Phonological development in American Sign Language-signing children: Insights from pseudosign repetition tasks.

In this study, we conducted a pseudosign (nonce sign) repetition task with 22 children (mean age: 6;04) acquiring American Sign Language (ASL) as a first language (L1) from deaf parents. Thirty-nine pseudosigns with varying complexity were developed and organized into eight categories depending on number of hands, number of simultaneous movement types, and number of movement sequences. Pseudosigns also varied in handshape complexity. The children's performance on the ASL pseudosign task improved with age, displaying relatively accurate (re)production of location and orientation, but much less accurate handshape and movement, a finding in line with real sign productions for both L1 and L2 signers. Handshapes with higher complexity were correlated with lower accuracy in the handshape parameter. We found main effects of sequential and simultaneous movement combinations on overall performance. Items with no movement sequence were produced with higher overall accuracy than those with a movement sequence. Items with two simultaneous movement types or a single movement type were produced with higher overall accuracy than those with three simultaneous movement types. Finally, number of hands did not affect the overall accuracy. Remarkably, movement sequences impose processing constraints on signing children whereas complex hands (two hands) and two simultaneous movement types do not significantly lower accuracy, indicating a capacity for processing multiple simultaneous components in signs. Spoken languages, in contrast, manifest greater complexity in temporal length. Hearing children's pseudoword repetition still displays high levels of accuracy on disyllabic words, with complexity effects affecting only longer multisyllabic words. We conclude that the pseudosign repetition task is an informative tool for studies of signing children's phonological development and that sheds light on potential modality effects for phonological development.

The XRF mapping of archaeological artefacts as the key to understanding of the past.

The article describes the X-ray fluorescence (XRF) studies on the chemical composition of archaeological artefacts. The mapping of the concentration of selected elements has been used to recognise the way of object production and the use. The obtained data allowed to obtain the new information, which is impossible to gain by use of different methods. 'The data obtained from the chemical composition of the particular parts of the objects may be used for the interpretation of the manufacturing technology or the primal form of the objects. Additionally, the knowledge obtained from the chemical composition of the different parts of the artefacts may be essential for the selection of the protection and conservation methods. The present studies can be useful to improve knowledge about the level of former craftsmanship. These knowledge allow us to exam archaeological artefacts in a new light, and these findings can also broaden the archaeological knowledge horizons and provide good bases for further detailed studies.

The microwave induced plasma with optical emission spectrometry (MIP-OES) in 23 elements determination in geological samples.

The article presents the optimisation, validation and application of the microwave induced plasma optical emission spectrometry (MIP-OES) dedicated for a routine determination of Ag, Al, B, Ba, Bi, Ca, Cd, Cr, Cu, Fe, Ga, In, K, Li, Mg, Mn, Mo, Na, Ni, Pb, Sr, Tl, Zn, in the geological samples. The three procedures of sample preparation has been proposed: sample digestion with the use of hydrofluoric acid for determination of total concentration of elements, extraction by aqua regia for determination of the quasi-total element concentration and extraction by hydrochloric acid solution to determine contents of the elements in acid leachable fraction. The detection limits were on the level 0.001-0.121 mg L(-1) (from 0.010-0.10 to 1.2-12 mg kg(-1) depend on the samples preparation procedure); the precision: 0.20-1.37%; accuracy 85-115% (for recovery for certified standards materials analysis and parallel analysis by independent analytical techniques: X-ray fluorescence (XRF) and flame absorption spectrometry (FAAS)). The conformity of the results obtained by MIP-OES analytical procedures with the results obtained by XRF and FAAS analysis allows to propose the procedures for studies of elemental composition of the fraction of the geological samples. Additionally, the MIP-OES technique is much less expensive than ICP techniques and much less time-consuming than AAS techniques.

Selected arsenic species: As(III), As(V) and dimethylarsenic acid (DMAA) in Xerocomus badius fruiting bodies.

The aim of the study was to determine the content of As(III), As(V) and DMAA (dimethylarsinic acid) in Xerocomus badius fruiting bodies collected from selected Polish forests from areas subjected to very low or high anthropopressure and some commercially available samples obtained from the Polish Sanitary Inspectorate. The arsenic species determination was provided by two independent HPLC-HG-AAS hyphenated systems. The results show high levels (up to 27.1, 40.5 and 88.3 mg kg(-1) for As(III), As(V) and DMAA, respectively) of arsenic and occurrence of different species in mushrooms collected from areas subjected to high anthropopressure and two commercially available samples. For mushroom samples collected from areas not subjected to high anthropopressure and two commercially available samples the arsenic species level was below 0.5 mg kg(-1) for each arsenic form. Therefore, the accumulation of arsenic by mushrooms may lead to high (toxic for humans) arsenic concentrations, and arsenic species levels should be monitored in mushroom foodstuffs.

Brown fat thermogenesis and body weight regulation in mice: relevance to humans.

Physiological, pharmacological and genetic studies in dogs, mice and rats have established that the uncoupling protein-1 (UCP1)-based brown adipose tissue system has an important role in the regulation of body temperature. Although it may be possible to create laboratory conditions in which mice with inactivated Ucp1 can survive in a modestly cooled environment, data overwhelmingly support the conclusion that the UCP1/BAT system has evolved to maintain body temperature at 37 °C. The corollary to this conclusion is that any influence UCP1/BAT might have on body weight regulation is a secondary function. The idea that BAT prevents obesity by burning off excess energy to maintain energy balance seems incompatible with evolutionary biology. Premodern humans spent an enormous amount of energy either running to catch their meal or avoiding becoming a meal themselves; consequently, there was no obesity. Nevertheless, although secondary to body temperature regulation, UCP1/BAT is extraordinarily effective at reducing adiposity and insulin resistance in mice and rats. Variation among mice in susceptibility to diet-induced obesity is correlated with the induction of brown adipocytes in traditional white fat depots (wBAT). Both genetic and cell biology-based experimentation have shown that the cellular origins of wBAT are different from those of interscapular-like brown adipocytes (iBAT). Do they have different functions? We have analyzed the effects of the early nutritional environment on the induction of brown adipocytes in inguinal fat to test the hypothesis that wBAT is primarily involved in body weight regulation. Although undernutrition during lactation severely suppresses wBAT at 21 days of age, undernourished mice fed a normal chow diet ad libitum at weaning recovered their normal wBAT and iBAT systems as young adults. The function of wBAT does not seem to be uniquely devoted to body weight regulation.

Using diffusion MRI for measuring the temperature of cerebrospinal fluid within the lateral ventricles.

AIM: Hypothermia is often induced to reduce brain injury in newborns, following perinatal hypoxic-ischaemic events, and in adults following traumatic brain injury, stroke or cardiac arrest. We aimed to devise a method, based on diffusion-weighted MRI, to measure non-invasively the temperature of the cerebrospinal fluid in the lateral ventricles. METHODS: The well-known temperature dependence of the water diffusion constant was used for the estimation of temperature. We carried out diffusion MRI measurements on a 3T Philips Achieva Scanner involving phantoms (filled with water or artificial cerebrospinal fluid while slowly cooling from 41 to 32 degrees C) and healthy adult volunteers. RESULTS: The estimated temperature of water phantoms followed that measured using a mercury thermometer, but the estimates for artificial cerebrospinal fluid were 1.04 degrees C lower. After correcting for this systematic difference, the estimated temperature within the lateral ventricles of volunteers was 39.9 degrees C. Using diffusion directions less sensitive to cerebrospinal fluid flow, it was 37.7 degrees C, which was in agreement with the literature. CONCLUSION: Although further improvements are needed, measuring the temperature within the lateral ventricles using diffusion MRI is a viable method that may be useful for clinical applications. We introduced the method, identified sources of error and offered remedies for each.

The role of human demographic history in determining the distribution and frequency of transferase-deficient galactosaemia mutations.

Classical or transferase-deficient galactosaemia is an inherited metabolic disorder caused by mutation in the human Galactose-1-phosphate uridyl transferase (GALT) gene. Of some 170 causative mutations reported, fewer than 10% are observed in more than one geographic region or ethnic group. To better understand the population history of the common GALT mutations, we have established a haplotyping system for the GALT locus incorporating eight single nucleotide polymorphisms and three short tandem repeat markers. We analysed haplotypes associated with the three most frequent GALT gene mutations, Q188R, K285N and Duarte-2 (D2), and estimated their age. Haplotype diversity, in conjunction with measures of genetic diversity and of linkage disequilibrium, indicated that Q188R and K285N are European mutations. The Q188R mutation arose in central Europe within the last 20 000 years, with its observed east-west cline of increasing relative allele frequency possibly being due to population expansion during the re-colonization of Europe by Homo sapiens in the Mesolithic age. K285N was found to be a younger mutation that originated in Eastern Europe and is probably more geographically restricted as it arose after all major European population expansions. The D2 variant was found to be an ancient mutation that originated before the expansion of Homo sapiens out of Africa.

Have we entered the brown adipose tissue renaissance?

In the 1970s and 1980s, it was observed that rodents could offset excess calories ingested when they were fed a human-like 'cafeteria diet'. Although it was erroneously concluded that this so-called diet-induced thermogenesis was because of brown adipose tissue (BAT), it led to efforts to test whether variations in brown fat in humans may explain the susceptibility to obesity. However, from evidence on the inability of ephedrine or beta-3 adrenergic agonists to induce BAT thermogenesis, it was concluded that the thermogenic role of BAT was unimportant in adult humans largely because humans had low numbers of brown adipocytes. Solid evidence on the actual numbers of brown adipocytes in humans was not available. We are now re-evaluating the role of BAT for the treatment of obesity given the following recent observations (i) studies in nuclear medicine by using PET/CT scanning reveal the presence of BAT in adult humans; and (ii) recent data suggest that a new transcription factor called PDRM16 may control the induction of BAT. These recent discoveries should revamp our effort to target the molecular development of brown adipogenesis in the treatment of obesity.

Litter decomposition and nitrogen and phosphorus dynamics in peatlands and uplands over 12 years in central Canada.

The large accumulation of organic matter in peatlands has been partially attributed to litter decomposition rates, which are slowed by a high water table. To test this, we examined whether there were significant differences in the decomposition and N and P dynamics of ten foliar litters and wood blocks at three pairs of upland forest and peatland sites in the transitional grassland, high boreal and low subarctic regions of central Canada, using litterbags collected over a 12-year period. At two of the three pairs, the decomposition rate, as determined by proportion of the original mass remaining after 12 years and by the exponential decay coefficient (k), was faster overall at the upland than at the peatland. In the third pair, there was no significant difference, despite the water table being close to the peat surface; warmer soil temperatures in the peatland than the upland may be the cause. In general, there were small losses or gains of N in the litters after 12 years, compared to the original litter, though there were some differences among litter types and sites, net gains in N likely reflecting the higher exogenous N availability. P was lost from most litters at the two northern pairs of sites, but at the transitional grassland pair, there were large net gains in P and greater variation among litters. The N:P ratio in the original litters ranged from 5 to 26 and after 12 years the ratio narrowed, with the site average of the ten litters ranging from 13 to 22, varying with the soil ratio. Decomposition rates and N and P dynamics after 12 years are different between upland and peatland sites: although the water table is a primary control on these differences, other factors such as temperature and soil nutrient status are also important.

Genotyping microarray as a novel approach for the detection of ATP7B gene mutations in patients with Wilson disease.

Wilson disease (WD) is an autosomal recessive inherited disorder of copper metabolism that is caused by mutations in the ATP7B gene. To date, more than 300 mutations have been described in this gene. Molecular diagnostics of WD utilizes restriction enzyme digestion, multiplex ligation-dependent probe amplification or a direct sequencing of the whole gene. To simplify and speed up the screening of ATP7B mutations, we have developed a genotyping microarray for the simultaneous detection of 87 mutations and 17 polymorphisms in the ATP7B gene based on the arrayed primer extension reaction. The patient's DNA is amplified in four multiplex polymerase chain reactions, fragmented products are annealed to arrayed primers spotted on a chip, which enables DNA polymerase extension reactions with fluorescently labeled dideoxynucleotides. The Wilson microarray was validated by screening 97 previously genetically confirmed WD patients. In total, we detected 43 mutations and 15 polymorphisms that represent a majority of the common mutations occurring in the Czech and Slovak populations. All screened sequence variants were detected with 100% accuracy. The Wilson chip appears to be a rapid, sensitive and cost-effective tool, representing the prototype of a disease chip that facilitates and speeds up the screening of potential WD patients.

UCP1: its involvement and utility in obesity.

Energy balance to prevent the development of obesity is dependent on energy expenditure. Although physical activity is the dominant mechanism for dissipating excess energy, a system of thermogenesis that evolved to protect the body from hypothermia is based upon the uncoupling of oxidative phosphorylation in brown adipocytes by the mitochondrial uncoupling protein (UCP1). It has been shown that upregulation of UCP1 by genetic manipulations or pharmacological agents can reduce obesity and improve insulin sensitivity. Recent evidence has shown the existence of two sources for brown adipocytes, one appearing as discrete brown fat depots during fetal development and the other appears during post-natal development as diffuse populations in traditional white fat depots. The latter can be induced by adrenergic stimulation depending on the genetic background of the animals and the nutritional environment. Understanding the biological and environmental factors controlling the expression of these two brown adipocyte populations promises to provide new strategies by which enhanced thermogenesis can be used to reduce obesity.International Journal of Obesity (2008) 32, S32-S38; doi:10.1038/ijo.2008.236.

Molecular screening of Smith-Lemli-Opitz syndrome in pregnant women from the Czech Republic.

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive metabolic disorder. SLOS is caused by the mutations in the gene for 3beta-hydroxysterol Delta(7) reductase (DHCR7; EC 1.3.1.21), which maps to chromosome 11q12-13. DHCR7 catalyses the final step in cholesterol biosynthesis-the reduction of 7-dehydrocholesterol to cholesterol. Clinical severity ranges from mild dysmorphism to severe congenital malformation and intrauterine lethality. Pregnant women are offered a biochemical screening test for Down syndrome in the second trimester, where the suspicion for SLOS could be registered, when the unconjugated estriol (uE3) level appears low. A group of 456 fetuses with a high risk for SLOS were examined by DNA analysis. We confirmed SLOS in 5 fetuses and 11 fetuses were carriers. One novel mutation (p.G30A) was detected. The most frequently found mutations, c.964-1G > C and p.W151X, are also the most severe ones. At least one of these mutations was detected in each fetus with SLOS. This suggests that the biochemical screening of pregnant women probably uncovers mainly more severely affected fetuses. We confirmed SLOS also in two patients whose prenatal screening was negative. Both of them had nonsense mutation on one allele. It stands to reason that some modifying factors may play a role in the reduction of the uE3 level in the mother's serum.

[Effect of amaranth oil and intermittent hypoxic training on ultrastructural and metabolic changes in the liver induced by fluorine and low doses of radiation].

Ultrastructural and metabolic changes were studied during chronic fluorine intoxication and low doses of radiation (total dose is 1 Gr) in liver cells and tissues in rats fed with amaranth oil and treated with intermittent hypoxic training (IHT). The obtained data detected the ordered and compact position of mitochondria, peroxisomes, lipoprotein droplets with light electronic density, glycogen granules and also agranular endoplasmatic retuculum channels, which may be linked with reorganization of metabolic pathway of energy supply from fat acids via gluconeogenesis. Simultaneously the decrease of TBA-reactive substances accumulation with the considerable increase in activity of the antioxidant enzymes (catalase, glutathione peroxidase) and index of general antioxidant activity have been established. Therefore, the combined effect of IHT and amaranth oil on adequate occurence of free radical reactions provides the effective adaptation of organism to fluorine intoxication and ionizing radiation via the restoration of homeostasis on metabolic and ultrastructural levels. The obtained results allow to recommend IHT and amaranth oil for complex correction of changes, induced by fluorine intoxication and ionizing radiation.

[Genetic databases. Though we were not the first ones, at least let us not to be the last]. / Genetické databáze. Kdyz uz nemuzeme být první, at' nejsme alespon poslední.

One of the most necessary tools of today's medical care is the well working database of personal genotypes. It could effectively reduce the increasing expenses because many of the genetic testing could be done only once a life. Any delay in establishing such database would bring not only internal, but also across-border complications due to internationalization of the genetic services. The most modem approach has been applied by the laws which put stress more against abuse than on collecting data. European laws including the Czech Republic seem to be much less progressive. General rules for data storage, and gene banking are still missing in the Czech Republic.

Maternal hyperphenylalaninemias in healthy Czech population of pregnant women: 30 years experience with screening, prevention and treatment.

INTRODUCTION: The increased level of phenylalanine (Phe) in maternal blood--hyperphenylalaninemia (mHPA) has a detrimental effect on the early development of healthy foetus (1965). The toxic effect causes spontaneous abortion or retards intrauterine growth, skeletal malformation, cardiac anomalies can appear. However the most frequent are microcephaly, mental retardation and hypotrophy. PATIENTS AND METHODS: Simultaneously with the introduction of obligatory "Newborn Screening Program" in CR also the facultative screening for mHPA was introduced ("Maternal Hyperphenylalaninemia Preventive Screening Program"). Since 1975 till now 222,990 healthy pregnant women (16-47 yrs) from city Prague and its area (cca 2 mil. inh.) have been screened for increased Phe in blood by Efron's chromatographic screening test (1964); Phe cut off value: 240 micromol/l. Nonfasting venous blood has been taken in 2nd-3rd month of pregnancy during the first antenatal visit. All positive cases have been verified with quantitative Phe estimation on amino acid analyzer incl. pterines analysis in urine. For differentiation of detected mHPAs the Güttler's scheme (1980) has been used. Mutations for Phe-hydroxylase gene analyzed by restriction enzyme digestion after Guldberg (1994). RESULTS: The average incidence of mHPA detected at the beginning of pregnancy was found 1:8675. The major part (65.3%) of all detected mHPA belongs to mild or moderate form of phenylketonuria (PKU) with most frequent PAH gene mutations R408W, Y414C, IVS11 nt8g-a, R158Q, IVS12ntlg-a and R261Q. 19.2% corresponds to atypical or classical PKU with prevailing mutation R408W. Only in 15.3% were detected non-PKU (persistent HPA) with mutations R408W, Y414C, IVS12ntlg-a, IV11nt8g-a and A403V. 28 offsprings born from pregnancies on low-phenylalanine diet (LPD) introduced at least 2 months before the conception and during the whole pregnancy show normal psychomotoric development. In 7 offsprings without LPD or after delayed introducing or on PLD or badly monitored showed malformations (microcephaly, hypotrophy, skeletal malformations) or died. DISCUSSION: Relatively high incidence of mHPA detected in healthy population of pregnant women of Prague area differs from findings of Buist (1989) or Levy (1994) from American pregnant women screened for mHPA from umbilical blood. We consider that screening performed at the beginning of pregnancy from nonfasting venous blood is more effective compared to umbilical blood from two reasons: the Phe level in maternal blood is increased during first trimester of pregnancy due to succing effect of placenta in comparison to decreased Phe level at the end of labour. Umbilical blood for screening of mHPA is not quite suitable to detect the atypical or mild forms of Phe disturbances which prevailed in our Slavonic population of pregnant women. (Tab. 5, Fig. 7, Ref. 16.)

Serum free carnitine in medium chain acyl-CoA dehydrogenase deficiency.

Medium chain acyl-CoA dehydrogenase (MCAD) deficiency is the most common disorder of fatty acid beta-oxidation and presents acutely with hypoglycemia, or a Reye-like illness with low free carnitine, often provoked by an infection or an excessive period of fasting. After acute attack these children are for the most time asymptomatic and may have normal plasma free carnitine concentrations. We observed a regularity in time course of serum free carnitine concentration during two attacks of Reye-like illness in patient with MCAD deficiency. Molecular investigation confirmed that the patient was homozygote for A985G mutation. Free carnitine was measured by enzymatic UV-test. First attack of severe hypoglycemia and Reye-like symptoms started at the age of 15 months and the second at the age of 25 months. In both episodes, treatment with intravenous glucose was given immediately, but without carnitine supplementation. Between the attacks patient was on a normal diet. In both attacks, low serum free carnitine concentration from the time of acute attack continually decreased for up to 8-13 days and then normalized at about 25 days after attack. We think that the time course of serum free carnitine may help in knowledge about carnitine depletion in MCAD deficiency. This is the first observation of this pattern during an acute attack and needs to be confirmed by other patients with MCAD deficiency. (Fig. 2, Ref. 7.).

Splicing mutations, mainly IVS6-1(G>T), account for 70% of fumarylacetoacetate hydrolase (FAH) gene alterations, including 7 novel mutations, in a survey of 29 tyrosinemia type I patients.

Hereditary tyrosinemia type I (HTI) is an autosomal recessive disease characterized by a deficiency in fumarylacetoacetate hydrolase (FAH) activity. In this work, the FAH genotype was established in a group of 29 HTI patients, most of them from the Mediterranean area. We identified seven novel mutations-IVS8-1(G>A, IVS10-2(A>T), 938delC, E6/I6del26, W78X, Q328X, and G343W-and two previously described mutations-IVS6-1(G>T) and IVS12+5(G>A). Fully 92.8% of the patients were carriers of at least one splice site mutation, with IVS6-1(G>T) accounting for 58.9% of the total number of alleles. The splice mutation group of patients showed heterogeneous phenotypic patterns ranging from acute forms with severe liver malfunction to chronic forms with renal manifestations and slow progressive hepatic alterations. Qualitative FAH cDNA expression was the same in all IVS6-1(G>T) homozygous patients regardless of their clinical picture. One patient with a heterozygous combination of a nonsense (Q328X) and a frameshift (938delC) mutation showed an atypical clinical picture of hypotonia and repeated infections. Despite the high prevalence of IVS12+5(G>A) in the northwestern European population, we found only two patients with this mutation in our group.