Skin responses to ultraviolet radiation: effects of constitutive pigmentation,sex, and ancestry

Constitutive skin pigmentation and skin responses to ultraviolet radiation were measured on a sample of volunteers (n=250) living in State College, PA, USA. The sample was composed of individuals of European American (n=190), Hispanic (n=45), and East Asian ancestry (n=15). Constitutive pigmentation was measured using the Adjusted Melanin Index (AMI), Erythemal Dose Response (EDR) was measured using the slope of a* at 24 h (Deltaa*), and Melanogenic Dose-Response (MDR) was measured using DeltaAM, the slope of AMI at 7 d. The relationships between constitutive skin pigmentation, EDR, MDR, sex, age, and ancestry were investigated. European Americans showed a lower constitutive pigmentation, had a significantly higher burn response (EDR), and had a significantly lower tanning response (MDR) than Hispanics and East Asians. No significant difference is seen between Hispanics and East Asians for either constitutive pigmentation or EDR. Constitutive pigmentation in females was slightly lower than in males in all three samples, but the difference was not significant. While no differences were observed in MDR between sexes, males had a stronger EDR than females regardless of population or constitutive pigmentation level, and this difference was significant in European Americans and Hispanics. We observed no age-related differences in any of the populations or measures investigated. We evaluated the relationship between constitutive pigmentation, EDR and MDR. There was a strong inverse correlation between constitutive pigmentation and EDR in the three samples (European Americans, R2=0.176, P < 0.001; Hispanics, R2=0.204, P=0.009; East Asians, R2=0.223, P=0.098) and a strong direct correlation between constitutive pigmentation and MDR in European Americans and Hispanics (European Americans, R2=0.094, P < 0.001; Hispanics, R2=0.164, P=0.012). In other words, persons with lower constitutive pigmentation both burn more and tan less than persons with higher pigmentation. However, after controlling for constitutive pigmentation, EDR and MDR were significantly correlated in European Americans (R2=0.041 P=0.006). Thus, the general observation that persons who burn more tan less is probable because of the common link that these two phenotypes have with constitutive skin pigmentation and, in fact, once pigmentation has been adjusted for, there is a positive correlation between tanning response and burning response in European Americans.     

A four-channel analysis of the tactile sensitivity of the fingertip: frequency selectivity,spatial summation,and temporal summation

Thresholds were measured for the detection of vibratory stimuli of variable frequency and duration applied to the index fingertip and thenar eminence through contactors of different sizes. The effects of stimulus frequency could be accounted for by the frequency characteristics of the Pacinian (P), non-Pacinian (NP) I, and NP III channels previously determined for the thenar eminence (Bolanowski et al., J Acoust Soc Am 84: 1680-1694, 1988; Gescheider et al., Somatosens Mot Res 18: 191-201, 2001). The effect of changing stimulus duration was also essentially identical for both sites, demonstrating the same amount of temporal summation in the P channel. Although the effect of changing stimulus frequency and changing stimulus duration did not differ for the two sites, the effect of varying the size of the stimulus was significantly greater for the thenar eminence than for the fingertip. The attenuated amount of spatial summation on the fingertip was interpreted as an indication that the mechanism of spatial summation consists of the operations of both neural integration and probability summation.     

Fgf3 and Fgf8 are required together for formation of the otic placode and vesicle

Fgf3 has long been implicated in otic placode induction and early development of the otocyst; however, the results of experiments in mouse and chick embryos to determine its function have proved to be conflicting. In this study, we determined fgf3 expression in relation to otic development in the zebrafish and used antisense morpholino oligonucleotides to inhibit Fgf3 translation. Successful knockdown of Fgf3 protein was demonstrated and this resulted in a reduction of otocyst size together with reduction in expression of early markers of the otic placode. fgf3 is co-expressed with fgf8 in the hindbrain prior to otic induction and, strikingly, when Fgf3 morpholinos were co-injected together with Fgf8 morpholinos, a significant number of embryos failed to form otocysts. These effects were made manifest at early stages of otic development by an absence of early placode markers (pax2.1 and dlx3) but were not accompanied by effects on cell division or death. The temporal requirement for Fgf signalling was established as being between 60% epiboly and tailbud stages using the Fgf receptor inhibitor SU5402. However, the earliest molecular event in induction of the otic territory, pax8 expression, did not require Fgf signalling, indicating an inductive event upstream of signalling by Fgf3 and Fgf8. We propose that Fgf3 and Fgf8 are required together for formation of the otic placode and act during the earliest stages of its induction.     

Distal-less and homothorax regulate multiple targets to pattern the Drosophila antenna

The Drosophila antenna is a highly derived appendage required for a variety of sensory functions including olfaction and audition. To investigate how this complex structure is patterned, we examine the specific functions of genes required for antenna development. The nuclear factors, Homothorax, Distal-less and Spineless, are each required for particular aspects of antennal fate. Coexpression of Homothorax, necessary for nuclear localization of its ubiquitously expressed partner Extradenticle, with Distal-less is required to establish antenna fate. Here we test which antenna patterning genes are targets of Homothorax, Distal-less and/or Spineless. We report that the antennal expression of dachshund, atonal, spalt, and cut requires Homothorax and/or Distal-less, but not Spineless. We conclude that Distal-less and Homothorax specify antenna fates via regulation of multiple genes. We also report for the first time phenotypic consequences of losing either dachshund or spalt and spalt-related from the antenna. We find that dachshund and spalt/spalt-related are essential for proper joint formation between particular antennal segments. Furthermore, the spalt/spalt-related null antennae are defective in hearing. Hearing defects are also associated with the human diseases Split Hand/Split Foot Malformation and Townes-Brocks Syndrome, which are linked to human homologs of Distal-less and spalt, respectively. We therefore propose that there are significant genetic similarities between the auditory organs of humans and flies.     

Differential binding to and biofilm formation on,HEp-2 cells by Salmonella enterica serovar Typhimurium is dependent upon allelic variation in the fimH gene of the fim gene cluster

Type 1 fimbria-mediated adherence to HEp-2 cells by two strains of Salmonella enterica serovar Typhimurium was found to be different. Although both strains exhibited a strong mannose-sensitive haemagglutination reaction with guinea pig erythrocytes, characteristic of the expression of type 1 fimbriae, only one of the strains adhered in large numbers to HEp-2 cells. Characterization of the fimH genes, encoding the fimbrial adhesins, indicated two allelic variants. Using fimH mutants of the two strains it was possible to demonstrate that binding to HEp-2 cells was associated with the presence of one of the alleles regardless of the host strain. Therefore, this differential binding was not a function of the type I fimbrial shaft or the presence of other types of fimbriae produced by one strain but not the other. These observations may explain the differences in HEp-2 binding by type 1 fimbriate strains of Salmonella previously reported by several groups. Also, our studies demonstrate that the FimH adhesin can influence the efficiency of biofilm formation on HEp-2 cells using once-flow-through continuous culture conditions. The formation of biofilms on eukaryotic cells using this procedure is more likely to represent those conditions found in the intestinal tract than conditions using batch culture techniques to investigate adherence and biofilm formation. Indeed, the increased efficiency of biofilm formation in the murine intestinal tract confirmed the role of one of the fimH alleles in this process.     

The cycloidea gene can respond to a common dorsoventral prepattern in Antirrhinum

Dorsoventral asymmetry in flowers of Antirrhinum depends on expression of the cycloidea gene in dorsal regions of floral meristems. To determine how cycloidea might be regulated we analysed its expression in several contexts. We show that cycloidea is activated shortly after floral induction, and that in addition to flowers, cycloidea can be asymmetrically expressed in shoots, even though these shoots show no marked dorsoventral asymmetry. Shoots expressing cycloidea include secondary branches lying just below the inflorescence, and shoots of floricaula mutants. Asymmetric cycloidea expression may also be observed within organ primordia, such as the sepals of terminal flowers produced by centroradialis mutants. Later expression of cycloidea within flowers can be modified by mutations in organ identity genes. Taken together, the results suggest that cycloidea can respond to a common dorsoventral pre-pattern in the apex and that the specific effects of cycloidea on the flower depend on interactions with floral-specific genes.     

Synthesis and structure-activity relationships of M(2)-selective muscarinic receptor ligands in the 1-[4-(4-arylsulfonyl)-phenylmethyl]-4-(4-piperidinyl)-piperazine family

The synthesis and muscarinic binding properties of compounds based on the 1-[4-(4-arylsulfonyl)phenylmethyl]-4-(1-aroyl-4-piperidinyl)-piperazine skeleton are described. For compounds, substituted with appropriately configured methyl groups at the benzylic center and at the piperazine 2-position, high levels of selective, M(2) subtype affinity could be obtained, particularly when the terminal N-aroyl residue was ortho-substituted.     

Synthesis and hybridization studies of a 5-aminopentanoic acid nucleobase (APN) dimer

We have prepared a 5-aminopentanoic acid nucleobase (APN) dimer and investigated its hybridization capabilities to complementary DNA using both UV melting and NMR techniques.     

Quaking is essential for blood vessel development

For nearly 40 years functional studies of the mouse quaking gene (qkI) have focused on its role in the postnatal central nervous system during myelination. However, the homozygous lethality of a number of ENU-induced alleles reveals that quaking has a critical role in embryonic development prior to the start of myelination. In this article, we show that quaking has a previously unsuspected and essential role in blood vessel development. Interestingly, we found that quaking, a nonsecreted protein, is expressed in the yolk sac endoderm, adjacent to the mesodermal site of developing blood islands, where the differentiation of blood and endothelial cells first occurs. Antibodies against PE-CAM-1, TIE-2 and SM-alpha-actin reveal that embryos homozygous for the qk(k2) allele have defective yolk sac vascular remodeling and abnormal vessels in the embryo proper at midgestation, coinciding with the timing of embryonic death. However, these mutants exhibit normal expression of Nkx2.5 and alpha-sarcomeric actin, indicating that cardiac muscle differentiation was normal. Further, they had normal embryonic heart rates in culture, suggesting that cardiac function was not compromised at this stage of embryonic development. Together, these results suggest that quaking plays an essential role in vascular development and that the blood vessel defects are the cause of embryonic death.     

Effect of massive sympathetic nervous system activation on coronary blood flow and myocardial energy pool

Our previous work indicates that myocardial ischemia could be the mechanism responsible for the left ventricular (LV) dysfunction that frequently develops after massive sympathetic nervous system (SNS) activation. In this study, coronary blood flow (CBF) and myocardial ATP, creatine phosphate, and lactate concentrations were measured after massively activating the SNS of anesthetized rabbits with an intracisternal injection of veratrine. CBF was measured at time 0 (baseline), and at 2, 10, and 20 min after SNS activation in one group, and at 0, 45, 90, and 150 min in a second group. Myocardial ATP, creatine phosphate, and lactate were measured at 0, 2, 10, 20, 90, and 150 min in separate groups of rabbits. SNS activation caused LV dysfunction in approximately 60% of the rabbits. SNS-related increases in CBF kept pace with the increases in myocardial energy demand as determined from the systolic pressure-heart rate product. The subendocardial-to-subepicardial blood flow ratio did not change significantly. Myocardial creatine phosphate concentration was depressed 2 min after SNS activation and remained depressed for at least 20 min. ATP fell continuously and was significantly lower than baseline by 20 min. Tissue lactate concentration was elevated at this time. By 90 min, the concentrations of all three metabolites had recovered. These results indicate that myocardial high-energy phosphate compounds fall after massive SNS activation, but ischemia does not appear to be the underlying mechanism.