bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of the Hematopoietic Stem Cell Niche
Authors: Celso Cristina Lo , Klein Rachael J. , Scadden David T. 
Published: November 2007

AbstractHematopoietic stem cells (HSCs) continuously replenish all blood cell lineages not only to maintain the normal rapid turnover of differentiated cells but also to respond to injury and stress. Cell‐extrinsic mechanisms are critical determinants of the fine balance between HSC self‐renewal and differentiation. The bone marrow microenvironment has emerged as a new area of intense study to identify which of its many components constitute the HSC niche and regulate HSC fate. While HSCs have been isolated, characterized and used in clinical practice for many years thanks to the development of very specific assays and technology (i.e., bone marrow transplants and fluorescence activated cell sorting), study of the HSC niche has evolved by combining experimental designs developed in different fields. In this unit we describe a collection of protocols spanning a wide range of techniques that can help every researcher tackling questions regarding the nature of the HSC niche. Curr. Protoc. Stem Cell Biol. 3:2A.5.1‐2A.5.31. © 2007 by John Wiley & Sons, Inc.
Cloning of Large Positive‐Strand RNA Viruses
Authors: V. Peremyslov Valera , V. Dolja Valerian 
Published: November 2007

AbstractFull‐length, biologically active cDNA clones of the positive‐strand RNA plant viruses are indispensable for investigating the functions of viral genes and control elements as well as generating virus‐derived gene expression and silencing vectors. Even though engineering of such clones for 4‐ to 10‐kb viral RNAs has become routine, it remains a challenging task for 15‐ to 20‐kb RNA genomes of the monopartite viruses in a family Closteroviridae. This unit describes strategic considerations and techniques used to generate an infectious cDNA clone of a closterovirus. The use of agroinfection to improve specific infectivity of the resulting clone is also explained. Curr. Protoc. Microbiol. 7:16F.1.1‐16F.1.26. © 2007 by John Wiley & Sons, Inc.
Fraser syndrome: A clinical study of 59 cases and evaluation of diagnostic criteria
Authors: van Haelst Mieke M. , Scambler Peter J. ,   Fraser Syndrome Collaboration Group, Hennekam Raoul C.M. 
Published: November 2007

AbstractFraser syndrome is an autosomal recessive congenital malformation syndrome characterized by cryptophthalmos, syndactyly, and urogenital defects. We studied the clinical features in 59 affected individuals from 40 families (25 consanguineous), and compared our findings to data from previous reviews. We found a higher frequency of abnormalities of the skull, larynx, umbilicus, urinary tract, and anus in our series of patients, and mental retardation and cleft lip with or without cleft palate were observed less frequently than previously reported. Clinical features in probands and sibs were remarkably similar. As can be expected prenatally diagnosed patients had more manifestations that gave rise to a pathological amount of amniotic fluid. Otherwise patients diagnosed before and after birth had similar frequencies of symptoms. Based on the present results we suggest an adaptation of diagnostic criteria for FS, including adding airway tract and urinary tract anomalies as major criteria. The specificity of the proposed diagnostic criteria was evaluated using the London Medical Database as a search tool. © 2007 Wiley‐Liss, Inc.
Acrofacial dysostosis syndrome type Rodriguez: Prenatal diagnosis and autopsy findings
Authors: Sermer David , Quercia Nada , Chong Karen , Chitayat David 
Published: November 2007

AbstractA new lethal form of acrofacial dysostosis (AFD) syndrome was delineated by Rodriguez et al. [Rodriguez et al. (1990); Am J Med Genet 35:484–489]. We report on a male fetus with mandibulofacial dysostosis, including phocomelia‐like upper limb deficiencies and lower limb anomalies which are characteristic of AFD Rodriguez type. The diagnosis was made on prenatal sonogram at 20 and at 24.1 weeks gestation. The severity of the upper limb defects, the involvement of lower limbs, and the absence of eyelid coloboma and polythelia excluded the possibility of other conditions associated with acrofacial dysostosis (AFD) including Nager acrofacial dysostosis syndrome (NADS) and postaxial acrofacial dysostosis syndrome (POADS). This case further delineates the AFD syndrome type Rodriguez. © 2007 Wiley‐Liss, Inc.
Genetics of sexual development: A new paradigm
Authors: Blecher Stan R. , Erickson Robert P. 
Published: November 2007

AbstractThe classical paradigm of human and mammalian sexual development, largely based on work of Alfred Jost, depicts the genetic factor(s) that determine(s) sex as influencing only the fate of the gonad. A maleness factor produces testes (Primary Sex Determination). These organs secrete hormones which cause male Secondary Sexual Differentiation. In absence of the maleness factor, by default the gonad becomes an ovary, and the absence of testicular hormones leads to female secondary differentiation. In this article a new paradigm is proposed, to accommodate recent findings. Sexual dimorphism precedes gonadal development, in a Pregonadal Stage. Furthermore, female development is not by default—both male (Y) and female (X) sex‐chromosomal primary sex‐determining mechanisms probably exist. The human/mammalian male Y‐chromosomal sex‐determining gene is now known (SRY/Sry), and a candidate for a non‐inactivated, X‐linked, female determining factor, is under study. However, the proximate gonad‐determining genes are probably on autosomes. Pathways between the primary factors and the proximate gonad‐determining genes are indirect and complex. A hypothetical gene Z has been proposed, that inhibits the testis determiner and is itself the target of suppression by SRY/Sry. Candidates for proximate testis and ovary‐determining factors and for Z also exist. The “default” concept has also been superseded with respect to secondary sexual differentiation. Absence of testicular hormones does not produce a normal female phenotype; ovarian genes and hormones are necessary. Finally, sex‐chromosomal sex‐determining genes influence the development not only of non‐gonadal organs of secondary sexual development, but also of organs outside of the reproductive system. © 2007 Wiley‐Liss, Inc.
Neuroimaging findings in macrocephaly–capillary malformation: A longitudinal study of 17 patients
Authors: Conway Robert L. , Pressman Barry D. , Dobyns William B. , Danielpour Moise , Lee John , Sanchez‐Lara Pedro A. , Butler Merlin G. , Zackai Elaine , Campbell Lindsey , Saitta Sulagna C. , Clericuzio Carol L. , Milunsky Jeff M. , Hoyme H. Eugene , Shieh Joseph , Moeschler John B. , Crandall Barbara , Lauzon Julie L. , Viskochil David H. , Harding Brian , Graham John M. 
Published: November 2007

AbstractHere, we report the neuroimaging findings and neurological changes in 17 unpublished patients with Macrocephaly–Capillary Malformation (M–CM). This syndrome has been traditionally known as Macrocephaly–Cutis Marmorata Telangiectatica Congenita (M–CMTC), but we explain why M–CM is a more accurate term for this overgrowth syndrome. We analyzed the 17 patients with available brain MRI or CT scans and compared their findings with features identified by a comprehensive review of published cases. White matter irregularities with increased signal on T2‐weighted images were commonly observed findings. A distinctive feature in more than half the patients was cerebellar tonsillar herniation associated with rapid brain growth and progressive crowding of the posterior fossa during infancy. In four such cases, we confirmed that the tonsillar herniation was an acquired event. Concurrently, with the development of these findings, ventriculomegaly (frequently obstructive) and dilated dural venous sinuses were observed in conjunction with prominent Virchow–Robin spaces in many of those in whom cerebellar tonsil herniation had developed. We postulate that this constellation of unusual features suggests a dynamic process of mechanical compromise in the posterior fossa, perhaps initiated by a rapidly growing cerebellum, which leads to congestion of the venous drainage with subsequently compromised cerebrospinal fluid reabsorption, all of which increases the posterior fossa pressure and leads to acquired tonsillar herniation. We make a distinction between congenital Chiari I malformation and acquired cerebellar tonsil herniation in this syndrome. We also observed numerous examples of abnormal cortical morphogenesis, including focal cortical dysplasia, polymicrogyria which primarily involved the perisylvian and insular regions, and cerebral and/or cerebellar asymmetric overgrowth. Other findings included a high frequency of cavum septum pellucidum or vergae, thickened corpus callosum, prominent optic nerve sheaths and a single case of venous sinus thrombosis. One patient was found to have a frontal perifalcine mass resembling a meningioma at age 5 years. This is the second apparent occurrence of this specific tumor in M–CM. © 2007 Wiley‐Liss, Inc.
Regional analysis on the occurrence of oral clefts in South America
Authors: Poletta F.A. , Castilla E.E. , Orioli I.M. , Lopez‐Camelo J.S. 
Published: November 2007

AbstractThe aim of this work was to search for unequal birth prevalence rates (BPRs) of cleft lip ± cleft palate (CL/P), and cleft palate only (CPO), among different geographic areas in South America, and to analyze phenotypic characteristics and associated risk factors in each identified cluster. Included were 5,128 CL/P cases, 1,745 CPO cases, and 3,712 controls (like‐sexed, non‐malformed liveborn infant, born immediately after a malformed one, in the same hospital), over 4,199,630 consecutive births. They were ascertained between 1967 and 2004, in 190 maternity hospitals of the ECLAMC (Estudio Colaborativo Latinoamericano de Malformaciones Congénitas) network, in 102 cities of all 10 South American countries. Non‐predefined geographical areas with significantly unusual cleft BPRs were identified with Kulldorf and Nagarwalla's spatial scan statistic, employing number of cases and births, and exact location of each hospital. Expected values were cleft BPRs registered for the entire ECLAMC hospital network. Syndromic and non‐syndromic clefts were considered for cluster analysis, and phenotypic characterization, while only non‐syndromic for risk factor analysis. Seven clusters for CL/P, and four for CPO, with unusual BPRs were identified. CL/P cases in high BPR areas were more severe than elsewhere in the sample, similar to a previous ECLAMC report on microtia. For CL/P, high BPR clusters were associated with high altitude above sea level, Amerindian ancestry, and low socioeconomic strata; low BPR clusters showed association with African Black ancestry. Advanced maternal age, a recognized risk factor for CPO, was also associated with the only identified geographic cluster for CPO. © 2007 Wiley‐Liss, Inc.
Muenke syndrome (FGFR3‐related craniosynostosis): Expansion of the phenotype and review of the literature
Authors: Doherty Emily S. , Lacbawan Felicitas , Hadley Donald W. , Brewer Carmen , Zalewski Christopher , Kim H. Jeff , Solomon Beth , Rosenbaum Kenneth , Domingo Demetrio L. , Hart Thomas C. , Brooks Brian P. , Immken LaDonna , Lowry R. Brian , Kimonis Virginia , Shanske Alan L. , Jehee Fernanda Sarquis , Bueno Maria Rita Passos , Knightly Carol , McDonald‐McGinn Donna , Zackai Elaine H. , Muenke Maximilian 
Published: November 2007

AbstractMuenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal and tarsal fusions, and the presence of the Pro250Arg mutation in the FGFR3 gene. Reduced penetrance and variable expressivity contribute to the wide spectrum of clinical findings in Muenke syndrome. To better define the clinical features of this syndrome, we initiated a study of the natural history of Muenke syndrome. To date, we have conducted a standardized evaluation of nine patients with a confirmed Pro250Arg mutation in FGFR3. We reviewed audiograms from an additional 13 patients with Muenke syndrome. A majority of the patients (95%) demonstrated a mild‐to‐moderate, low frequency sensorineural hearing loss. This pattern of hearing loss was not previously recognized as characteristic of Muenke syndrome. We also report on feeding and swallowing difficulties in children with Muenke syndrome. Combining 312 reported cases of Muenke syndrome with data from the nine NIH patients, we found that females with the Pro250Arg mutation were significantly more likely to be reported with craniosynostosis than males (P < 0.01). Based on our findings, we propose that the clinical management should include audiometric and developmental assessment in addition to standard clinical care and appropriate genetic counseling. Published 2007 Wiley‐Liss, Inc.
A study of 534 fetal pathology cases from prenatal diagnosis referrals analyzed from 1989 through 2000
Authors: Laury Anna , Sanchez‐Lara Pedro A. , Pepkowitz Samuel , Graham John M. 
Published: November 2007

AbstractUseful and meaningful counseling following the discovery of a fetal loss or fetal anomalies requires an accurate diagnosis. In order to achieve this, our center utilized a multidisciplinary approach which included an ultrasonographer, perinatologist, genetic counselor, dysmorphologist, clinical geneticist, and pathologist. In this article, we report our experience with the analysis and evaluation of 534 cases seen between 1989 and 2000. In total, we were able to identify the cause of fetal loss in 369 cases (69%). In 98/369 cases (18.4%) the condition was attributed to a Mendelian process and in 78 (14.6%), to chromosomal abnormalities. The overall average maternal age was 31.6 years, the maternal age in cases of chromosomal abnormality was slightly higher (33.3 years). Our findings described below reiterate the clinical usefulness of a team specifically trained in the approach to fetal loss and/or fetal anomalies. © 2007 Wiley‐Liss, Inc.
Nonsense‐mediated decay and the molecular pathogenesis of mutations in SALL1 and GLI3
Authors: Furniss Dominic , Critchley Paul , Giele Henk , Wilkie Andrew O.M. 
Published: November 2007

AbstractMutations in SALL1 and GLI3 are responsible for human limb malformation syndromes. The molecular pathophysiology of these mutations is incompletely understood, and many conclusions have been drawn from studies performed in the mouse. We identified truncating mutations in SALL1 and GLI3 in patients with limb malformation and studied the contribution of nonsense‐mediated decay (NMD) to the expression of mutant mRNA in patient‐derived fibroblasts. Quantification of the relative proportions of mutant and wild‐type alleles was performed by pyrosequencing. In SALL1, a mutant allele causing Townes–Brocks syndrome was unexpectedly resistant to NMD, whereas a different mutation causing a much milder phenotype was susceptible to NMD. In GLI3, all three mutant alleles tested were susceptible to NMD. This work provides novel insights into the molecular pathophysiology of SALL1 and GLI3 mutations, extends the phenotypic spectrum of SALL1 mutations, and provides an example of a human mutation which does not follow the usual accepted positional rules governing mammalian NMD. © 2007 Wiley‐Liss, Inc.
X‐chromosome inactivation patterns in monozygotic twins and sib pairs discordant for nonsyndromic cleft lip and/or palate
Authors: Kimani Jane W. , Shi Min , Daack‐Hirsch Sandra , Christensen Kaare , Moretti‐Ferreira Danilo , Marazita Mary L. , Field L. Leigh , Canady John W. , Murray Jeffrey C. 
Published: November 2007

AbstractNonsyndromic clefts of the lip and/or palate are common birth defects with a strong genetic component. Based on unequal gender ratios for clefting phenotypes, evidence for linkage to the X chromosome and the occurrence of several X‐linked clefting syndromes, we investigated the role of skewed X chromosome inactivation (XCI) in orofacial clefts. Our samples consisted of female monozygotic (MZ) twins (n = 8) and sister pairs (n = 152) discordant for nonsyndromic clefting. We measured the XCI pattern in peripheral blood lymphocyte DNA using a methylation based androgen receptor gene assay. Skewing of XCI was defined as the deviation in inactivation pattern from a 50:50 ratio. Our analysis revealed no significant difference in the degree of skewing between twin pairs (P = 0.3). However, borderline significant differences were observed in the sister pairs (P = 0.02), with the cleft lip with cleft palate group showing the most significant result (P = 0.01). We did not find evidence for involvement of skewed XCI in the discordance for clefting in our sample of female MZ twins. However, results from the paired sister study suggest the potential contribution of skewed XCI to orofacial clefting, particularly cleft lip and palate. © 2007 Wiley‐Liss, Inc.
The face of Joubert syndrome: A study of dysmorphology and anthropometry
Authors: Braddock Stephen R. , Henley Kimberly M. , Maria Bernard L. 
Published: November 2007

AbstractJoubert syndrome (JS) is an autosomal recessive disorder characterized by cerebellar vermis hypoplasia, hypotonia, developmental delay, apnea/hypernea and ophthalmologic abnormalities. Since its description, most attention has focused on hindbrain malformations and the hallmark molar tooth sign (MTS) when visualized on axial magnetic resonance imaging (MRI). Few reports have described a characteristic clinical phenotype of JS and a large cohort of patients has not undergone dysmorphology examinations. In addition, very little is known about other conditions which share some of the clinical and radiological features of JS, including, Arima, Senior‐Löken, Dekaban, COACH, and Varadi (OFD VI) syndromes. The purpose of this study was to document the morphologic characteristics of Joubert syndrome based upon detailed dysmorphology and anthropometric examinations in a large cohort of JS individuals to determine whether JS is associated with a specific pattern of malformation. Dysmorphology findings included long face, frontal prominence, bitemporal narrowing, ptosis, prominent nasal bridge and tip, prognathism, eyebrow abnormalities, trapezoid shaped mouth, lower lip eversion, and thick ear lobes. Anthropometric analyses showed several significant differences in measurements including bizygomatic, frontal, nasal, and mandibular dimensions. When compared to controls, younger JS patients had significantly increased facial widths whereas older patients had longer mandibular arc lengths. These data indicate that JS lacks a clear, specific recognizable pattern of malformation, despite being associated with several dysmorphic facial characteristics and distinct anthropometric facial patterns, which change with age. Variability and overlap of features in JS and other hindbrain syndromes makes clinical diagnosis difficult and probably reflects genetic heterogeneity within the cohort of patients with the MTS. © 2007 Wiley‐Liss, Inc.
Haplotype evolution of SLITRK1, a candidate gene for Gilles de la Tourette Syndrome
Authors: Speed William C. , O'Roak Brian J. , Tárnok Zsanett , Barta Csaba , Pakstis Andrew J. , State Matthew W. , Kidd Kenneth K. 
Published: November 2007

AbstractGilles de la Tourette syndrome (GTS) is a complex disorder with a clear genetic component but no clearly identified genes with variation of etiologic relevance. Various candidate regions and genes show some evidence of affecting risk, though clearly not all patients/families can be explained by any one of them. Resequencing one candidate gene, SLITRK1, has identified four new variants. Including them, we have typed over 2,300 normal individuals from 44 populations for 11 SNPs spanning the gene. The unusual global pattern seen is that one non‐ancestral haplotype is the single most common haplotype worldwide. Other haplotypes appear to result from accumulation of mutations with no evidence of historical recombination. Although there is no evidence of selection, the haplotype frequency variation seen around the world will need to be considered in any future association studies of this locus with GTS or any other neuropsychiatric disorder. © 2007 Wiley‐Liss, Inc.
Biomechanical model of pronation efficiency: New insight into skeletal adaptation of the hominoid upper limb
Authors: Galtés Ignasi , Jordana Xavier , Cos Mònica , Malgosa Assumpció , Manyosa Joan 
Published: November 2007

AbstractDespite considerable literature on the functional anatomy of the hominoid upper limb, there are no quantitative approaches relating to bone design and the resulting muscular‐activity enhancement. The purpose of this study is to quantitatively analyze the relationship between the rotational efficiency of the pronator teres muscle and the design of the skeletal structures on which it acts. Using conventional scan images of a human forearm for three rotational positions, this study develops an original biomechanical model that defines rotational efficiency as a mathematical function expressing a geometrical relationship between the origin and insertion muscular sites. The results show that this parameter varies throughout the entire pronation range, being maximal when the forearm lies around its functional position. Moreover, the rotational‐efficiency formula allows us to demonstrate, by several simulation conditions, that an improvement in pronation efficiency is derived from a large shaft radius curvature, a large humeral medial epicondyle, and a more proximal pronator teres radial attachment. The fact that forearm pronation efficiency can be inferred, even quantified, throughout the entire rotational range, by applying the biomechanical model developed here allows us to undertake anatomical approaches in the field of Evolutionary Anthropology, to interpret more precisely how skeletal design is related to upper‐limb function in extant and fossil primate taxa. Am J Phys Anthropol, 2008. © 2007 Wiley‐Liss, Inc.
Delineating genetic relationships among the Maya
Authors: Ibarra‐Rivera Lisa , Mirabal Sheyla , Regueiro Manuela M. , Herrera Rene J. 
Published: November 2007

AbstractBy 250 AD, the Classic Maya had become the most advanced civilization within the New World, possessing the only well‐developed hieroglyphic writing system of the time and an advanced knowledge of mathematics, astronomy and architecture. Though only ruins of the empire remain, 7.5 million Mayan descendants still occupy areas of Mexico, Guatemala, Belize, El Salvador, and Honduras. Although they inhabit distant and distinct territories, speak more than 28 languages, and have been historically divided by warfare and a city‐state‐like political system, and they share characteristics such as rituals, artistic, architectural motifs that distinguish them as unequivocally Maya. This study was undertaken to determine whether these similarities among Mayan communities mirror genetic affinities or are merely a reflection of their common culture. Four Mayan populations were investigated (i.e., the K'iche and Kakchikel from Guatemala and the Campeche and Yucatan from Mexico) and compared with previously published populations across 15 autosomal STR loci. As a whole, the Maya emerge as a distinct group within Mesoamerica, indicating that they are more similar to each other than to other Mesoamerican groups. The data suggest that although geographic and political boundaries existed among Mayan communities, genetic exchanges between the different Mayan groups have occurred, supporting theories of extensive trading throughout the empire. Am J Phys Anthropol, 2008. © 2007 Wiley‐Liss, Inc.