bluuebunny/crossref_metadata_2025 huggingface dataset:
Iron Homeostasis: Hepcidin Regulation
Authors: Camaschella Clara , Silvestri Laura
Published: December 2013

The liver hormone hepcidin is the key regulator of systemic iron homeostasis in mammals. Hepcidin controls the release of iron into plasma by binding and degrading the sole cellular iron exporter ferroportin on the surface of enterocytes, macrophages, and hepatocytes. The transcription of hepcidin is enhanced in conditions of increased body iron through the bone morphogenic protein–sons of mothers against decapentaplegic (BMP6–SMAD) signaling pathway that uses hemojuvelin (HJV) as a coreceptor. Mutational inactivation of HJV, BMP6, and other components of the pathway leads to iron overload in both humans and mice, similar to what occurs in hepcidin inactivation. Because hepcidin is an antimicrobial peptide, its transcription is also increased in inflammation, especially in response to IL‐6, through JAK2‐STAT3 activation. Inhibition of the BMP–SMAD signaling reduces the hepcidin response to inflammatory cytokines, indicating a crosstalk between the two regulatory pathways. In conditions of increased iron requirement, such as iron deficiency, hypoxia, or stimulated erythropoiesis, hepcidin expression is inhibited by multiple, yet incompletely understood, mechanisms. The main hepcidin inhibitor is TMPRSS6 encoding a serine protease, which negatively affects the BMP–SMAD signaling. Mutational inactivation of this protease leads to inappropriately high hepcidin synthesis, defective intestinal iron absorption, and iron‐deficient iron‐refractory anemia in both mice and humans. Other molecules may contribute to hepcidin inhibition, including a soluble form of HJV, hypoxia, or mediators released by maturing erythroid cells, but their molecular mechanisms are uncertain.

Although the picture of all potential hepcidin regulators is still incompletely defined, the identification of hepcidin and of its regulatory pathways has revolutionized our understating of iron metabolism and clarified the pathophysiology of iron‐related disorders. In addition, the discovery of the role of the hepcidin–ferroportin axis in the control of systemic iron homeostasis has stimulated a great interest in developing targeted drugs to control several human disorders characterized by iron deregulation. Novel promising therapeutic strategies are under development and some newly synthesized components have already been shown to be effective in animal models.
Iron Starvation Response inSaccharomyces cerevisiae
Authors: Philpott Caroline C. , Smith Pamela M.
Published: December 2013

Iron deficiency is the most common human nutritional disorder in the world, affecting more than 2 billion individuals; yet, the mechanisms behind many of the manifestations of iron deficiency remain obscure. Iron uptake and utilization has been studied in detail in the budding yeastSaccharomyces cerevisiae. Single‐celled organisms are similar to humans in their susceptibility to iron deficiency. Yeast respond to iron deficiency by the uptake of iron from the extracellular environment, the mobilization of iron from sites of intracellular storage, and the conservation of iron through metabolic adaptations.
Nickel Homeostasis: Mechanism and function ofNikR
Authors: Jones Michael D. , Sydor Andrew M. , Zamble Deborah B.
Published: December 2013

Nickel plays an important role in many organisms as a cofactor of enzyme active sites. However, nickel ions can be toxic and therefore require a robust regulation system. Found in a wide variety of bacteria and archaea,NikRis a transcription factor that regulates intracellular nickel homeostasis. The activities ofNikRhomologs from several microorganisms have been examined in detail both in vitro and in vivo. Ni2+loading promotesDNAbinding byNikR, an activity supplemented by additional, homolog‐specific cation requirements. Furthermore, there is evidence that the mechanism of nickel‐activatedDNAbinding includes stabilization of secondary structural elements of the protein that promote the formation of nonspecificDNAcontacts. Although a key function ofNikRis to regulate nickel uptake, the extent of its influence and its connection with other cellular pathways varies between organisms. Common features and contrasting activities withinNikRhomologs are presented and major outstanding questions are described.
Zinc Transport: Regulation
Authors: Kambe Taiho
Published: December 2013

Zinc homeostasis in cells is tightly controlled within narrow boundaries through the highly integrated processes of zinc uptake, sequestration, and efflux across the cell membrane, which enable a variety of zinc‐dependent proteins and enzymes to play physiologically important roles in numerous and varied biological responses. Thus, zinc transport proteins are essential to these processes. In general, two solute carrier (SLC) transporters, ZnT and ZIP, primarily regulate zinc transport in metazoans, but other membrane proteins (such as permeable channels) are also involved in zinc transport. Zinc exists as a divalent cation under physiological conditions, and thus it is transported across the cell membrane in this state, unlike iron and copper, which are reduced or oxidized before or after transport. This feature of zinc suggests that the expression levels of active zinc transporters at the cellular sites where they normally operate are important for defining net zinc transport, and thus the regulated expression of zinc transporters is critical for systemic and cellular zinc homeostasis. Regulation of zinc transport by ZnT and ZIP transporters is achieved by the coordination of a number of processes such as posttranslational modifications, modulation of transporter expression, and trafficking and degradation, in a zinc‐dependent or a zinc‐independent manner. In both transporters, the conserved amino acid residues in the putative intramembranous zinc‐binding sites, which are essential for zinc transport activity, appear to be involved in zinc selectivity.
Toxicity: Resistance Pathways for Metalloids and Toxic Metals
Authors: Liu Zijuan , Rensing Christopher , Rosen Barry P.
Published: December 2013

One of the initial challenges of the earliest cells would have been the ability to detoxify heavy metal ions and metalloids. This article focuses on microbial pathways for transport and biotransformation of the metalloid arsenic and the heavy metals cadmium and zinc. The emphasis is on recent findings on transporters and enzymes responsible for their uptake, efflux, redox cycling, and methylation.
Copper TransportingATPases in Mammalian Cells
Authors: Yang Nan , Lutsenko Svetlana
Published: December 2013

Copper‐transportingATPases (Cu‐ATPases) are essential for growth and development of mammalian organisms. These ubiquitous and evolutionarily conserved transporters participate in the biosynthesis of copper‐dependent enzymes and maintain copper levels within the range necessary to meet metabolic demands and avoid toxicity.Cu‐ATPasesare the key components of sophisticated cellular machinery that evolved to provide precise inter‐ and intracellular distribution of metals, and the function of these transporters is tightly regulated. Copper along with a growing number of cytosolic proteins controls the activity, stability, and localization ofCu‐ATPases; this regulation ensures balance between the delivery of copper to metalloenzymes in various cell compartments and copper export. Inactivating mutations in human Cu‐ATPases ATP7AandATP7Bare associated with debilitating and often lethal disorders (Menkes disease and Wilson's disease, respectively). Biochemical and biophysical studies ofATP7AandATP7Brevealed multiple metal‐binding sites, complex multi‐domain architecture, and a significant role of interdomain interactions in the function and regulation of these transporters. This article summarizes the current data on the structure and mechanism of human Cu‐ATPases ATP7AandATP7B, as well as the biochemical basis of their regulation.
Copper in Immune Cells
Authors: Djoko Karrera Y. , Achard Maud E.S. , McEwan Alastair G.
Published: December 2013

Copper is an essential trace nutrient but when used in slight excess it is highly cytotoxic. This toxicity has been exploited for centuries in medicine and agriculture, and today, the use of copper as an antimicrobial agent is still widespread. Intriguingly, this transition metal ion has recently emerged in a physiological role in the host innate immune response. Macrophages have been observed to use copper ions to promote killing of invading pathogens. These findings coincide with the wealth of reports that identify genes conferring copper resistance as key virulence factors in several medically significant pathogens, includingMycobacterium tuberculosis, Salmonellasp.,Streptococcus pneumoniae, Neisseria gonorrhoeae, Pseudomonas aeruginosa, andListeria monocytogenes. Here we summarize the present understanding of the role of copper ions at the host–pathogen interface.
Physiological reactivity in a community sample of sexually aggressive young men: A test of competing hypotheses
Authors: Peterson Zoë D. , Janssen Erick , Goodrich David , Heiman Julia R.
Published: December 2013

Men's sexually aggressive behavior potentially could relate to either physiological hyporeactivity or hyperreactivity, and these two different physiological profiles could be associated with different underlying causes of sexual aggression. Thus, measurement of physiological reactivity could provide insight into mechanisms relevant to the etiology of sexual aggression. The relationship between sexual aggression and physiological reactivity was investigated in 78 community men (38 sexually aggressive and 40 non‐aggressive men). In a laboratory protocol, the men were exposed to neutral, negative‐affect‐inducing, and positive‐affect‐inducing stimuli. Men's salivary cortisol concentrations and electrodermal activity (EDA) were measured throughout the laboratory procedure. Sexually aggressive men demonstrated (1) lower overall cortisol levels and (2) lower EDA reactivity in some conditions as compared to non‐aggressive men. Results of this study were consistent with the idea that men's sexual aggression is associated with physiological hyporeactivity, a physiological profile that has been found to be associated with externalizing behaviors and psychopathic traits. Aggr. Behav. 40:152–164, 2014. © 2013 Wiley Periodicals, Inc.
Enhanced Field Ionization Enabled by Metal Induced Surface States on Semiconductor Nanotips
Authors: Karaagac H. , Islam M. Saif
Published: December 2013

Recent progress in the realization of material structures with quantum confinement and high surface to volume ratio in nanoscale interwoven metal and semiconductor building blocks offers a strong potential to build highly functional nanodevices. Ultra‐sharp tips with distinct material dependent properties of metal and semiconductor exhibit important functionalities in devices including gas ionization sensors, field emission devices, and ion‐mobility spectrometry. Herein, a dramatically enhanced field ionization process and a device based on charged particle beams for which the geometrical and surface properties of the constituent semiconductor nanotips are engineered with controlled introduction of metallic impurities to realize close to three orders of magnitude reduction in the ionization electric‐field strength are described. Experimentally observed low voltage field ionization phenomenon is explained using the geometrical field enhancement, surface states induced by controlled introduction of metallic impurities, and polarizabilities of gas particles at the nanotips. The nanotips are employed to design field ionization gas sensors whose nanoscale pristine semiconductor tips are controllably decorated with atomic metal impurities to boost the electron tunneling properties under extremely low bias voltages. These devices also outperform their solid‐state macroscopic counterparts in terms of simplicity of their construction and higher selectivity.
Body frame variation and adiposity in development, a mixed‐longitudinal study of “cape coloured” children
Authors: Teghan Lucas , Henneberg Maciej
Published: December 2013

Objectives

The obesity epidemic is impacting both developed and undeveloped countries worldwide. It has only been recently that wide scale public campaigning has focused on prevention rather than intervention. Individual variations in food metabolism and energy expenditure may be responsible for much of the adiposity present amongst individuals. This article studies individual variation in relationship between lean trunk size and adiposity.

Methods

A mixed longitudinal growth study was conducted between 1986 and 1995 among urban and rural “Cape Coloured” schoolchildren from the Western Cape Province of South Africa. The sample consists of 127 females and 130 males between the ages of 6 and 20 years measured 6–9 times each. Correlations between age‐standardized triceps, subscapular and abdominal skinfold thicknesses and quotient indices obtained by expressing trunk length, lower limb, and upper limb lengths and bi‐acromial and bi‐iliocristal diameters as percentages of body height were explored for each year of growth.

Results

Significant correlation coefficients (P < 0.05) between 0.087 and 0.511 were found in both males and females, between bi‐acromial and bi‐iliocristal indices and three skinfold thicknesses, but not between trunk and limb lengths and skinfolds.

Conclusions

Skeletal frame width and amount of adiposity are correlated. The correlation persists longitudinally throughout childhood and adolescence in individuals living in very poor, as well as, in good environmental conditions. Am. J. Hum. Biol. 26:151–155, 2014. © 2013 Wiley Periodicals, Inc.
Haploinsufficiency of BMP4 gene may be the underlying cause of Frías syndrome
Authors: Martínez‐Fernández María Luisa , Bermejo‐Sánchez Eva , Fernández Belén , MacDonald Alexandra , Fernández‐Toral Joaquín , Martínez‐Frías María Luisa
Published: December 2013

In 2005, we reported on a family as having Frías syndrome (OMIM: 609640), with four affected members displaying a pattern of congenital defects nearly identical to those observed in a mother and son described by Frias [Frías et al. (1975). Birth Defects Orig Artic Ser 11:30–33]. These defects included growth deficiency, facial anomalies, and hand and foot alterations. We had the opportunity to study this family again due to the birth of another affected girl, who presented with similar facial characteristics to those of her elder half‐sister and the rest of affected relatives, which consisted of mild exophthalmia, bilateral palpebral ptosis, downslanting palpebral fissures, and hypertelorism. We performed array‐CGH, which identified an identical interstitial deletion of chromosome 14q22.1–q22.3 in the mother and two daughters. The deletion is 4.06 Mb in length and includes the BMP4 gene, a member of the bone morphogenetic protein (BMP) family of secreted proteins. A review of the literature showed that deletions or mutations of this gene underlie congenital defects affecting brain, eye, teeth, and digit development. Although the clinical manifestations of the current family correlate with the defects observed in patients having either 14q22–q23 deletions or mutations of BMP4, they show a milder phenotype. In order to understand the clinical variability, we evaluated the already known functional characteristics of the BMP gene members. This gene family plays an important role during early embryogenesis, and the complex synergistic functions and redundancies of the BMPs led us to conclude that haploinsufficiency of BMP4 is likely to be responsible for the clinical expression of Frías syndrome. © 2013 Wiley Periodicals, Inc.
Gómez‐López‐hernández syndrome versus rhombencephalosynapsis spectrum: A rare co‐occurrence with bipartite parietal bone
Authors: Abdel‐Salam Ghada M.H. , Abdel‐Hadi Sawsan , Thomas Manal M. , Eid Ola M. , Ali Manal M. , Afifi Hanan H.
Published: December 2013

Rhombencephalosynapsis (RES) is a rare hindbrain malformation that could occur in isolation or as a part of a syndrome for example, Gómez‐López‐Hernández syndrome (GLH) or VACTERL‐H. We identified male patient with severe RES. Ventriculomegaly, agenesis of septum pellucidum, very thin corpus callosum with interhemispheric cyst were additional neuroimaging findings. He had brachyturricephaly, midface retrusion, low‐set posteriorly rotated ears and bilateral parietal well circumscribed areas of alopecia. No corneal anesthesia was observed; thus, demonstrating many of the diagnostic criteria of GLH. Interestingly, he additionally had bilateral bipartite parietal bone (BPB) that is an extremely rare anomaly of the parietal sutures. This is the first co‐occurrence of this rare anomaly with GLH. We believe the presence of this unique finding could represent an important clue for understanding the pathogenesis of this malformation. © 2013 Wiley Periodicals, Inc.
Partial trisomy 1q41‐qter and partial trisomy 9pter‐9q21.32 in a newborn infant: An array CGH analysis and review
Authors: Akalin Ibrahim , Bozdag Senol , Spielmann Malte , Basaran Sarenur Yilmaz , Nanda Indrajit , Klopocki Eva
Published: December 2013

We report on a girl who presented with distinctive abducted hip and hyperextended knee. Cytogenetic analysis detected an extra derivative chromosome resulting from a balanced translocation in the mother and 3:1 segregation. Using array comparative genomic hybridization (CGH) in combination with conventional high resolution GTG banding, we designate the karyotype as 47, XX, +der(9)t(1;9)(q41;q21.32)mat, indicating tertiary trisomy of chromosome segments 1q41‐qter and 9pter‐9q21.32. A review and genotype–phenotype correlation suggested that the patient represented most of the manifestations of duplication of chromosome arms 1q and 9p. To our knowledge, a similar case has so far not been reported. © 2013 Wiley Periodicals, Inc.
Changing interpretation of chromosomal microarray over time in a community cohort with intellectual disability
Authors: Palmer Emma , Speirs Helen , Taylor Peter J , Mullan Glenda , Turner Gill , Einfeld Stewart , Tonge Bruce , Mowat David
Published: December 2013

Chromosomal microarray (CMA) is the first‐line diagnostic test for individuals with intellectual disability, autism, or multiple congenital anomalies, with a 10–20% diagnostic yield. An ongoing challenge for the clinician and laboratory scientist is the interpretation of variants of uncertain significance (VOUS)—usually rare, unreported genetic variants. Laboratories differ in their threshold for reporting VOUS, and clinical practice varies in how this information is conveyed to the family and what follow‐up is arranged. Workflows, websites, and databases are constantly being updated to aid the interpretation of VOUS. There is a growing literature reporting new microdeletion and duplication syndromes, susceptibility, and modifier copy number variants (CNVs). Diagnostic methods are also evolving with new array platforms and genome builds. In 2010, high‐resolution arrays (Affymetrix 2.7 M Oligo and SNP, 50 kB resolution) were performed on a community cohort of 67 individuals with intellectual disability of unknown aetiology. Three hundred and one CNVs were detected and analyzed using contemporary resources and a simple scoring system. Thirteen (19%) of the arrays were assessed as potentially pathogenic, 4 (6%) as benign and 50 (75%) of uncertain clinical significance. The CNV data were re‐analyzed in 2012 using the contemporary interpretative resources. There was a statistically significant difference in the assessment of individual CNVs (P < 0.0001). An additional eight patients were reassessed as having a potentially pathogenic array (n = 21, 31%) and several additional susceptibility or modifier CNVs were identified. This study highlights the complexity involved in the interpretation of CMA and uniquely demonstrates how, even on the same array platform, it can be subject to change over time. © 2013 Wiley Periodicals, Inc.
Somatic and germ‐line mosaicism of deletion 15q11.2–q13 in a mother of dyzigotic twins with Angelman syndrome
Authors: Sánchez Javier , Fernández Raquel , Madruga Marcos , Bernabeu‐Wittel José , Antiñolo Guillermo , Borrego Salud
Published: December 2013

Angelman syndrome (AS, OMIM105830) is a neurogenetic disorder caused by different genetic mechanisms. Determining the genetic mechanism is essential to establish the recurrence risk and the accuracy of genetic/reproductive counseling. The majority of AS patients present with a deletion of the 15q11.2–q13 region on the maternally derived chromosome. The other genetic mechanisms are: paternal disomy of chromosome 15, imprinting center defects, and mutations in the ubiquitin–protein ligase E3A gene (UBE3A). Different recurrence risks are associated with each specific genetic mechanism involved. We report on the study of dizygotic twins with classic phenotypic AS due to deletion of the same maternally derived chromosome 15. The mother presented with hypopigmented macular lesions on the inner side of both arms. Fibroblast culture studies of the maternal hypopigmented skin areas from both arms showed mosaicism for a normal cell line and for a second cell line with a 15q11.2–q13 deletion. This family represents the first demonstrated case of maternal somatic and germ line mosaicism for 15q11.2–q13 deletion as the cause of AS. © 2013 Wiley Periodicals, Inc.
Compound heterozygous deletions in pseudoautosomal region 1 in an infant with mild manifestations of langer mesomelic dysplasia
Authors: Tsuchiya Takayoshi , Shibata Minoru , Numabe Hironao , Jinno Tomoko , Nakabayashi Kazuhiko , Nishimura Gen , Nagai Toshiro , Ogata Tsutomu , Fukami Maki
Published: December 2013

Haploinsufficiency of SHOX on the short arm pseudoautosomal region (PAR1) leads to Leri–Weill dyschondrosteosis (LWD), and nullizygosity of SHOX results in Langer mesomelic dysplasia (LMD). Molecular defects of LWD/LMD include various microdeletions in PAR1 that involve exons and/or the putative upstream or downstream enhancer regions of SHOX, as well as several intragenic mutations. Here, we report on a Japanese male infant with mild manifestations of LMD and hitherto unreported microdeletions in PAR1. Clinical analysis revealed mesomelic short stature with various radiological findings indicative of LMD. Molecular analyses identified compound heterozygous deletions, that is, a maternally inherited ∼46 kb deletion involving the upstream region and exons 1–5 of SHOX, and a paternally inherited ∼500 kb deletion started from a position ∼300 kb downstream from SHOX. In silico analysis revealed that the downstream deletion did not affect the known putative enhancer regions of SHOX, although it encompassed several non‐coding elements which were well conserved among various species with SHOX orthologs. These results provide the possibility of the presence of a novel enhancer for SHOX in the genomic region ∼300 to ∼800 kb downstream of the start codon. © 2013 Wiley Periodicals, Inc.
Four patients with Sillence type I osteogenesis imperfecta and mild bone fragility, complicated by left ventricular cardiac valvular disease and cardiac tissue fragility caused by type I collagen mutations
Authors: Vandersteen Anthony M. , Lund Allan M. , Ferguson David J.P. , Sawle Philip , Pollitt Rebecca C. , Holder Susan E. , Wakeling Emma , Moat Neil , Pope F. Michael
Published: December 2013

Osteogenesis imperfecta (OI) type I is a hereditary disorder of connective tissue (HDCT) characterized by blue or gray sclerae, variable short stature, dentinogenesis imperfecta, hearing loss, and recurrent fractures from infancy. We present four examples of OI type I complicated by valvular heart disease and associated with tissue fragility. The diagnosis of a type I collagen disorder was confirmed by abnormal COL1A1 or COL1A2 gene sequencing. One patient was investigated with electrophoresis of collagens from cultured skin fibroblasts, showing structurally abnormal collagen type I, skin biopsy showed unusual histology and abnormal collagen fibril ultra‐structure at electron microscopy. The combined clinical, surgical, histological, ultra‐structural, and molecular genetic data suggest the type I collagen defect as contributory to cardiac valvular disease. The degree of tissue fragility experienced at cardiac surgery in these individuals, also reported in a small number of similar case reports, suggests that patients with OI type I need careful pre‐operative assessment and consideration of the risks and benefits of cardiac surgery. © 2013 Wiley Periodicals, Inc.
Periventricular nodular heterotopia and transverse limb reduction defect in a woman with interstitial 11q24 deletion in the Jacobsen syndrome region
Authors: So Joyce , Stockley Tracy , Stavropoulos Dimitri J.
Published: December 2013

Jacobsen syndrome (JS) is a disorder of developmental delay, growth retardation, thrombocytopenia, dysmorphic features, and cardiac abnormalities, among other congenital anomalies. JS is caused by contiguous gene deletion in distal chromosome 11q, generally varying in size from 7 to 20 Mb. Periventricular nodular heterotopia (PVNH) is a neuronal migration disorder in which neurons are abnormally located in nodules along the edges of the lateral ventricles. PVNH can also be seen with other congenital anomalies, including a recurrent association with distal limb defects. Transverse limb defects have previously been reported in two patients with JS. We report on a patient with a 3.162 Mb interstitial deletion at chromosome region 11q24 overlapping the region commonly affected in JS. The patient had PVNH and a transverse limb reduction defect, with minimal typical findings of JS. This is the first report of PVNH associated with a microdeletion at chromosome 11q and may represent an expansion of the phenotypic spectrum associated with JS. This is the third report of transverse limb reduction defects in association with JS, supporting a widening of the skeletal phenotypic spectrum in JS to include more severe limb anomalies. ETS1 is proposed as a candidate gene for involvement in limb anomalies in JS. © 2013 Wiley Periodicals, Inc.
Surgical intervention for esophageal atresia in patients with trisomy 18
Authors: Nishi Eriko , Takamizawa Shigeru , Iio Kenji , Yamada Yasumasa , Yoshizawa Katsumi , Hatata Tomoko , Hiroma Takehiko , Mizuno Seiji , Kawame Hiroshi , Fukushima Yoshimitsu , Nakamura Tomohiko , Kosho Tomoki
Published: December 2013

Trisomy 18 is a common chromosomal aberration syndrome involving growth impairment, various malformations, poor prognosis, and severe developmental delay in survivors. Although esophageal atresia (EA) with tracheoesophageal fistula (TEF) is a potentially fatal complication that can only be rescued through surgical correction, no reports have addressed the efficacy of surgical intervention for EA in patients with trisomy 18. We reviewed detailed clinical information of 24 patients with trisomy 18 and EA who were admitted to two neonatal intensive care units in Japan and underwent intensive treatment including surgical interventions from 1982 to 2009. Nine patients underwent only palliative surgery, including six who underwent only gastrostomy or both gastrostomy and jejunostomy (Group 1) and three who underwent gastrostomy and TEF division (Group 2). The other 15 patients underwent radical surgery, including 10 who underwent single‐stage esophago‐esophagostomy with TEF division (Group 3) and five who underwent two‐stage operation (gastrostomy followed by esophago‐esophagostomy with TEF division) (Group 4). No intraoperative death or anesthetic complications were noted. Enteral feeding was accomplished in 17 patients, three of whom were fed orally. Three patients could be discharged home. The 1‐year survival rate was 17%: 27% in those receiving radical surgery (Groups 3 and 4); 0% in those receiving palliative surgery (Groups 1 and 2). Most causes of death were related to cardiac complications. EA is not an absolute poor prognostic factor in patients with trisomy 18 undergoing radical surgery for EA and intensive cardiac management. © 2013 Wiley Periodicals, Inc.
Congenital neutropenia with retinopathy, a new phenotype without intellectual deficiency or obesity secondary to VPS13B mutations
Authors: Gueneau Lucie , Duplomb Laurence , Sarda Pierre , Hamel Christian , Aral Bernard , Chehadeh Salima El , Gigot Nadège , St‐Onge Judith , Callier Patrick , Thevenon Julien , Huet Frédéric , Carmignac Virginie , Droin Nathalie , Faivre Laurence , Thauvin‐Robinet Christel
Published: December 2013

Over one hundred VPS13B mutations are reported in Cohen syndrome (CS). Most cases exhibit a homogeneous phenotype that includes intellectual deficiency (ID), microcephaly, facial dysmorphism, slender extremities, truncal obesity, progressive chorioretinal dystrophy, and neutropenia. We report on a patient carrying two VPS13B splicing mutations with an atypical phenotype that included microcephaly, retinopathy, and congenital neutropenia, but neither obesity nor ID. RNA analysis of the IVS34+2T_+3AinsT mutation did not reveal any abnormal splice fragments but mRNA quantification showed a significant decrease in VPS13B expression. RNA sequencing analysis up‐ and downstream from the IVS57+2T>C mutation showed abnormal splice isoforms. In contrast to patients with typical CS, who express only abnormal VPS13B mRNA and truncated protein, a dose effect of residual normal VPS13B protein possibly explains the incomplete phenotype in the patient. This observation emphasizes that VPS13B analysis should be performed in cases of congenital neutropenia associated with retinopathy, even in the absence of ID, therefore extending the VPS13B phenotype spectrum. © 2013 Wiley Periodicals, Inc.
Mild developmental delay and obesity in two patients with mosaic 1p36 deletion syndrome
Authors: Shimada Shino , Maegaki Yoshihiro , Osawa Makiko , Yamamoto Toshiyuki
Published: December 2013

We identified mosaic 1p36 deletions in two patients with developmental delay, distinctive features, and obesity, who can walk alone and communicate with others. Thus, their neurological defects are milder than those in typical patients with 1p36 deletion syndrome because most patients with 1p36 deletion cannot acquire expressive language. Chromosomal microarray testing revealed 3.0 and 4.5 Mb aberrations in the subtelomeric region of the short arm of chromosome 1. Mean signal ratios of the identified aberrations were −0.4 and −0.5, indicating mosaicism, which was confirmed by fluorescence in situ hybridization analysis with a mosaic ratio of 70% and 77%, respectively. Previous studies demonstrated that deletion of the distal 2–3 Mb region would be responsible for hyperphagia and obesity seen in patients. On the other hand, the severity of the neurological defect often correlates with the size of the terminal deletion of 1p36, and patients with larger deletions of 1p36 would usually show severely impaired developmental milestones and be immobile and aphasic. In such cases, hyperphagia and obesity could be clinically masked. In this study, two patients with mosaic deletions of 1p36 showed obesity as a consequence of hyperphagia. This study suggests that patients with 1p36 deletion would be at risk for hyperphagia and obesity when they have both risk factors, that is, (1) deletions including the 2–3 Mb critical region and (2) milder phenotypes that allow them to reach food on their own and to overeat. © 2013 Wiley Periodicals, Inc.
An open‐label pilot study of N‐acetylcysteine for skin‐picking in Prader–Willi syndrome
Authors: Miller Jennifer L. , Angulo Moris
Published: December 2013

Prader–Willi syndrome (PWS) is a complex neurodevelopmental disorder caused by an abnormality on the long arm of chromosome 15 (q11‐q13) that results in a host of behavioral characteristics including excessive interest in food, skin picking, difficulty with a change in routine, and obsessive and compulsive behaviors. Skin‐picking can result in serious and potentially life‐threatening infections. Recent evidence suggests that the excitatory neurotransmitter glutamate is dysregulated in obsessive‐compulsive behaviors, and modulation of the glutaminergic pathway may decrease compulsive behaviors, such as recurrent hair pulling or skin‐picking behaviors. N‐acetylcysteine (NAC), a derivative of the amino acid cysteine, is thought to act either via modulation of NMDA glutamate receptors or by increasing glutathione in pilot studies. Thirty‐five individuals with confirmed PWS (ages 5–39 years, 23 females/12 males) and skin‐picking behavior for more than 1 year were treated with N‐acetylcysteine (Pharma‐NAC®) at a dose of 450–1,200 mg/day. Skin‐picking symptoms and open lesions were assessed after 12 weeks of treatment by counting and measuring lesions before and after the medication. All 35 individuals had improvement in skin‐picking behaviors. Ten (29%) individuals (six males and four females) did not have complete resolution of skin‐picking behavior, but had significant reduction in the number of active lesions. Longer‐term, placebo‐controlled trials are needed to further assess the potential benefit of this treatment. © 2013 Wiley Periodicals, Inc.
The worm has turned
Authors: Graham Bryony J. , Hay Deborah , Hughes Jim , Higgs Doug
Published: December 2013

Our understanding of biological processes in humans is often based on examination of analogous processes in other organisms. The nematode worm Caenorhabditis elegans has been a particularly valuable model, leading to Nobel prize winning discoveries in development and genetics. Until recently, however, the worm has not been widely used as a model to study transcription due to the lack of a comprehensive catalogue of its RNA transcripts. A recent study by Chen et al. uses next‐generation sequencing to address this issue, mapping the transcription initiation sites in C. elegans and finding many unexpected similarities between the transcription of enhancers and promoters in the worm and mammalian genomes. As well as providing a valuable resource for researchers in the C. elegans community, these findings raise the possibility of using the worm as a model to investigate some key, current questions about transcriptional regulation that remain technically challenging in more complex organisms.
Functionalized Tricyclic Cytosine Analogues Provide Nucleoside Fluorophores with Improved Photophysical Properties and a Range of Solvent Sensitivities
Authors: Rodgers Brittney J. , Elsharif Nada A. , Vashisht Nisha , Mingus Macy M. , Mulvahill Mark A. , Stengel Gudrun , Kuchta Robert D. , Purse Byron W.
Published: December 2013

Tricyclic cytosines (tC and tCO frameworks) have emerged as a unique class of fluorescent nucleobase analogues that minimally perturb the structure of B‐form DNA and that are not quenched in duplex nucleic acids. Systematic derivatization of these frameworks is a likely approach to improve on and diversify photophysical properties, but has not so far been examined. Synthetic methods were refined to improve on tolerance for electron‐donating and electron‐withdrawing groups, resulting in a series of eight new, fluorescent cytidine analogues. Photophysical studies show that substitution of the framework results in a pattern of effects largely consistent across tC and tCO and provides nucleoside fluorophores that are brighter than either parent. Moreover, a range of solvent sensitivities is observed, offering promise that this family of probes can be extended to new applications that require reporting on the local environment.
A Mechanistic Study of the Spontaneous Hydrolysis of Glycylserine as the Simplest Model for Protein Self‐Cleavage
Authors: Mihaylov Tzvetan T. , Parac‐Vogt Tatjana N. , Pierloot Kristine
Published: December 2013

A common feature of several classes of intrinsically reactive proteins with diverse biological functions is that they undergo self‐catalyzed reactions initiated by an N→O or N→S acyl shift of a peptide bond adjacent to a serine, threonine, or cysteine residue. In this study, we examine the N→O acyl shift initiated peptide‐bond hydrolysis at the serine residue on a model compound, glycylserine (GlySer), by means of DFT and ab initio methods. In the most favorable rate‐determining transition state, the serine COO− group acts as a general base to accept a proton from the attacking OH function, which results in oxyoxazolidine ring closure. The calculated activation energy (29.4 kcal mol−1) is in excellent agreement with the experimental value, 29.4 kcal mol−1, determined by 1H NMR measurements. A reaction mechanism for the entire process of GlySer dipeptide hydrolysis is also proposed. In the case of proteins, we found that when no other groups that may act as a general base are available, the N→O acyl shift mechanism might instead involve a water‐assisted proton transfer from the attacking serine OH group to the amide oxygen. However, the calculated energy barrier for this process is relatively high (33.6 kcal mol−1), thus indicating that in absence of catalytic factors the peptide bond adjacent to serine is no longer a weak point in the protein backbone. An analogous rearrangement involving the amide N‐protonated form, rather than the principle zwitterion form of GlySer, was also considered as a model for the previously proposed mechanism of sea‐urchin sperm protein, enterokinase, and agrin (SEA) domain autoproteolysis. The calculated activation energy (14.3 kcal mol−1) is significantly lower than the experimental value reported for SEA (≈21 kcal mol−1), but is still in better agreement as compared to earlier theoretical attempts.
Rational Design of Carboxyl Groups Perpendicularly Attached to a Graphene Sheet: A Platform for Enhanced Biosensing Applications
Authors: Bonanni Alessandra , Chua Chun Kiang , Pumera Martin
Published: December 2013

Graphene oxide (GO)‐based materials offer great potential for biofunctionalization with applications ranging from biosensing to drug delivery. Such biofunctionalization utilizes specific functional groups, typically a carboxyl moiety, as anchoring points for biomolecule. However, due to the fact that the exact chemical structure of GO is still largely unknown and poorly defined (it was postulated to consist of various oxygen‐containing groups, such as epoxy, hydroxyl, carboxyl, carbonyl, and peroxy in varying ratios), it is challenging to fabricate highly biofunctionalized GO surfaces. The predominant anchoring sites (i.e., carboxyl groups) are mainly present as terminal groups on the edges of GO sheets and thus account for only a fraction of the oxygen‐containing groups on GO. Herein, we suggest a direct solution to the long‐standing problem of limited abundance of carboxyl groups on GO; GO was first reduced to graphene and consequently modified with only carboxyl groups grafted perpendicularly to its surface by a rational synthesis using free‐radical addition of isobutyronitrile with subsequent hydrolysis. Such grafted graphene oxide can contain a high amount of carboxyl groups for consequent biofunctionalization, at which the extent of grafting is limited only by the number of carbon atoms in the graphene plane; in contrast, the abundance of carboxyl groups on “classical” GO is limited by the amount of terminal carbon atoms. Such a graphene platform embedded with perpendicularly grafted carboxyl groups was characterized in detail by X‐ray photoelectron spectroscopy, cyclic voltammetry, and electrochemical impedance spectroscopy, and its application was exemplified with single‐nucleotide polymorphism detection. It was found that the removal of oxygen functionalities after the chemical reduction enhanced the electron‐transfer rate of the graphene. More importantly, the introduction of carboxyl groups promoted a more efficient immobilization of DNA probes on the electrode surface and improved the performance of graphene as a biosensor in comparison to GO. The proposed material can be used as a universal platform for biomolecule immobilization to facilitate rapid and sensitive detection of DNA or proteins for point‐of‐care investigations. Such reactive carboxyl groups grafted perpendicularly on GO holds promise for a highly efficient tailored biofunctionalization for applications in biosensing or drug delivery.
Tetrafluorination of Sugars as Strategy for Enhancing Protein–Carbohydrate Affinity: Application to UDP‐Galp Mutase Inhibition
Authors: N'Go Inès , Golten Samuel , Ardá Ana , Cañada Javier , Jiménez‐Barbero Jesús , Linclau Bruno , Vincent Stéphane P.
Published: December 2013

Tetrafluorinated analogues of both UDP‐galactopyranose and UDP‐galactofuranose have been synthesized and assayed against UDP‐galactopyranose mutase, a key enzyme for Mycobacterium tuberculosis cell wall biosynthesis. Competition assays and STD‐NMR spectroscopy techniques have evidenced not only the first unambiguous case of affinity enhancement through local sugar polyfluorination, but also showed that tetrafluorination can still have a beneficial effect on binding when monofluorination at the same position does not.
ChemInform Abstract: Scalable Synthesis of Fe3O4/C Composites with Enhanced Electrochemical Performance as Anode Materials for Lithium‐Ion Batteries.
Authors: Hu Meijuan , Jiang Yinzhu , Yan Mi
Published: December 2013

Fe3O4/C composites are obtained from mixtures of Fe2O3 and sucrose in flowing argon at 500 °C for 2 h.
ChemInform Abstract: Extreme‐Rate Capable and Highly Stable SiCO—TiO2 Hybrids for Li Ion Battery Anodes.
Authors: Behera Shantanu , Raj Rishi
Published: December 2013

The title hybrid material for Li ion battery anodes is prepared from a slurry of 1,3,5,7‐tetravinyl‐1,3,5,7‐tetramethylcyclotetrasiloxane, dicumyl peroxide as radical initiator, and TiO2 nanoparticles.
ChemInform Abstract: CuCrO2 Delafossite: A Stable Copper Catalyst for Chlorine Production.
Authors: Amrute Amol P. , Larrazabal Gaston O. , Mondelli Cecilia , Perez‐Ramirez Javier
Published: December 2013

Single‐phase cuprous delafossites CuMO2 (M: Cr, Al, Ga, Fe, Mn) are synthesized by solid state reaction of equimolar mixtures of Cu2O and M2O3 (1273—1423 K, 30 h).
ChemInform Abstract: Mesoporous Ta3N5 Microspheres Prepared from a High‐Surface‐Area, Microporous, Amorphous Precursor and Their Visible‐Light‐Driven Photocatalytic Activity.
Authors: Cao Jing , Ren Ling , Li Na , Hu Changwen , Cao Minhua
Published: December 2013

Mesoporous Ta3N5 microspheres are prepared by nitridation of a microporous amorphous Ta2O5 precursor under NH3 flow at 750 °C for 9 h.
ChemInform Abstract: Convenient Preparation of Ternary Carbidoaluminates — The Example MgAl2C2.
Authors: Kubus Mariusz , Meyer H.‐Juergen
Published: December 2013

β‐MgAl2C2 is synthesized in high yield by a solid state metathesis reaction of Al powder, MgCl2, and Li2C2 (Nb container, 900 °C, 2 d).
ChemInform Abstract: High‐Pressure Synthesis and Characterization of the Actinide Borate Phosphate U2[BO4][PO4].
Authors: Hinteregger Ernst , Wurst Klaus , Perfler Lukas , Kraus Florian , Huppertz Hubert
Published: December 2013

The new title compound is synthesized in a Walker‐type multianvil apparatus from UO3, H3BO3, and P4O10 (12.5 GPa, 1000 °C, 5 min).
ChemInform Abstract: Insights on Growth and Nanoscopic Investigation of Uncommon Iron Oxide Polymorphs.
Authors: Carraro Giorgio , Maccato Chiara , Bontempi Elza , Gasparotto Alberto , Lebedev Oleg I. , Turner Stuart , Depero Laura E. , Van Tendeloo Gustaaf , Barreca Davide
Published: December 2013

Chemical vapor deposition of Fe2O3 nanomaterials on Si(100) at temperatures between 400 and 550 °C selectively yields β‐ and ε‐Fe2O3 polymorphs under dry oxygen or oxygen and water vapor reaction environments, respectively.
ChemInform Abstract: Ionic Liquid Iodinating Reagent for Mild and Efficient Iodination of Aromatic and Heteroaromatic Amines and Terminal Alkynes.
Authors: Nouzarian Mahboobe , Hosseinzadeh Rahman , Golchoubian Hamid
Published: December 2013

Significant advantages of the novel dichloroiodate ionic liquid with respect to reported iodination protocols are its simplicity, considerably fast reaction, solvent‐free conditions, regioselectivity, good product yields and reusability of the ionic liquid reagent.
ChemInform Abstract: Fe‐Promoted Cross Coupling of Homobenzylic Methyl Ethers with Grignard Reagents via sp3 C—O Bond Cleavage.
Authors: Luo Shuang , Yu Da‐Gang , Zhu Ru‐Yi , Wang Xin , Wang Lei , Shi Zhang‐Jie
Published: December 2013

The title reaction is proposed to proceed through a sequence of dehydroalkoxylation to form a vinyl intermediate, followed by Fe‐catalyzed selective carbometallation to form a benzylic Grignard reagent.
ChemInform Abstract: Transition Metal‐Free Sodium Borohydride Promoted Controlled Hydration of Nitriles to Amides.
Authors: Verma Praveen Kumar , Kumar Neeraj , Sharma Upendra , Bala Manju , Kumar Vishal , Singh Bikram
Published: December 2013

An efficient and sustainable process for the selective hydration of nitriles is developed which tolerates a variety of functional groups.
ChemInform Abstract: Mechanosynthesis of γ‐Nitro Dicarbonyl Compounds via CaCl2‐Catalyzed Michael Addition.
Authors: Jia Chunman , Chen Da , Zhang Chunyan , Zhang Qi , Cao Bennan , Zhao Zendong
Published: December 2013

An efficient strategy for the ball mill‐conducted mechanosynthesis of γ‐nitro dicarbonyl compounds is developed.
ChemInform Abstract: Phosphoramidate Tantalum Complexes for Room‐Temperature C—H Functionalization: Hydroaminoalkylation Catalysis.
Authors: Garcia Pierre , Lau Ying Yin , Perry Mitchell R. , Schafer Laurel L.
Published: December 2013

A new catalytic hydroaminoalkylation reaction at room temperature using an easily prepared tantal complex is presented.
ChemInform Abstract: An Efficient Reverse Diels—Alder Approach for the Synthesis of N‐Alkyl Bismaleimides.
Authors: Rao Venkataramanarao , Navath Suryakiran , Kottur Mohankumar , McElhanon James R. , McGrath Dominic V.
Published: December 2013

A simple strategy is developed to synthesize bismaleimides (IV) via alkylation of the Diels—Alder product (I) followed by a Retro‐Diels‐Alder reaction.
ChemInform Abstract: Asymmetric Addition of Cyanide to β‐Nitroalkenes Catalyzed by Chiral Salen Complexes of Titanium(IV) and Vanadium(V).
Authors: North Michael , Watson James M.
Published: December 2013

A variety of aliphatic nitroalkenes is applied in the reaction to afford the products with high yields and enantioselectivities.
ChemInform Abstract: Novel Role of p‐Toluenesulfonamide in the Preparation of 4,5‐Diaminocyclopent‐2‐enones.
Authors: Liu Jinqian , Yu Jianjun , Zhu Mengyun , Li Jun , Zheng Xingzhou , Wang Limin
Published: December 2013

A new protocol for the preparation of title compounds (III) via reaction of N‐tosylimines (I) with amines (II) is developed, in which p‐tosylamide acts as leaving group.
ChemInform Abstract: The First General Route for Efficient Synthesis of 18O Labelled Alcohols Using the HOF·CH3CN Complex.
Authors: Gatenyo Julia , Vints Inna , Rozen Shlomo
Published: December 2013

A novel method for converting boronic acids (I) to alcohols (II) is developed using the acetonitrile complex of hypofluorous acid.
ChemInform Abstract: Iridium‐Catalyzed Synthesis of ω‐Hydroxy Homoallylic Alcohols.
Authors: Obora Yasushi , Sawaguchi Takuya , Tsubakimoto Keiko , Yoshida Hiroshi , Ogawa Shinji , Hatanaka Shintaro
Published: December 2013

The Ir‐catalyzed reaction of α,ω‐diols (I) with 1‐arylpropynes (II) affords title compounds (III) bearing alkyl chains of different lengths.
ChemInform Abstract: Novel Preparation of Chiral α‐Amino Acids Using the Mitsunobu—Tsunoda Reaction.
Authors: Noisier Anais F. M. , Harris Craig S. , Brimble Margaret A.
Published: December 2013

The Mitsunobu reaction of N‐protected amino acid ester (I) with alcohols (II) and (IV) in the presence of cyanomethylene tributylphosphorane affords desired non‐natural α‐amino acid derivatives (III) and (V), respectively.
ChemInform Abstract: Syntheses and Evaluation of Novel Isoliquiritigenin Derivatives as Potential Dual Inhibitors for Amyloid‐Beta Aggregation and 5‐Lipoxygenase.
Authors: Chen Yi‐Ping , Zhang Zi‐Ying , Li Yan‐Ping , Li Ding , Huang Shi‐Liang , Gu Lian‐Quan , Xu Jun , Huang Zhi‐Shu
Published: December 2013

The compounds (IIIa)‐(IIId) show more effective abilities for both title mentioned targets than the reference compounds Resv and ISL.