bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytogenetic diagnosis of the fragile X syndrome: Efficiency, utilization, and trends
Authors: Shapiro Lawrence R. , Wilmot Patrick L. , Shapiro Deborah A. , Pettersen Isabel M. , Casamassima Anthony C.
Published: June 2005

In order to assess the impact of the increasing awareness of the fra(X) syndrome and a broader approach to fra(X) testing, we analyzed our laboratory experience for 1980‐1988. In 1981–1986, there was an avearage of 80 cases/year (62 male; 18 female). The 103 (74 male; 29 female) cases in 1987 represent a 45% increase over the prior 3 years; this sustained in 1988 with 106 cases.

The fra(X) positive yield decreased from a high of 49% in 1980 to an average of 20% (range 15–24%) in 1981–1984, 10% (range 9–11%), in 1985–1987 and 7% in 1988. The positive rate for males and females was nearly identical in both time periods. The positive yield for mentally retaded individuals with a family history of mental retardation dropped from an average of 20% for 1981–1984 and 33% for 1985–87 to 13% for 1988; hopwever, the positive fra(X) rate for mentally retarded individuals decreased from an average of 23% in 1981–1984 to 9% in 1985–1987 and 7% in 1988.

The decreasing fra(X) yield and increasing case load are directly attributable to the relaxation of criteria for referral and testing related to the referral of all mentally retarded patients, and to the perceived malpractice liability for not doing a “complete” evaluation. Although the burden for cytogenetic laboratories is considerable, the yield of positive fra(X) cases is still worthwhile, and may be maximized by the use of improved screening criteria.
Duplication 3q(q21 → qter) without limb anomalies
Authors: Ismail Suzan R. , Kousseff Boris G. , Kotb Samia M. , Kholeif Soha F.
Published: June 2005

We report on a 2.5‐month‐old boy with hypertelorism, hypertrichosis, anteverted nostrils, malformed ears, thin lips, downturned corners of the mouth, micrognathia, short neck, cryptorchidism, and bilateral simian creases without limb anomalies. Cytogenetic studies showed a duplication 3q → qter 46,XY,der(6),t(3;6)(q21;p25)pat. The absence of limb anomalies is noteworthy; all 12 previously reported patients with the same duplication had limb anomalies. The uniqueness of this report provokes speculations regarding limb morphogenesis in embryos with chromosome anomalies. The concepts of chronogenetics, heterochrony, and developmental field defects appear relevant to yet another set of patients with chromosome anomalies.
Congenital nystagmus in a (46, XX/45,X) mosaic woman from a family with X‐linked congenital nystagmus
Authors: Gutmann David H. , Brooks Michael L. , Emanuel Beverly S. , McDonald‐McGinn Donna M. , Zackai Elaine H.
Published: June 2005

X‐linked congenital nystagmus is a rare disorder in which affected males manifest binocular uniplanar nystagmus with associated head oscillation. In the families previously reported, affected females have been described. We report on a multigeneration family with X‐linked congenital nystagmus with an affected woman. She was a (46,XX/45,X) mosaic. Magnetic resonance images of the brain of affected individuals were normal.
Molecular detection of constitutional deletions in patients with retinoblastoma
Authors: Blanquet Véronique , Créau‐Goldberg Nicole , Grouchy Jean De , Turleau Catherine
Published: June 2005

The recent cloning of the retinoblastoma (RB) gene as well as the identification of intragenic polymorphisms afford the necessary tools for the analysis of rearrangements using molecular hybridization. We searched for constitutional deletions by Southern blotting in 67 in dependent patients with normal karyotype comprising 15 familial and 52 sporadic cases. Among the latter, 33 were bilaterally and 19 unilaterally affected. We detected 6 deletions using cDNA probes covering almost all of the RB gene, as well as a genomic probe of the 5′ part of the gene. With this approach, the incidence of detectable deletions was around 10%. No hot spots for deletion breakpoints were found. Asymptomatic carriers were detected in 2 families. The effectiveness of genetic counselling was largely improved by this approach.
Creativity in medical genetics and dysmorphology
Authors: Hecht Frederick , Hecht Barbara K.
Published: June 2005

One gauge of creativity in medical genetics and dysmorphology is the eponym. Conditions named for people reflect their powers of observation and analysis. We examined the fields and ages of 210 eponymous physicians and scientists whose biographies were published by Peter and Greta Beighton [1986] in The Man Behind the Syndrome. Twenty fields were represented with the dominant fields being, in order, pediatrics, neurology, general and internal medicine, pathology, radiology, and orthopedics. The ages of the eponymous workers averaged 43 years at the time of their relevant publications. Fully a fifth of the contributions were made by persons aged 30 years or less, or 60 years or more, suggesting that eponymous fame may come to workers of talent independent of age.
Molecular and clinical overlap of Angelman and Prader‐Willi syndrome phenotypes
Authors: Kirkilionis A. J. , Chudley A. E. , Gregory C. A. , Hamerton J. L.
Published: June 2005

The Prader‐Willi (PWS) and Angelman syndromes (AS) share the same apparent cytogenetic and molecular lesions of 15q11‐13 and yet exhibit distinct clinical phenotypes. The etiology of PWS or AS appears to depend on the parental origin of the aberrant chromosome 15. Substantial clinical overlap has not been reported between deletion‐positive PWS and AS patients. In the present study, we report the clinical, cytogenetic, and molecular findings in three AS patients. The first patient is a mentally retarded woman with a visible deletion of 15q11‐13 with typical craniofacial, behavioral, and neurologic changes of AS. This patient is hyperphagic, and she is moderately obese for her height. Her hands and feet are small. These manifestations are more characteristic of PWS and not of AS. The molecular studies showed deletions of maternal origin for five distal PWCR loci. The most proximal locus, D15S18, was not deleted. These findings are identical to those found in our third AS patient who does not have any PWS features. To the best of our knowledge, this is the first report of concurrence of hyperphagia with consequent obesity and the AS phenotype in a patient with a del 15(q11‐13) of maternal origin. These clinical findings suggest that overlap in the symptoms of PWS and AS can occur. Our second AS patient presents with atypical molecular findings in that he cannot be classed into any of the three proposed sub‐groups of AS patients and may be representative of a fourth sub‐group of AS patients.
Fuhrmann syndrome of right‐angle bowed femora, absence of fibulae and digital anomalies: Two further cases
Authors: Lipson Anthony H. , Kozlowski Kazimierz , Barylak Antoni , Marsden William
Published: June 2005

We describe 2 patients with bilateral right‐angle bowing of femora, absence of fibulae, and reduced, flattened and nail‐less toes and symmetrical fingernail deficiency in a consanguineous family of ethnic South Vietnamese Baptists and a non‐consanguineous Polish family. These cases are similar to those reported by Fuhrmann et al. (in “Skeletal Dysplasias,” New York: Alan R. Liss, Inc., pp 519–524), indicating possible autosomal recessive inheritance of this rare non‐lethal limb malformation syndrome.
Chromosome rearrangements among couples with pregnancy losses and other adverse reproductive outcomes
Authors: Gadow Enrique C. , Lippold Santiago , Otano Lucas , Serafin Eva , Scarpati Raul , Matayoshi Tetsuji
Published: June 2005

During the years 1975–1987, 1,364 cytogenetic studies were performed in 682 couples with history of adverse pregnancy outcome. Thirty‐six balanced translocations were detected, 24 (3.5%) in women and 12 (1.7%) in men. Before 1982, all 234 couples studied had 2 or more spontaneous abortions with unknown pedigrees, with an incidence of 6.8% of balanced translocations. During 1982–1987, complete pedigree analysis was performed on a subset of 448 couples, who were then classified into 3 groups. Group I; 321 couples with 2 or more spontaneous abortions, but no other adverse outcome; group II; 37 couples with at least one or more spontaneous abortions plus a malformed child or stillbirth; and group III; 90 couples with one or more spontaneous abortions plus a sib having at least a malformed child or repetitive spontaneous abortions. The incidence of balanced translocations in these 3 groups was 2.8%, 5.4%, and 10.0%, respectively. When group III was compared with group I, the frequency of translocations was significantly different (P < 0.02).

Robertsonian translocations were predominantly detected in women, raising the possibility that prezygotic failure producing primary sterility may occur in men with such translocations.
New syndrome: Mother and son with hypertelorism, downslanting palpebral fissures, malar hypoplasia, and apparently low‐set ears associated with joint and scrotal anomalies
Authors: Seaver Laurie H. , Cassidy Suzanne B.
Published: June 2005

We report on a mother and son with a similar syndrome of hypertelorism and telecanthus, epicanthal folds, downslanting palpebral fissures, ptosis, broad nasal bridge, malar hypoplasia, thin upper lip, smooth philtrum, and apparently low‐set prominent ears. The son also has a hypoplastic shawl scrotum, cryptorchidism, and genu valgum. His language development was delayed at 18 months, but subsequently improved and was normal at age 3. The mother has the additional findings of marked cubitus valgus, hyperextensible joints, dull normal intelligence and a bleeding diathesis. This pattern of multiple congenital anomalies may represent a new syndrome.
Monozygotic twins discordant for fibular aplasia
Authors: Halal Fahed
Published: June 2005

We report on monozygotic (MZ) twins, one with the fibular aplasia developmental field defect, and the other with ectrosyndactyly of the hand. This may represent a coincidental occurrence of two sporadic events, or syndromal fibular aplasia.
Relative order and location of DNA sequences on chromosome 21 linked to familial Alzheimer disease
Authors: Pulst Stefan‐Matthias , Yang‐Feng Teresa , Korenberg Julie R.
Published: June 2005

Recently, a gene causing familial Alzheimer disease (FAD) was linked to DNA probes on chromosome 21 by genetic analysis. To investigate the precise physical location of these DNA probes, we have constructed a physical map of this region of chromosome 21 by using quantitative Southern blot analysis of cell lines aneuploid for parts of chromosome 21. The following DNA sequences were investigated: D21S16, D21S13, FB68L (cDNA probe for the amyloid protein precursor [APP] gene), and D21S1. We find that all DNA probes are located in the same region of chromosome 21, in q11.2‐q21.05. We further show that D21S16 must be centromeric to D21S13, because D21S16, but not D21S13 is present in one copy in a cell line with deletion of the region 21pter‐21q 11.2. High resolution chromosome analysis is presented to define this breakpoint. This new panel of aneuploid cell lines will allow the rapid mapping of new DNA probes in the vicinity of the FAD gene.
Characterization of the 5q‐ breakpoint in an acute nonlymphocytic leukemia patient using pulsed‐field gel electrophoresis
Authors: Thornton Donald E. , Theil Karl , Payson Robert , Balcerzak Stanley P. , Chiu Ing‐Ming
Published: June 2005

Multiple genes of hematopoietic importance have been localized to the long arm of chromosome 5 including granulocyte‐macrophage colony stimulating factor (GM‐CSF) and interleukins (IL) 3, 4 and 5 to 5q23‐31, colony stimulating factor 1 (CSF1) to 5q33.1 and its receptor (c‐fms) to 5q33.3. The genes coding for platelet‐derived growth factor receptor (PDGFR) and acidic fibroblast growth factor (FGFA) have been localized to 5q31‐32 and 5q31.3‐33.2, respectively. These genes fall in the region of chromosome 5 which is deleted in the 5q‐ refractory anemia syndrome (5q‐ RA) and acute nonlymphocytic leukemia (ANLL). We have characterized this region in a 5q‐ patient with therapy‐related ANLL (t‐ANLL) by pulsed‐field gel electrophoresis and Southern blotting analysis utilizing DNA probes for PDGFR, c‐fms, and FGFA. A single 300 kbp MluI restriction fragment was detected in the patient using a PDGFR probe as compared to a 200 kbp fragment in normal controls. BssHII digestions also showed restriction fragment length difference. Similar data for both MluI and BssHII digestions were also obtained when c‐fms was used as a probe. Southern blotting analysis of EcoRI‐digested DNA showed that each of the PDGFR, c‐fms, and FGFA alleles were deleted. These results suggested that one chromosome 5 has a large deletion involving PDGFR, c‐fms and FGFA, which is consistent with the cytogenetic analysis of the patient. In contrast, the other chromosome 5, which appeared normal cytogenetically, may have a smaller deletion (or alteration) in proximity to but not involving any of these 3 genes.
Alagille syndrome with de Novo del(20) (p 11.2)
Authors: Teebi Ahmad S. , Murthy D. S. Krishna , Ismail E. A. R. , Redha A. A.
Published: June 2005

We report on an Arab boy with Alagille syndrome and a de novo deletion of the short arm of chromosome 20 with a 46,XY, del(20)(p11.2) chromosome constitution. Other reported cases are briefly reviewed.
Progressive bilateral nasal alar collapse: A dominantly inherited trait
Authors: Cole Heath , Bodurtha Joann , Salbert Bonnie Anne , Wolf Barry
Published: June 2005

We describe a 47‐year‐old woman with progressive bilateral collapse of the alae nasi first noted at age 16 years. Her dizygotic twin daughters have similar nasal collapse beginning at age 20 years. This condition appears to be inherited as a dominant trait. Although plastic surgical correction has been successful for a phenotypically similar condition due to trauma, surgical correction must be considered cautiously in individuals with an atraumative, possibly inherited, progressive form of the disorder.
Completeness of catalogs of autosomal dominant, autosomal recessive, and X‐linked phenotypes
Authors: Kate Leo P Ten
Published: June 2005

The completeness of McKusick's catalogs of Mendelian Inheritance in Man (MIM) as to the number of phenotypes included was studied by estimating the degree of concordance with the Dutch Gene Catalog of the Department of Medical Genetics of the University of Groningen, The Netherlands. On a total of 355 Mendelian phenotypes described in persons living in The Netherlands or originating from this country, there were nine disease entities which were not present in MIM. As judged from this comparison MIM attains 97.5% completeness (95% CI: 95.3–98.7%). Similar comparisons with data from other countries are needed before a final conclusion can be reached. Corresponding contributors in different countries or linguistic areas might further improve MIM's completeness. © 1992 Wiley‐Liss, Inc.
New autosomal recessive syndrome of sparse hair, osteopenia, and mental retardation in Mennonite sisters
Authors: Kaler Stephen G. , Garrity Ann M. , Stern Harvey J. , Rosenbaum Kenneth N. , Orrison Bonnie M. , Marini Joan C. , Bernardini Isa , Saal Howard M.
Published: June 2005

We report on 2 Mennonite sisters with a syndrome of sparse hair, osteopenia, mental retardation, minor facial abnormalities, joint laxity, and hypotonia. Their asymptomatic consanguineous parents (inbreeding coefficient F = 1/64) have 6 other offspring, 3 of whom died in infancy of type II osteogenesis imperfecta (OI), and 3 of whom are normal. We analyzed collagens synthesized by cultured fibroblasts from these 2 sisters and their parents and detected no major abnormalities. Results of chromosomal and metabolic evaluations including amino acid analysis of plasma, urine, and hair were unremarkable. A literature search and survey of a computerized syndrome identification database did not disclose an identical phenotype. The sisters bear superficial resemblance to several known syndromes which we excluded on clinical and/or biochemical grounds. We conclude that they represent a new autosomal recessive syndrome, distinct from type II OI and perhaps unique to the Mennonite population or to this particular family. © 1992 Wiley‐Liss, Inc.
Linkage analysis of a candidate locus (HLA) in autosomal dominant sacral defect with anterior meningocele
Authors: Chatkupt Sansnee , Speer Marcy C. , Ding Yulan , Thomas Marc , Stenroos Edward S. , Dermody James J. , Koenigsberger M. Richard , Ott Jurg , Johnson William G.
Published: June 2005

Sacral defect with anterior meningocele (SDAM) is a type of caudal dysgenesis. It is present at birth and becomes symptomatic later in life, usually because of obstructive labor in females, chronic constipation, rectal fistula and abscess, or meningitis. The inheritance is autosomal dominant. HLA has been implicated in caudal dysgenesis because of analogy with disorders of the T‐locus complex, a tail length determining gene in mice which is linked to the major histocompatibility complex, H‐2. Members of a 5‐generation family with sacral defect and anterior meningocele (SDAM) were typed with polymorphic markers (dinucleotide repeats D6S89, D6S105, D6S109, and TCTE1) linked to HLA. Two‐point and multipoint analysis exclude the HLA region as the location for the SDAM gene in this family. © 1994 Wiley‐Liss, Inc.
Apparently new syndrome of short stature, lumbar malsegmentation, and minor facial anomalies in two brothers
Authors: Leipälä Jaana A. , Kaitila Ilkka
Published: June 2005

We describe a previously unrecognized syndrome in two brothers with short stature, webbed neck, unusual face, moderate malsegmentation of the lumbar spine, and unilateral Legg‐Perthes‐Calvé type “disease” of the hip. Autosomal recessive inheritance is proposed, although we cannot exclude the possibility of an X‐linked recessive or an autosomal dominant condition with germinal mosaicism. © 1994 Wiley‐Liss, Inc.
Biochemical and biological properties of urinary follicle‐stimulating hormone (FSH) from the rhesus monkey (Macaca mulatta)
Authors: Matteri Robert L. , Warikoo Pradeep K. , Bavister Barry D.
Published: June 2005

Follicle‐stimulating hormone (FSH) is routinely used for the induction of superovulation in women. Homologous gonadotropin preparations that could be used for reproductive studies in macaques would have valuable research applications. Accordingly, we set out to characterize the physical and biological characteristics of urinary FSH (UFSH) in the ovariectomized rhesus monkey. In urine from 7 monkeys, concentrations of bioactive FSH ranged from 16 to 57 μg/1, relative to cynFSH‐RPI (NIDDK). UFSH was contrasted to pituitary FSH (PFSH) by non‐reducing SDS‐polyacrylamide gel electrophoresis (PAGE), native disc PAGE, and FPLC chromatofocusing. The apparent molecular weights of UFSH and PFSH are similar (approximately 35 kD); however, UFSH is more negatively charged and demonstrates a lower overall isoelectric (pl) range than PFSH. The bioactivity of UFSH was assessed by the stimulation of aromatase activity in cultured Sertoli cells and by induction of follicular maturation in hamsters. Two fractions of pituitary FSH, which differed in isoelectric properties, were obtained by chromatofocusing. The in vivo biological activity of FSH‐A (acidic, pl 3.8–4.6) and UFSH (pl 3.5–4.5) were similar, but greater than FSH‐B (basic, pl 4.6–5.5). These results support the hypothesis that heavily sialylated, low pl FSH expresses high in vivo bioactivity. This may reflect the well‐known effect of sialic acid in prolonging the circulating half‐life of glycoproteins. Thus, the quality and quantity of FSH present in ovariectomized rhesus monkey urine indicates that this may be a useful source for the preparation of enriched hormone preparations. © 1992 Wiley‐Liss, Inc.
Rhodopsin: A Structural Primer for G‐Protein Coupled Receptors
Authors: Stenkamp Ronald E. , Teller David C. , Palczewski Krzysztof
Published: June 2005

An overview of the rhodopsin crystal structure provides a structural basis for understanding the structures and functions of other G‐protein coupled receptors (GPCRs). All of the structural details observed to date for rhodopsin will not necessarily carry over to other GPCRs, but major features such as the arrangement of the seven transmembrane helices, the retinal/ligand binding site, the D(E)RY and NPXXY sequence and structural motifs, and the bent helices are likely characteristics of the GPCRs most closely related to rhodopsin. A general view of these structural features is presented here.
Recent Advances in Melatonin Receptor Ligands
Authors: Zlotos Darius P.
Published: June 2005

Melatonin is a hormone exerting its multiple actions mainly through two G‐protein‐coupled receptors MT1 and MT2. Exploring the physiological role of each of these subtypes requires subtype selective MT1 and MT2 ligands. While several MT2‐selective ligands were developed in the 1990s, no selective agonists and antagonists for the MT1 subtype were described. The present article reviews mela toninergic ligands developed in the current millennium focusing on subtype selective agents and on drug candidates. Notable compounds are the MT1‐selective agonists 35 and 134, MT1‐selective antagonists 117 and 131, MT2‐selective agonists 58, 70, 79, 97 and 125, MT2‐selective antagonists 27, 73 and 119, and the highly potent non‐selective agonist 120. The non‐selective agonists agomelatine 2, and ramelteon 87 are drug candidates as antidepressive agent and for the treatment of insomnia and circadian rhythm disfunction, respectively.
Microarray analysis of genes in fetal central nervous system after ethylnitrosourea administration
Authors: Katayama Kei‐ichi , Ueno Masaki , Yamauchi Hirofumi , Nakayama Hiroyuki , Doi Kunio
Published: June 2005

BACKGROUND: Ethylnitrosourea (ENU), a monofunctional alkylating agent, induces apoptosis and cell cycle arrest in neuroepithelial cells, neural stem cells in the fetal central nervous system (CNS). These effects occur immediately after the administration of ENU to pregnant animals resulting in fetal brain anomalies and long‐term effects include brain tumors in the offspring. METHODS: Changes in gene expression were investigated in the fetal CNS after ENU administration to pregnant rats using microarray to identify the genes involved in the injury and recovery of the fetal CNS. RESULTS: The up‐regulation of 21 genes in injury and 15 genes in recovery phases and down‐regulation of 5 genes in injury and 3 genes in recovery phases were identified. The genes up‐regulated in the injury phase contained p53‐target genes that mediate apoptosis and cell cycle arrest, and those in the recovery phase contained cell proliferation‐promoting genes. The genes down‐regulated in the injury phase contained cholesterol biosynthesis‐related genes. In addition, there were some genes that have not been identified to be involved in the CNS injury and recovery. CONCLUSIONS: The present study will provide a better understanding of the mechanisms of development, regeneration and carcinogenesis of the CNS as well as the mechanisms of ENU‐induced fetal CNS injury and recovery. Birth Defects Res B 74:255–260, 2005. © 2005 Wiley‐Liss, Inc.
Critical window of male reproductive tract development in rats following gestational exposure to di‐n‐butyl phthalate
Authors: Carruthers Christina M. , Foster Paul M.D.
Published: June 2005

BACKGROUND: Gestational exposure to di‐n‐butyl phthalate (DBP), a ubiquitous environmental contaminant, has been shown to interfere with the development of the male reproductive tract by acting as an antiandrogen. This study was conducted to identify the critical days for the abnormal development of the male reproductive tract, specifically the testis and epididymis. METHODS: Timed‐pregnant Sprague‐Dawley rats were dosed with DBP at 500 mg/kg/day on gestation day (GD) 14 and 15, 15 and 16, 16 and 17, 17 and 18, 18 and 19, or 19 and 20 (GD 0=plug day). Anogenital distance (AGD) was measured on postnatal day (PND) 1 and 13, while areloa number was recorded on PND 13 only. After weaning, males were allowed to mature to PND 90 at which time they were necropsied. Areloa number and AGD were recorded and testes, epididymides, seminal vesicles, prostate gland, kidneys, and liver weighed. Blood serum was collected and assayed for total testosterone concentration. RESULTS: There were no observable effects on litter size, sex ratio, serum testosterone concentration, or mortality of pups. Statistically significant permanent reductions in AGD were seen in males exposed prenatally to DBP on GD 15 and 16 or GD 18 and 19. On PND 13, areola were present in males exposed to DBP on GD 15 and 16, 16 and 17, 17 and 18, and 19 and 20. However, permanent retention occurred only in males after DBP exposure on GD 16 and 17. Exposure to DBP on only GD 17 and 18 elicited a reduction in epididymal weights; while exposure on only GD 16 and 17 caused a significant increase in the weights of the testes due to edema. In this study, epididymal and testicular malformations were most prevalent after exposure to DBP on any gestational day. Epididymal malformations, characterized by agenesis of various regions and small or flaccid testes were significantly increased in DBP‐exposed males only on GD 16 and 17. CONCLUSIONS: These findings suggest that 2‐day DBP exposure is highly detrimental to the developing reproductive tract of the male fetus and the critical window for abnormal development is GD 16–18. Birth Defects Res B 74:277–285, 2005. Published 2005 Wiley‐Liss, Inc.
Proliferation of dinoflagellates: blooming or bleaching
Authors: Wong Joseph T.Y. , Kwok Alvin C.M.
Published: June 2005

The dinoflagellates, a diverse sister group of the malaria parasites, are the major agents causing harmful algal blooms and are also the symbiotic algae of corals. Dinoflagellate nuclei differ significantly from other eukaryotic nuclei by having extranuclear spindles, no nucleosomes and enormous genomes in liquid crystal states. These cytological characteristics were related to the acquisition of prokaryotic genes during evolution (hence Mesokaryotes), which may also account for the biochemical diversity and the relatively slow growth rates of dinoflagellates. The fact that the proliferation of many dinoflagellates is sensitive to turbulence may be due to the physiological requirements of the genome's liquid crystal states. Mechanical stress and anti‐microtubule drugs induce cell cycle arrest mainly in G1, implicating a role for the permanent cortical microtubular cytoskeleton in mechanotransduction. The cell cycles of photosynthetic dinoflagellates are also gated by the circadian rhythm, with cell division occurring mainly at the end of the dark phase. Cell growth and the biosynthesis of many toxins occur during the light phase, corresponding to G1 in the cell cycle. The dinoflagellates also embody several options for coupling cell cycle progression to cell growth, enabling them to make the best use of available resources and possibly preparing them for a symbiotic existence. BioEssays 27:730–740, 2005. © 2005 Wiley Periodicals, Inc.
Multiple but dissectible functions of FEN‐1 nucleases in nucleic acid processing, genome stability and diseases
Authors: Shen Binghui , Singh Purnima , Liu Ren , Qiu Junzhuan , Zheng Li , Finger L. David , Alas Steve
Published: June 2005

Flap EndoNuclease‐1 (FEN‐1) is a multifunctional and structure‐specific nuclease involved in nucleic acid processing pathways. It plays a critical role in maintaining human genome stability through RNA primer removal, long‐patch base excision repair and resolution of dinucleotide and trinucleotide repeat secondary structures. In addition to its flap endonuclease (FEN) and nick exonuclease (EXO) activities, a new gap endonuclease (GEN) activity has been characterized. This activity may be important in apoptotic DNA fragmentation and in resolving stalled DNA replication forks. The multiple functions of FEN‐1 are regulated via several means, including formation of complexes with different protein partners, nuclear localization in response to cell cycle or DNA damage and post‐translational modifications. Its functional deficiency is predicted to cause genetic diseases, including Huntington's disease, myotonic dystrophy and cancers. This review summarizes the knowledge gained through efforts in the past decade to define its structural elements for specific activities and possible pathological consequences of altered functions of this multirole player. BioEssays 27:717–729, 2005. © 2005 Wiley Periodicals, Inc.
β1 integrins and neural stem cells: making sense of the extracellular environment
Authors: Campos Lia Scotti
Published: June 2005

Neural Stem Cells (NSC) are present in the developing and adult CNS. In both the embryonic and adult neurogenic regions, β1 integrins may act as sensors for the changing extracellular matrix. Here we highlight the integrative functions that β1 integrins may play in the “niche” by regulating NSC growth factor responsiveness in a timely and spatially controlled manner. β1 integrins may provide NSC with the capacity to react to a dynamic “niche”, and to respond adequately by either remaining as stem cells or by differentiating and migrating away to shape the developing cortex. © 2005 Wiley Periodicals, Inc. BioEssays 27:698–707, 2005. © 2005 Wiley Periodicals, Inc.
Chromosome ends: different sequences may provide conserved functions
Authors: Louis Edward J. , Vershinin Alexander V.
Published: June 2005

The structures of specific chromosome regions, centromeres and telomeres, present a number of puzzles. As functions performed by these regions are ubiquitous and essential, their DNA, proteins and chromatin structure are expected to be conserved. Recent studies of centromeric DNA from human, Drosophila and plant species have demonstrated that a hidden universal centromere‐specific sequence is highly unlikely. The DNA of telomeres is more conserved consisting of a tandemly repeated 6–8 bp Arabidopsis‐like sequence in a majority of organisms as diverse as protozoan, fungi, mammals and plants. However, there are alternatives to short DNA repeats at the ends of chromosomes and for telomere elongation by telomerase. Here we focus on the similarities and diversity that exist among the structural elements, DNA sequences and proteins, that make up terminal domains (telomeres and subtelomeres), and how organisms use these in different ways to fulfil the functions of end‐replication and end‐protection. BioEssays 27:685–697, 2005. © 2005 Wiley Periodicals, Inc.
Hox and wings
Authors: Deutsch Jean
Published: June 2005

In many bilaterian phyla, appendages are morphological traits that characterise the identity of the various body parts. In pterygote insects, wings are dorsal appendages on the thorax. The famous “bithorax” fly created by Ed Lewis is the emblematic example of the role of Hox genes.1 Now, Tomoyasu et al.,2 using classical genetics, transgenesis and RNAi, have examined the function of thoracic Hox genes in the beetle Tribolium castaneum. Beetles have rigid elytra in place of the first pair of wings. Instead of the expected transformation of the elytron into a wing, loss of Hox genes' function leads to the homeotic transformation of the second pair of dorsal appendages, the wings, into elytra. This has important consequences for the way that we see the role of Hox genes in development and evolution. BioEssays 27:673–675, 2005. © 2005 Wiley Periodicals, Inc.
Association by guilt: identification of DLX5 as a target for MeCP2 provides a molecular link between genomic imprinting and Rett syndrome
Authors: Bapat Sharmila , Galande Sanjeev
Published: June 2005

Rett syndrome (RTT) is an X‐linked dominant neurodevelopmental disorder affecting almost exclusively girls. Although mutations in methyl‐CpG‐binding protein (MeCP2) are known to be associated with RTT, gene expression patterns are not significantly altered in MeCP2‐deficient cells. A recent study1 identified MeCP2‐mediated histone modification and formation of a higher‐order chromatin loop structure specifically associated with silent chromatin at the Dlx5–Dlx6 locus in normal cells, and its absence thereof in RTT patients. This altered expression of Dlx5 through loss of silent chromatin loop formation provides a molecular mechanism underlying RTT and proposes a novel role for MeCP2 in chromatin organization and imprinting. © 2005 Wiley Periodicals, Inc. BioEssays 27:676–680, 2005. © 2005 Wiley Periodicals, Inc.
Psychosocial factors and interleukin‐6 among women with advanced ovarian cancer
Authors: Costanzo Erin S. , Lutgendorf Susan K. , Sood Anil K. , Anderson Barrie , Sorosky Joel , Lubaroff David M.
Published: June 2005

BACKGROUND

Relations among psychological stress, depression, social support, and interleukin‐6 (IL‐6, a proinflammatory cytokine) have been documented in humans and animals. Because elevated IL‐6 is associated with a poorer prognosis among ovarian cancer patients and has been implicated in the metastasis of ovarian cancer, the current study examined relations between psychosocial factors and IL‐6 among women with advanced‐stage ovarian cancer.

METHODS

Sixty‐one ovarian cancer patients completed assessments of social support, distressed mood, and quality of life before surgery. Peripheral blood was drawn preoperatively, and the plasma was assayed for IL‐6. Ascites samples were also assayed for IL‐6 for a subset of patients.

RESULTS

Both IL‐6 levels and distressed mood were elevated among patients. After statistically adjusting effects of age and disease stage, social attachment was associated with lower levels of IL‐6 in peripheral blood (P= 0.03), whereas poorer health‐related quality of life was associated with higher IL‐6 (Pvalues ranged from 0.01 to 0.03 on different measures). This pattern of relations was also found in the ascites. Moreover, IL‐6 levels in peripheral blood plasma correlated significantly with IL‐6 in the ascites (P< 0.001), suggesting that peripheral IL‐6 reflects IL‐6 levels at the site of the tumor.

CONCLUSIONS

Results suggest that social support may play a protective role with respect to IL‐6 elevations, and IL‐6 may be an independent marker of health‐related quality of life among ovarian cancer patients. Processes involving IL‐6 represent possible pathways by which behavioral factors may contribute to disease outcomes among women with ovarian cancer. Cancer 2005. © 2005 American Cancer Society.
Fused Tetracyclic Heterocycles by Thermally Initiated Intramolecular Criss‐Cross Cycloaddition of 3‐Substituted Homoallenylaldazines
Authors: Zachová Hana , Man Stanislav , Nečas Marek , Potáček Milan
Published: June 2005

The thermally initiated intramolecular criss‐cross cycloaddition of 3‐substituted homoallenylaldazines 5 has been explored. Their cyclization led to interesting new fused heterocyclic systems 6 consisting of four five‐membered rings with two nitrogen heteroatoms. The azines were prepared by the reaction of homoallenyl aldehydes 4 with hydrazine. The homoallenyl aldehydes 4 were synthesized by the Claisen rearrangement of new N,N‐disubstituted 4‐[(2‐methylprop‐1‐en‐1‐yl)oxy]but‐2‐yn‐1‐amines 3a–f prepared by Mannich reaction of 2‐methylprop‐1‐en‐1‐yl prop‐2‐yn‐1‐yl ether (2). The success of the reaction was based on the improved solvent‐free synthesis of 1‐chloro‐2‐methylpropyl prop‐2‐yn‐1‐yl ether (1) and its conversion to isolable 2‐methylprop‐1‐en‐1‐yl prop‐2‐yn‐1‐yl ether (2) in high yield. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
A Highly Selective Fluorescent Chemosensor for H2PO4– Based on a Calix[4]arene Tetraamide Derivative
Authors: Chen Qi‐Yin , Chen Chuan‐Feng
Published: June 2005

A new neutral fluorescent chemosensor 5 based on a calix[4]arene tetraamide derivative has been synthesized. It exhibits high selectivity for H2PO4– over a wide range of anions, and the selectivity for H2PO4– is more than 2700‐fold higher than for F–. In acetonitrile, the fluorescence intensity of 5 is efficiently enhanced about 130 % [(I – I0)/I0] upon the addition of 5 equiv. of H2PO4–. From the fluorescence titration experiments, the association constant for 5/H2PO4– (1:2) was calculated to be 5.48 × 109 M–2. Furthermore, the 1H NMR spectral and X‐ray crystal studies suggested that multiple hydrogen‐bonding interactions occur between 5 and H2PO4–.
A Total Synthesis of (+)‐ and (–)‐Dihydrokavain with a Sonochemical Blaise Reaction as the Key Step
Authors: Wang Fang‐Dao , Yue Jian‐Min
Published: June 2005

Starting from 2,3‐O‐isopropylidene‐D‐glyceraldehyde (2) as chiral material, the naturally occurring (S)‐(+)‐dihydrokavain (1a) was synthesized by a procedure that involves a sonochemical Blaise reaction as the key step. The absolute configuration of (S)‐(+)‐dihydrokavain (1a) is demonstrated for the first time by total synthesis from a chiral source. Its opposite enantiomer, (R)‐(–)‐dihydrokavain (1b), was also synthesized after inversion of the chiral center in a Mitsunobu reaction. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Sequential Diastereoselective Addition of Allylic and Homoallylic Grignard Reagents to 2‐Acyl‐perhydro‐1,3‐benzoxazines and Ring‐Closing Metathesis: an Asymmetric Route to Azepin‐3‐ol and Azocin‐3‐ol Derivatives
Authors: Pedrosa Rafael , Andrés Celia , Gutiérrez‐Loriente Agustín , Nieto Javier
Published: June 2005

Chiral 2‐acyl‐3‐allyl‐substituted perhydrobenzoxazines derived from (–)‐8‐aminomenthol react with allyl or homoallyl Grignard reagents to provide the corresponding tertiary alcohols in very good yields and with excellent diastereoselectivities. The 1,8‐ and 1,9‐azadienes prepared in this way participate in RCM reactions to give good yields of seven‐ and eight‐membered nitrogen heterocycles. The yields of the RCM reaction increased when the hydrochlorides were used instead of the neutral azadienes. The removal of the chiral adjuvant allowed the preparation of enantiopure azepin‐3‐ol and azocin‐3‐ol derivatives. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Steric Effects in Isolated Molecules: Gas‐Phase Basicity of Methyl‐Substituted Acetophenones
Authors: Böhm Stanislav , Gal Jean‐François , Maria Pierre‐Charles , Kulhánek Jiří , Exner Otto
Published: June 2005

The energies of 14 methyl‐substituted acetophenones and of their protonated forms were calculated within the framework of the density functional theory at the B3LYP/6‐311+G(d,p) level. The gas‐phase basicities of some members of this series were measured using Fourier transform ion cyclotron resonance mass spectrometry in order to complete the known data. The protonated forms exist in two configurations differing in the position of the hydrogen atom; their equilibrium depends strongly on the substitution pattern. Taking into account all conformational equilibria, the experimental and calculated basicities agreed to within 2.7 kJ mol–1. Substituent effects were tentatively resolved into polar and steric contributions by comparing the corresponding ortho and para derivatives. The steric effect of the ortho‐methyl groups defined in this way has a clear physical meaning proven by several correlations; it destabilizes the neutral acetophenone molecules but destabilizes the cations even more. Hence it is base‐weakening relative to the steric effect on the acidity of substituted benzoic acids, which is acid‐strengthening. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Hybrid Bioorganic–Inorganic Materials Prepared by Site‐Specific Ligation of Peptides to Functionalized Polydisperse Silica Particles
Authors: Joly Pascal , Ardès‐Guisot Nicolas , Kar Samiran , Granier Michel , Durand Jean‐Olivier , Melnyk Oleg
Published: June 2005

We describe the synthesis of semicarbazide‐ or glyoxylyl‐functionalized polydisperse silica particles and their use for the preparation of hybrid polypeptide–silica materials. The peptides were attached to the surface of functionalized silicas by site‐specific α‐oxo hydrazone or semicarbazone ligation. The reaction of semicarbazide silicas with a model glyoxylyl peptide was found to be very efficient under stoichiometric conditions and led to ligation yields of about 90 %. The use of glyoxylyl silicas and of hydrazinoacetyl peptides led to lower yields. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Strategies for the Total Asymmetric Synthesis of Heliannuols K and L: Scope and Limitations
Authors: Lecornué Frédéric , Paugam Renée , Ollivier Jean
Published: June 2005

Kulinkovich reactions of oxa‐esters bearing terminal double bonds afford cyclopropanols by intramolecular cyclization. These can undergo Saegusa oxidation to provide β‐chloro‐oxacycloalkanones and can then be then dehydrohalogenated into oxacycloalkenones. Through a judicious choice of starting esters, diverse aryl‐fused benzoxocinones possessing the basic skeleton of sesquiterpenes, such as heliannuols, can be obtained. Although the syntheses of certain compounds in racemic form seem accessible, however, improvements through new strategies are still required for the total asymmetric synthesis. This article describes the first synthesis of enantiomerically enriched OMe‐heliannuol K and the first stereo‐ and enantioselective synthesis of heliannuol L, and new approaches and studies of their limitations in the preparation of these products are detailed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Influence of the Conformation of Salen Complexes on the Stereochemistry of the Asymmetric Epoxidation of Olefins
Authors: Scheurer Andreas , Maid Harald , Hampel Frank , Saalfrank Rolf W. , Toupet Loic , Mosset Paul , Puchta Ralph , van Eikema Hommes Nico J. R.
Published: June 2005

Compared with Katsuki’s or Jacobsen’s catalysts (R,R,R,R)‐1 or (R,R)‐2, the phenomenon of reversed asymmetric induction in the course of the epoxidation of unfunctionalised olefins in the presence of (salen)manganese complex (S,S)‐3 is indirectly explained by means of quantumchemical calculations, as well as by 1H NMR spectra of salen ligand (S,S)‐10 and diamagnetic low‐spin nickel complex (S,S)‐7 and by its X‐ray structure analysis. Whereas in (R,R,R,R)‐1 and (R,R)‐2 the phenyl and cyclohexyl substituents occupy equatorial positions, the origin for the reversed enantioselection caused by manganese catalyst (S,S)‐3, is based on an axial position of the acyclic heteroalkyl substituents in the diimine backbone of (S,S)‐3 as exemplarily confirmed by model nickel complex (S,S)‐7. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Tricarbonyl(naphthoquinone)chromium: Synthesis and Application in [4+2] Cycloaddition Reactions
Authors: Möhring Daniel , Nieger Martin , Lewall Burhanshah , Dötz Karl Heinz
Published: June 2005

Tricarbonyl(naphthoquinone)chromium (9) has been prepared in an 82 % overall yield by direct complexation of TBS‐protected naphthohydroquinone (6) and subsequent deprotection/oxidation. Complex 9 underwent [4+2] cycloaddition reactions with a series of dienes to give products in good to excellent yields. The cycloaddition reaction revealed that the tricarbonylchromium fragment exhibits perfect endo selectivity and has an anti‐directing role, as established by X‐ray analyses of the Diels–Alder products 10–13. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Allylation of Aldehyde and Imine Substrates with In Situ Generated Allylboronates – A Simple Route to Enatioenriched Homoallyl Alcohols
Authors: Sebelius Sara , Szabó Kálmán J.
Published: June 2005

Allylation of aldehyde and imine substrates was achieved using easily available allylacetates and diboronate reagents in the presence of catalytic amounts of palladium. This operationally simple one‐pot reaction has a broad synthetic scope, as many functionalities including, acetate, carbethoxy, amido and nitro groups are tolerated. The allylation reactions proceed with excellent regio‐ and stereoselectivity affording the branched allylic isomer. By employment of commercially available chiral diboronates enantioenriched homoallyl alcohols (up to 53 % ee) could be obtained. The mechanistic studies revealed that the in situ generated allylboronates react directly with the aldehyde substrates, however the allylation of the sulfonylimine substrate requires palladium catalysis. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Enhanced extrastriate visual response to bandpass spatial frequency filtered fearful faces: Time course and topographic evoked‐potentials mapping
Authors: Pourtois Gilles , Dan Elise S. , Grandjean Didier , Sander David , Vuilleumier Patrik
Published: June 2005

We compared electrical brain responses to fearful vs. neutral facial expressions in healthy volunteers while they performed an orthogonal gender decision task. Face stimuli either had a broadband spatial‐frequency content, or were filtered to create either low spatial‐frequency (LSF) or high spatial‐frequency (HSF) faces, always overlapped with their complementary SF content in upside‐down orientation to preserve the total stimulus energy. We tested the hypothesis that the coarse LSF content of faces might be responsible for an early modulation of event‐related potentials (ERPs) to fearful expressions. Consistent with previous findings, we show that broadband images of fearful faces, relative to neutral faces, elicit a higher global field power of approximately 130 ms poststimulus onset, corresponding to an increased P1 component over lateral occipital electrodes, with neural sources located within the extrastriate visual cortex. Bandpass filtering of faces strongly affected the latency and amplitude of ERPs, with a suppression of the normal N170 response for both LSF and HSF faces, irrespective of expression. Critically, we found that LSF information from fearful faces, unlike HSF information, produced a right‐lateralized enhancement of the lateral occipital P1, without any change in the scalp topography, relative to unfiltered (broadband) fearful faces. These results demonstrate that an early P1 response to fear expression depends on a visual pathway preferentially tuned to coarse‐magnocellular inputs, and can persist unchanged even when the N170 generators are disrupted by SF filtering. Hum Brain Mapp, 2005. © 2005 Wiley‐Liss, Inc.
Visual evoked potentials recovered from fMRI scan periods
Authors: Becker Robert , Ritter Petra , Moosmann Matthias , Villringer Arno
Published: June 2005

Simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) may allow functional imaging of the brain at high temporal and spatial resolution. Artifacts generated in the EEG signal during MR acquisition, however, continue to pose a major challenge. Due to these artifacts, an interleaved modus has often been used for “evoked potential” experiments, i.e., only EEG signals recorded between MRI scan periods were assessed. An obvious disadvantage of this approach is the loss of a portion of the EEG information, which might be relevant for the specific scientific issue. In this study, continuous, simultaneous EEG‐fMRI measurements were carried out. Visual evoked potentials (VEPs) could be reconstructed reliably from periods during MR scanning and in between successive scans. No significant differences between both VEPs were detected. This indicates sufficient artifact removal as well as physiological correspondence of VEPs in both periods. Simultaneous continuous VEP‐fMRI recordings are thus shown to be feasible. Hum Brain Mapp, 2005. © 2005 Wiley‐Liss, Inc.