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Eight Is Enough?: The Ethics Of The California Octuplets Case, Scott Paeth Oct 2012

Eight Is Enough?: The Ethics Of The California Octuplets Case, Scott Paeth

Scott R. Paeth

The recent California octuplets case raises a number of important issues that need to be addressed in the context of the increasingly widespread practice of in vitro fertilization. This paper explores some of those issues as looked at from the perspective of protestant theological ethics and public theology, examining the moral responsibilities of the various participants in the process, both before and after the octuplets’ birth, including the mother, her doctors, the health care bureaucracy, the wider society, and the media. Each of these participants failed in significant respects to consider the ethical implications of the births in this complicated …


Micronesia: Steps In The Right Direction, Aydin Nazmi Aug 2012

Micronesia: Steps In The Right Direction, Aydin Nazmi

Aydin Nazmi

As I watch the hazy orange sun sink into the still blue sea overlooking Chuuk lagoon, I marked the end of another seemingly ordinary day in the Federated States of Micronesia. But this October day was special—it marked the beginning of a promising new era in Chuuk’s fight against HIV and AIDS. For the past few months, several proceedings had set into motion a cascade of events that would ultimately (hopefully) benefit and educate the people of Chuuk state.


Seasonality Of Infant Feeding Practices In Three Brazilian Birth Cohorts, David A. González-Chica, Helen Gonçalves, Aydin Nazmi, Iná S. Santos, Aluísio J. D. Barros, Alicia Matijasevich, Cesar G. Victora Aug 2012

Seasonality Of Infant Feeding Practices In Three Brazilian Birth Cohorts, David A. González-Chica, Helen Gonçalves, Aydin Nazmi, Iná S. Santos, Aluísio J. D. Barros, Alicia Matijasevich, Cesar G. Victora

Aydin Nazmi

Background We assessed the influence of season of birth on duration of breastfeeding and other feeding patterns in three population-based birth cohort studies in the city of Pelotas, Southern Brazil. Methods In 1982, 1993 and 2004, all hospital-born children in the city were enrolled in three cohort studies (n =  5914, 5249 and 4287, respectively). Children and their mothers were periodically visited in the first 2 years of life, to collect information on the duration of breastfeeding and the ages at which different types of foods were introduced on a regular basis. Two independent variables were studied: month of birth …


Use Of Highly Polymorphic Dna Probes For Genotypic Analysis Following Bone Marrow Transplantation, Robert Knowlton, Valerie Brown, Jeffrey Braman, David Barker, James Schumm, Christine Murray, Tak Takvorian, Jerome Ritz, Helen Donis-Keller Aug 2012

Use Of Highly Polymorphic Dna Probes For Genotypic Analysis Following Bone Marrow Transplantation, Robert Knowlton, Valerie Brown, Jeffrey Braman, David Barker, James Schumm, Christine Murray, Tak Takvorian, Jerome Ritz, Helen Donis-Keller

Helen Donis-Keller

The use of DNA markers known as restriction fragment length polymorphisms is a sensitive and informative method of distinguishing patient and allogeneic donor cells after bone marrow transplantation. To apply the test, it is necessary in each case to find DNA probes that display patient-specific and donor-specific bands in Southern transfer hybridization. We have isolated a set of 12 cloned DNAs from highly polymorphic loci by which siblings can usually be distinguished. With just four of these probes, we can expect to distinguish the genotypes of the recipient and a sibling donor in more than 99% of cases (except between …


Mutations In The Ret Proto-Oncogene Are Associated With Men 2a And Fmtc, Helen Donis-Keller, Shenshen Dou, David Chi, Katrin Carlson, Koi Toshima, Terry Lairmore, James Howe, Jeffrey Moley, Paul Goodfellow, Samuel Wells Aug 2012

Mutations In The Ret Proto-Oncogene Are Associated With Men 2a And Fmtc, Helen Donis-Keller, Shenshen Dou, David Chi, Katrin Carlson, Koi Toshima, Terry Lairmore, James Howe, Jeffrey Moley, Paul Goodfellow, Samuel Wells

Helen Donis-Keller

Multiple endocrine neoplasia type 2A (MEN 2A) and familial medullary thyroid carcinoma (FMTC) are dominantly inherited conditions which predispose to the development of endocrine neoplasia. Evidence is presented that sequence changes within the coding region of the RET proto-oncogene, a putative transmembrane tyrosine kinase, may be responsible for the development of neoplasia in these inherited disorders. Single strand conformational variants (SSCVs) in exons 7 and 8 of the RET proto-oncogene were identified in eight MEN 2A and four FMTC families. The variants were observed only in the DNA of individuals who were either affected or who had inherited the MEN2A …


Single Missense Mutation In The Tyrosine Kinase Catalytic Domain Of The Ret Protooncogene Is Associated With Multiple Endocrine Neoplasia Type 2b., Katrin Carlson, Shenshen Dou, David Chi, N. Scavarda, Koi Toshima, C. Jackson, Samuel Wells, Paul Goodfellow, Helen Donis-Keller Aug 2012

Single Missense Mutation In The Tyrosine Kinase Catalytic Domain Of The Ret Protooncogene Is Associated With Multiple Endocrine Neoplasia Type 2b., Katrin Carlson, Shenshen Dou, David Chi, N. Scavarda, Koi Toshima, C. Jackson, Samuel Wells, Paul Goodfellow, Helen Donis-Keller

Helen Donis-Keller

Multiple endocrine neoplasia type 2B (MEN 2B) is a human cancer syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytomas, mucosal neuromas, ganglioneuromas of the intestinal tract, and skeletal and ophthalmic abnormalities. It appears both as an inherited disorder and as de novo disease. Sequence analysis of germ-line DNA from MEN 2B patients revealed the existence of the same point mutation in the RET protooncogene in 34 unrelated individuals. This sequence difference was not observed in 93 unaffected individuals, including the normal parents of 14 de novo MEN 2B patients. The mutation (ATG-->ACG) results in the replacement of methionine with …


A Genetic Linkage Map Of The Human Genome, Helen Donis-Keller, Philip Green, Cynthia Helmes, Samuel Cartinhour, Barbara Weiffenbach, Karen Stephens, Tim Keith, Donald Bowden, Douglas Smith, Eric Lander, David Botstein, Gita Akots, Kenneth Rediker, Thomas Gravius, Valerie Brown, Marcia Rising, Carol Parker, Jody Powers, Diane Watt, Erick Kauffman, Angela Bricker, Pamela Phipps, Hans Muller-Kahle, Thomas Fulton, Siu Ng, James Schumm, Jeffrey Braman, Robert Knowlton, David Barker, Steven Crooks, Steven Lincoln, Mark Daly, Jeff Abrahamson Aug 2012

A Genetic Linkage Map Of The Human Genome, Helen Donis-Keller, Philip Green, Cynthia Helmes, Samuel Cartinhour, Barbara Weiffenbach, Karen Stephens, Tim Keith, Donald Bowden, Douglas Smith, Eric Lander, David Botstein, Gita Akots, Kenneth Rediker, Thomas Gravius, Valerie Brown, Marcia Rising, Carol Parker, Jody Powers, Diane Watt, Erick Kauffman, Angela Bricker, Pamela Phipps, Hans Muller-Kahle, Thomas Fulton, Siu Ng, James Schumm, Jeffrey Braman, Robert Knowlton, David Barker, Steven Crooks, Steven Lincoln, Mark Daly, Jeff Abrahamson

Helen Donis-Keller

We report the construction of a linkage map of the human genome, based on the pattern of inheritance of 403 polymorphic loci, including 393 RFLPs, in a panel of DNAs from 21 three-generation families. By a combination of mathematical linkage analysis and physical localization of selected clones, it was possible to arrange these loci into linkage groups representing 23 human chromosomes. We estimate that the linkage map is detectably linked to at least 95% of the DNA in the human genome.


Genetic Analysis Of Eight Loci Tightly Linked To Neurofibromatosis 1, Karen Stephens, Philip Green, V. Riccardi, Siu Ng, Marcia Rising, David Barker, J. Darby, K. Falls, F. Collins, H. Willard, Helen Donis-Keller Aug 2012

Genetic Analysis Of Eight Loci Tightly Linked To Neurofibromatosis 1, Karen Stephens, Philip Green, V. Riccardi, Siu Ng, Marcia Rising, David Barker, J. Darby, K. Falls, F. Collins, H. Willard, Helen Donis-Keller

Helen Donis-Keller

The genetic locus for neurofibromatosis 1 (NF1) has recently been mapped to the pericentromeric region of chromosome 17. We have genotyped eight previously identified RFLP probes on 50 NF1 families to determine the placement of the NF1 locus relative to the RFLP loci. Thirty-eight recombination events in the pericentromeric region were identified, eight involving crossovers between NF1 and loci on either chromosomal arm. Multipoint linkage analysis resulted in the unique placement of six loci at odds greater than 100:1 in the order of pter-A10-41-EW301-NF1-EW207-CRI-L581-CRI-L946 -qter. Owing to insufficient crossovers, three loci--D17Z1, EW206, and EW203--could not be uniquely localized. In this …


A Polymorphic Dna Marker Linked To Cystic Fibrosis Is Located On Chromosome 7, Robert Knowlton, Odile Cohen-Haguenauer, Nguyen Van Cong, Jean Frézal, Valerie Brown, David Barker, Jeffrey Braman, James Schumm, Lap-Chee Tsui, Manuel Buchwald, Helen Donis-Keller Aug 2012

A Polymorphic Dna Marker Linked To Cystic Fibrosis Is Located On Chromosome 7, Robert Knowlton, Odile Cohen-Haguenauer, Nguyen Van Cong, Jean Frézal, Valerie Brown, David Barker, Jeffrey Braman, James Schumm, Lap-Chee Tsui, Manuel Buchwald, Helen Donis-Keller

Helen Donis-Keller

Although cystic fibrosis (CF) is among the most common inherited diseases in Caucasian populations, the basic biochemical defect is not yet known. CF is inherited as an autosomal recessive trait apparently due to mutations in a single gene, whence the efforts made to identify the genetic locus responsible by linkage studies. Two markers have recently been identified that are genetically linked to CF: one is a genetic variation in serum level of activity of the enzyme paraoxonase, and the other is a restriction fragment length polymorphism (RFLP) identified with a randomly isolated DNA probe. We report here that the genetic …


Chromosomal Bar Codes Produced By Multicolor Fluorescence In Situ Hybridization With Multiple Yac Clones And Whole Chromosome Painting Probes, Christoph Lengauer, Michael Speicher, Susanne Popp, Anna Jauch, Masafumi Taniwaki, Ramaiah Nagaraja, Harold Riethman, Helen Donis-Keller, Michele D'Urso, David Schelssinger, Thomas Cremer Aug 2012

Chromosomal Bar Codes Produced By Multicolor Fluorescence In Situ Hybridization With Multiple Yac Clones And Whole Chromosome Painting Probes, Christoph Lengauer, Michael Speicher, Susanne Popp, Anna Jauch, Masafumi Taniwaki, Ramaiah Nagaraja, Harold Riethman, Helen Donis-Keller, Michele D'Urso, David Schelssinger, Thomas Cremer

Helen Donis-Keller

Colored chromosome staining patterns, termed chromosomal ‘bar codes’ (CBCs), were obtained on human chromosomes by fluorescence in situhybridization (FISH) with pools of Alu-PCR products from YAC dones containing human DNA inserts ranging from 100 kbp to 1 Mbp. In contrast to conventional G- or R-bands, the chromosomal position, extent, Individual color and relative signal intensity of each ‘bar’ could be modified depending on probe selection and labeling procedures. Alu-PCR amplification products were generated from 31 YAC clones which mapped to 37 different chromosome bands. For multiple color FISH, Alu-PCR amplification products from various clones were either biotinylated or labeled …


Predictive Dna Testing And Prophylactic Thyroidectomy In Patients At Risk For Multiple Endocrine Neoplasia Type 2a, Samuel Wells, David Chi, Koi Toshima, Louis Dehner, Cheryl Coffin, S. Dowton, Jennifer Ivanovich, Mary Debenedettl, William Dilley, Jeffrey Moley, Jeffrey Norton, Helen Donis-Keller Aug 2012

Predictive Dna Testing And Prophylactic Thyroidectomy In Patients At Risk For Multiple Endocrine Neoplasia Type 2a, Samuel Wells, David Chi, Koi Toshima, Louis Dehner, Cheryl Coffin, S. Dowton, Jennifer Ivanovich, Mary Debenedettl, William Dilley, Jeffrey Moley, Jeffrey Norton, Helen Donis-Keller

Helen Donis-Keller

Background: Missense germ-line mutations in the RET protooncogene are associated with multiple endocrine neoplasia type 2A (MEN 2A). Detection of these mutant alleles in kindred members predicts disease inheritance and provides the basis for preventative thyroidectomy. Methods: A polymerase chain reaction (PCR)-based genetic test for the 19 known RET mutations was designed to study 132 members of 7 kindreds with MEN 2A. Haplotypes also were constructed using genetic markers flanking the MEN 2A locus. Plasma calcitonin (CT) concentrations were determined before and after provocative testing. Results: Direct DNA testing and haplotype analysis showed that 21 of 58 kindred members at …


Rapid Inversion: Running Animals And Robots Swing Like A Pendulum Under Ledges, Jean-Michel Mongeau, Brian Mcrae, Ardian Jusufi, Paul Birkmeyer, Aaron M. Hoover, Ronald Fearing, Robert J. Full Jul 2012

Rapid Inversion: Running Animals And Robots Swing Like A Pendulum Under Ledges, Jean-Michel Mongeau, Brian Mcrae, Ardian Jusufi, Paul Birkmeyer, Aaron M. Hoover, Ronald Fearing, Robert J. Full

Aaron M. Hoover

Escaping from predators often demands that animals rapidly negotiate complex environments. The smallest animals attain relatively fast speeds with high frequency leg cycling, wing flapping or body undulations, but absolute speeds are slow compared to larger animals. Instead, small animals benefit from the advantages of enhanced maneuverability in part due to scaling. Here, we report a novel behavior in small, legged runners that may facilitate their escape by disappearance from predators. We video recorded cockroaches and geckos rapidly running up an incline toward a ledge, digitized their motion and created a simple model to generalize the behavior. Both species ran …


Antibacterial Activity Of Lactobacillus Acidophilus Strains Isolated From Honey Marketed In Malaysia Against Selected Multiple Antibiotic Resistant (Mar) Gram-Positive Bacteria, Mohamed Mustafa Aween, Asma Saleh Elmabrok Jul 2012

Antibacterial Activity Of Lactobacillus Acidophilus Strains Isolated From Honey Marketed In Malaysia Against Selected Multiple Antibiotic Resistant (Mar) Gram-Positive Bacteria, Mohamed Mustafa Aween, Asma Saleh Elmabrok

Asma Saleh Elmabrok

Abstract: A total of 32 lactic acid bacteria (LAB) were isolated from 13 honey samples commercially marketed in Malaysia, 6 strains identified as Lactobacillus acidophilus by API CHL50. The isolates had antibacterial activities against multiple antibiotic resistant’s Staphylococcus aureus (25 to 32 mm), Staphylococcus epidermis (14 to 22 mm) and Bacillus subtilis (12 to 19 mm) in the agar overlay method after 24 h incubation at 30 ◦C. The crude supernatant was heat stable at 90 ◦C and 121 ◦C for 1 h. Treatment with proteinase K and RNase II maintained the antimicrobial activity of all the supernatants except sample …


A New Class Of Homoserine Lactone Quorum-Sensing Signals, Amy Schaefer, E Greenberg, Colin Oliver, Yasuhiro Oda, Jean Huang, Gili Bittan-Banin, Caroline Peres, Silke Schmidt, Katarina Juhaszova, Janice Sufrin, Caroline Harwood May 2012

A New Class Of Homoserine Lactone Quorum-Sensing Signals, Amy Schaefer, E Greenberg, Colin Oliver, Yasuhiro Oda, Jean Huang, Gili Bittan-Banin, Caroline Peres, Silke Schmidt, Katarina Juhaszova, Janice Sufrin, Caroline Harwood

Jean J. Huang

Quorum sensing is a term used to describe cell-to-cell communication that allows cell-density-dependent gene expression. Many bacteria use acyl-homoserine lactone (acyl-HSL) synthases to generate fatty acyl-HSL quorum-sensing signals, which function with signal receptors to control expression of specific genes. The fatty acyl group is derived from fatty acid biosynthesis and provides signal specificity, but the variety of signals is limited. Here we show that the photosynthetic bacterium Rhodopseudomonas palustris uses an acyl-HSL synthase to produce p-coumaroyl-HSL by using environmental p-coumaric acid rather than fatty acids from cellular pools. The bacterium has a signal receptor with homology to fatty acyl-HSL receptors …


Acyl‐Hsl Signal Decay: Intrinsic To Bacterial Cell–Cell Communications, Ya-Juan Wang, Jean Huang, Jared Leadbetter May 2012

Acyl‐Hsl Signal Decay: Intrinsic To Bacterial Cell–Cell Communications, Ya-Juan Wang, Jean Huang, Jared Leadbetter

Jean J. Huang

No abstract available.


The Acid Stress Response Of The Cyanobacterium Synechocystis Sp. Strain Pcc 6308, Jean Huang, Nancy Kolodny, Jennifer Redfearn, Mary Allen May 2012

The Acid Stress Response Of The Cyanobacterium Synechocystis Sp. Strain Pcc 6308, Jean Huang, Nancy Kolodny, Jennifer Redfearn, Mary Allen

Jean J. Huang

The cyanobacterium Synechocystis sp. strain PCC 6308 has been shown to exhibit predictable physiological responses to acid stress. Originally isolated from a Wisconsin lake, this cyanobacterium grows optimally under alkaline conditions in the laboratory. After acid stress at a pH of between 4.4 and 7.7, cells return to exponential growth following a lag phase. The organism's response to this tolerable acid stress involves cell concentration-dependent neutralization of the external medium to pH 6 or above within 5 min, maintenance of a transmembrane pH gradient, and maintenance of photosystem II efficiency. Lethal acid stress, at a pH below 4.4, results in …


Identification Of Quip, The Product Of Gene Pa1032, As The Second Acyl-Homoserine Lactone Acylase Of Pseudomonas Aeruginosa Pao1, Jean Huang, Ashley Petersen, Marvin Whiteley, Jared Leadbetter May 2012

Identification Of Quip, The Product Of Gene Pa1032, As The Second Acyl-Homoserine Lactone Acylase Of Pseudomonas Aeruginosa Pao1, Jean Huang, Ashley Petersen, Marvin Whiteley, Jared Leadbetter

Jean J. Huang

The relevance of the acyl homoserine lactone (acyl-HSL) quorum signals N-3-oxododecanoyl-homoserine lactone (3OC12HSL) and N-butanoyl-homoserine lactone to the biology and virulence of Pseudomonas aeruginosa is well investigated. Previously, P. aeruginosa was shown to degrade long-chain, but not short-chain, acyl-HSLs as sole carbon and energy sources (J. J. Huang, J.-I. Han, L.-H. Zhang, and J. R. Leadbetter, Appl. Environ. Microbiol. 69:5941-5949, 2003). A gene encoding an enzyme with acyl-HSL acylase activity, pvdQ (PA2385), was identified, but it was not required for acyl-HSL utilization. This indicated that P. aeruginosa encodes another acyl-HSL acylase, which we identify here. A comparison …


Utilization Of Acyl-Homoserine Lactone Quorum Signals For Growth By A Soil Pseudomonad And Pseudomonas Aeruginosa Pao1, Jean Huang, Jong-In Han, Lian-Hui Zhang, Jared Leadbetter May 2012

Utilization Of Acyl-Homoserine Lactone Quorum Signals For Growth By A Soil Pseudomonad And Pseudomonas Aeruginosa Pao1, Jean Huang, Jong-In Han, Lian-Hui Zhang, Jared Leadbetter

Jean J. Huang

Acyl-homoserine lactones (AHLs) are employed by several Proteobacteria as quorum-sensing signals. Past studies have established that these compounds are subject to biochemical decay and can be used as growth nutrients. Here we describe the isolation of a soil bacterium, Pseudomonas strain PAI-A, that degrades 3-oxododecanoyl-homoserine lactone (3OC12HSL) and other long-acyl, but not short-acyl, AHLs as sole energy sources for growth. The small-subunit rRNA gene from strain PAI-A was 98.4% identical to that of Pseudomonas aeruginosa, but the soil isolate did not produce obvious pigments or AHLs or grow under denitrifying conditions or at 42°C. The quorum-sensing bacterium P. aeruginosa, which …


Method Of Identifying Agents That Inhibit Quorum Sensing Activity Of Gamma-Proteobacteria, Jean Huang, Jared Leadbetter May 2012

Method Of Identifying Agents That Inhibit Quorum Sensing Activity Of Gamma-Proteobacteria, Jean Huang, Jared Leadbetter

Jean J. Huang

Screening assays that allow for the identification of agents that increase acyl homoserine lactone (AHL) acylase expression and/or AHL acylase activity in γ-proteobacteria such as Pseudomonas aeruginosa. Such agents are useful, for example, for inhibiting quorum sensing activity of such bacteria by increasing degradation of long chain, but not short chain, AHLs and, therefore, can be useful for treating infections by such bacteria.


Production Of Hydrogen Gas From Light And The Inorganic Electron Donor Thiosulfate By Rhodopseudomonas Palustris, Jean Huang May 2012

Production Of Hydrogen Gas From Light And The Inorganic Electron Donor Thiosulfate By Rhodopseudomonas Palustris, Jean Huang

Jean J. Huang

A challenge for photobiological production of hydrogen gas (H2) as a potential biofuel is to find suitable electron-donating feedstocks. Here, we examined the inorganic compound thiosulfate as a possible electron donor for nitrogenase-catalyzed H2 production by the purple nonsulfur phototrophic bacterium (PNSB) Rhodopseudomonas palustris. Thiosulfate is an intermediate of microbial sulfur metabolism in nature and is also generated in industrial processes. We found that R. palustris grew photoautotrophically with thiosulfate and bicarbonate and produced H2 when nitrogen gas was the sole nitrogen source (nitrogen-fixing conditions). In addition, illuminated nongrowing R. palustris cells converted about 80% of available electrons from thiosulfate …


Self-Assembling Short Oligopeptides And The Promotion Of Angiogenesis, Alisha Sarang-Sieminski, Daria Narmoneva, Olumuyiwa Oni, Shugang Zhang, Jonathan Gertler, Roger Kamm, Richard Lee Apr 2012

Self-Assembling Short Oligopeptides And The Promotion Of Angiogenesis, Alisha Sarang-Sieminski, Daria Narmoneva, Olumuyiwa Oni, Shugang Zhang, Jonathan Gertler, Roger Kamm, Richard Lee

Alisha L. Sarang-Sieminski

Because an adequate blood supply to and within tissues is an essential factor for successful tissue regeneration, promoting a functional microvasculature is a crucial factor for biomaterials. In this study, we demonstrate that short self-assembling peptides form scaffolds that provide an angiogenic environment promoting long-term cell survival and capillary-like network formation in three-dimensional cultures of human microvascular endothelial cells. Our data show that, in contrast to collagen type I, the peptide scaffold inhibits endothelial cell apoptosis in the absence of added angiogenic factors, accompanied by enhanced gene expression of the angiogenic factor VEGF. In addition, our results suggest that the …


Salmon Fibrin Supports An Increased Number Of Sprouts And Decreased Degradation While Maintaining Sprout Length Relative To Human Fibrin In An In Vitro Angiogenesis Model, Alisha Sarang-Sieminski, Keith Gooch Apr 2012

Salmon Fibrin Supports An Increased Number Of Sprouts And Decreased Degradation While Maintaining Sprout Length Relative To Human Fibrin In An In Vitro Angiogenesis Model, Alisha Sarang-Sieminski, Keith Gooch

Alisha L. Sarang-Sieminski

Salmon-derived fibrin has been proposed as a preferred alternative to human or bovine fibrin because of its reduced potential for disease transmission. Here we evaluate salmon fibrin as an alternative ECM support for therapeutic angiogenesis applications, such as vascularizing engineered tissues. Human umbilical vein endothelial cells (HUVEC) seeded on gelatin beads and suspended in either salmon or human fibrin sprouted and formed capillary-like structures. Sprout length was generally increased with the addition of bFGF and VEGF and further increased with the addition of phorbol myristate acetate (PMA). The number of sprouts per bead was increased 61-188% in salmon fibrin relative …


Migration Of Tumor Cells In 3d Matrices Is Governed By Matrix Stiffness Along With Cell-Matrix Adhesion And Proteolysis, Alisha Sarang-Sieminski, Muhammad Zaman, Linda Trapani, Drew Mackellar, Haiyan Gong, Roger Kamm, Alan Wells, Douglas Lauffenburger, Paul Matsudaira Apr 2012

Migration Of Tumor Cells In 3d Matrices Is Governed By Matrix Stiffness Along With Cell-Matrix Adhesion And Proteolysis, Alisha Sarang-Sieminski, Muhammad Zaman, Linda Trapani, Drew Mackellar, Haiyan Gong, Roger Kamm, Alan Wells, Douglas Lauffenburger, Paul Matsudaira

Alisha L. Sarang-Sieminski

Cell migration on 2D surfaces is governed by a balance between counteracting tractile and adhesion forces. Although biochemical factors such as adhesion receptor and ligand concentration and binding, signaling through cell adhesion complexes, and cytoskeletal structure assembly/disassembly have been studied in detail in a 2D context, the critical biochemical and biophysical parameters that affect cell migration in 3D matrices have not been quantitatively investigated. We demonstrate that, in addition to adhesion and tractile forces, matrix stiffness is a key factor that influences cell movement in 3D. Cell migration assays in which Matrigel density, fibronectin concentration, and β1 integrin binding are …


Association Between Prostate Cancer In Black Americans And An Allele Of The Padprp Pseudogene Locus On Chromosome 13, Helen Donis-Keller, Jennifer Doll, B Suarez Apr 2012

Association Between Prostate Cancer In Black Americans And An Allele Of The Padprp Pseudogene Locus On Chromosome 13, Helen Donis-Keller, Jennifer Doll, B Suarez

Helen Donis-Keller

Black American men have a higher incidence of cancer of the prostate (CAP), multiple myeloma, and lung cancer than do white American men (discussed by Lyn et al.1993a). The basis for these differences no doubt includes environmental influences, because American blacks have also been found to have a higher incidence of CAP than do African blacks. However, genetic factors may play a role as well. For example, Lyn et al. (1993a) reported an increase in the frequency of an allele of the poly(ADPribose)polymerase (PADPRP) pseudogene locus onchromosome 13 in black Americans with CAP, suggesting the presence of a disease-susceptibility locus. …


Identification Of Sonic Hedgehog As A Candidate Gene Responsible For Holoprosencephaly, Helen Donis-Keller, E Belloni, M Muenke, E Roessler, G Traverse, J Siegel-Bartelt, A Frumkin, H Mitchell, C Helms, A Hing, H Heng, B Kroop, D Martindale, J Rommens, L Tsui, S Scherer Apr 2012

Identification Of Sonic Hedgehog As A Candidate Gene Responsible For Holoprosencephaly, Helen Donis-Keller, E Belloni, M Muenke, E Roessler, G Traverse, J Siegel-Bartelt, A Frumkin, H Mitchell, C Helms, A Hing, H Heng, B Kroop, D Martindale, J Rommens, L Tsui, S Scherer

Helen Donis-Keller

Holoprosencephaly (HPE) is a genetically and phenotypically heterogenous disorder involving the development of forebrain and midface, with an incidence of 1:16,000 live born and 1:250 induced abortions. This disorder is associated with several distinct facies and phenotypic variability: in the most extreme cases, anophthalmia or cyclopia is evident along with a congenital absence of the mature nose. The less severe form features facial dysmorphia characterized by ocular hypertelorism, defects of the upper lip and/or nose, and absence of the olfactory nerves or corpus callosum. Several intermediate phenotypes involving both the brain and face have been described. One of the gene …


Functional Characterization Of An Epidermal Growth Factor Receptor/Ret Chimera, Helen Donis-Keller, Sunil Pandit, Timothy O'Hare, Linda Pike Apr 2012

Functional Characterization Of An Epidermal Growth Factor Receptor/Ret Chimera, Helen Donis-Keller, Sunil Pandit, Timothy O'Hare, Linda Pike

Helen Donis-Keller

The RET (combined in ransfection) gene encodes a receptor tyrosine kinase homolog involved in innervation of the gut and renal development. A chimeric epidermal growth factor receptor (EGFR)/RET receptor was constructed which contained the extracellular and transmembrane domains of the EGF receptor fused to the intracellular domain of RET. This construct was expressed in NIH 3T3 cells, and the functional properties of the receptor were characterized and compared with those of the wild type EGF receptor. Whereas the EGF receptor exhibited both high and low affinity binding sites for 125I-EGF, the EGFR/RET chimera exhibited only low affinity binding …


7q11.23 Deletions In Williams Syndrome Arise As A Consequence Of Unequal Meiotic Crossover, Helen Donis-Keller, Zsolt Urbán, C Helms, G Fekete, Katalin Csiszár, D Bonnet, A Munnich, C Boyd Apr 2012

7q11.23 Deletions In Williams Syndrome Arise As A Consequence Of Unequal Meiotic Crossover, Helen Donis-Keller, Zsolt Urbán, C Helms, G Fekete, Katalin Csiszár, D Bonnet, A Munnich, C Boyd

Helen Donis-Keller

Williams syndrome (WS) (Williams et al. 1961; Beurenet al. 1962) is a multisystem disorder characterized by mental retardation, a specific neurobehavioral profile,characteristic facies, infantile hypercalcemia, cardiovascular abnormalities, progressive joint limitation, hernias, and soft skin. Recent studies have shown that hemizygosity at the elastin (ELN) gene locus on chromosome7q is associated with WS (Ewart et al. 1993). Furthermore, two FISH studies using cosmid recombinants containing the 5' or the 3' end of the ELN gene revealed deletion of the entire ELN gene in 90%-96% of classical WS cases (Lowery et al. 1995; Nickerson et al. 1995). However, the size of the …


Comparative Genomic Hybridization Of Human Malignant Gliomas Reveals Multiple Amplification Sites And Nonrandom Chromosomal Gains And Losses, Helen Donis-Keller, Evelin Schròck, Gundula Thiel, Tanka Lozanova, Stanislas Du Manoir, Marie-Christine Meffert, Anna Jauch, Michael Speicher, Peter Nürnberg, Siegfried Vogel, Werner Janisch, Thomas Ried, Regine Witkowski, Thomas Cremer Apr 2012

Comparative Genomic Hybridization Of Human Malignant Gliomas Reveals Multiple Amplification Sites And Nonrandom Chromosomal Gains And Losses, Helen Donis-Keller, Evelin Schròck, Gundula Thiel, Tanka Lozanova, Stanislas Du Manoir, Marie-Christine Meffert, Anna Jauch, Michael Speicher, Peter Nürnberg, Siegfried Vogel, Werner Janisch, Thomas Ried, Regine Witkowski, Thomas Cremer

Helen Donis-Keller

Nine human malignant gliomas (2 astrocytomas grade III and 7 glioblastomas) were analyzed using comparative genomic hybridization (CGH). In addition to the amplification of the EGFR gene at 7p12 in 4 of 9 cases, six new amplification sites were mapped to 1q32, 4q12, 7q21.1, 7q21.2-3, 12p, and 22q12. Nonrandom chromosomal gains and losses were identified with overrepresentation of chromosome 7 and underrepresentation of chromosome 10 as the most frequent events (1 of 2 astrocytomas, 7 of 7 glioblastomas). Gain of a part or the whole chromosome 19 and losses of chromosome bands 9pter-23 and 22q13 were detected each in five …


Recombinant Mapping Of The Familial Hyperinsulinism Gene To An 0.8 Cm Region On Chromosome 11p15.1 And Demonstration Of A Founder Effect In Ashkenazi Jews, Helen Donis-Keller, Benjamin Glaser, Ken Chiu, Li Liu, Roberto Anker, Ann Nestorowicz, Nancy Cox, Heddy Landau, Kalser Nurit, Paul Thornton, Charles Stanley, Erol Cerasl, Lester Baker, M. Alan Permutt Apr 2012

Recombinant Mapping Of The Familial Hyperinsulinism Gene To An 0.8 Cm Region On Chromosome 11p15.1 And Demonstration Of A Founder Effect In Ashkenazi Jews, Helen Donis-Keller, Benjamin Glaser, Ken Chiu, Li Liu, Roberto Anker, Ann Nestorowicz, Nancy Cox, Heddy Landau, Kalser Nurit, Paul Thornton, Charles Stanley, Erol Cerasl, Lester Baker, M. Alan Permutt

Helen Donis-Keller

A gene for autosomal recessive familial hyperinsulinism (HI) (OMIM: 256450), a neonatal metabolic disease characterized by inappropriate insulin secretion in the presence of severe hypoglycemia, was recently mapped to a 6.6 cM interval between the markers D11S926 and D11S928 onchromosome 11p in 15 families (1). In the current study we evaluated six additional families and five new markers, and further localized the gene between D11S419 and D11S1310. Using genotype data from CEPH Version 7 and data generated from this study, this region was estimated to be 0.8 cM in length. Significant linkage disequilibrium between markers and the HIgene was observed …


Sequence-Ready Contig For The 1.4-Cm Ductal Carcinoma In Situ Loss Of Heterozygosity Region On Chromosome 8p22–P23, Helen Donis-Keller, Jen Wang, Diane Radford, Matthew Holt, C Helms, A Goate, W Brandt, M Parik, Nancy Phillips, K Deschryver, M Schuh, Keri Fair, Jon Ritter, P Marshall Apr 2012

Sequence-Ready Contig For The 1.4-Cm Ductal Carcinoma In Situ Loss Of Heterozygosity Region On Chromosome 8p22–P23, Helen Donis-Keller, Jen Wang, Diane Radford, Matthew Holt, C Helms, A Goate, W Brandt, M Parik, Nancy Phillips, K Deschryver, M Schuh, Keri Fair, Jon Ritter, P Marshall

Helen Donis-Keller

We report the construction of an ∼1.7-Mb sequence-ready YAC/BAC clone contig of 8p22–p23. This chromosomal region has been associated with frequent loss of heterozygosity (LOH) in breast, ovarian, prostate, head and neck, and liver cancer. We first constructed a meiotic linkage map for 8p to resolve previously reported conflicting map orders from the literature. The target region containing a putative tumor suppressor gene was defined by allelotyping 65 cases of sporadic ductal carcinoma in situ with 18 polymorphic markers from 8p. The minimal region of loss encompassed the interval between D8S520 and D8S261, and one tumor had loss of D8S550 …