Genomic organization of the human hairless gene (HR) and identification of a mutation underlying congenital atrichia in an Arab Palestinian family

Congenital atrichia is a rare form of hereditary human hair loss, characterized by the complete shedding of hair shortly after birth, together with the formation of papular lesions on the skin. Recently, we cloned the human homolog of the mouse hairless gene and identified pathogenic mutations in several families with inherited congenital atrichia. Here, we present the genomic organization of the human hairless gene (HGMW-approved symbol HR), which spans over 14 kb on chromosome 8p12 and is organized into 19 exons. In addition, we report the identification of a 22-bp deletion mutation in exon 3 of the hairless gene in a large consanguineous Arab Palestinian family from a village near Jerusalem, Israel. These findings extend the body of evidence implicating mutations in the hairless gene as an underlying cause of congenital atrichia in humans.     

Congenital atrichia in five Arab Palestinian families resulting from a deletion mutation in the human hairless gene

Congenital atrichia is a rare autosomal recessive disorder of hair development, characterized by complete loss of hair shortly after birth. Evidence of linkage to chromosome 8p12 has been established, implicating the human homolog of the mouse hairless (hr) gene as a candidate gene. We have previously identified missense mutations in families with congenital atrichia. Here, we report the first deletion mutation (2147del C) in exon 9 of the human hairless gene leading to a frameshift and downstream premature termination codon in five Palestinian families of Arab origin. Received: 31 July 1998 / Accepted: 31 August 1998     

Dehydroepiandrosterone sulfate treatment for atrichia pubis

OBJECTIVE: To evaluate the efficacy of oral dehydroepiandrosterone sulfate (DHEAS) treatment for atrichia pubis in female adolescents. STUDY DESIGN: Two XY female adolescents with 17-hydroxylase deficiency and 2 XX females with panhypopituitarism presenting with atrichia pubis were treated with a daily dosage of DHEAS 10 mg/m2 body surface in addition to their regular substitution therapy. The dosage was increased according to clinical response. Pubic hair stages, growth and serum DHEAS were evaluated and in 1 case also serum IGFs and IGFBPs. RESULTS: A dosage of 10 mg/m2 for 1 year led to serum DHEAS levels at the lower limit of the normal range. 15 mg/m2 was needed to achieve pubic hair stage 4-5 and axillary hair in patients with 17-hydroxylase deficiency. In panhypopituitarism, pubic hair developed at a slower pace and reached stage 4 on a dosage of 25-30 mg/m2. Baseline serum IGF-I SDS was -0.67 and did not change on the initial dosage of DHEAS, in combination with submaximal estrogen substitution (10 microg ethinyl estradiol). On the combination of 15 mg/m2 DHEAS and full estrogen substitution, IGF-I SDS increased to an average of -0.15. IGFBP-3 SDS increased from 1.4 to a mean of 2.6 in the first year, and went back to 1.4 in the second year. IGFBP-6 SDS was low at baseline (-2.5) and rose to -1.9 and -1.7 IGF-II and IGFBP-1 showed an irregular pattern. CONCLUSIONS: Oral administration of DHEAS in a dosage of 15 mg/m2 o.d. is an efficacious treatment for atrichia pubis. For females with a panhypopituitarism a higher dosage appears needed. Given this and other biological actions of DHEAS, substitution therapy with DHEAS or DHEA to females with adrenal androgen deficiency appears rational.     

Genetik der monogenen isolierten Alopezien

The monogenic inherited isolated alopecias comprise a group of clinically and genetically heterogeneous forms of hairlessness or hair loss. Clinical classification of the isolated alopecias is based on the onset of the disorder, the regions affected, and the structure of the hair shaft. Men and women are equally affected, and the mode of inheritance is autosomal dominant or autosomal recessive. Since the identification of the keratin gene KRT86 as a cause of the so-called monilethrix in 1997, mutations in nine other genes have been identified for various isolated alopecias. These include other keratin genes for monilethrix (KRT81 and KRT83), the hairless gene for atrichia congenita/papular atrichia, the corneodesmosin gene for the autosomal dominant form of hypotrichosis simplex, and the genes desmoglein 4, lipase H, and the G-protein-coupled receptor P2RY5 (LPAR6) for the autosomal recessive forms of hypotrichosis. Molecular genetic and pathophysiological studies of these rare disorders of hair development have contributed significantly to our understanding of the basic mechanisms of hair loss as well as the physiological mechanisms of hair growth.     

Mechanism of JmjC-containing protein Hairless in the regulation of vitamin D receptor function

The JmjC-domain-containing protein Hairless (HR) and the vitamin D receptor (VDR) play a critical role in the maintenance of hair growth. Mutations in HR or VDR cause alopecia in humans and mice. Here we show that HR interacts with VDR and induces VDR relocalization in the nuclei. HR associates and colocalizes with nuclear receptor co-repressor (N-CoR) which is localized to subnuclear structures termed matrix-associated deacetylase (MAD) bodies. It is found that the HR mutants (C622G, N970S, D1012N, V1136D), associated with alopecia universalis congenita (AUC) or atrichia with papular lesions (APL), exhibit an abnormal subcellular distribution in addition to the impaired co-repressor activity with VDR. Studies on deletion mutants of HR indicate that the JmjC domain contributes to the co-repressor activity of HR. Our work provides new clues and evidence for the understanding on the role of HR in hair growth.     

The gene for hypotrichosis of Marie Unna maps between D8S258 and D8S298: exclusion of the hr gene by cDNA and genomic sequencing.

Hypotrichosis of Marie Unna (MU) is an autosomal dominant hair-loss disorder with onset in childhood. A genomewide search for the gene was performed in a large Dutch family using 400 fluorescent microsatellite markers. Linkage was detected with marker D8S258, and analysis of this family and a further British kindred with additional markers in the region gave a combined maximum two-point LOD score of 13.42, with D8S560. Informative recombinants placed the MU gene in a 2.4-cM interval between markers D8S258 and D8S298. Recently, recessive mutations in the hr gene were reported in families with congenital atrichia, and this gene was previously mapped close to the MU interval. By radiation-hybrid mapping, we placed the hr gene close to D8S298 but were unable to exclude it from the MU interval. This, with the existence of the semidominant murine hr allele, prompted us to perform mutation analysis for this gene. Full-length sequencing of hr cDNA obtained from an affected individual showed no mutations. Similarly, screening of all exons of the hr gene amplified from the genomic DNA of an affected individual revealed no mutations. Analysis of expressed sequences and positional cloning of the MU locus is underway.     

Type Specimens and identity of the described species of Conus II. The species described by Solander, Chemnitz, Born, and Lightfoot between 1766 and 1786

Twenty-three species of Conus were described by authors other than Linnaeus between 1766 and 1786. Of these, 3 are Eocene species from England described by Solander in Brander (1766), and the remainder are Recent. Chemnitz (1777) described one valid species. Of the 10 species described by Born (1778), 7 are valid, 2 are junior synonyms of Linnaean species, and 1 is a nomen dubium. Solander in [Lightfoot] (1786) described 5 species, of which 3 are valid and 2 are junior synonyms of Linnaean species. Lightfoot (1786) described 4 species, of which 1 is valid and 3 are junior synonyms of Linnaean species.
Holotypes of 7 species and lectotypes of 3 species exist, and representatives of lecto-types of 10 species have been selected. All of these types are illustrated photographically.
Between 1758 and 1786, 60 species of Conus were described, of which 45 are now considered valid. Of these, 42 are Recent.     

Hairless contains a novel nuclear matrix targeting signal and associates with histone deacetylase 3 in nuclear speckles

Hair follicle cycling is a highly regulated and dynamic cellular process consisting of phases of growth, regression, and quiescence. The hairless (hr) gene encodes a nuclear factor that is highly expressed in the skin, where it appears to be an essential regulator during the regression in the catagen hair follicle. In hairless mice, as well as humans with congenital atrichia, the absence of hr protein initiates a premature and abnormal catagen due to defects in the signaling required for hair follicle remodeling. Here, we report that hr protein is a nuclear protein that is tightly associated with the nuclear matrix scaffold. Using a series of deletion constructs of the mouse hr gene, we monitored the sub-cellular localization of the recombinant protein by in situ immunolocalization and biochemical fractionation after nuclear matrix extraction of transiently transfected cells. We identified a novel nuclear matrix-targeting signal (NMTS) in the hr protein and mapped the domain to amino acid residues 111-186 of the mouse hr sequence. Furthermore, we provide evidence that this region not only mediates the interaction of hr with components of the nuclear architecture, but also specifies the sub-nuclear location of the hr protein to nuclear domains containing deacetylase activity. The N-terminal region directs hr to a speckled nuclear pattern that co-localizes with the histone deacetylase 3 (HDAC), but not with HDAC1 or HDAC7. Based on our findings, we propose that hr protein is part of a specific multi-protein repressor complex and that hr may be involved in chromatin remodeling.     

Ademosynoides asiaticus Martynov, 1936, the earliest known member of an extant beetle family (Insecta, Coleoptera, Trachypachidae)

Fossil beetles are described from Kedrovka beds of the locality Babii Kamen’, Kuznetsk Basin, Siberia. According to different authors, this locality is dated to the terminal Permian or basal Triassic. SEM studies have shown that Ademosynoides asiaticus Martynov, 1936, described from this locality, should be placed in the family Trachypachidae, which makes it the earliest known extant family of beetles. In addition to the re-studied holotype, further material is described for this species; a new species of the same genus and a new genus and species of the same family are also described. As a result, almost 10% of the 78 beetle fossils known from this locality are identified as belonging to Trachypachidae. Unfortunately, the study of these beetles is complicated by the rather poor preservation quality and very small size of the majority of the fossils, which usually cannot be properly studied without using SEM. However, even in this case there is no full certainty that the results are absolutely reliable.     

Fluorescence polarization assay of plasmin, plasminogen, and plasminogen activator

A chromatographic method involving medium-pressure liquid chromatography on alumina impregnated with silver nitrate is described for the separation of a series of closely related C₂₇ sterol precursors of cholesterol differing only in the number and location of olefinic double bonds. The features of the described system are compared with those of previously described thin-layer, gas-liquid, gravity column, and high-pressure liquid chromatographic methods.     

The discovery of a potent, intracellular, orally bioavailable, long duration inhibitor of human neutrophil elastase--GW311616A a development candidate

The discovery of a potent intracellular inhibitor of human neutrophil elastase which is orally active and has a long duration of action is described. The pharmacodynamic and pharmacokinetic properties of a trans-lactam development candidate, GW311616A, are described.     

The generaAniptodera, Halosarpheia, Nais andPhaeonectriella from freshwater habitats

The generic concepts inAniptodera, Halosarpheia, Nais andPhaeonectriella are discussed and those species occurring in freshwater are described, some with illustrations. Five new species:Aniptodera lignicola, A. mauritaniensis, A. megalospora, A. palmicola, Phaeonectriella appendiculata are also described. A key to the freshwater species in the above genera and a synoptic diagram of their ascospores are provided.     

Design,construction, and operation of some all-glass pilot-plant fermetors

The design, Construction, and operation of a 400 liter all-glass fermentor, made from industrial glass Components, is described in detail. Outline details are also given for 100 and liter vessels of similar construction. The performance of the 400 liter fermentor with a variety of organisms is discussed. Harvesting performance. Using a disk-stak centrifuge, is also described.     

Two new species of Tovlinius Zaitzev, from China, with a key to the genera of Bombyliinae from China and a second key to the world species (Diptera, Bombyliidae, Bombyliinae, Bombyliini)

The genus Tovlinius Zaitzev is a Palaearctic genus with just one previously described species, Tovlinius albissimus Zaitzev. Tovlinius is here recorded from China for the first time, and two new species Tovlinius pyramidatussp. n. and Tovlinius turriformissp. n. are described and illustrated. A key to the genera of Bombyliinae from China and a second key to the World species of Tovlinius are also presented herein.     

HOME RANGE, BEHAVIOUR, AND RECRUITMENT RATES OF TWO BLACK RHINOCEROS POPULATIONS

During the period 1964 – 1966 biological studies were conducted of two black rhinoeeros Diceros bicornis L. populations in northern Tanzania. One population occupies the caldera of Ngorongoro and the other the area in the vicinity of Olduvai Gorge. Detailed records were made of each rhinoeeros observatson and 182 individuais were seen in the two study areas during the three-year period.
The black rhinoeeros is a very sedentary species, and the size of the home range is governed by several factors which are described in the^text. The home range of an immature rhinoeeros is larger than that of an adult individual. The adult rhinoeeros, especially the male, is essentially a solitary animal, but immatures frequently join up with a companion.
Activity patterns are described and illustrated, and are similar in the two study areas. Behaviour of the species follows welldefined patterns, and territorial behaviour is uncommon. Vocal communication in the species is described. The significance of dung piles, used regularly by the species, is considered and the results of experiments iflsing faecal samples are described. Relations with two carnivores are discussed.
The recruztment rates of the two populations are almost identical, i.e. 7.0% at Ngorongoro and 7.2% at Olduvai. Various reproductive characteris-tics affecting recruitment rates, such as age at maturity, gestation period and interval between successive calves are described using records obtained from zoological gardens and from field observations.
The results of the studies indIcate that the rhinoeeros population of the Ngorongoro Conservation Area is considerably higher than was formerly believed. The future of the species in the area appears favourable, providing its habitats are not destroyed through encroaching cultivation.     

褐巢蛾属分类修订(鳞翅目,巢蛾科,巢蛾亚科)

对褐巢蛾属 Metanomeuta Meyrick进行了修订,重新描述了模式种,讨论了其形态变异;记述2个新种,即岳西褐巢蛾 Metanomeuta yuexiensis sp.nov.和疏刺褐巢蛾 Metanomeutaspinisparsula sp.nov..文中提供了成虫和外生殖器特征图,给出了分种检索表及分布图.模式标本保存在南开大学昆虫标本室.岳西褐巢蛾,新种 Metanomeuta yuexiensis sp.nov.(图3,10,13)该种与金冠褐巢蛾 Metanomeuta fulvicrinis Meyrick外部相似,但可通过外生殖器特征区别:颚形突卵圆形,末端钝圆;雌性后阴片中部微凹,前阴片不明显,囊导管基部2/3具瘤突,交配囊长卵形.正模♂,安徽岳西温泉(30°52'N,116°22'E),1995-08-08,胡祥富采,外生殖器玻片号JQ07191.副模：8♂♂,1♀,安徽岳西温泉,1995-07-25～08-22,胡祥富采. 疏刺褐巢蛾,新种Metanomeuta spinisparsula sp.nov.(图4,11,14)该种与金冠褐巢蛾Metanomeuta fulvicrinis 相似,区别在于:体为深褐色,翅面无任何斑纹;雄性颚形突略呈舌状,末端突出,抱器腹除端部有一枚较大刺突外,无明显小刺或小刺束;雌性导管端片小且非杯状,囊导管仅基部1/2 具瘤突.正模♂,湖南石门县壶瓶山江坪(29°35'N,111°22'E;480m),2002-01-05,于海丽采,外生殖器玻片号JQO6091;副模1♀,采集资料同正模.