governed by the interaction amongst the hydroxyl groups of Span 60. A variation in the gelator proportion resulted in the alteration in the d-spacing, crystallite size and lattice strain. The variation in the above-mentioned properties was found to affect the viscoelastic properties of the oleogels as was predicted from the Weichert model. The drug release studies suggested that the drug diffusion due to the gelator network relaxation during drug release was predominant as compared to the Fickian diffusion. The results suggested that it is possible to alter not only the release profile of drugs but also the physical properties (of the oleogels) by tailoring the gelator concentration.