Linkage to Xq28 in a family with nonspecific X-linked mental retardation

Linkage analysis was performed in a family with nonspecific X-linked mental retardation (MRX). Affected individuals had no clinical characteristics other than mental retardation. Linkage was detected to the marker loci DXS477, DXS465, DXS52, DXS15 and F8C with maximum lod scores of 1.70, 1.32, 2.52, 1.70, and 1.09, respectively ( = 0.0). The results strongly indicate that the gene for mental retardation in the family studied maps close to DXS52.     

Hypersensitivity symptoms associated with exposure to cellular telephones: no causal link

The hypothesis that there exist hypersensitive persons who perceive subjective symptoms from radiofrequency (RF) fields emitted by hand held mobile phones (cellular phones) was tested using double blind provocation experiments. We also tested whether sensitive subjects are able to determine whether the phone is on or off by sensing RF fields. The study group consisted of 20 volunteers (13 women and 7 men) who reported themselves as being sensitive to cellular phones. The RF exposure sources were one analogue NMT phone (900 MHz) and two digital GSM phones (900 and 1800 MHz). The duration of a test session was 30 min, and three or four sessions were performed in random order for each subject during 1 day. The subjects were asked to report symptoms or sensations as soon as they perceived any abnormal feelings. In addition, the subjects' blood pressure, heart rate, and breathing frequency were monitored every 5 min. The results of the study indicated that various symptoms were reported, and most of them appeared in the head region. However, the number of reported symptoms was higher during sham exposure than during real exposure conditions. In addition, none of the test persons could distinguish real RF exposure from sham exposure. Hence, we conclude that adverse subjective symptoms or sensations, though unquestionably perceived by the test subjects, were not produced by cellular phones.     

Mutations in the Small GTPase Gene RAB39B Are Responsible for X-linked Mental Retardation Associated with Autism, Epilepsy, and Macrocephaly

Human Mental Retardation (MR) is a common and highly heterogeneous pediatric disorder affecting around 3% of the general population; at least 215 X-linked MR (XLMR) conditions have been described, and mutations have been identified in 83 different genes, encoding proteins with a variety of function, such as chromatin remodeling, synaptic function, and intracellular trafficking. The small GTPases of the RAB family, which play an essential role in intracellular vesicular trafficking, have been shown to be involved in MR. We report here the identification of mutations in the small GTPase RAB39B gene in two male patients. One mutation in family X (D-23) introduced a stop codon seven amino acids after the start codon (c.21C > A; p.Y7X). A second mutation, in the MRX72 family, altered the 5′ splice site (c.215+1G > A) and normal splicing. Neither instance produced a protein. Mutations segregate with the disease in the families, and in some family members intellectual disabilities were associated with autism spectrum disorder, epileptic seizures, and macrocephaly. We show that RAB39B, a novel RAB GTPase of unknown function, is a neuronal-specific protein that is localized to the Golgi compartment. Its downregulation leads to an alteration in the number and morphology of neurite growth cones and a significant reduction in presynaptic buttons, suggesting that RAB39B is required for synapse formation and maintenance. Our results demonstrate developmental and functional neuronal alteration as a consequence of downregulation of RAB39B and emphasize the critical role of vesicular trafficking in the development of neurons and human intellectual abilities.     

Human cytomegalovirus DNA polymerase catalytic subunit pUL54 possesses independently acting nuclear localization and ppUL44 binding motifs

The catalytic subunit of human cytomegalovirus (HCMV) DNA polymerase pUL54 is a 1242-amino-acid protein, whose function, stimulated by the processivity factor, phosphoprotein UL44 (ppUL44), is essential for viral replication. The C-terminal residues (amino acids 1220-1242) of pUL54 have been reported to be sufficient for ppUL44 binding in vitro. Although believed to be important for functioning in the nuclei of infected cells, no data are available on either the interaction of pUL54 with ppUL44 in living mammalian cells or the mechanism of pUL54 nuclear transport and its relationship with that of ppUL44. The present study examines for the first time the nuclear import pathway of pUL54 and its interaction with ppUL44 using dual color, quantitative confocal laser scanning microscopy on live transfected cells and quantitative gel mobility shift assays. We showed that of two nuclear localization signals (NLSs) located at amino acids 1153-1159 (NLSA) and 1222-1227 (NLSB), NLSA is sufficient to confer nuclear localization on green fluorescent protein (GFP) by mediating interaction with importin alpha/beta. We also showed that pUL54 residues 1213-1242 are sufficient to confer ppUL44 binding abilities on GFP and that pUL54 and ppUL44 can be transported to the nucleus as a complex. Our work thus identified distinct sites within the HCMV DNA polymerase, which represent potential therapeutic targets and establishes the molecular basis of UL54 nuclear import.     

α-Synuclein and Its A30P Mutant Affect Actin Cytoskeletal Structure and Dynamics

The function of α-synuclein, a soluble protein abundant in the brain and concentrated at presynaptic terminals, is still undefined. Yet, α-synuclein overexpression and the expression of its A30P mutant are associated with familial Parkinson''s disease. Working in cell-free conditions, in two cell lines as well as in primary neurons we demonstrate that α-synuclein and its A30P mutant have different effects on actin polymerization. Wild-type α-synuclein binds actin, slows down its polymerization and accelerates its depolymerization, probably by monomer sequestration; A30P mutant α-synuclein increases the rate of actin polymerization and disrupts the cytoskeleton during reassembly of actin filaments. Consequently, in cells expressing mutant α-synuclein, cytoskeleton-dependent processes, such as cell migration, are inhibited, while exo- and endocytic traffic is altered. In hippocampal neurons from mice carrying a deletion of the α-synuclein gene, electroporation of wild-type α-synuclein increases actin instability during remodeling, with growth of lamellipodia-like structures and apparent cell enlargement, whereas A30P α-synuclein induces discrete actin-rich foci during cytoskeleton reassembly. In conclusion, α-synuclein appears to play a major role in actin cytoskeletal dynamics and various aspects of microfilament function. Actin cytoskeletal disruption induced by the A30P mutant might alter various cellular processes and thereby play a role in the pathogenesis of neurodegeneration.     

Assessment of exposure to intermediate frequency electric fields and contact currents from a plasma ball

While electric fields at intermediate frequencies are not widely utilized for industrial technologies, surprisingly, certain toys emit the highest electric fields found in our living environment. These toys, plasma balls, are devices that use high voltage to create ionized light discharges. In this study, we assessed exposure to electric fields and contact/induced current from a recreational plasma ball device. The electric field strength was measured as a function of distance from the device, and the contact/induced current was measured with a current clamp in different exposure situations with point or grasping contact. The characteristic spectra of the electric field and contact current were measured, and both the multiple frequency rule and weighting of the spectra were applied according to the International Commission on Non-Ionizing Radiation Protection (ICNIRP) 1998 and 2010 guidelines. The results indicate that the recommended reference levels for the general public are exceeded at distances <1.2 m, and that the contact currents in the hand may be twice higher than recommended by the general public guidelines.     

Bone Health and Risk Factors of Cardiovascular Disease - A Cross-Sectional Study in Healthy Young Adults

Objective

Both osteoporosis and cardiovascular disease (CVD) are diseases that comprise a growing medical and economic burden in ageing populations. They share many risk factors, including ageing, low phy-sical activity, and possibly overweight. We aimed to study associations between individual risk factors for CVD and bone mineral density (BMD) and turnover markers (BTMs) in apparently healthy cohort.

Design

A cross-sectional assessment of 155 healthy 32-year-old adults (74 males) was performed for skeletal status, CVD risk factors and lifestyle factors.

Methods

We analysed serum osteocalcin, procollagen I aminoterminal propeptide (P1NP), collagen I carboxy-terminal telopeptide (ICTP) and urine collagen I aminoterminal telopeptide (U-NTX), as well as serum insulin, plasma glucose, triglyceride and HDL-cholesterol levels. BMD, fat and lean mass were asses-sed using DXA scanning. Associations were tested with partial correlations in crude and adjusted mo-dels. Bone status was compared between men with or without metabolic syndrome (defined according to the NCEP-ATPIII criteria) with multivariate analysis.

Results

Osteocalcin and P1NP correlated inversely with insulin (R = −0.243, P = 0.003 and R = −0.187, P = 0.021) and glucose (R = −0.213, P = 0.009 and R = −0.190, P = 0.019), but after controlling for fat mass and lifestyle factors, the associations attenuated with insulin (R = −0.162, P = 0.053 and R = −0.093, P = 0.266) and with glucose (R = −0.099, P = 0.240 and R = −0.133, P = 0.110), respectively. Whole body BMD associated in-versely only with triglycerides in fully adjusted model. In men with metabolic syndrome, whole body BMD, osteocalcin and P1NP were lower compared to healthy men, but these findings disappeared in fully adjusted model.

Conclusions

In young adults, inverse associations between BTM/BMD and risk factors of CVD appeared in crude models, but after adjusting for fat mass, no association continued to be present. In addition to fat mass, lifestyle factors, especially physical activity, modified the associations between CVD and bone charac-teristics. Prospective studies are needed to specify the role of mediators and lifestyle factors in the prevention of CVD and osteoporosis.     

Serial duplication of 10 (q21→q22) in a mentally retarded boy with congenital malformations

Summary A boy with congenital malformations and a serial duplication of 10(q21q22) is reported. His clinical picture is compared with that of a previously reported patient with a similar karyotype.     

Cellular phone use does not acutely affect blood pressure or heart rate of humans

A recent study raised concern about increase of resting blood pressure after a 35 min exposure to the radiofrequency (RF) field emitted by a 900 MHz cellular phone. In this randomized, double blind, placebo controlled crossover trial, 32 healthy subjects were submitted to 900 MHz (2 W), 1800 MHz (1 W) cellular phone exposure, and to sham exposure in separate sessions. Arterial blood pressure (arm cuff method) and heart rate were measured during and after the 35 min RF and sham exposure sessions. We evaluated cardiovascular responses in terms of blood pressure and heart rate during controlled breathing, spontaneous breathing, head-up tilt table test, Valsalva manoeuvre and deep breathing test. Arterial blood pressure and heart rate did not change significantly during or after the 35 min RF exposures at 900 MHz or 1800 MHz, compared to sham exposure. The results of this study indicate that exposure to a cellular phone, using 900 MHz or 1800 MHz with maximal allowed antenna powers, does not acutely change arterial blood pressure and heart rate.