The Sjogren's syndrome-associated autoantigen Ro52 is an E3 ligase that regulates proliferation and cell death

Patients affected by Sj?gren's syndrome and systemic lupus erythematosus (SLE) carry autoantibodies to an intracellular protein denoted Ro52. Although the serologic presence of Ro52 autoantibodies is used clinically for diagnostic purposes, the function of the protein or why it is targeted as an autoantigen in several rheumatic conditions has not been elucidated. In this study, we show that the expression of Ro52 is significantly increased in PBMC of patients with Sj?gren's syndrome and SLE, and demonstrate that Ro52 is a RING-dependent E3 ligase involved in ubiquitination. Overexpression of Ro52, but not of Ro52 lacking the RING domain, in a mouse B cell line lead to decreased growth in steady state and increased cell death after activation via the CD40 pathway. The role of Ro52 in activation-mediated cell death was further confirmed as a reduction in Ro52 expression restored cell viability. These findings suggest that the increased expression of the Ro52 autoantigen in patients may be directly involved in the reduced cellular proliferation and increased apoptotic cell death observed in Sj?gren's syndrome and SLE, and may thus contribute to the autoantigenic load and induction of autoimmune B and T cell responses observed in rheumatic patients.     

The chemosensory basis for behavioral divergence involved in sympatric host shifts. I. Characterizing olfactory receptor neuron classes responding to key host volatiles

The recent shift of Rhagoletis pomonella from its native host hawthorn to introduced, domestic apple has been implicated as an example of sympatric speciation. Recent studies suggest that host volatile preference might play a fundamental role in host shifts and subsequent speciation in this group. Single sensillum electrophysiology was used to test a proposed hypothesis that differences in R. pomonella olfactory preference are due to changes in the number or odor specificity of olfactory receptor neurons. Individuals were analyzed from apple, hawthorn, and flowering dogwood-origin populations, as well as from the blueberry maggot, Rhagoletis mendax Curran (an outgroup). Eleven compounds were selected as biologically relevant stimuli from previous electroantennographic/behavioral studies of the three R. pomonella populations to host fruit volatiles. Cluster analysis of 99 neuron responses showed that cells from all tested populations could be grouped into the same five classes, ranging from those responding to one or two volatiles to those responding to several host volatiles. Topographical mapping also indicated that antennal neuron locations did not differ by class or fly taxa. Our results do not support the hypothesis that differences in host preference among Rhagoletis populations are a result of alterations in the number or class of receptor neurons responding to host volatiles.     

Thermographic mapping of the skin surface of the head in bald-headed male subjects

Thermal patterns on the skin are related to skin blood perfusion. While knowledge concerning thermal distribution patterns of the face are well established, the thermal distribution patterns of the skin surface of other aspects of the head has only been investigated once previously in a study employing low resolution thermographic equipment [van Dulken, H., van Voss, S.F.C.H, 1971. The normal thermographic patterns of the human head. Acta Neurochir. 23, 247–58.] The purpose of the study was to re-examine the thermal distribution patterns of the surface of the entire head in 12 healthy bald headed male subjects (mean age 39±7.8 (SD) years) using a high definition infrared (IR) thermographic camera. The thermal distribution patterns were monitored using dynamic infrared thermography (DIRT) before, during and after a 2 min local skin cooling procedure with a pair of fans. Infrared thermal images (thermograms) were taken of the superior, anterior, lateral and posterior aspects of the head. The thermal patterns in general followed the anatomical location of the main superficial arteries and veins of the head as described in anatomy books although there were some variations, especially with regard to the forehead and top of the head (superior aspect), ranging from an asymmetrical distribution pattern to a lack of a clear thermal pattern. The thermal patterns in the left and right lateral thermograms in each individual were relatively symmetrical. During the rewarming period the helix, auricular lobule of the auricles and the nose were relatively cold. The frontal thermograms were characterized by cool nasal and cheek areas and a clear warm area surrounding the eyes, especially around the inner canthus.     

A field test for host fruit odour discrimination and avoidance behaviour for Rhagoletis pomonella flies in the western United States

Prezygotic isolation due to habitat choice is important to many models of speciation-with-gene-flow. Habitat choice is usually thought to occur through positive preferences of organisms for particular environments. However, avoidance of non-natal environments may also play a role in choice and have repercussions for post-zygotic isolation that preference does not. The recent host shift of Rhagoletis pomonella (Diptera: Tephritidae) from downy hawthorn, Crataegus mollis, to introduced apple, Malus domestica, in the eastern United States is a model for speciation-with-gene-flow. However, the fly is also present in the western United States where it was likely introduced via infested apples ≤ 60 years ago. R. pomonella now attacks two additional hawthorns in the west, the native C. douglasii (black hawthorn) and the introduced C. monogyna (English ornamental hawthorn). Flight tunnel tests have shown that western apple-, C. douglasii- and C. monogyna-origin flies all positively orient to fruit volatile blends of their respective natal hosts in flight tunnel assays. Here, we show that these laboratory differences translate to nature through field-trapping studies of flies in the state of Washington. Moreover, western R. pomonella display both positive orientation to their respective natal fruit volatiles and avoidance behaviour (negative orientation) to non-natal volatiles. Our results are consistent with the existence of behaviourally differentiated host races of R. pomonella in the west. In addition, the rapid evolution of avoidance behaviour appears to be a general phenomenon for R. pomonella during host shifts, as the eastern apple and downy hawthorn host races also are antagonized by non-natal fruit volatiles.     

Olfactory neuron responsiveness and pheromone blend preference in hybrids between Ostrinia furnacalis and Ostrinia nubilalis (Lepidoptera: Crambidae)

The olfactory receptor neuron (ORN) and behavioral responses of hybrids between the Asian corn borer (ACB), Ostrinia furnacalis, and the E-strain European corn borer (ECB(E)), Ostrinia nubilalis were examined and compared to the parental populations. In hybrids and both parents, the large-spike-size ORN was capable of responding to all four pheromone components of ACB and ECB, despite differences in which compounds elicited the greatest spike frequency in each population. There was a small-spiking ORN more narrowly tuned to the minor pheromone components in both ACB and ECB(E). In hybrids the homologous small-spiking ORN was tuned primarily to the ECB(E) minor pheromone component, with some responsiveness to the ACB minor component. Both species and all the hybrids had an intermediate spike-size ORN tuned primarily to their common behavioral antagonist. Dominance of responsiveness to the ECB(E) versus the ACB minor pheromone component on the small-spiking ORN may explain the greater tendency of hybrids to fly upwind to the ECB(E) pheromone blend than the ACB blend. This finding points toward a distinct evolutionary role for this ORN in allowing a pheromone shift.     

Independence and interdependence of Dif and Frz chemosensory pathways in Myxococcus xanthus chemotaxis

Dif and Frz, two Myxococcus xanthus chemosensory pathways, are required in phosphatidylethanolamine (PE) chemotaxis for excitation and adaptation respectively. DifA and FrzCD, the homologues of methyl-accepting chemoreceptors in the two pathways, were examined for methylation in the context of chemotaxis and inter-pathway interactions. Evidence indicates that DifA may not undergo methylation, but signals transmitting through DifA do modulate FrzCD methylation. Results also revealed that M. xanthus possesses Dif-dependent and Dif-independent PE-sensing mechanisms. Previous studies showed that FrzCD methylation is decreased by negative chemostimuli but increased by attractants such as PE. Results here demonstrate that the Dif-dependent sensory mechanism suppresses the increase in FrzCD methylation in attractant response and elevates FrzCD methylation upon negative stimulation. In other words, FrzCD methylation is governed by opposing forces from Dif-dependent and Dif-independent sensing mechanisms. We propose that the Dif-independent but Frz-dependent PE sensing leads to increases in FrzCD methylation and subsequent adaptation, while the Dif-dependent PE signalling suppresses or diminishes the increase in FrzCD methylation to decelerate or delay adaptation. We contend that these antagonistic interactions are crucial for effective chemotaxis in this gliding bacterium to ensure that adaptation does not occur too quickly relative to the slow speed of M. xanthus movement.     

DDB accumulates at DNA damage sites immediately after UV irradiation and directly stimulates nucleotide excision repair.

Damaged DNA-binding protein, DDB, is a heterodimer of p127 and p48 with a high specificity for binding to several types of DNA damage. Mutations in the p48 gene that cause the loss of DDB activity were found in a subset of xeroderma pigmentosum complementation group E (XP-E) patients and have linked to the deficiency in global genomic repair of cyclobutane pyrimidine dimers (CPDs) in these cells. Here we show that with a highly defined system of purified repair factors, DDB can greatly stimulate the excision reaction reconstituted with XPA, RPA, XPC.HR23B, TFIIH, XPF.ERCC1 and XPG, up to 17-fold for CPDs and approximately 2-fold for (6-4) photoproducts (6-4PPs), indicating that no additional factor is required for the stimulation by DDB. Transfection of the p48 cDNA into an SV40-transformed human cell line, WI38VA13, was found to enhance DDB activity and the in vivo removal of CPDs and 6-4PPs. Furthermore, the combined technique of recently developed micropore UV irradiation and immunostaining revealed that p48 (probably in the form of DDB heterodimer) accumulates at locally damaged DNA sites immediately after UV irradiation, and this accumulation is also observed in XP-A and XP-C cells expressing exogenous p48. These results suggest that DDB can rapidly translocate to the damaged DNA sites independent of functional XPA and XPC proteins and directly enhance the excision reaction by core repair factors.     

Vision and Eating Behavior

Objective: Eating behavior is influenced by internal and external factors. Vision is one part of the complex pattern of factors influencing the amount of food consumed during a meal. The aim of this study was to explore the impact of vision on the microstructure of eating behavior and the subjective motivation to eat. Research Methods and Procedures: Nine blind subjects and nine matched seeing control subjects consumed a standardized meal registered by VIKTOR, an eating monitor, measuring the microstructure of the eating behavior. The eating behavior of the control subjects was registered twice, with and without blindfold. Results: The eating behavior of the blind subjects did not differ from that of seeing control subjects. However, the eating behavior of seeing subjects eating with blindfold demonstrated a clear impact of vision on eating behavior. When blindfolded, subjects ate 22% less food (p < 0.05), had shorter meal durations (p < 0.05), and had less decelerated eating curves (p < 0.05). Despite a smaller amount of food consumed when blindfolded, the reported feeling of fullness was identical to that reported after the larger meal consumed without blindfold. Discussion: The importance of vision in regulating our eating behavior is further stressed in this study. Eating with a blindfold decreased the intake of food, without making subjects feel less full. Eating blindfolded, therefore, may force subjects to rely more on internal signals. These results might be used as an aid in the development of new treatment strategies for obese subjects.