Altered cell surface expression of human MC1R variant receptor alleles associated with red hair and skin cancer risk

The human melanocortin-1 receptor gene (MC1R) encodes a G-protein coupled receptor that is primarily expressed on melanocytes, where it plays a key role in pigmentation regulation. Variant alleles are associated with red hair colour and fair skin, known as the RHC phenotype, as well as skin cancer risk. The R151C, R160W and D294H alleles, designated 'R', are strongly associated with the RHC phenotype and have been proposed to result in loss of function receptors due to impaired G-protein coupling. We recently provided evidence that the R151C and R160W variants can efficiently couple to G-proteins in response to alpha-melanocyte stimulating hormone. The possibility that altered cellular localization of the R151C and R160W variant receptors could underlie their association with RHC was therefore considered. Using immunofluorescence and ligand binding studies, we found that melanocytic cells exogenously or endogenously expressing MC1R show strong surface localization of the wild-type and D294H alleles but markedly reduced cell surface expression of the R151C and R160W receptors. In additional exogenous expression studies, the R variant D84E and the rare I155T variant, also demonstrated a significant reduction in plasma membrane receptor numbers. The V60L, V92M and R163Q weakly associated RHC alleles, designated 'r', were expressed with normal or intermediate cell surface receptor levels. These results indicate that reduced receptor coupling activity may not be the only contributing factor to the genetic association between the MC1R variants and the RHC phenotype, with MC1R polymorphisms now linked to a change in receptor localization.

Intrapartum fetal scalp lactate sampling for fetal assessment in the presence of a non-reassuring fetal heart rate trace (Protocol)

This is the protocol for a review and there is no abstract. The objectives are as follows: To evaluate the effectiveness and risks of fetal scalp lactate sampling in the assessment of fetal wellbeing during labour, compared with no testing or alternative additional testing (pH, fetal pulse oximetry, etc) for women exhibiting a non-reassuring cardiotocograph trace. A secondary objective of the review is to determine whether effectiveness and risks of intrapartum fetal scalp lactate sampling is influenced by the following: stage of labour; gestation less than 37 completed weeks, greater than or equal to 37 completed weeks; additional tests performed to confirm the presence or absence of fetal acidemia during labour.

Accuracy and applications of group MEG studies using cortical source locations estimated from participants' scalp surfaces

We contend that powerful group studies can be conducted using magnetoencephalography (MEG), which can provide useful insights into the approximate distribution of the neural activity detected with MEG without requiring magnetic resonance imaging (MRI) for each participant. Instead, a participant's MRI is approximated with one chosen as a best match on the basis of the scalp surface from a database of available MRIs. Because large inter-individual variability in sulcal and gyral patterns is an inherent source of blurring in studies using grouped functional activity, the additional error introduced by this approximation procedure has little effect on the group results, and offers a sufficiently close approximation to that of the participants to yield a good indication of the true distribution of the grouped neural activity. T1-weighted MRIs of 28 adults were acquired in a variety of MR systems. An artificial functional image was prepared for each person in which eight 5 × 5 × 5 mm regions of brain activation were simulated. Spatial normalisation was applied to each image using transformations calculated using SPM99 with (1) the participant's actual MRI, and (2) the best matched MRI substituted from those of the other 27 participants. The distribution of distances between the locations of points using real and substituted MRIs had a modal value of 6 mm with 90% of cases falling below 12.5 mm. The effects of this -approach on real grouped SAM source imaging of MEG data in a verbal fluency task are also shown. The distribution of MEG activity in the estimated average response is very similar to that produced when using the real MRIs. © 2003 Wiley-Liss, Inc.

Topographic studies of scalp potentials evoked by pattern presentation

The waveform and scalp distribution of the visual evoked potentials elicited by stimuli in the foveal and parafoveal regions have been investigated in a group of normal humans using a 16-channel `brain mapping' system. The waveform and topography of the responses to pattern onset and pattern reversal stimulation were investigated, using 4 x 4o full field and 4 x 2o lateral and altitudinal half-field stimuli. The responses were composed of several successive peaks which are in some respects consistent with those demonstrated by other workers using larger field sizes. The differences in the behaviour of these components with respect to the position of the stimulus in the visual field were suggestive of origins in different areas of the visual cortex and/or different visual mechanism. Of particular interest were the major early positive components `P90' and `P95' of the responses to pattern onset and pattern reversal stimulation respectively. More detailed exploration of the behaviour of these major early positive components was carried out using `M-scaled' stimuli selected to activate one square centimetre patches of striate cortex and associated extrastriate re-projections, positioned at different points in the foveal and parafoveal area of the visual field. The inter- and intra-subject variability in amplitude and localisation of the signals elicited by these targets was considered to be a reflection of the individual variations in relationship of visual field projections with the pattern of gyri and fissures on the proximal surface of the occipital lobe. The behaviour of component P90 of the onset response is consistent with a lateral origin in extrastriate visual cortex; that of P95 of the pattern reversal response is consistent in some respects with a striate cortical origin, but in others with a partial origin in extrastriate cortex.

Multiple Dipole Source Models for Scalp-Recorded Event-Related Potentials: Example from Complex Visual Processing in the Human Brain

2000 Mathematics Subject Classification: 62P10, 92C20

Merle Hoffman (long, blond hair), director of "Choices" an abortion clinic in NYC. Rally in front of St. Patrick's Cathedral

General note: Title and date provided by Bettye Lane.

Mother cutting son's hair

Inscriptions: Verso: [stamped] Photograph by Freda Leinwand. [463 West Street, Studio 229G, New York, NY 10014].

Mother cutting son's hair

Inscriptions: Verso: [stamped] Photograph by Freda Leinwand. [463 West Street, Studio 229G, New York, NY 10014].

(Table 2) Mercury concentration in hair of Northwest Greenland polar bears (Ursus maritimus)

Hair samples from 117 Northwest Greenland polar bears (Ursus maritimus) were taken during 1892-2008 and analyzed for total mercury (hereafter Hg). The sample represented 28 independent years and the aim of the study was to analyze for temporal Hg trends. Mercury concentrations showed yearly significant increases of 1.6-1.7% (p < 0.0001) from 1892 to 2008 and the two most recent median concentrations from 2006 and 2008 were 23- to 27-fold higher respectively than baseline level from 1300 A.D. in the same region (Nuullit). This indicates that the present (2006-2008) Northwest Greenland polar bear Hg exposure is 95.6-96.2% anthropogenic in its origin. Assuming a continued anthropogenic increase, this model estimated concentrations in 2050 and 2100 will be 40- and 92-fold the baseline concentration, respectively, which is equivalent to a 97.5 and 98.9% man-made contribution. None of the 2001-2008 concentrations of Hg in Northwest Greenland polar bear hair exceeded the general guideline values of 20-30 µg/g dry weight for terrestrial wildlife, whereas the neurochemical effect level of 5.4 µg Hg/g dry weight proposed for East Greenland polar bears was exceeded in 93.5% of the cases. These results call for detailed effect studies in main target organs such as brain, liver, kidney, and sexual organs in the Northwest Greenland polar bears.

The Game is On! The Adventure of the Girl with the Light Blue Hair

The Game is On! is a series of short animated films that put copyright and creativity under the magnifying glass of Sherlock Holmes, providing a unique, research-led and open access resource for school-aged learners and other creative users of copyright. Drawing inspiration from well-known copyright and public domain work, as well as recent copyright litigation, these films provide a springboard for exploring key principles and ideas underpinning copyright law, creativity, and the limits of lawful appropriation and reuse.

Each episode comes accompanied by a number of related Case Files: supplementary educational materials aimed at suggesting points of discussion about copyright for teachers and students.