An N-ethyl-n-nitrosourea induced corticotropin-releasing hormone promoter mutation provides a mouse model for endogenous glucocorticoid excess

Cushing's syndrome, which is characterized by excessive circulating glucocorticoid concentrations, maybe due to ACTH-dependent or -independent causes that include anterior pituitary and adrenal cortical tumors, respectively. ACTH secretion is stimulated by CRH, and we report a mouse model for Cushing's syndrome due to an N-ethyl-N-nitrosourea (ENU) induced Crh mutation at -120 bp of the promoter region, which significantly increased luciferase reporter activity and was thus a gain-of-function mutation. Crh -120/+ mice, when compared with wild-type littermates, had obesity, muscle wasting, thin skin, hair loss, and elevated plasma and urinary concentrations of corticosterone. In addition, Crh-120/+ mice had hyperglycemia, hyperfructosaminemia, hyperinsulinemia, hypercholesterolemia, hypertriglyceridemia, and hyperleptinemia but normal adiponectin. Crh -120/+ mice also had low bone mineral density, hypercalcemia, hypercalciuria, and decreased concentrations of plasma PTH and osteocalcin. Bone histomorphometry revealed Crh-120/+ mice to have significant reductions in mineralizing surface area, mineral apposition, bone formation rates, osteoblast number, and the percentage of corticoendosteal bone covered by osteoblasts, which was accompanied by an increase in adipocytes in the bone marrow. Thus, a mouse model for Cushing's syndrome has been established, and this will help in further elucidating the pathophysiological effects of glucocorticoid excess and in evaluating treatments for corticosteroid-induced osteoporosis.

Il mundus muliebris nelle fonti latine e nei contesti Pompeiani

The subject of the study is the classical Latin concept 'mundus muliebris', usually translated simply as women’s toiletry items. The task of the research is, on one hand, to find a more accurate and comprehensive literary definition for the concept as used in the early Imperial period, and on the other, to examine whether it is possible to find corresponding groupings of material objects among the finds from Pompeian houses destroyed by the eruption of Mount Vesuvius in AD 79. The study is based on two different bodies of evidence, literary and material, and consequently uses two independent methods of research. In the philological part of the study, all occurrences of the concept 'mundus muliebris' in classical Latin texts were identified and analysed in their proper literary context, paying special attention to information about the nature of the objects included (name, owner, quantity, value, location in the house). On the basis of this analysis, mirrors were chosen as the key elements of the archaeological research, being ̶ hypothetically ̶ the most probable objects to be found among any extant 'mundus muliebris' contexts in Pompeian houses. In the archaeological part of the study, all mirrors deposited in the Archaeological Storerooms of Pompeii, mostly unpublished, were examined, together with their original find contexts. For more detailed documentation, classification, as well as quantitative and functional analysis, the fifty-nine best preserved household or shop contexts were chosen. Among these contexts, only a few ‘ideal’ groups closely corresponding to the literary definitions were found. However, in most cases a functional artifact pattern of toiletry items could indeed be found grouped together with the mirror. The arrangement of the contexts in the domestic space also revealed a clear pattern. Firstly, the contexts consistently seem to be found in the place of storage, inside locked boxes, not in the place of use. Secondly, they show that for the storage of such objects small closed rooms flanking the main entrance of the house were preferred. Culturally, 'mundus muliebris' can be described as a very complex multi-layered concept intimately interrelated with the female gender, an instrument of its bodily creation and a symbol of its nature. Concretely, it has at its core mirrors and instruments for the care of skin and hair, and includes, in more technical definitions, washing equipment as well. In the Roman domus, lacking specific women’s quarters, this box containing toiletries and other personal objects could be defined as the true, although mobile, private space of the household’s female members.

Effect of sorghum ergot (Claviceps africana) on the performance of steers (Bos taurus) in a feedlot.

The effect of ergot (Claviceps africana) in naturally infected sorghum was assessed in feedlot rations. Thirty-two Hereford steers (Bos taurus) in individual pens with access to shade were adapted to feedlot conditions and then offered one of four rations containing 0, 4.4, 8.8 or 17.6 mg/kg of ergot alkaloids (84% dihydroergosine, 10% dihydroelymoclavine and 6% festuclavine), equivalent to ~0, 10, 20 or 40 g/kg ergot (sclerotia/sphacelia) in the rations. These rations were withdrawn at noon on the second day because of severe hyperthermia and almost complete feed refusal in ergot-fed steers. After recovery on ergot-free rations for 5 days, treatment groups were incrementally introduced, over a further 3–12 days, to rations containing 0, 1.1, 2.2 or 4.4 mg/kg of alkaloids (~0, 2.5, 5 or 10 g/kg ergot, respectively). Relative exposure to ergot was maintained, so that the zero- (control), low-, medium- and high-ergot groups remained so. Steers were individually fed ad libitum, and water was freely available. Steers in all ergot-fed groups had significantly elevated rectal temperatures at 0800–1000 hours, even when the temperature–humidity index was only moderate (~70), and displayed other signs of hyperthermia (increased respiration rate, mouth breathing, excessive salivation and urination), as the temperature–humidity index increased to 73–79 during the day. Plasma prolactin was significantly reduced in ergot-fed groups. Voluntary feed intakes (liveweight basis) of the ergot-fed groups were significantly reduced, averaging 94, 86 and 86%, respectively, of the feed intakes of the control group. Hair coats were rough. While the control steers grew from a mean initial liveweight of 275 kg to a suitable slaughter weight of 455 kg in 17 weeks (growth rate 1.45 kg/day), ergot-fed groups gained only 0.77–1.10 kg/day and took at least 5 weeks longer to reach the slaughter weight, despite removal of ergot at the same time as control steers were sent to slaughter. Sorghum ergot, even at low concentrations (1.1 mg alkaloids/kg feed) is severely detrimental to the performance of steers in the feedlot.

No genetic support for a contribution of prostaglandins to the aetiology of androgenetic alopecia

MADAM, Androgenetic alopecia (AGA) is a common age-dependent trait, characterized by a progressive loss of hair from the scalp. The hair loss may commence during puberty and up to 80% of white men experience some degree of AGA during their lifetime.1 Research has established that two essential aetiological factors for AGA are a genetic predisposition and the presence of androgens (male sex hormones).1,2 A recent meta-analysis of genome-wide association studies (GWAS) has increased the number of identified loci associated with this trait at the molecular level to a total of eight.3 However, despite these successes, a large fraction of the genetic contribution remains to be identified. One way to identify further genetic loci is to combine the resource of GWAS datasets with knowledge about specific biological factors likely to be involved in the development of disease. The focused evaluation of a limited number of candidate genes in GWAS datasets avoids the necessity for extensive correction for multiple testing, which typically limits the power for detecting genetic loci at a genome-wide level.4 Because the presence of genetic association suggests that candidate genes are likely to operate early in the causative chain of events leading to the phenotype, this approach may also function to favour biological pathways for their importance in the development of AGA.

Androgenetic alopecia: Identification of four genetic risk loci and evidence for the contribution of WNT signaling to its etiology

The pathogenesis of androgenetic alopecia (AGA, male-pattern baldness) is driven by androgens, and genetic predisposition is the major prerequisite. Candidate gene and genome-wide association studies have reported that single-nucleotide polymorphisms (SNPs) at eight different genomic loci are associated with AGA development. However, a significant fraction of the overall heritable risk still awaits identification. Furthermore, the understanding of the pathophysiology of AGA is incomplete, and each newly associated locus may provide novel insights into contributing biological pathways. The aim of this study was to identify unknown AGA risk loci by replicating SNPs at the 12 genomic loci that showed suggestive association (5 x 10(-8)hair follicle tissue suggest that WNT10A has a functional role in AGA etiology. Thus, our study provides genetic evidence supporting an involvement of WNT signaling in AGA development.

Students at a Landheim school

Group of unidentified young women wearing flower wreaths in their hair with one unidentified man on the steps of a building; students at a Landheim school

Six novel susceptibility Loci for early-onset androgenetic alopecia and their unexpected association with common diseases

Androgenetic alopecia (AGA) is a highly heritable condition and the most common form of hair loss in humans. Susceptibility loci have been described on the X chromosome and chromosome 20, but these loci explain a minority of its heritable variance. We conducted a large-scale meta-analysis of seven genome-wide association studies for early-onset AGA in 12,806 individuals of European ancestry. While replicating the two AGA loci on the X chromosome and chromosome 20, six novel susceptibility loci reached genome-wide significance (p = 2.62x10(-)(9)-1.01x10(-)(1)(2)). Unexpectedly, we identified a risk allele at 17q21.31 that was recently associated with Parkinson's disease (PD) at a genome-wide significant level. We then tested the association between early-onset AGA and the risk of PD in a cross-sectional analysis of 568 PD cases and 7,664 controls. Early-onset AGA cases had significantly increased odds of subsequent PD (OR = 1.28, 95% confidence interval: 1.06-1.55, p = 8.9x10(-)(3)). Further, the AGA susceptibility alleles at the 17q21.31 locus are on the H1 haplotype, which is under negative selection in Europeans and has been linked to decreased fertility. Combining the risk alleles of six novel and two established susceptibility loci, we created a genotype risk score and tested its association with AGA in an additional sample. Individuals in the highest risk quartile of a genotype score had an approximately six-fold increased risk of early-onset AGA [odds ratio (OR) = 5.78, p = 1.4x10(-)(8)(8)]. Our results highlight unexpected associations between early-onset AGA, Parkinson's disease, and decreased fertility, providing important insights into the pathophysiology of these conditions.

Effects of externally supplied protein on root morphology and biomass allocation in Arabidopsis

Growth, morphogenesis and function of roots are influenced by the concentration and form of nutrients present in soils, including low molecular mass inorganic N (IN, ammonium, nitrate) and organic N (ON, e.g. amino acids). Proteins, ON of high molecular mass, are prevalent in soils but their possible effects on roots have received little attention. Here, we investigated how externally supplied protein of a size typical of soluble soil proteins influences root development of axenically grown Arabidopsis. Addition of low to intermediate concentrations of protein (bovine serum albumen, BSA) to IN-replete growth medium increased root dry weight, root length and thickness, and root hair length. Supply of higher BSA concentrations inhibited root development. These effects were independent of total N concentrations in the growth medium. The possible involvement of phytohormones was investigated using Arabidopsis with defective auxin (tir1-1 and axr2-1) and ethylene (ein2-1) responses. That no phenotype was observed suggests a signalling pathway is operating independent of auxin and ethylene responses. This study expands the knowledge on N form-explicit responses to demonstrate that ON of high molecular mass elicits specific responses.

Suspected Pyrrolizidine Alkaloid Hepatotoxicosis in Wild Southern Hairy-Nosed Wombats (Lasiorhinus latifrons)

Southern hairy-nosed wombats (Lasiorhinus latifrons) inhabiting degraded habitat in South Australia were recently identified with extensive hair loss and dermatitis and were in thin to emaciated body condition. Pathological and clinicopathological investigations on affected juvenile wombats identified a toxic hepatopathy suggestive of plants containing pyrrolizidine alkaloids, accompanied by photosensitive dermatitis. Hepatic disease was suspected in additional wombats on the basis of serum biochemical analysis. Preliminary toxicological analysis performed on scats and gastrointestinal contents from wombats found in this degraded habitat identified a number of toxic pyrrolizidine alkaloids consistent with ingestion of Heliotropeum europaeum. Although unpalatable, ingestion may occur by young animals due to decreased availability of preferred forages in degraded habitats and the emergence of weeds around the time of weaning of naive animals. Habitat degradation leading to malnutrition and ingestion of toxic weed species is a significant welfare issue in this species.

Portrait of an old Man

Bust of Rabbi with luxuriant white beard wearing a plain black coat and tall black cap. The background is dark-gray. The hair and beard are exquisite, obtained with very fine brushes and textured use of white paint. The psychological study of the face is also unusually high quality.

Portrait of Mathilde Wiener Monasch (?) d.1864.

Mrs. Monasch is shown as a young woman wearing a gray translucent shawl and a lace bonnet with ornate flaps coming down over the ears. Some of her black hair is showing. She is shown in a 3/4 view; the eyes are lustrous, the corners of the mouth are raised in a half smile. On backing of original frame: "Zum Andencken von Ihren Schwiegersohn, J. Wollstein d. 20th February 1839" (In memory of your son-in-law J. Wollstein Feb 20th, 1839).

Visionary Portrait.

The expressionist head of a young man emerges from the dark shadows. His face is a long oval, with full lips and strongly flared nostrils, framed by black hair and small black beard.

Role of Eda and Troy pathways in ectodermal organ development

Several organs of the embryo develop as appendages of the ectoderm, the outermost layer of the embryo. These organs include hair follicles, teeth and mammary glands, which all develop as a result of reciprocal tissue interactions between the surface epithelium and the underlying mesenchyme. Several signalling molecules regulate ectodermal organogenesis the most important ones being Wnts, fi broblast growth factors (Fgfs), transforming growth factor -βs (Tgf-βs) including bone morphogenetic proteins (Bmps), hedgehogs (Hhs), and tumour necrosis factors (Tnfs). This study focuses on ectodysplasin (EDA), a signalling molecule of the TNF superfamily. The effects of EDA are mediated by its receptor EDAR, an intracellular adapter protein EDARADD, and downstream activation of the transcription factor nuclear factor kappa-B (NF-кB). Mice deficient in Eda (Tabby mice), its receptor Edar (downless mice) or Edaradd (crinkled mice) show identical phenotypes characterised by defective ectodermal organ development. These mouse mutants serve as models for the human syndrome named hypohidrotic ectodermal dysplasia (HED) that is caused by mutations either in Eda, Edar or Edaradd. The purpose of this study was to characterize the ectodermal organ phenotype of transgenic mice overexpressing of Eda (K14-Eda mice), to study the role of Eda in ectodermal organogenesis using both in vivo and in vitro approaches, and to analyze the potential redundancy between the Eda pathway and other Tnf pathways. The results suggest that Eda plays a role during several stages of ectodermal organ development from initiation to differentiation. Eda signalling was shown to regulate the initiation of skin appendage development by promoting appendageal cell fate at the expense of epidermal cell fate. These effects of Eda were shown to be mediated, at least in part, through the transcriptional regulation of genes that antagonized Bmp signalling and stimulated Shh signalling. It was also shown that Eda/Edar signalling functions redundantly with Troy, which encodes a related TNF receptor, during hair development. This work has revealed several novel aspects of the function of the Eda pathway in hair and tooth development, and also suggests a previously unrecognized role for Eda in mammary gland development.

Role of cell cycle regulators in development of the inner ear

The inner ear originates from an ectodermal thickening called the otic placode. The otic placode invaginates and closes to an otic vesicle, the otocyst. The otocyst epithelium undergoes morphogenetic changes and cell differentiation, leading to the formation of the labyrinth-like mature inner ear. Epithelial-mesenchymal interactions control inner ear morphogenesis, but the modes and molecules are largely unresolved. The expressions of negative cell cycle regulators in the epithelium of the early-developing inner ear have also not been elucidated. The mature inner ear comprises the hearing (cochlea) and balance (vestibular) organs that contain the nonsensory and sensory cells. In mammals, the inner ear sensory cells, called hair cells, exit the cell cycle during embryogenesis and are mitotically quiescent during late-embryonic differentiation stages and postnatally. The mechanisms that maintain this hair cell quiescense are largely unresolved. In this work I examined 1) the epithelial-mesenchymal interactions involved in inner ear morphogenesis, 2) expression of negative cell cycle regulators in the epithelium of the early developing inner ear and 3) the molecular mechanisms that maintain the postmitotic state of inner ear sensory cells. We observed that during otocyst stages, epithelial fibroblast growth factor 9 (Fgf9) communicates with the surrounding mesenchyme, where its receptors are expressed. Fgf9 inactivation leads to reduced proliferation of the surrounding vestibular mesenchyme and to the absence of semicircular canals. Semicircular canal development is blocked, since fusion plates do not form. These results show that the mesenchyme directs fusion plate formation and give direct evidence for the existence of reciprocal epithelial-mesenchymal interactions in the developing inner ear. Cyclin-dependent kinase inhibitors (CKIs) are negative regulators of proliferation. We show that the members of the Cip/Kip family of CKIs (p21Cip1, p27Kip1 and p57Kip2) are expressed in the early-developing inner ear. Our expression data suggest that CKIs divide the otic epithelium into proliferative and nonproliferative compartments that may underlie shaping of the otocyst. At later stages, CKIs regulate proliferation of the vestibular appendages, and this may regulate their continual growth. In addition to restricting proliferation, CKIs may play a role in regional differentiation of various epithelial cells. Differentiating and adult inner ear hair cells are postmitotic and do not proliferate in response to serum or mitogenic growth factors. In our study, we show that this is the result of the activity of negative cell cycle regulators. Based on expression profiles, we first focused on the retinoblastoma (Rb) gene, which functions downstream of the CKIs. Analysis of the inner ear phenotype of Rb mutant mice show, that the retinoblastoma protein regulates the postmitotic state of hair cells. Rb inactivation leads to hyperplasia of vestibular and cochlear sensory epithelia that is a result of abnormal cell cycle entry of differentiated hair cells and of delayed cell cycle exit of the hair cell precursor cells. In addition, we show that p21Cip1 and p19Ink4d cooperate in maintaining the postmitotic state of postnatal auditory hair cells. Whereas inactivation of p19Ink4d alone leads to low-level S-phase entry (Chen et al., 2003) and p21Cip1 null mutant mice have a normal inner ear phenotype, codeletion of p19Ink4d and p21Cip1 triggers high-level S-phase entry of auditory hair cells during early postnatal life, which leads to supernumerary hair cells. The ectopic hair cells undergo apoptosis in all of the mutant mice studied, DNA damage being the immediate cause of this death. These findings demonstrate that the maintenance of the postmitotic state of hair cells is regulated by Rb and several CKIs, and that these cell cycle regulators are critical for the lifelong survival of hair cells. These data have implications for the future design of therapies to induce hair cell regrowth.

Fungal flora of rice field soils

Qualitative and quantitative assessment of the fungal flora of rice field soils yielded 102 species of fungi belonging to 44 genera, when dilution plate, soil plate, root-washing and baiting techniques were employed. The order of efficacy of the methods used was: root-washing > soil plate > dilution plate > baiting. Baiting method, used specifically to isolate aquatic and keratinophilic fungi from soils was studied in detail with reference to the former. Qualitatively, corn leaf bait was the most efficient one while pine pollens and hemp seeds were least efficient. A semi-quantitative method was employed to study the statistically significant differences among the different factors used. Among the keratinophilic baits,viz., human hair, fowl’s feather and wool, wool bait was least efficient. The results of this investigation are discussed.