bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parasomnias and Abnormal Sleep-Related Movements
Authors: Lee-Chiong Teofilo 
Published: November 2023

Abstract
Parasomnias are undesirable physical phenomena or behavior that develop during the sleep period. These abnormal events or experiences are not principally abnormalities of the states of sleep and wakefulness, and they are not generally associated with major complaints of excessive sleepiness or insomnia. Parasomnias can manifest as activation of skeletal muscles or the autonomic nervous system during sleep. They usually occur intermittently or episodically either within sleep or during its transition to and from wakefulness. Occasionally, parasomnias may give rise to violent and potentially injurious behavior.
Parasomnias can be classified into three groups based on the American Academy of Sleep Medicine International Classification of Sleep Disorders (ICSD; second edition; see References) (Box 7–1).
1. Disorders of arousal from non–rapid eye movement (NREM) sleep, including confusional arousals, sleepwalking, and sleep terrors
2. Parasomnias usually associated with rapid eye movement (REM) sleep, including REM sleep behavior disorder (including parasomnia overlap disorder and status dissociatus), recurrent isolated sleep paralysis, and nightmare disorder
3. Other parasomnias, including sleep-related dissociative disorder, sleep enuresis, sleep-related groaning (catathrenia), exploding head syndrome, sleep-related hallucinations, and sleep-related eating disorder.
Linguistics In The Courtroom
Authors: Shuy Roger W 
Published: November 2023

Abstract
This is a practical guide for both beginning and established linguists who have been asked by lawyers to address the language issues in their civil and criminal cases. Author Roger W. Shuy deals with issues of how to become an expert, how to start and manage a practice of consulting on law cases, how to address the issue of professional ethics, how to work with lawyers, write reports, affidavits, and participate successfully in depositions, direct examination, and cross examination at trial. The book also suggests ways that linguists can use their forensic linguistic experiences in their publications and classroom teaching, along with suggestions of recent books that forensic linguists may need for their personal libraries.
Human Malformations and Their Genetic Basis
Authors: Epstein Charles J 
Published: November 2023

Abstract
Of the many problems encountered in the practice of clinical genetics, perhaps the most perplexing, in terms of understanding pathogenesis, have been the conditions characterized by the presence of congenital malformations. Winter (1996) estimated that approximately 1 in 40 (2.5%) newborns has recognizable congenital abnormalities at birth. These occur half the time as single malformations and half the time as multiple malformations. It has also been estimated that of the more than 1750 inherited human disorders that result in altered morphogenesis, more than 1000 are multiple malformation syndromes (Wilson, 1992).
Development of the Vascular System
Authors: Barnes Carmen M , Christison-Lagay Emily R , Huang, Sui , Kaipainen Arja 
Published: November 2023

Abstract
The formation of the vascular system is one of the earliest events of embryogenesis occurring shortly after implantation. Its formation not only provides a network by which the developing embryos receive oxygen and nutrients but also the cells of vascular origin themselves produce instructive trophic factors that promote organogenesis (reviewed by Risau, 1997; Yancopoulos et al., 1998).
The Development of Bone and Cartilage
Authors: Murakami Shunichi , Akiyama, Haruhiko , Crombrugghe Benoit De 
Published: November 2023

Abstract
The formation of bone occurs through two distinct mechanisms. More than 95% of the skeleton is formed by the complex process of endochondral ossi7cation, which involves a cartilage intermediate. The other bones, namely some craniofacial bones, are formed directly from the condensations of mesenchymal cells without cartilage intermediate, a process described as intramembranous ossi7cation. Bones contain both bone-forming osteoblasts, which arise from mesenchymal cells, and bone-resorbing osteoclasts, which arise from macrophage/ monocytic cells. The coexistence of the two cell types insures bone homeostasis, which is the result of a functional steady-state characterized by an equilibrium between bone synthesis and bone resorption. In cartilage, a single cell lineage, represented by different subpopulations of chondrocytes, constitutes the only cell type of this tissue. Cartilage in articular surfaces, which line the extremities of many bones, and cartilage in the nose, ears, and throat are never replaced by bone and persist as permanent cartilage. It is not clearly understood why chondrocytes in such cartilage do not develop into bone.
Development of the Endodermal Derivatives in Lung, Liver, Pancreas, and Gut
Authors: Stanger Ben Z 
Published: November 2023

Abstract
The derivatives of endoderm display an extraordinary diversity of function, including gas exchange, digestion, nutrient absorption, detoxi7cation, and endocrine regulation. A wide range of developmental disorders is attributable to the abnormalities of endoderm function, corresponding to the steps that normally give rise to these tissues. These include (1) endoderm formation (gastrulation) and spatial speci7cation (patterning), (2) physical formation of the primitive organ anlagen (budding), (3) shaping of tissue architecture (morphogenesis), and (4) creation of speci7c functional cell types within the organ (differentiation). This chapter reviews the development of the lung, liver, pancreas, and gut, focusing on the molecular determinants of each of these processes.
GLI3 and the Pallister–Hall and Greig Cephalopolysyndactyly Syndromes
Authors: Biesecker Leslie G 
Published: November 2023

Abstract
Pallister–Hall syndrome (PHS) and Greig cephalopolysyndactyly syndrome (GCPS) are distinct, pleiotropic developmental anomaly syndromes that are caused by mutations in GLI3 and inherited in an autosomal dominant pattern. The major anomalies in PHS include hypothalamic hamartoma, central or postaxial polydactyly, and airway anomalies. The major anomalies of GCPS include macrocephaly with hypertelorism and preor postaxial polydactyly. Both disorders have a wide spectrum of severity but are clinically distinct. The GLI3 gene encodes a C2H2-type zinc 7nger transcription factor that is downstream in the sonic hedgehog (SHH) signaling pathway. The mutational spectrum of GLI3 mutations in patients with GCPS is broad, including translocations, gross and molecular deletions, amino acid substitutions, and frameshift and nonsense mutations. The mutational spectrum of PHS typically comprises only frameshift mutations that preserve the zinc 7nger binding domain of GLI3. A hypothesis has been proposed to explain the correlation of these two phenotypes and the associated mutations.
WISP3 and Progressive Pseudorheumatoid Dysplasia
Authors: suwairi Wafaa , Warman matthew L 
Published: November 2023

Abstract
Mutation in Wnt-1 inducible signaling pathway protein 3 (WISP3) (CCN6), a member of the CCN (CTGF, CEF10/Cyr61, Nov, and, now, WISP1, WISP2, and WISP3) family of secreted growth regulators causes the autosomal recessive disorder progressive pseudorheumatoid dysplasia (PPD) (Hurvitz et al., 1999). Of the six members of the CCN gene family, only WISP3 has been associated with a human Mendelian disease phenotype. The precise developmental pathway by which WISP3 causes disease is unknown. The ability to regulate diverse pathways [e.g., bone morphogenetic protein, Wnt, transforming growth factor-β (TGF-β), Integrin, and insulin-like growth factor 1 (IGF1)] has been identi3ed among CCN family members. However, most activities have been identi3ed ex vivo or using nonphysiologic levels of messenger RNA (mRNA)/protein in vivo. Consequently, the roles of Wisp3 and the other CCN family members in the physiologic, in vivo, regulation of developmental and homeostatic pathways require further investigation.
AXIN2, Tooth Agenesis, and Colorectal Cancer
Authors: Nieminen Pekka , Lammi, Laura , Järvinen Heikki J 
Published: November 2023

Abstract
Mutations in the human AXIN2 gene cause dominantly inherited tooth agenesis with severe but variable phenotype. At the same time, they predispose to colorectal cancer. The role of AXIN2 as a regulator of Wnt (wingless)-signaling is in line with the well-established role of deregulated β-catenin activity in promoting colon cancer. However, while for tooth agenesis the underlying pathogenesis is less obvious, this finding highlights the importance of signal regulation for organogenesis. As genetic background for tooth agenesis, one of the most common developmental anomalies in man, is still largely unknown, it will be interesting to find whether other connections between tooth agenesis and cancer predisposition will be identified.
AMH/MIS and Its Receptors: The Persistent Müllerian Duct Syndrome
Authors: Picard Jean-Yves 
Published: November 2023

Abstract
Antimüllerian hormone (AMH), also called müllerian inhibiting substance (MIS), is a member of the transforming growth factor-β (TGF-β) family, produced exclusively by the gonads, that plays an important role in sex differentiation and gonadal function.
TWIST1 and the Saethre–Chotzen Syndrome
Authors: Jabs Ethylin Wang 
Published: November 2023

Abstract
Saethre–Chotzen syndrome (OMIM 101400) is one of the most common craniosynostosis syndromes with autosomal dominant inheritance. The most frequently observed features are the premature fusion of coronal sutures resulting in brachycephaly, low frontal hairline, facial asymmetry, ptosis of the eyelids, prominent helical crus, syndactyly, and broad great toes. This syndrome is caused by mutations in the TWIST1 gene that map to chromosome 7p21 and codes for a basic helix–loop–helix (bHLH) transcription factor (OMIM 601622). At least 97 different mutations, including missense and nonsense changes, small insertions and deletions leading to frameshifts, and duplications, have been identified in patients. These mutations lead to loss of the ability of the HLH domain to dimerize or the basic region to bind to its target(s). Loss of the entire gene and potential regulatory elements as far away as a few megabases from the coding region of TWIST1 can also cause the Saethre–Chotzen syndrome phenotype. Chromosomal rearrangements or deletions involving the 7p21-p22 region are more often found than intragenic mutations in patients with mental retardation. Twist1 heterozygous null mice with craniofacial and limb abnormalities that resemble Saethre–Chotzen syndrome further support loss of function as the mechanism by which mutant TWIST1 leads to the phenotype. Previously, patients with Saethre–Chotzen-like features and duplication of the great toe or radial ray hypoplasia were diagnosed as having separate clinical entities, Robinow–Sorauf or Baller–Gerold syndrome, respectively. These patients also have TWIST1 mutations and are now thought to represent phenotypic variability in the Saethre– Chotzen syndrome. Normally, TWIST1 has an inhibitory role in osteoblast and myocyte differentiation which is mediated through targets such as histone acetyltransferase, cell cycle regulators, and cytokines. Thus, loss of this inhibitory effect in Saethre–Chotzen syndrome leads to increased osteoblast proliferation, decreased differentiation, and apoptosis resulting in synostosis at cranial sutures and abnormalities of limb development. Potential modifiers of the effect of TWIST1 mutations include interacting proteins and components of several developmental pathways including the bHLH proteins TWIST2, SNAI1, SNAI2, ID1, and HAND2; transcription factors RUNX2, MSX2, and ALX4; and fibroblast growth factor receptors (FGFRs). Selection of dimer partners and posttranslational modification are additional mechanisms by which the severity of craniosynostosis and limb anomalies are modulated in Saethre–Chotzen syndrome.
Introduction to Notch Signaling
Authors: Miyamoto Alison , Weinmaster Gerry 
Published: November 2023

Abstract
During the earliest stages of embryogenesis, &gt;ve signaling pathways direct the majority of developmental decisions: Wnt, TGF-α, Hedgehog, RTK, and Notch (Gerhart, 1999). Consistent with Notch signal transduction regulating a wide variety of cell types during specication, patterning, and morphogenesis, mutations in Notch signaling elements are causative in a number of human diseases (Hansson et al., 2004), some of which will be discussed in the following chapters.
NF1 and Neurofibromatosis 1
Authors: Daginakatte Girish C , Gutmann David H 
Published: November 2023

Abstract
Neurofibromatosis 1 (NF1, OMIM 162200) is a common genetic disorder with an estimated prevalence of approximately 1 in 3500, regardless of gender, ethnic background, or race (Friedman, 1999). It is transmitted in an autosomal dominant inheritance pattern with complete penetrance, but variable expressivity.
HOXD10 and Congenital Vertical Talus
Authors: Shrimpton Antony E , Levinsohn E Mark 
Published: November 2023

Abstract
Congenital vertical talus (CVT), also known as “rocker bottom foot” deformity, is a dislocation of the talonavicular joint, with rigid dorsal dislocation of the navicular over the neck of the talus. This dislocation results in a characteristic radiographic vertical orientation of the talus. This condition is usually associated with multiple other congenital deformities (e.g., myelomeningocoele neuromuscular syndromes, and aneuploidies) and only rarely as an isolated deformity (Hamanishi, 1984). An identical mutation, a recurrent missense mutation (M319K; 956T&gt;A) in the HOXD10 transcription factor gene, is the only mutation so far identified in autosomal dominant isolated CVT families. In one family, it had variable expression, manifesting in a Charcot-Marie-Tooth (CMT)-like pes cavus claw toe appearance in a minority of carriers. The finding of M319K, twice, in isolated CVT families implies a specific dominant gain of function disease mechanism. To date, no mutations have been identified in nonfamiliar isolated CVT cases.
EYA1 and the Branchio–Oto–Renal Syndrome
Authors: Alkuraya Fowzan S , Moy, Robert T , Maas Richard L 
Published: November 2023

Abstract
Mutation of Eyes Absent 1 (EYA1) is an established cause of Branchio–Oto–Renal (BOR) syndrome (OMIM 113650). EYA1, the EYA1 gene product, which belongs to a highly conserved family of transcriptional coactivators that are recruited along with members of the Six family of homeoproteins to specific enhancers. EYA1 also encodes a novel protein phosphatase function. Thus, EYA1 heterozygosity is thought to underlie the BOR phenotype through impairment of either or both functions. The resultant phenotype typically includes deafness with associated otic, renal, and branchial abnormalities, although highly variable expressivity often means that all three BOR characteristics are rarely found in a single patient. Thus, EYA1 mutation can also result in the simpler Branchio–Oto (BO) syndrome. Not surprisingly, mutation in the SIX1 gene that encodes a molecular interactor with the EYA1 protein can also cause BOR and BO syndromes.
NKX2-5 and Congenital Heart Disease
Authors: Gazit Avihu Z , Foerster, Susan N , Jay Patrick Y 
Published: November 2023

Abstract
Nkx2-5 is a homeodomain-containing transcription factor that is required for normal embryonic cardiac development (see Chapter 10). Loss of the homologous gene tinman in Drosophila results in absence of the dorsal vessel, the %y equivalent of the heart. A homozygous null mutation of Nkx2-5 in mouse causes arrest of cardiac development during looping of the heart tube and embryonic lethality. The heterozygous null mutation in mice replicates some of the defects observed in humans. The )rst reported patients had a familial syndrome of atrial septal defect (ASD) and atrioventricular (AV) conduction block. Additional mutations have been discovered in a wide range of congenital heart defects, including ventricular septal defect (VSD), tetralogy of Fallot, hypoplastic left heart syndrome, and Ebstein malformation of the tricuspid valve. Mutations of Nkx2-5 are also associated with deleterious effects on cardiac rhythm and function in some patients. The diagnosis and management of such patients are discussed. Finally, mouse models and biochemical experiments suggest that developmental pathogenesis involves numerous molecular interactions between Nkx2-5, modi)er genes, other transcription factors, and gene-regulatory sequences. The many interactions and subtle hemodynamic variables likely in%uence the spectrum of cardiac phenotypes associated with Nkx2-5 mutations.
FOXC2 and Lymphedema Distichiasis
Authors: Erickson Robert P 
Published: November 2023

Abstract
ymphedema distichiasis (LD) is a dominantly inherited syndrome of high penetrance and extremely variable expression. Its most constant feature is distichiasis, a double row of eyelashes due to secondary eyelashes growing from the meibomian glands. Lymphedema is typical of adolescent onset but can be so severe as to cause hydrops fetalis and may not appear at all. LD results from heterozygosity for null mutations at FOXC2. FOXC2 is a member of the forkhead transcription factor family. This gene family codes for transcription factors with both positive and negative effects on transcription. The pattern of embryonic expression of Foxc2 and the phenotype of homozygous nulls predict the extra clinical features seen in LD: cleft palate, cardiac abnormalities, extradural spinal cysts, and ptosis. To date, only 4 of 49 published mutations have been missense, strongly suggesting that it is haplode&ciency, which results in the phenotype.
RSK2 (RPS6KA3) and the Coffi n–Lowry Syndrome
Authors: Zeniou Maria , Jacquot Sylvie , Delaunoy, Jean-Pierre , Hanauer Andr 
Published: November 2023

Abstract
loss-of-function mutations in the gene encoding the protein kinase ribosomal S6 serine/threonine kinase 2 (RSK2) are responsible for Coffin–Lowry syndrome (CLS; OMIM 303600), a syndromic form of X-linked mental retardation. Cardinal features of CLS are growth and psychomotor retardation, characteristic facial and digital abnormalities, and progressive skeletal deformations.
IRF6 and the Van der Woude Popliteal Pterygium Syndromes and the Risk for Nonsyndromic Cleft Lip and Palate
Authors: Schutte Brian C , Dixon, Michael J , Murray Jeffrey C 
Published: November 2023

Abstract
Van der Woude syndrome (VWS; OMIM 119300) is a highly penetrant, autosomal dominant orofacial clefting disorder. VWS is characterized by clefts of the lip and/or palate with accompanying paramedian lower lip pits. An allelic variant, the popliteal pterygium syndrome (PPS), includes additional features of lower extremity pterygia, genital anomalies, skin overlapping the great toe, and other occasional features. Mutations in the transcription factor interferon regulatory factor 6 (IRF6) account for most cases of VWS/PPS with limited evidence for locus heterogeneity. Although VWS and PPS are relatively rare disorders, common variants in IRF6 also contribute to isolated cleft lip and palate. Isolated cleft lip and palate is a common birth defect with a prevalence of approximately 1 per 1000 live births. Thus, IRF6 is a critical component of the molecular cascade driving development of the lip and palate. Gene expression studies and mouse models are now providing additional insights into the role of this gene and others in the IRF6 developmental pathway in both facial and epithelial development.
Posttranscriptional Control: Nuclear RNA Processing
Authors: SWANSON MAURICE S , ARIS JOHN P 
Published: November 2023

Abstract
Normal development of human tissues requires the activation of specific genes during various embryonic stages so that stage-specific protein isoforms and other gene products appear in their proper developmental windows. While transcriptional initiation starts the gene expression cascade, nascent transcripts must be modified and the mature RNA products correctly localized within the cell. Most of the nuclear processing machinery is devoted toward producing the major RNAs required for the translational apparatus (Fig. 125–1). Pre-messenger RNAs (pre-mRNAs) are transcribed by RNA polymerase II (Pol II) and modified (capped) at the 5′ end by 7-methylguanosine, introns are removed by the spliceosome and the mature 3′ ends of mRNAs are generated by endonucleolytic cleavage which is generally followed by polyadenylation. Ribosomes begin life in the nucleolus where pre-ribosomal RNA (pre-rRNA) processing involves a series of nucleolytic cleavage steps as well as nucleotide modifications which results the synthesis of subunit precursors. These precursors are subsequently exported into the cytoplasm for the final modification steps required to form functional subunits. A similar biogenesis pathway is followed by pre-transfer RNAs (pre-tRNAs) although the majority of these processing events occur outside of the nucleolus. Overall, the cell expends an enormous amount of metabolic energy on these RNA processing and localization pathways. Recent estimates suggest that the spliceosome alone may be composed of hundreds of protein factors in addition to the five small nuclear RNAs (snRNAs) (Jurica and Moore, 2003). Mutations in any one of these factors, or the cis-acting elements to which they bind, may result in human disease.
UBE3A and the Angelman Syndrome
Authors: Rayburn Lowell , Wagstaff Joseph 
Published: November 2023

Abstract
Angelman syndrome (AS) is a neurodevelopmental disorder caused by deficiency of the ubiquitin-protein ligase UBE3A in the brain.
The genetic pathogenesis of AS is complex, because the UBE3A gene shows parent-specific differential expression, or imprinting, limited to the brain. In most tissues, the maternal and paternal alleles of UBE3A are expressed equally; in some brain regions, however, the maternal allele is expressed at a much higher level than the paternal allele. AS results from any of a number of genetic mechanisms that lead to absence of a functional allele of UBE3A inherited from the mother; absence of a functional paternal allele of UBE3A causes no phenotypic effects. The protein product of UBE3A, also known as E6-AP (E6-associated protein), was first identified as a cellular protein that forms a complex with the E6 proteins of high-risk human papillomaviruses (HPVs); this complex ubiquitinates the p53 tumor suppressor, thereby targeting it for degradation by the proteasome. In normal human tissues, however, p53 does not appear to be a UBE3A substrate. The substrate(s) of UBE3A that fail to be ubiquitinated in the brains of AS patients, and that lead to the neurological manifestations of AS, remain to be identified.