Serum levels of adiponectin differentiate generalized lipodystrophies from anorexia nervosa.

PURPOSE: The differential diagnosis of lipodystrophy involves other disorders characterized by severe fat loss and may be sometimes challenging. Owing to the rarity of lipodystrophy, it is relevant to search for tools and assays that differentiate it from other diseases that may mimic it. We conducted a study on leptin and high molecular weight (HMW) adiponectin serum concentrations in a series of patients diagnosed with lipodystrophy and compared them with those found in anorexia nervosa, one of the illnesses that may be cause of a missed diagnosis of lipodystrophy. METHODS: Leptin and HMW adiponectin serum concentrations were measured in six patients diagnosed with generalized lipodystrophy (GL), six with progeroid syndromes (PS), 13 with familial partial lipodystrophy type 1 (FPLD1, Kobberling syndrome), 10 with familial partial lipodystrophy type 2 (FPLD2, Dunnigan syndrome), 18 with acquired partial lipodystrophy (APL) and 12 affected by anorexia nervosa (AN). Measurements were compared to those obtained in 12 normal weight healthy subjects. RESULTS: Serum leptin concentrations were reduced to a similar degree in GL, PS and AN, proportionally to the extent of fat loss. Serum concentrations of HMW adiponectin were found extremely low in patients with GL and PS, while comparable to normal weight subjects in patients with AN. CONCLUSION: Serum HMW adiponectin can be regarded as a useful tool to discriminate between generalized lipodystrophy syndromes (including PS) and AN.

Minute Impurities Contribute Significantly to Olfactory Receptor Ligand Studies: Tales from Testing the Vibration Theory.

Several studies have attempted to test the vibrational hypothesis of odorant receptor activation in behavioral and physiological studies using deuterated compounds as odorants. The results have been mixed. Here, we attempted to test how deuterated compounds activate odorant receptors using calcium imaging of the fruit fly antennal lobe. We found specific activation of one area of the antennal lobe corresponding to inputs from a specific receptor. However, upon more detailed analysis, we discovered that an impurity of 0.0006% ethyl acetate in a chemical sample of benzaldehyde-d5 was entirely responsible for a sizable odorant-evoked response in Drosophila melanogaster olfactory receptor cells expressing dOr42b. Without gas chromatographic purification within the experimental setup, this impurity would have created a difference in the responses of deuterated and nondeuterated benzaldehyde, suggesting that dOr42b be a vibration sensitive receptor, which we show here not to be the case. Our results point to a broad problem in the literature on use of non-GC-pure compounds to test receptor selectivity, and we suggest how the limitations can be overcome in future studies.

Ziziphora tenuior L. essential oil from Dana Biosphere Reserve (Southern Jordan); Chemical characterization and assessment of biological activities.

ETHNOPHARMACOLOGIC RELEVANCE: Ziziphora tenuior L. (Lamiaceae) is a medicinal plant in Jordan, which is included in various antimicrobial, antiseptic, expectorant and wound healing preparations. It is used for the treatment of cough, stomach ache, dysentery, fever, uterus infection, gut inflammation and painful menstruation. AIM OF THE STUDY: The aim of this study was to assess, for the first time, the chemical composition of the essential oil of Z. tenuior originated from southern Jordan and its antifungal effects against several yeasts. Concomitantly, the mechanisms behind the anti-fungal activity against Candida albicans were also disclosed. Since the Z. tenuior traditional uses are related with inflammatory-associated conditions, the putative anti-inflammatory activity of the oil was also unveiled. Importantly, the potential toxicity of pharmacologically active concentrations was screened in different types of mammalian cells. MATERIALS AND METHODS: Z. tenuior essential oil, isolated by hydrodistillation, was analyzed by gas chromatography, gas chromatography-mass spectrometry and 13C nuclear magnetic resonance spectroscopy. Antifungal activity was evaluated against yeasts, dermatophytes and Aspergillus strains. Germ tube inhibition and biofilm formation assays were evaluated using C. albicans. Assessment of cell viability was made by the MTT assay using different types of mammalian cells, including hepatocytes, keratinocytes and macrophages. The in vitro anti-inflammatory potential of the oil was evaluated by measuring nitric oxide production using lipopolysaccharide-stimulated mouse macrophages. RESULTS: Oxygen-containing monoterpenes are the main oil compounds: pulegone (46.8%), p-menth-3-en-8-ol (12.5%), isomenthone (6.6%) and 8-hydroxymenthone (6.2%). The highest antifungal activity was against Cryptococcus neoformans, with a MIC value of 0.16µL/mL. The oil revealed an important inhibitory effect on germ tube formation with a filamentation inhibition rate higher than 80% at 0.16µL/mL. The amount of the attached biomass was reduced. Importantly, concentrations devoid of toxicity on several mammalian cell types still displayed anti-inflammatory activity (0.16 and 0.32µL/mL). CONCLUSIONS: These findings add significant information to the pharmacological activity of Z. tenuior, thus justifying and reinforcing the use of this plant in traditional medicine. Additionally, the antifungal and anti-inflammatory potential of the oil at non-toxic concentrations, opens new avenues for its further exploitation, for instance in health-care product development.

Protective role of olesoxime against wild-type α-synuclein-induced toxicity in human neuronally differentiated SHSY-5Y cells.

BACKGROUND AND PURPOSE: Parkinson's disease (PD) is usually diagnosed clinically from classical motor symptoms, while definitive diagnosis is made postmortem, based on the presence of Lewy bodies and nigral neuron cell loss. α-Synuclein (ASYN), the main protein component of Lewy bodies, clearly plays a role in the neurodegeneration that characterizes PD. Additionally, mutation in the SNCA gene or copy number variations are associated with some forms of familial PD. Here, the objective of the study was to evaluate whether olesoxime, a promising neuroprotective drug can prevent ASYN-mediated neurotoxicity. EXPERIMENTAL APPROACH: We used here a novel, mechanistically approachable and attractive cellular model based on the inducible overexpression of human wild-type ASYN in neuronally differentiated human neuroblastoma (SHSY-5Y) cells. This model demonstrates gradual cellular degeneration, coinciding temporally with the appearance of soluble and membrane-bound ASYN oligomers and cell death combining both apoptotic and non-apoptotic pathways. KEY RESULTS: Olesoxime fully protected differentiated SHSY-5Y cells from cell death, neurite retraction and cytoplasmic shrinkage induced by moderate ASYN overexpression. This protection was associated with a reduction in cytochrome c release from mitochondria and caspase-9 activation suggesting that olesoxime prevented ASYN toxicity by preserving mitochondrial integrity and function. In addition, olesoxime displayed neurotrophic effects on neuronally differentiated SHSY-5Y cells, independent of ASYN expression, by promoting their differentiation. CONCLUSIONS AND IMPLICATIONS: Because ASYN is a common underlying factor in many cases of PD, olesoxime could be a promising therapy to slow neurodegeneration in PD.

Cholesteryl ester transfer protein (CETP) -629C/A polymorphism and it's effects on the serum lipid levels in metabolic syndrome patients.

Metabolic syndrome is a relatively common disorder with significant morbidity worldwide. Cholesteryl ester transfer protein (CETP) plays a central role in the metabolism of lipoproteins. In this study the effect of -629C/A polymorphism on the concentration of CETP and plasma lipids pattern was elicited in metabolic syndrome patients and control subjects. For this, a sample of 200 patients diagnosed with metabolic syndrome disorder was studied in comparison with 200 healthy controls. This study was performed by using polymerase chain reaction and restriction fragment length polymorphisms. Genotype distribution and allelic frequencies were determined and compared in metabolic syndrome and healthy controls. To determine the relationship between -629C/A polymorphism and lipid levels, lipids and CETP concentration were measured in metabolic syndrome and normal subjects. The results showed a significant difference between two groups in terms of FBS, cholesterol, TG, HDL-C, LDL-C levels as well as BMI, waist circumference, systolic and diastolic blood pressure. The genotype frequencies for this polymorphism differed significantly between metabolic syndrome patients and controls (in control group: CC% 20.5, CA% 76, AA% 3.5 and in patient group: CC% 28.5, CA% 53.5, AA% 18) (p < 0.05) while there was no significant difference in the frequency of the alleles. In the two groups, the levels of the cholesteryl ester transfer protein in AA genotype were lower than other genotypes. In the control group, individuals with AA genotype had the highest levels of LDL-C and TC plasma concentration. Considering the results of this study, it can be concluded that the -629 AA genotype was associated with high cholesterol; high LDL-C and low CETP level, so that it can be related to metabolic syndrome.

Occurrence of Lily mottle virus on Lilium in Italy.

Lily mottle virus (LMoV), a member of the genus Potyvirus, is one of the main viruses infecting lily. Symptoms on lily differ according to the susceptibility and sensitivity of different cultivars and hybrids. They range from leaf mottle or mosaic, vein clearing, chlorotic and yellow streaking, leaf curling, and necrotic spots, to milder forms of leaf symptoms. Plants may even be symptomless at some stages of growth. A varietal collection of Lilium from the early 1990s is held in Pistoia Province (Tuscany, Italy) and is composed of Asian hybrids obtained from intraspecific breeding of commercial cultivars. During a survey conducted from May to June 2010, several plants showing vein clearing, leaf mottle, leaf mosaic, and reddish brownish necrotic spots were observed. Leaf samples from 60 symptomatic or symptomless lily plants, belonging to 20 cultivars, were collected and tested for the presence of LMoV. Samples were assayed by double-antibody sandwich (DAS)-ELISA and eight of them, belonging to four different cultivars, tested positive. Total RNA was extracted from 2 g of leaf tissue of every collected sample according to the protocol described earlier (3) and cDNA synthesis was performed with an iScript cDNA Synthesis Kit (Bio-Rad, Hercules, CA). Samples were tested by reverse transcription (RT)-PCR and real-time PCR assays using primers LMoV1 (5'-GCAAATGAGACACTCAATGCTG-3') and LMoV2 (5'-CGTGCGTGAAGTAACTTCATAG-3') designed to amplify 651 bp of the coat protein (CP) gene of LMoV (1). Results obtained with RT-PCR and real-time PCR exactly matched those achieved with ELISA assay, and the eight positive samples showed amplicons of the expected size. PCR products from five infected samples were directly sequenced from both directions and submitted in GenBank (Accessions Nos. JQ655106 to JQ655110). Our isolates share more than 99% nucleotide identity among each other. Comparison with other LMoV-CP gene sequences present in GenBank showed nucleotide identities ranging from 93 to 94% with LMoV isolates from South Korea (GenBank Accession Nos. GQ150683 to GQ150686), China (GenBank Accession Nos. EU348826, AJ748256, AJ564636, and AJ564637), Australia (GenBank Accession No. JN127341), and Japan (GenBank Accession No. AB570195). To our knowledge, this is the first report of LMoV on Lilium in Italy where this virus was already reported to infect escarole (2). Considering the economic importance of Lilium production as a flowering plant in Pistoia Province, and in several other areas of Italy, the report of LMoV present on lilies suggests the use of healthy propagation material and the adoption of preventive measures to avoid its diffusion. References: (1) J.-H. Lim et al. Korean J. Microbiol. 45:251, 2009. (2) V. Lisa et al. Plant Dis. 86:329, 2002. (3) D. J. MacKenzie et al. Plant Dis. 81:222, 1997.

Breastfeeding perceptions in communities in Mangochi district in Malawi.

AIM: To investigate mothers' perceptions of breastfeeding and influences from their social network. METHODS: A cross-sectional survey was carried out in Mangochi district, Malawi where questionnaire data from 157 rural and 192 semi-urban mother-infant pairs were obtained. RESULTS: The proportion of mothers who thought that exclusive breastfeeding should last for 6 months and those who reported to have actually exclusively breastfed were 40.1% and 7.5% respectively. Of those who reported practising exclusive breastfeeding for 6 months, 77.5% stated that exclusive breastfeeding should last for 6 months. This opinion was independently associated with giving birth in a Baby-Friendly facility, OR = 5.22; 95% CI (1.92-14.16). Among the mothers who thought that exclusive breastfeeding should last for less than 6 months, 43.9% reported having been influenced in their opinion by health workers. Infant crying was the most common (62.4%) reason for stopping exclusive breastfeeding. CONCLUSION: The findings illustrate the positive impact health workers can have, as well as the need to raise awareness of the benefits of exclusive breastfeeding among both health workers and mothers. Furthermore, continued counselling of mothers on how to deal with stressful infant behaviour such as crying may assist to prolong exclusive breastfeeding.

Unusual oxygen binding behavior of a 24-meric crustacean hemocyanin.

Hemocyanins from Crustacea usually are found as 1x6 or 2x6-meric assemblies. An exception is the hemocyanin isolated from thalassinidean shrimps where the main component is a 24-meric structure. Our analysis of oxygen binding data of the thalassinidean shrimp Upogebia pusilla based on a three-state MWC-model revealed that despite the 24-meric structure the functional properties can be described very well based on the hexamer as allosteric unit. In contrast to the hemocyanins from other thalassinidean shrimps the oxygen affinity of hemocyanin from U. pusilla is increased upon addition of l-lactate. A particular feature of this hemocyanin seems to be that l-lactate already enhances oxygen affinity under resting conditions which possibly compensates the rather low intrinsic affinity observed in absence of l-lactate. The fast rate of oxygen dissociation might indicate that in this hemocyanin a higher cooperativity is less important than a fast response of saturation level to changes in oxygen concentration.

Structure of the N-terminal oligomerization domain of DnaD reveals a unique tetramerization motif and provides insights into scaffold formation.

DnaD is a primosomal protein that remodels supercoiled plasmids. It binds to supercoiled forms and converts them to open forms without nicking. During this remodeling process, all the writhe is converted to twist and the plasmids are held around the periphery of large scaffolds made up of DnaD molecules. This DNA-remodeling function is the sum of a scaffold-forming activity on the N-terminal domain and a DNA-dependent oligomerization activity on the C-terminal domain. We have determined the crystal structure of the scaffold-forming N-terminal domain, which reveals a winged-helix architecture, with additional structural elements extending from both N- and C-termini. Four monomers form dimers that join into a tetramer. The N-terminal extension mediates dimerization and tetramerization, with extensive interactions and distinct interfaces. The wings and helices of the winged-helix domains remain exposed on the surface of the tetramer. Structure-guided mutagenesis and atomic force microscopy imaging indicate that these elements, together with the C-terminal extension, are involved in scaffold formation. Based upon our data, we propose a model for the DnaD-mediated scaffold formation.

The molecular heterogeneity of hemocyanin: Structural and functional properties of the 4x6-meric protein of Upogebia pusilla (Crustacea).

The structural properties of the hemocyanin isolated from the Mediterranean mud shrimp, Upogebia pusilla (Decapoda: Thalassinidea), were investigated. Our intent was to make use of the U. pusilla case to perform a structural comparison between crustacean and chelicerate 4x6-meric hemocyanins. The thalassinidean hemocyanin appears similar in size but different in structural organization compared to the chelicerate 4x6-mer. Ultracentrifuge analyses on the purified protein revealed a sedimentation coefficient of 39S, typical of 4x6 hemocyanins. Electron micrographs are in agreement with a model in which four 2x6-meric building blocks are arranged in a tetrahedron-like quaternary structure and not in the quasi-square-planar orientation characteristic of the chelicerate protein. Size-exclusion chromatography-fast protein chromatography analysis showed elevated instability of the protein in absence of divalent ions or at pH values higher than 8.0. This analysis also shows that the dissociation of the U. pusilla 4x6-meric hemocyanin into hexamers occurs without any intermediate 2x6-meric state, in contrast with the dissociation profile of the chelicerate protein exhibiting several dissociation intermediates. The oxygen-binding properties of U. pusilla hemocyanin were studied to disclose possible effects by the typical allosteric effectors that modulate the functional properties of crustacean hemocyanin. A marked Bohr and lactate effect, but no significant influence of urate, on the oxygen affinity of U. pusilla hemocyanin were found.

A comparative assessment of heavy metal accumulation in soft parts and byssus of mussels from subarctic, temperate, subtropical and tropical marine environments.

Existing data on metal concentrations in mussels from subarctic, temperate, subtropical and tropical waters were analyzed using multivariate statistics in order to assess regional variations in metal contamination. Potential errors were reduced by only analyzing data from surveys that employed the same protocols, analytical methodologies and analysts. Factor analysis demonstrated that mussels inhabiting extremely contaminated areas (e.g. from Japanese and Swedish metallurgy sources) could be separated from mussels from other contaminated areas, and that metals such as Cd, Pb, Cu and Zn could be used to identify heavily contaminated samples while Co, Fe, Cr and Ni concentrations were good markers for exposure to inputs from different industrial sources. Furthermore byssus, like soft tissue, selectively and sensitively reflects variations of certain metal concentrations in ambient waters and thus serves as a reliable biomonitor for these contaminants in a variety of coastal and estuarine areas.

Determination of intrinsic viscosity of poly(ethylene terephthalate) using infrared spectroscopy and multivariate calibration method.

A methodology was developed to determine the intrinsic viscosity of poly(ethylene terephthalate) (PET) using diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and multivariate calibration (MVC) methods. Multivariate partial least squares calibration was applied to the spectra using mean centering and cross validation. The results were correlated to the intrinsic viscosities determined by the standard chemical method (ASTM D 4603-01) and a very good correlation for values in the range from 0.346 to 0.780dLg(-1) (relative viscosity values ca. 1.185-1.449) was observed. The spectrophotometer detector sensitivity and the humidity of the samples did not influence the results. The methodology developed is interesting because it does not produce hazardous wastes, avoids the use of time-consuming chemical methods and can rapidly predict the intrinsic viscosity of PET samples over a large range of values, which includes those of recycled materials.

Leptina en relación con el sexo, el índice de masa corporal, el estadio puberal y la insulina en niños con déficit de hormonas de crecimiento con y sin tratamiento sustitutivo / Leptin levels and their correlation with sex, body mass index, pubertal status and insulin concentrations in growth-hormone treated and untreated adolescents with growth hormone deficiency

Introducción: En este estudio nos proponemos investigar las concentraciones de leptina y su relación con el sexo, el índice de masa corporal, el estadio puberal y las concentraciones de insulina en un grupo de adolescentes con deficiencia de hormona de crecimiento que recibía tratamiento con la hormona, en un grupo con deficiencia que no recibía tratamiento y en un grupo de control sano. Métodos: Se estudió a 22 sujetos con déficit de hormona de crecimiento; 15 recibían hormona de crecimiento (grupo A) y 7 no la recibían (grupo B). La edad del grupo A era de 12 ± 2,9 años, 7 mujeres y 8 varones, 7 prepúberes y el resto puberales; recibieron 0,1 U/kg/día de hormona de crecimiento por un período de 3,8 ± 1,2 años. La edad del grupo B era de 13,6 ± 1,8, 3 mujeres y 4 varones, 3 prepuberales y el resto puberales que nunca habían recibido hormona de crecimiento. Diecinueve sujetos sanos sin deficiencia de hormona de crecimiento, ajustados por edad ósea e índice de masa corporal más que por edad cronológica participaron como controles (grupo C); 9 mujeres y 10 varones, 11 prepúberes y 8 puberales. Se les tomó el peso y la talla, se calculó el índice de masa corporal y se determinaron las concentraciones basales de leptina e insulina. Resultados: No hubo diferencias en las variables antropométricas y en las concentraciones de insulina y leptina entre los grupos. Se detectó un valor significativamente elevado de leptina en las mujeres y en los pacientes puberales, en los grupos A y C. No se encontraron diferencias significativas en el índice de masa corporal según el sexo, pero sí entre sujetos prepuberales y puberales. La elevación de la leptina en las mujeres fue evidente tanto en el grupo prepuberal como en el puberal, mientras que no se observaron diferencias en relación con el índice de masa corporal. Las variables independientes que predijeron significativamente la concentración de leptina fueron el sexo y el índice de masa corporal. Conclusiones: a) La concentración de leptina e insulina no fue diferente en niños con deficiencia de hormona de crecimiento comparados con niños sanos, ajustados para el índice de masa corporal; b) se confirma el dimorfismo sexual, caracterizado por concentraciones más elevadas de leptina en las mujeres, evidente desde la edad prepuberal y que persiste en los estados de deficiencia de hormona de crecimiento, y c) el índice de masa corporal y el sexo fueron las variables independientes predictoras de las concentraciones de leptina (AU)

Introduction: The aim of this study was to investigate leptin levels and their correlation with gender, body mass index (BMI), pubertal status and insulin concentrations in a group of growth hormone deficient (GHD) adolescents treated with growth hormone (GH), a group of untreated GHD subjects and a group of healthy controls. Methods: We studied 22 GHD subjects; 15 were receiving GH (group A) and seven were not receiving GH (Group B). The mean chronological age in group A was 12.0 ± 2.9 years. There were seven girls and eight boys; seven were prepubertal and the rest were pubertal. All subjects in group A received 0.1 IU/Kg/day of GH for a period of 3.8 ± 1.2 years. The mean age of group B was 13.6 ± 1.8 years. There were three girls and four boys; three were prepubertal, while the rest were pubertal. None had received GH treatment. Nineteen healthy subjects without GHD, matched for bone age and BMI participated in the study as controls (group C). There were 9 girls and 10 boys; 11 were prepubertal, while 8 were pubertal. Weight and height were measured, BMI was calculated and basal leptin and insulin levels were measured. Results: No differences among groups were found in anthropometric variables or insulin and leptin levels. Leptin levels were significantly elevated in girls and in pubertal patients in groups A and C. BMI did not significantly differ between sexes but was significantly different between prepubertal and pubertal subjects. The increase of leptin concentrations in girls was evident in both prepubertal and pubertal subjects, while no differences were noted in relation to BMI. The independent variables that predicted leptin levels were sex and BMI. Conclusions: a) No differences in leptin and insulin levels were found between subjects with GHD and controls, matched for BMI values. b) A sexual dimorphism characterized by increased leptin levels in girls was evident from prepubertal age and persisted in GHD.c) The independent variables that predicted leptin concentrations were BMI and sex (AU)

Factors influencing acceptability of voluntary counselling and HIV-testing among pregnant women in Northern Tanzania.

Guided by the conceptual framework of the Health Belief Model, this study aimed to identify factors associated with pregnant women's expressed willingness to accept voluntary counselling and HIV-testing (VCT). A cross-sectional interview survey of 500 pregnant women, complemented by focus group discussions, was conducted in the Kilimanjaro region of Tanzania. Constructs derived from the Health Belief Model explained 41.7% of women's willingness to accept VCT. Perceived high personal susceptibility to HIV/AIDS, barriers related to confidentiality and partner involvement, self-efficacy regarding alternative feeding methods and religion were all shown to be associated with willingness to accept VCT. The women's acceptance of VCT seems to depend upon their perceiving that VCT and alternative feeding strategies provide clear benefits, primarily for the child. Whether a positive attitude to VCT and alternative feeding strategies are transformed into actual behaviour depends on a set of complicated decisions in which several potential psychological consequences are assessed. Sharing the diagnosis with partners may not have the intended effect if there is a lack of sensitivity to the women's fear of blame and rejection. If pregnant women are to fully participate in and benefit from mother-to-child-transmission prevention efforts, their partners must be committed and involved in the process.

Sensible improvements induced by ionic liquids in the reaction of modified carbasugars with bases for the building of constrained carbanucleosides.

Starting from racemic 4-hydroxy-4-methyl-2-cyclopentenone, a family of enantiopure carbanucleosides locked in the northern conformation has been synthesized. The use of ionic liquids was determinant in the last step resulting in a tangible increase of the yields and dramatic reduction of reaction times and volumes of organic solvents. To our knowledge, this is the first example of the use of ionic liquids in the coupling of carbasugars with heterocyclic bases.

[Concentration of thyrotropic hormone and free thyroxin in children with Down's syndrome]. / Concentraciones de hormona tirotropa y tiroxina libre en niños con síndrome de Down.

The incidence of hypothyroidism is higher among children with Down syndrome than among children in the general population. The frequency of hypothyroidism is higher in the areas of endemic goiter than in other areas. The aim of this paper was to study the concentrations of TSH and FT4 in children with Down syndrome residents of Mérida, a region of Venezuelan Andes. At the Centro de Estudio y Prevención del Retardo Mental y Alteraciones en el Desarrollo (CEPREMAD), the thyroid function was studied in 48 children (1 month to 6 years old), who had Down syndrome, and in 123 healthy children of similar ages. All the children were referred to the Center for thyroid function evaluation. Two (4.2%) of the 48 children with Down syndrome had congenital hypothyroidism and 22 (45.8%) had subclinical hypothyroidism (high concentration of thyrotropin-TSH). Among the control children, only 14% had elevated levels of TSH. There were no differences in relation to the gender. In conclusion in children with Down syndrome, the frequency of high concentrations of TSH was three times higher than the frequency among the healthy children. The frequency of hypothyroidism was similar to that found in areas without endemic goiter.

Decreased bone mineral density and bone formation markers shortly after diagnosis of clinical type 1 diabetes mellitus.

We recently demonstrated that children with type 1 diabetes mellitus (DM) have decreased lumbar spine bone mineral density (BMD) as early as four years after clinical diagnosis of the disease. In order to determine whether osteopenia is already present in patients very early on after diagnosis of clinical DM, we evaluated the bone mineral status of a group of newly diagnosed children (5.8 +/- 1.5 mo after diagnosis). We studied 23 prepubertal children (7 M, 16 F) with a mean chronological age of 9.5 +/- 2.2 yr and a mean glycosylated hemoglobin of 8.9 +/- 2.4%. Lumbar spine and femoral neck BMD were measured by dual X-ray absorptiometry, while bone turnover was assessed by the determination of the serum concentration of the carboxy-terminal propeptide of type I collagen (PICP) and the carboxy-terminal cross-linked telopeptide of type I collagen (N-telopeptide). Results were compared to those of age, height, and pubertal status matched controls. Lumbar spine BMD Z-scores were decreased in patients compared to controls (Z-scores of -0.89 +/- 1.2, with 10 of 22 patients showing values >1 SD below the mean). When lumbar spine Z-scores were analyzed in those patients with <3 months or > or =3 months since diagnosis of DM a significant difference was noticed between groups (-0.648 +/- 1.12 vs -1.267 +/- 1.17; p <0.02). No significant differences were noted in femoral neck BMD and total BMD between groups. Serum PICP levels were decreased when compared to controls (233.6 +/- 39.3 vs 375.9 +/- 50.7 microg/l; p <0.002), while serum N-telopeptide concentrations, although increased, were not significantly different (9.3 +/- 1.3 vs 5.7 +/- 1.5 microg/l). In summary, early on after the diagnosis of type 1 DM, children present with decreased lumbar spine BMD and decreased bone formation markers.

Protein folds propelled by diversity.

Many proteins involved in key biological processes are modular in nature. A group of these, the beta-propeller proteins, fold by packing 4-stranded beta-sheets in a circular array. The members of this group are increasingly numerous and, although their modular building blocks all preserve the same basic conformation, they do not have similar sequences. These proteins have extreme functional and phylogenetic diversity. Here, features of the beta-propeller fold are reviewed through comparisons of available structural coordinates. Structure-based sequence alignments combined with analyses of superpositions of individual modular units reveal conserved general features such as hydrogen bonds, beta-turns and positions of hydrophobic contacts. The lack of significant sequence identity is compensated by sets of interactions which stabilise the fold differently in distinct structures. Re-occurring aspartates make contacts to exposed backbone amides in turns or peptide connections within the same sheet. The sole factor responsible for the number of sheets that assemble in the array is the size of the hydrophobic residues that pack into the cores between the sheets. Whilst there is no overall sequence conservation, it may be possible to detect new members of this fold through sequence searches that take into account the repeated nature of the modular assembly as well as the positions of hydrophobic residues and H-bonding side chains.