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Author

W S Ward

Other affiliations: Johnson University
Bio: W S Ward is an academic researcher from Rutgers University. The author has contributed to research in topics: Sperm & Nuclear matrix. The author has an hindex of 10, co-authored 10 publications receiving 1314 citations. Previous affiliations of W S Ward include Johnson University.
Topics: Sperm, Nuclear matrix, Chromatin, DNA, Gene

Papers
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Journal ArticleDOI
TL;DR: Sperm nuclei contain a unique structure termed the sperm nuclear annulus to which the entire complement of DNA appears to be anchored when the nuclear matrix is disrupted during decondensation, and the structural organization of sperm DNA is likely to be just as vital to the proper functioning of the spermatozoa.
Abstract: Mammalian sperm DNA is the most tightly compacted eukaryotic DNA, being at least sixfold more highly condensed than the DNA in mitotic chromosomes. To achieve this high degree of packaging, sperm DNA interacts with protamines to form linear, side-by-side arrays of chromatin. This differs markedly from the bulkier DNA packaging of somatic cell nuclei and mitotic chromosomes, in which the DNA is coiled around histone octamers to form nucleosomes. The overall organization of mammalian sperm DNA, however, resembles that of somatic cells in that both the linear arrays of sperm chromatin and the 30-nm solenoid filaments of somatic cell chromatin are organized into loop domains attached at their bases to a nuclear matrix. In addition to the sperm nuclear matrix, sperm nuclei contain a unique structure termed the sperm nuclear annulus to which the entire complement of DNA appears to be anchored when the nuclear matrix is disrupted during decondensation. In somatic cells, proper function of DNA is dependent upon the structural organization of the DNA by the nuclear matrix, and the structural organization of sperm DNA is likely to be just as vital to the proper functioning of the spermatozoa.

679 citations

Journal ArticleDOI
W S Ward1
TL;DR: A new model for DNA packaging in sperm nuclei is presented, in which each individual DNA loop domain in the sperm chromatin is condensed into a toroid-shaped structure termed the DNA loop doughnut.
Abstract: In the four decades since the discovery of the basic structure of the DNA double helix, researchers have been investigating the more dynamic tertiary structures that DNA assumes in the various forms of chromatin. The tertiary structure of DNA is important because it is directly related to the function of the genome: for the cell to access the information that is present in the genome accurately and efficiently, the DNA must be in an organized form. This paper reviews the recent work on one particular enigmatic structural form of eukaryotic DNA, that of the highly condensed spermatozoa. Based on the literature and on recently completed experiments in the field, a new model for DNA packaging in sperm nuclei is presented. In this model, each individual DNA loop domain in the sperm chromatin is condensed into a toroid-shaped structure termed the DNA loop doughnut.

138 citations

Journal ArticleDOI
TL;DR: The data suggest that at least in the mouse, the only component of the spermatozoa that is crucial for participation in embryologic development is the sperm nucleus with a stable nuclear matrix.
Abstract: We have been interested in determining the minimally required elements in the sperm head that are necessary in order for the paternal genome to participate in embryogenesis. We used an ionic detergent, mixed alkyltrimethylammonium bromide (ATAB), plus dithiothreitol (DTT) to remove the acrosome and almost all of the perinuclear theca, leaving only the sperm nucleus morphologically intact. We also tested the stability of the sperm nuclear matrix by the ability to form nuclear halos. Sperm nuclei washed in freshly prepared 0.5% ATAB 1 2m M DTT completely decondensed when extracted with salt, but nuclei washed in the same buffer that was 1 wk old, and then extracted with salt, produced nuclear halos, indicating stable nuclear matrices. When we treated sperm heads with freshly prepared ATAB1DTT and injected them into oocytes, none of the oocytes developed into live offspring. In contrast, sperm heads treated in the same way but with 1-wk-old ATAB1DTT solution could support development of about 30% of the oocytes to live offspring. Electron microscopy demonstrated that most of the perinuclear theca had been removed in both cases. These data suggest that at least in the mouse, the only component of the spermatozoa that is crucial for participation in embryologic development is the sperm nucleus with a stable nuclear matrix.

123 citations

Journal ArticleDOI
TL;DR: The sperm nucleus contains one haploid copy of the genome that is completely transcriptionally silent and is not being replicated, but this "silent" chromatin nevertheless contains a complex organization at all levels that suggests functional requirements for their existence.
Abstract: The sperm nucleus contains one haploid copy of the genome that is completely transcriptionally silent and is not being replicated. Recent evidence has revealed that this "silent" chromatin nevertheless contains a complex organization at all levels. This includes DNA loop domain formation by the sperm nuclear matrix that is gene specific and highly ordered folding patterns of the chromosomes, particularly with respect to centromere and telomere positioning. Such specificity in the sperm DNA organization suggests functional requirements for their existence. As these begin to emerge, the sperm nucleus is becoming an important model for the study of the eukaryotic genome.

107 citations

Journal ArticleDOI
TL;DR: The need for prompt diagnosis and accurate staging of bladder cancer cannot be over-emphasized, as delays in diagnosing the tumor are clearly associated with a poor prognosis.

97 citations


Cited by
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Journal ArticleDOI
23 Jul 2009-Nature
TL;DR: It is shown that the retained nucleosomes are significantly enriched at loci of developmental importance, including imprinted gene clusters, microRNA clusters, HOX genes clusters, and the promoters of stand-alone developmental transcription and signalling factors.
Abstract: Because nucleosomes are widely replaced by protamine in mature human sperm, the epigenetic contributions of sperm chromatin to embryo development have been considered highly limited. Here we show that the retained nucleosomes are significantly enriched at loci of developmental importance, including imprinted gene clusters, microRNA clusters, HOX gene clusters, and the promoters of stand-alone developmental transcription and signalling factors. Notably, histone modifications localize to particular developmental loci. Dimethylated lysine 4 on histone H3 (H3K4me2) is enriched at certain developmental promoters, whereas large blocks of H3K4me3 localize to a subset of developmental promoters, regions in HOX clusters, certain noncoding RNAs, and generally to paternally expressed imprinted loci, but not paternally repressed loci. Notably, trimethylated H3K27 (H3K27me3) is significantly enriched at developmental promoters that are repressed in early embryos, including many bivalent (H3K4me3/H3K27me3) promoters in embryonic stem cells. Furthermore, developmental promoters are generally DNA hypomethylated in sperm, but acquire methylation during differentiation. Taken together, epigenetic marking in sperm is extensive, and correlated with developmental regulators.

1,154 citations

Journal ArticleDOI
01 Dec 2005-Urology
TL;DR: Optimal resection techniques, role of repeat transurethral resection in high-grade T1 tumors, random bladder biopsy, and prostatic urethral biopsy are discussed, and appropriate recommendations are made according to the strength of available evidence.

869 citations

Journal ArticleDOI
TL;DR: Screening for sperm DNA damage may provide useful information in cases of male idiopathic infertility and in those men pursuing assisted reproduction, and treatment should include methods for prevention of spermDNA damage.
Abstract: Sperm DNA integrity is essential for the accurate transmission of genetic information. It has a highly compact and complex structure and is capable of decondensation-features that must be present in order for a spermatozoon to be considered fertile. Any form of sperm chromatin abnormalities or DNA damage may result in male infertility. In support of this conclusion, it was reported that in-vivo fecundity decreases progressively when > 30% of the spermatozoa are identified as having DNA damage. Several methods are used to assess sperm chromatin/DNA, which is considered an independent measure of sperm quality that may yield better diagnostic and prognostic approaches than standard sperm parameters (concentration, motility and morphology). The clinical significance of this assessment lies in its association not only with natural conception rates, but also with assisted reproduction success rates. Also, it has a serious impact on the offspring and is highly prognostic in the assessment of fertility in cancer patients. Therefore, screening for sperm DNA damage may provide useful information in cases of male idiopathic infertility and in those men pursuing assisted reproduction. Treatment should include methods for prevention of sperm DNA damage.

783 citations

Journal ArticleDOI
TL;DR: A critical systematic review of the available literature on the clinical and economic burden of bladder cancer in developed countries, with a focus on the cost effectiveness of interventions aimed at reducing that burden, suggests that non-surgical treatment strategies for the management of invasive disease aiming at bladder preservation may not be cost effective.
Abstract: The aim of this paper was to conduct a critical systematic review of the available literature on the clinical and economic burden of bladder cancer in developed countries, with a focus on the cost effectiveness of interventions aimed at reducing that burden.Forty-four economic studies were included in the review. Because of long- term survival and the need for lifelong routine monitoring and treatment, the cost per patient of bladder cancer from diagnosis to death is the highest of all cancers, ranging from 96000-187000 US dollars (2001 values) in the US. Overall, bladder cancer is the fifth most expensive cancer in terms of total medical care expenditures, accounting for almost 3.7 billion US dollars (2001 values) in direct costs in the US. Screening for bladder cancer in the general population is currently not recommended. The economic value of relatively new and less expensive urine assays and molecular urinary tumour markers has not been assessed. However, the literature suggests that screening patients suspected of having bladder cancer and using less invasive diagnostic procedures is cost effective. Very few cost-effectiveness studies have evaluated intravesical therapies such as bacillus Calmette-Guerin and mitomycin in the management of superficial disease and no robust recommendations can be drawn. Economic analyses suggest that non-surgical treatment strategies for the management of invasive disease aiming at bladder preservation may not be cost effective, because they have not consistently demonstrated survival benefits and do not eliminate the need for subsequent radical cystectomy. The literature suggests that the current conventional frequent follow-up and monitoring of patients can be cost effectively replaced by less frequent and less invasive monitoring, and should rely more heavily on intravesical chemotherapy to reduce the need for cystoscopies. Bladder cancer is a fairly common and costly malignancy. Nevertheless, the existing literature only contributes marginally to our knowledge concerning the burden of bladder cancer and the economic value of various interventions. The limited value of the literature in this area may be attributed to (i) being published as abstracts rather than full peer-reviewed evaluations; (ii) employing questionable methodologies; and (iii) being in many cases nearly obsolete, rendering them less relevant to, if not in conflict with, current clinical practice. Consequently, opportunities exist to conduct meaningful economic research in all areas of the management of bladder cancer, including screening, diagnosis, follow-up and treatment, especially with respect to new and innovative pharmaceutical and other technologies.

746 citations