The ability to replace organs and tissues on demand could save or improve millions of lives each year globally and create public health benefits on par with curing cancer. Unmet needs for organ and tissue preservation place enormous logistical limitations on transplantation, regenerative medicine, drug discovery, and a variety of rapidly advancing areas spanning biomedicine. A growing coalition of researchers, clinicians, advocacy organizations, academic institutions, and other stakeholders has assembled to address the unmet need for preservation advances, outlining remaining challenges and identifying areas of underinvestment and untapped opportunities. Meanwhile, recent discoveries provide proofs of principle for breakthroughs in a family of research areas surrounding biopreservation. These developments indicate that a new paradigm, integrating multiple existing preservation approaches and new technologies that have flourished in the past 10 years, could transform preservation research. Capitalizing on these opportunities will require engagement across many research areas and stakeholder groups. A coordinated effort is needed to expedite preservation advances that can transform several areas of medicine and medical science.
We identified and produced antibodies to the major proteins that interact with poly(A)+ RNAs in the yeast Saccharomyces cerevisiae. The major proteins which were cross-linked by UV light to poly(A)+ RNA in intact yeast cells had apparent molecular weights of 72,000, 60,000, and 50,000. The poly(A) segment of the RNA was selectively cross-linked to the 72,000-molecular-weight protein (72K protein). Mice immunized with purified UV-cross-linked RNA-protein (RNP) complexes produced antibodies to the three major RNP proteins. A yeast genomic DNA library constructed in the Agtll expression vector was screened with the anti-RNP serum, and recombinant bacteriophage clones were isolated. One recombinant phage, XYPA72.1, bearing a 2.5-kilobase insert, produced a large ,I-galactosidase-RNP fusion protein. mRNA and heterogeneous nuclear RNA are found in eucaryotic cells in association with specific proteins to form RNA-protein complexes known as messenger ribonucleoprotein (RNP) particles (mRNPs) and heterogeneous nuclear ribonucleoprotein particles (hnRNPs), respectively. The complexes are the structural units of these polynucleotides and are likely to be involved in mRNA biogenesis, metabolism, and function (11,13,32). Therefore, the proteins which form hnRNP and mRNP complexes are of considerable interest and have been extensively studied (1, 11-13, 24, 48). Despite a great deal of effort, little is known about the biochemical functions of RNP proteins. Until recently, it has been difficult to identify unambiguously the genuine RNP proteins since nonspecific RNA-protein interactions are likely to occur during cell fractionation. UV cross-linking of proteins to RNA in intact cells overcomes these difficulties and allows the identification of proteins which bind heterogeneous nuclear RNA and mRNA in vivo (11,16,51,54). To learn more about these proteins and about the RNP complexes, we have immunized mice with purified UV-crosslinked RNP complexes and have produced antibodies to several of the major RNP proteins in vertebrate cells (1,12,13).Much of the knowledge of RNP proteins has come from work with higher eucaryotes (12,24,48 (7) and is one of the most conserved and extensively investigated eucaryotic RNP proteins. Although many important functions in mRNA metabolism have been attributed to this protein, little is known about its function, amino acid sequence, and metabolism. This is because specific probes, such as antibodies or gene sequences, have not been available from any species.We report here the identification of the proteins that interact with poly(A)+ RNAs in yeast by UV cross-linking and the production of antibodies to the proteins. Using these antibodies, we identified the poly(A)-binding protein in yeast
Objective To evaluate the possible role of endocrine-disrupting compounds (EDCs) on female reproductive disorders emphasizing developmental plasticity and the complexity of endocrine-dependent ontogeny of reproductive organs. Declining conception rates and the high incidence of female reproductive disruptions warrant evaluation of the impact of EDCs on female reproductive health. Design Publications related to the contribution of EDCs to disorders of the ovary (aneuploidy, polycystic ovary syndrome, and altered cyclicity), uterus (endometriosis, uterine fibroids, fetal growth restriction, and pregnancy loss), breast (breast cancer, reduced duration of lactation), and pubertal timing were identified, reviewed, and summarized at a workshop. Conclusion(s) The data reviewed illustrate that EDCs contribute to numerous human female reproductive disorders and emphasize the sensitivity of early life-stage exposures. Many research gaps are identified that limit full understanding of the contribution of EDCs to female reproductive problems. Moreover, there is an urgent need to reduce the incidence of these reproductive disorders, which can be addressed by correlative studies on early life exposure and adult reproductive dysfunction together with tools to assess the specific exposures and methods to block their effects. This review of the EDC literature as it relates to female health provides an important platform on which women’s health can be improved.
Enhanced long-term survival rates of young women with cancer and advances in reproductive medicine and cryobiology have culminated in an increased interest in fertility preservation methods in girls and young women with cancer. Present data suggest that young patients with cancer should be referred for fertility preservation counselling quickly to help with their coping process. Although the clinical application of novel developments, including oocyte vitrification and oocyte maturation in vitro, has resulted in reasonable success rates in assisted reproduction programmes, experience with these techniques in the setting of fertility preservation is in its infancy. It is hoped that these and other approaches, some of which are still regarded as experimental (eg, ovarian tissue cryopreservation, pharmacological protection against gonadotoxic agents, in-vitro follicle growth, and follicle transplantation) will be optimised and become established within the next decade. Unravelling the complex mechanisms of activation and suppression of follicle growth will not only expand the care of thousands of women diagnosed with cancer, but also inform the care of millions of women confronted with reduced reproductive fitness because of ageing.
Many studies demonstrate that there is still a significant gender bias, especially at higher career levels, in many areas including science, technology, engineering, and mathematics (STEM). We investigated field-dependent, gender-specific effects of the selective pressures individuals experience as they pursue a career in academia within seven STEM disciplines. We built a unique database that comprises 437,787 publications authored by 4,292 faculty members at top United States research universities. Our analyses reveal that gender differences in publication rate and impact are discipline-specific. Our results also support two hypotheses. First, the widely-reported lower publication rates of female faculty are correlated with the amount of research resources typically needed in the discipline considered, and thus may be explained by the lower level of institutional support historically received by females. Second, in disciplines where pursuing an academic position incurs greater career risk, female faculty tend to have a greater fraction of higher impact publications than males. Our findings have significant, field-specific, policy implications for achieving diversity at the faculty level within the STEM disciplines.
BACKGROUND Fertility preservation (FP) is an important quality of life issue for cancer survivors of reproductive age. Despite the existence of broad international guidelines, the delivery of oncofertility care, particularly amongst paediatric, adolescent and young adult patients, remains a challenge for healthcare professionals (HCPs). The quality of oncofertility care is variable and the uptake and utilization of FP remains low. Available guidelines fall short in providing adequate detail on how oncofertility models of care (MOC) allow for the real-world application of guidelines by HCPs. OBJECTIVE AND RATIONALE The aim of this study was to systematically review the literature on the components of oncofertility care as defined by patient and clinician representatives, and identify the barriers, facilitators and challenges, so as to improve the implementation of oncofertility services. SEARCH METHODS A systematic scoping review was conducted on oncofertility MOC literature published in English between 2007 and 2016, relating to 10 domains of care identified through consumer research: communication, oncofertility decision aids, age-appropriate care, referral pathways, documentation, training, supportive care during treatment, reproductive care after cancer treatment, psychosocial support and ethical practice of oncofertility care. A wide range of electronic databases (CINAHL, Embase, PsycINFO, PubMed, AEIPT, Education Research Complete, ProQuest and VOCED) were searched in order to synthesize the evidence around delivery of oncofertility care. Related citations and reference lists were searched. The review was undertaken following registration (International prospective register of systematic reviews (PROSPERO) registration number CRD42017055837) and guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). OUTCOMES A total of 846 potentially relevant studies were identified after the removal of duplicates. All titles and abstracts were screened by a single reviewer and the final 147 papers were screened by two reviewers. Ten papers on established MOC were identified amongst the included papers. Data were extracted from each paper and quality scores were then summarized in the oncofertility MOC summary matrix. The results identified a number of themes for improving MOC in each domain, which included: the importance of patients receiving communication that is of a higher quality and in different formats on their fertility risk and FP options; improving provision of oncofertility care in a timely manner; improving access to age-appropriate care; defining the role and scope of practice of all HCPs; and improving communication between different HCPs. Different forms of decision aids were found useful for assisting patients to understand FP options and weigh up choices. WIDER IMPLICATIONS This analysis identifies core components for de...
Federal funding is associated with the quality of science and researchers' professional advancement. 1 Female junior faculty received less university start-up support than males in one study, 2 a factor associated with early-career attrition rates. 3 We investigated another potential association: the size of National Institutes of Health (NIH) grant awards to first-time awardees.Methods | Using the public NIH Principal Investigators (PI) database, we analyzed grant amounts to first-time female and male grant awardees from 2006 to 2017. A PI's sex was determined algorithmically from first names. First-time PIs had no prior NIH awards as far back as 1985.To examine factors related to funding, we first compared the median number of articles published per year, the median number of citations per article, and the number of areas of research expertise in published articles for first-time female and male PIs prior to their first NIH grant, using Microsoft Academic Graph (MAG). Areas of research expertise were estimated from the articles' research topic as reported in MAG. Only articles with the PI as the last author were counted. 4 To further control for confounding, we examined awardees of the top 10 most highly funded grants awarded to individual PIs only, which represents $14 billion in funding or 58% of all NIH funds awarded to 19 559 first-time PIs. Also, we investigated awardees at the same 14 Big Ten and 8 Ivy League universities ($1.8 billion in funding or 7.5% of NIH funds awarded to 8039 first-time PIs), as well as the top 50 NIH most highly funded institutions ($9 billion in funding or 38% of funding awarded to 20 335 first-time PIs). The 2-sided Mann-Whitney test of medians (threshold P < .05) and Python software (version 2.7.12) were used in the analyses.
The alterations in morphology and function of the ovarian follicle as it matures, ovulates, and becomes a corpus luteum are dramatic. A variety of steroid and polypeptide hormones influence these processes, and the ovary in turn produces specific hormonal signals for endocrine regulation. One such signal is inhibin, a heterodimeric protein that suppresses the secretion of follicle-stimulating hormone from pituitary gonadotrophs. Rat inhibin complementary DNA probes have been used to examine the levels and distribution of inhibin alpha-and beta A-subunit messenger RNAs in the ovaries of cycling animals. Striking, dynamic changes have been found in inhibin messenger RNA accumulation during the developmental maturation of the ovarian follicle.
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