G protein-coupled receptor P2Y5 and its ligand LPA are involved in maintenance of human hair growth

Hypotrichosis simplex is a group of nonsyndromic human alopecias. We mapped an autosomal recessive form of this disorder to chromosome 13q14.11-13q21.33, and identified homozygous truncating mutations in P2RY5, which encodes an orphan G protein-coupled receptor. Furthermore, we identified oleoyl-L-alpha-lysophosphatidic acid (LPA), a bioactive lipid, as a ligand for P2Y5 in reporter gene and radioligand binding experiments. Homology and studies of signaling transduction pathways suggest that P2Y5 is a member of a subgroup of LPA receptors, which also includes LPA4 and LPA5. Our study is the first to implicate a G protein-coupled receptor as essential for and specific to the maintenance of human hair growth. This finding may provide opportunities for new therapeutic approaches to the treatment of hair loss in humans.     

Comparing the Long-Term Evolution of ``Cognitive Invariances' in Physics with a Dynamics in States of Consciousness

It is shown that the evolution of physics canin several regards be described by elements of``regression', i.e., that within a certaintradition of ideas one begins with theconstruction of most ``plausible' statements(axioms) at hand, and then ``works onselfbackwards' with respect to developmental terms.As a consequence of this strategy, the furtherwork proceeds along such a ``regressive' path,the more one arrives at concepts andrelationships which are unexpected or evencounter-intuitive in terms of our everydayexperiences. However, a comparable phenomenology is wellknown from studies on states of consciousness.In particular, the evolutionary logic of theconstructions of major ``cognitive invariances'in physics, which is in part due to everincreasing rates of data processing, ismirrored in a logic of states of consciousnesswhich deviate from a ``normal' state of dailyroutine along increasing levels of centralnervous arousal. Examples are given from the evolution ofphysics, and future perspectives are brieflyoutlined on the basis thereof.     

CALENDAR EFFECTS IN MONTHLY TIME SERIES MODELS

1. Introduction In the 1960s the attempts to describe an economy by large macroeconometric models were under heavy critique. These models with hundreds of macroeconomic variables and equations, could track the data very well over the historical period where the model parameters are estimated but often performed poorly when are used for out-of-sample forecasting. Part of the disillusionment with these efforts was the discovery that univariate time series models with low order autoregressive and…     

Bipolar affective disorders linked to DNA markers on chromosome 11

An analysis of the segregation of restriction fragment length polymorphisms in an Old Order Amish pedigree has made it possible to localize a dominant gene conferring a strong predisposition to manic depressive disease to the tip of the short arm of chromosome 11.     

Transgeneration memory of stress in plants

Owing to their sessile nature, plants are constantly exposed to a multitude of environmental stresses to which they react with a battery of responses. The result is plant tolerance to conditions such as excessive or inadequate light, water, salt and temperature, and resistance to pathogens. Not only is plant physiology known to change under abiotic or biotic stress, but changes in the genome have also been identified. However, it was not determined whether plants from successive generations of the original, stressed plants inherited the capacity for genomic change. Here we show that in Arabidopsis thaliana plants treated with short-wavelength radiation (ultraviolet-C) or flagellin (an elicitor of plant defences), somatic homologous recombination of a transgenic reporter is increased in the treated population and these increased levels of homologous recombination persist in the subsequent, untreated generations. The epigenetic trait of enhanced homologous recombination could be transmitted through both the maternal and the paternal crossing partner, and proved to be dominant. The increase of the hyper-recombination state in generations subsequent to the treated generation was independent of the presence of the transgenic allele (the recombination substrate under consideration) in the treated plant. We conclude that environmental factors lead to increased genomic flexibility even in successive, untreated generations, and may increase the potential for adaptation.     

Evidence against Ha-ras-1 involvement in sporadic and familial melanoma

It was recently reported that different rare alleles at the Ha-ras-1 locus occurred at a significantly higher combined frequency in cancer patients than in an unaffected population. In particular, melanoma patients were reported to have a significantly higher frequency of such alleles. We have examined the frequency of rare Ha-ras-1 alleles in a large number of cases of sporadic melanoma. Our results indicate that the distribution of rare alleles in this population does not differ from that found in normal populations. Also, to test the hypothesis that a hereditary predisposition to melanoma could be inherited via an allele at the Ha-ras-1 locus, we examined the transmission of the segment of the short arm of chromosome 11 (11p) carrying the Ha-ras-1 locus in a number of families previously shown to exhibit a hereditary predisposition to melanoma and its precursor lesion, the dysplastic nevus syndrome (DNS). Our genetic linkage results thus obtained strongly exclude the association of a predisposition to melanoma or the precursor lesion with the inheritance of the Ha-ras-1 locus or the segment of chromosome 11 on which it is located. These results imply that hereditary predisposition to melanoma is associated with genes other than the Ha-ras-1 locus, contradicting the original suggestion of Krontiris et al., made on the basis of either an inadequate sample size or other misleading experimental factors.