Damage-induced phosphorylation of Sld3 is important to block late origin firing.

Origins of replication are activated throughout the S phase of the cell cycle such that some origins fire early and others fire late to ensure that each chromosome is completely replicated in a timely fashion. However, in response to DNA damage or replication fork stalling, eukaryotic cells block activation of unfired origins. Human cells derived from patients with ataxia telangiectasia are deficient in this process due to the lack of a functional ataxia telangiectasia mutated (ATM) kinase and elicit radioresistant DNA synthesis after γ-irradiation(2). This effect is conserved in budding yeast, as yeast cells lacking the related kinase Mec1 (ATM and Rad3-related (ATR in humans)) also fail to inhibit DNA synthesis in the presence of DNA damage. This intra-S-phase checkpoint actively regulates DNA synthesis by inhibiting the firing of late replicating origins, and this inhibition requires both Mec1 and the downstream checkpoint kinase Rad53 (Chk2 in humans). However, the Rad53 substrate(s) whose phosphorylation is required to mediate this function has remained unknown. Here we show that the replication initiation protein Sld3 is phosphorylated by Rad53, and that this phosphorylation, along with phosphorylation of the Cdc7 kinase regulatory subunit Dbf4, blocks late origin firing in Saccharomyces cerevisiae. Upon exposure to DNA-damaging agents, cells expressing non-phosphorylatable alleles of SLD3 and DBF4 (SLD3-m25 and dbf4-m25, respectively) proceed through the S phase faster than wild-type cells by inappropriately firing late origins of replication. SLD3-m25 dbf4-m25 cells grow poorly in the presence of the replication inhibitor hydroxyurea and accumulate multiple Rad52 foci. Moreover, SLD3-m25 dbf4-m25 cells are delayed in recovering from transient blocks to replication and subsequently arrest at the DNA damage checkpoint. These data indicate that the intra-S-phase checkpoint functions to block late origin firing in adverse conditions to prevent genomic instability and maximize cell survival

Polymorphous low-grade adenocarcinoma of the parotid gland : case report and review of the literature

Polymorphous low-grade adenocarcinoma (PLGA) is difficult to diagnose both clinically and histologically due to its indolent presentation, and because of its morphological diversity that includes several microscopic patterns. The aggressive biologic behavior seen in minor salivary glands as compared to major glands is apparently associated histologically to a predominance of the papillary pattern in the former. Biologic behavior of PLGA in the major salivary glands is uncertain, as some cases have developed recurrences and metastases independently of the presence of a papillary pattern. A case of PLGA originated de novo in parotid gland is presented a 60 year-old male, treatment was surgically excised through superficial parotidectomy and to postoperative radiotherapy (46 Gy). Forty-eight months later the patient is alive with no signs of recurrence, as well as a review of the literature, with particular emphasis in its differential diagnosis and biological behavior

Tumors of the oral cavity : CO2 laser management

Cancer of the oral cavity combined with oropharyngeal cancer is the sixth leading cause of death for cancer worldwide. Surgery remains the standard treatment for this disease in early clinical and locally advanced stages. Numerous studies have shown that laser management is useful for premalignant lesions in the oral cavity; however, there is no conclusive evidence that its use is appropriate in cancer of the oral cavity and that results are comparable with traditional surgery. The objective of this study is to determine cancer control after wide local resection with CO2 laser for oral malignant neoplasms. Retrospective study in patients with tumors of the oral cavity who were considered for surgical resection with CO2 laser from January 2006-December 2015. Demographic data, treatment modalities, histopathological diagnosis and clinical stage variables were obtained. All resections were done with the use of the microspot. Patients with cancer of the tongue were not included because a specific protocol for these patients does exist in our institution. There were twenty patients, 10 male and 10 female with a average age of 58 years (range: 20-92 years). Mean age was 53.5 years for females and 63 years for males. Twelve (60%) patients are alive and disease free and four (20%) were lost free of disease. CO2 laser is an acceptable surgical method for the management of small lesions in the oral cavity. We cannot rule out that small lesions of the oral cavity with positive neck could be managed in this manner, adding treatment to the neck, producing an adequate local regional control. However, this hypothesis requires additional studies

The End or Beginning? Either Way, the Credits Are Not Rolling Yet!

(First paragraph) Thank you to all our reviewers, editorial board members, authors, and those who chose the Journal of Urban Mathematics Education (JUME) as their outlet of choice this past year. JUME has had many recent successes, and we in the editorial team plan to release the salient performance data for the journal. For JUME to advance its mission, we believe that accountability and transparency are essential. To this end, our readers will from now on receive an annual progress report about JUME in our first issue of each year

Engaging Undergraduates in Science Research: Not Just About Faculty Willingness.

Despite the many benefits of involving undergraduates in research and the growing number of undergraduate research programs, few scholars have investigated the factors that affect faculty members' decisions to involve undergraduates in their research projects. We investigated the individual factors and institutional contexts that predict faculty members' likelihood of engaging undergraduates in their research project(s). Using data from the Higher Education Research Institute's 2007-2008 Faculty Survey, we employ hierarchical generalized linear modeling to analyze data from 4,832 science, technology, engineering, and mathematics (STEM) faculty across 194 institutions to examine how organizational citizenship behavior theory and social exchange theory relate to mentoring students in research. Key findings show that faculty who work in the life sciences and those who receive government funding for their research are more likely to involve undergraduates in their research project(s). In addition, faculty at liberal arts or historically Black colleges are significantly more likely to involve undergraduate students in research. Implications for advancing undergraduate research opportunities are discussed

Consecuencias del estrés calórico sobre la reproducción del ganado vacuno

Heat stress represents one of the major environmental factors that adversely affect the reproductive performance of cattle. In this paper the behavioral adjustments, physical mechanisms and physiological responses to heat loss are described; bos indicus adaptive advantages with respect to bos Taurus, pathophysiology of heat stress and heat stress effects in animal reproduction, both the male and the female.El estrés calórico representa unos de los principales factores del medio ambiente que repercuten negativamente en el desempeño reproductivo del ganado vacuno. En este trabajo se describen los ajustes conductuales, mecanismos físicos y respuestas fisiológicas para la pérdida calórica; ventajas adaptativas del bos indicus con respecto al bos Taurus, fisiopatología del estrés calórico y repercusiones del estrés calórico en la reproducción animal, tanto en el macho como en la hembra