The Toll/NF-κB pathway, first identified in studies of dorsal-ventral polarity in the early Drosophila embryo, is well known for its role in the innate immune response. Here, we reveal that the Toll/NF-κB pathway is essential for wound closure in late Drosophila embryos. Toll mutants and Dif dorsal (NF-κB) double mutants are unable to repair epidermal gaps. Dorsal is activated on wounding, and Dif and Dorsal are required for the sustained down-regulation of E-cadherin, an obligatory component of the adherens junctions (AJs), at the wound edge. This remodeling of the AJs promotes the assembly of an actin-myosin cable at the wound margin; contraction of the actin cable, in turn, closes the wound. In the absence of Toll or Dif and dorsal (dl), both E-cadherin down-regulation and actin-cable formation fail, thus resulting in open epidermal gaps. Given the conservation of the Toll/NF-κB pathway in mammals and the epithelial expression of many components of the pathway, this function in wound healing is likely to be conserved in vertebrates.

BACKGROUND

Patient-centered communication is a core competency in modern health care and associated with higher levels of patient satisfaction, improved patient health outcomes, and lower levels of burnout among physicians. The objective of the present study was to develop a questionnaire assessing medical student and physician self-efficacy in patient-centeredness (SEPCQ) and explore its psychometric properties.

METHODS

A preliminary 88-item questionnaire (SEPCQ-88) was developed based on a review of the literature and medical student portfolios and completed by 448 medical students from Aarhus University. Exploratory Principal Component analysis resulted in a 27-item version (SEPCQ-27) with three underlying self-efficacy factors: 1) Exploring the patient perspective, 2) Sharing information and power, and 3) Dealing with communicative challenges. The SEPCQ-27 was completed by an independent sample of 291 medical students from 2 medical schools and 101 hospital physicians.

RESULTS

Internal consistencies of total and subscales were acceptable for both students and physicians (Cronbach's alpha (range): 0.74-0.95). There were no overall indications of gender-related differential item function (DIF), and a Confirmatory Factor Analysis (CFA) indicated good fit (CFI = 0.98; NNFI = 0.98; RMSEA = 0.05; SRMR = 0.07). Responsiveness was indicated by increases in SEPCQ scores after a course in communication and peer-supervision (Cohen's d (range): 0.21 to 0.73; p: 0.053 to 0.001). Furthermore, positive associations were found between increases in SEPCQ-scores and course-related motivation to learn (medical students) and between SEPCQ scores and years of clinical experience (physicians).

CONCLUSIONS

The final SEPCQ-27 showed satisfactory psychometric properties, and preliminary support was found for its construct validity, indicating that the SEPCQ-27 may be a valuable measure in future patient centered communication training and research.

Our objective was to examine cross-cultural comparability of standard scales of the Effort-Reward Imbalance occupational stress scales by item response theory (IRT) analyses. Data were from 20,256 Japanese employees, 1464 Dutch nurses and nurses' aides, 2128 representative employees from post-communist countries, 963 Swedish representative employees, 421 Chinese female employees, 10,175 employees of the French national gas and electric company and 734 Spanish railroad employees, sanitary personnel and telephone operators. The IRT likelihood ratio model was used for differential item functioning (DIF) and differential test functioning (DTF) analyses. Despite the existence of DIF, most comparisons did not show discernible differences in the relations between Effort-Reward total score and level of the underlying trait across cultural groups. In the case that DTF was suspected, excluding an item with significant DIF improved the comparability. The full cross-cultural comparability of Effort-Reward Imbalance scores can be achieved with the help of IRT analysis.

Background: Cross-reactivity against human coronaviruses with Flebogamma^® DIF and Gamunex^®-C, two available intravenous immunoglobulins (IVIG), has been reported. In this study, these IVIG were tested for neutralization activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), SARS-CoV and Middle East respiratory syndrome CoV (MERS-CoV). Materials & methods: Neutralization capacity of lots of IVIG manufactured prior to COVID-19 pandemic was assessed against these viruses in cell culture. Infectivity neutralization was quantified by percent reduction in plaque-forming units and/or cytopathic/cytotoxic methods. Results: All IVIG preparations showed neutralization of SARS-CoV-2 isolates. All IVIG lots produced neutralization of SARS-CoV. No IVIG preparation showed significant neutralizing activity against MERS-CoV. Conclusion: The tested IVIG contain antibodies with significant in vitro cross-neutralization capacity against SARS-CoV-2 and SARS-CoV, but not MERS-CoV. These preparations are currently under evaluation as potential therapies for COVID-19.

Keywords: COVID-19; MERS-CoV; SARS-CoV; SARS-CoV-2; cross-neutralization; intravenous immunoglobulin.

Background and aims Research examining problematic mobile phone use has increased markedly over the past 5 years and has been related to "no mobile phone phobia" (so-called nomophobia). The 20-item Nomophobia Questionnaire (NMP-Q) is the only instrument that assesses nomophobia with an underlying theoretical structure and robust psychometric testing. This study aimed to confirm the construct validity of the Persian NMP-Q using Rasch and confirmatory factor analysis (CFA) models. Methods After ensuring the linguistic validity, Rasch models were used to examine the unidimensionality of each Persian NMP-Q factor among 3,216 Iranian adolescents and CFAs were used to confirm its four-factor structure. Differential item functioning (DIF) and multigroup CFA were used to examine whether males and females interpreted the NMP-Q similarly, including item content and NMP-Q structure. Results Each factor was unidimensional according to the Rach findings, and the four-factor structure was supported by CFA. Two items did not quite fit the Rasch models (Item 14: "I would be nervous because I could not know if someone had tried to get a hold of me;" Item 9: "If I could not check my smartphone for a while, I would feel a desire to check it"). No DIF items were found across gender and measurement invariance was supported in multigroup CFA across gender. Conclusions Due to the satisfactory psychometric properties, it is concluded that the Persian NMP-Q can be used to assess nomophobia among adolescents. Moreover, NMP-Q users may compare its scores between genders in the knowledge that there are no score differences contributed by different understandings of NMP-Q items.

OBJECTIVE

The pediatric patient-reported outcomes measurement information system (PROMIS) was developed to provide self-reported item banks and short forms for children and adolescents (aged 8-17 years) experiencing a chronic illness to assess their quality of life and symptoms. The pediatric PROMIS short forms have been translated into Chinese and applied in children with cancer in China. This study aimed to describe psychometric properties of the Anxiety and Depression measures.

METHODS

A total of 232 children and adolescents with cancer were recruited in hospital-based inpatient and outpatient clinics. Eight Chinese versions of pediatric PROMIS (C-Ped-PROMIS) measures were administered. Categorical confirmatory factor analysis (CCFA) were conducted to evaluate scale dimensionality and item local dependence of the C-Ped-PROMIS Anxiety and Depression items. Multiple indicator multiple cause models were used to analyze differential item functioning (DIF), item response theory parameters were calculated, and test information against T scores was reported for each measure.

RESULTS

The results of the CCFA confirmed that both C-Ped-PROMIS Anxiety and Depression scales appropriately measure the theoretical constructs as designed. No significant DIF was found for the items of the two scales according to age and gender. Both scales have high test reliability as long as their T scores are not on the low or high extremes.

CONCLUSIONS

The pediatric PROMIS Anxiety and Depression measures were developed to provide efficient and flexible assessment of emotional distress domains. Our results provide evidence that the two C-Ped-PROMIS measures can be readily applied to measure anxious and depressive symptoms in Chinese children with cancer.

To evaluate the reliability and validity of six PROMIS measures (anxiety, depression, fatigue, pain interference, physical function, and sleep disturbance) telephone-administered to a diverse, population-based cohort of localized prostate cancer patients.

Newly diagnosed men were enrolled in the North Carolina Prostate Cancer Comparative Effectiveness and Survivorship Study. PROMIS measures were telephone-administered pre-treatment (baseline), and at 3-months and 12-months post-treatment initiation (N = 778). Reliability was evaluated using Cronbach's alpha. Dimensionality was examined with bifactor models and explained common variance (ECV). Ordinal logistic regression models were used to detect potential differential item functioning (DIF) for key demographic groups. Convergent and discriminant validity were assessed by correlations with the legacy instruments Memorial Anxiety Scale for Prostate Cancer and SF-12v2. Known-groups validity was examined by age, race/ethnicity, comorbidity, and treatment.

Each PROMIS measure had high Cronbach's alpha values (0.86-0.96) and was sufficiently unidimensional. Floor effects were observed for anxiety, depression, and pain interference measures; ceiling effects were observed for physical function. No DIF was detected. Convergent validity was established with moderate to strong correlations between PROMIS and legacy measures (0.41-0.77) of similar constructs. Discriminant validity was demonstrated with weak correlations between measures of dissimilar domains (-0.20--0.31). PROMIS measures detected differences across age, race/ethnicity, and comorbidity groups; no differences were found by treatment.

This study provides support for the reliability and construct validity of six PROMIS measures in prostate cancer, as well as the utility of telephone administration for assessing HRQoL in low literacy and hard-to-reach populations.

The Hopkins Symptom Checklist (HSCL-10) is widely used for both clinical and epidemiological purposes to measure psychological distress among adolescents and adults.

The purpose of this study was to investigate the psychometric properties of the HSCL-10 among adolescents in Norway using Rasch analysis.

The study is based on cross-sectional data from the Norwegian Youth Health Surveys, conducted by the Norwegian Institute of Public Health in 2001 and 2009. The target group comprised of 15- to 16-year olds (Grade 10 students) in Hedmark County, Norway. Ten items with four response categories, intended to measure anxiety and depression, were analysed. The analysis focused on invariance, including differential item functioning (DIF) across genders and years of investigations. In addition, the categorization of the items, targeting, possible multidimensionality and response dependency, was analysed.

The HSCL-10 shows good reliability and on the whole, the items work well. However, one item, 'Sleeping difficulties', clearly misfit and some items work differently for boys and girls and between years of investigations. There is also need for a better targeting of the scale.

The HSCL-10 has the potential to measure the psychological distress among adolescents but there is a room for improvement. Further judgement needs to be made as to whether the misfitting item 'Sleeping difficulties' should be removed or retained.

OBJECTIVE

To assess the prognostic value of texture analysis for single hepatocellular carcinomas (HCCs) after hepatectomy.

METHODS

A total of 61 HCC patients were enrolled in this retrospective study. Textural characteristics of the computed tomography (CT) images were quantified. The differences between the hepatic arterial phase and the portal venous phase were obtained (the Dif.). The receiver operating characteristic (ROC) curves were used for data screening. Cox regression analyses were performed to determine independent factors adjusted with the derived clinical and radiological variables. Model identifications were based on Akaike information criteria. Kaplan-Meier and log-rank tests were performed for overall survival (OS) and disease-free survival (DFS).

RESULTS

ROC and Cox regression analyses identified five parameters. Filter 1.0 achieved the best performance, in which the Dif.Scale 1.2 was a superior indicative independent marker for OS (p=0.05). Kaplan-Meier analyses further demonstrated that the Dif.Scale2.2 at filter 0 (p=0.001), Dif.Scale1.2 (p=0.006), Dif.Scale3.2 (p=0.005) at filter 1.0, Dif.Wavelet 8 at filter 1.5 (p<0.001), and corona (p=0.032) were associated with OS. Moreover, Dif.Scale 2.2 at filter 0 (p=0.039), Dif.Scale1.2 at filter 1.0 (p=0.001), and Dif.Wavelet 8 at filter 1.5 (p=0.007) were associated with DFS, while the Barcelona-Clínic Liver Cancer (BCLC) parameters showed no statistical correlation with OS (p=0.057).

CONCLUSIONS

For patients with a single HCC treated by hepatectomy, the textural features for Gabor and Wavelet, especially the varying Dif., potentially provided prognostic information beyond traditional indicators such as those of the BCLC.

BACKGROUND

The NF-kappaB/Rel pathway functions in the establishment of dorsal-ventral polarity and in the innate humoral and cellular immune response in Drosophila. An important aspect of all NF-kappaB/Rel pathways is the translocation of the Rel proteins from the cytoplasm to the nucleus, where they function as transcription factors.

RESULTS

We have identified a new protein, Tamo, which binds to Drosophila Rel protein Dorsal, but not to Dorsal lacking the nuclear localization sequence. Tamo does not bind to the other Drosophila Rel proteins, Dif and Relish. The Tamo-Dorsal complex forms in the cytoplasm and Tamo also interacts with a cytoplasmically orientated nucleoporin. In addition Tamo binds the Ras family small GTPase, Ran. Tamo functions during oogenesis and, based on phenotypic analysis, controls the levels of nuclear Dorsal in early embryos. It further regulates the accumulation of Dorsal in the nucleus after immune challenge.

CONCLUSIONS

Tamo has an essential function during oogenesis. Tamo interacts with Dorsal and proteins that are part of the nuclear import machinery. We propose that tamo modulates the levels of import of Dorsal and other proteins.

Scores on the Boston Naming Test (BNT) are frequently lower for African American when compared with Caucasian adults. Although demographically based norms can mitigate the impact of this discrepancy on the likelihood of erroneous diagnostic impressions, a growing consensus suggests that group norms do not sufficiently address or advance our understanding of the underlying psychometric and sociocultural factors that lead to between-group score discrepancies. Using item response theory and methods to detect differential item functioning (DIF), the current investigation moves beyond comparisons of the summed total score to examine whether the conditional probability of responding correctly to individual BNT items differs between African American and Caucasian adults. Participants included 670 adults age 52 and older who took part in Mayo's Older Americans and Older African Americans Normative Studies. Under a two-parameter logistic item response theory framework and after correction for the false discovery rate, 12 items where shown to demonstrate DIF. Of these 12 items, 6 ("dominoes," "escalator," "muzzle," "latch," "tripod," and "palette") were also identified in additional analyses using hierarchical logistic regression models and represent the strongest evidence for race/ethnicity-based DIF. These findings afford a finer characterization of the psychometric properties of the BNT and expand our understanding of between-group performance.

Stalk cell differentiation in Dictyostelium can be induced by the differentiation-inducing factor, DIF, or by conditions that decrease intracellular pH (pHi). We have investigated whether cytoplasmic acidification acts directly to induce expression of pDd56 and pDd63, two DIF-regulated genes, specifically expressed in prestalk cells. The weak base methylamine, which increases pHi, inhibits DIF-induced transcription. The weak acid 5,5-dimethyl-2,4-oxazolidinedione (DMO), which decreases pHi, stimulates DIF-induction of the two prestalk genes. After relatively long incubation periods, DMO also induces a low level of prestalk gene expression in the absence of added DIF. However, unlike DIF-mediated induction, the apparent DMO-mediated induction decreases to undetectable levels when the cell density is reduced from 10(7) to 10(5) cells/ml. This indicates that DMO does not itself induce gene expression, but acts to enhance the effects of an autonomously secreted stalk-inducing factor, presumably DIF. These results suggest that the effects of DIF on gene expression are regulated by intracellular pH, but do not support a role for protons as direct intermediates in the DIF signal transduction pathway.

DIF (differentiation-inducing factor) is a putative morphogen that induces stalk cell differentiation in the lower eukaryote, Dictyostelium discoideum. In this study, we have examined the effects of DIF on growth and the intracellular calcium concentration ([Ca2+]i) in rat pancreatic acinar AR42J cells. Growth of AR42J cells was inhibited when DIF was present in the media, and approximately 50% growth inhibition was attained with 20 microM DIF. DIF was also found to raise [Ca2+]i in a dose-dependent manner (1-40 microM), both in the presence and absence of extracellular Ca2+. These results suggest that DIF elicits both calcium influx from the extracellular space and calcium release from intracellular pool(s), thereby inhibiting cell growth in AR42J.

Xer site-specific recombination at the Escherichia coli chromosomal site dif converts chromosomal dimers to monomers, thereby allowing chromosome segregation during cell division. dif is located in the replication terminus region and binds the E. coli site-specific recombinases EcoXerC and EcoXerD. The Haemophilus influenzae Xer homologues, HinXerC and HinXerD, bind E. coli dif and exchange strands of dif Holliday junctions in vitro. Supercoiled dif sites are not recombined by EcoXerC and EcoXerD in vitro, possibly as a consequence of a regulatory process, which ensures that in vivo recombination at dif is confined to cells that can initiate cell division and contain dimeric chromosomes. In contrast, the combined action of HinXerC and EcoXerD supports in vitro recombination between supercoiled dif sites, thereby overcoming the barrier to dif recombination exhibited by EcoXerC and EcoXerD. The recombination products are catenated and knotted molecules, consistent with recombination occurring with synaptic complexes that have entrapped variable numbers of negative supercoils. Use of catalytically inactive recombinases provides support for a recombination pathway in which HinXerC-mediated strand exchange between directly repeated duplex dif sites generates a Holliday junction intermediate that is resolved by EcoXerD to catenated products. These can undergo a second recombination reaction to generate odd-noded knots.

Removal of a G-rich element from the DIF-inducible, prestalk-, and stalk-specific ecmB gene reduces expression but cell-type specificity is retained. The ecmB element will functionally substitute for a homologous sequence upstream of CP2, a cAMP-inducible gene and is bound by GBF, the factor which interacts with the CP2 G box. These results suggest that the G box may play a similar stimulatory role in these two independently regulated genes where it presumably interacts with different ancillary promoter elements.

We show that pDd56 and pDd63, two related DIF-inducible genes of Dictyostelium, respectively encode the ST310 and ST430 polypeptides identified by Morrissey, Devine, and Loomis (1984, Dev. Biol. 103, 414-424). We localize the two proteins by immunoelectron microscopy to the extracellular matrix surrounding the stalk cells and the stalk tube. Coupled with their predicted amino acid sequence and biochemical properties, this suggests that they are structural proteins of the stalk.

We propose that the prestalk/prespore pattern in Dictyostelium is generated in two steps: In a first process, an intermingled, non-position dependent prestalk/prespore pattern is generated by a cell-restricted autocatalysis and the antagonistic action of a long-ranging substrate which becomes depleted during this autocatalysis. By computer simulations we show that the assumed interaction accounts for several experimentally observed features of the prestalk/prespore pattern: The size-independent ratio of both cell types, the pattern regulation after removal of one cell type, the development towards one or the other pathway before the slug obtains its final shape or even before aggregation is completed. Our hypothetical substrate may be identical with an experimentally found differentiation-inducing factor (DIF). Alternative molecular realizations of the basic mechanism are discussed. A second process leads to the aggregation of the prestalk cells in a particular region of the aggregate, the future tip region. Interactions which enable tip formation and the coupling between the prestalk/prespore and the tip-forming system are discussed. Our model shows that the formation of a single large patch of differentiated cells and its size regulation requires conflicting parameters. By a separation into a mechanism which determines the position and a second one which determines the size of a structure, each mechanism can be optimized individually without requiring compromises for the other. Such a separation also seems to occur in other developmental systems.

A direct immunofluorescence (DIF) technique (Imagen) and two enzyme immunoassay (EIA) techniques (Chlamydiazyme and IDEIA) were compared for the detection of Chlamydia trachomatis in genital specimens from 502 attenders at a genitourinary medicine clinic. Eighty-two attenders were regarded as infected: 67 with positive results by at least two of the three techniques and 15 by virtue of elementary bodies detected in stored EIA buffer samples. With a positivity criterion of greater than or equal to 6 bodies Imagen was 76% sensitive for men and 61% sensitive for women. The sensitivity of Chlamydiazyme was 73% for men and 90% for women; comparative values for IDEIA were 80% and 71%, respectively. All three techniques were over 98% specific. Sampling order appeared to influence the sensitivity of IDEIA for specimens from men. All three techniques were less sensitive in the absence of cervicitis. The performances of the EIA techniques compared favourably with that of the more established technique of DIF.

BACKGROUND

The flow of information within cellular pathways largely relies on specific protein-protein interactions. Discovering such interactions that are mostly mediated by peptide recognition modules (PRM) is therefore a fundamental step towards unravelling the complexity of varying pathways. Since peptides can be recognized by more than one PRM and high-throughput experiments are both time consuming and expensive, it would be preferable to narrow down all potential peptide ligands for one specific PRM by a computational method. We at first present Domain Interaction Footprint (DIF) a new approach to predict binding peptides to PRMs merely based on the sequence of the peptides. Second, we show that our method is able to create a multi-classification model that assesses the binding specificity of a given peptide to all examined PRMs at once.

RESULTS

We first applied our approach to a previously investigated dataset of different SH3 domains and predicted their appropriate peptide ligands with an exceptionally high accuracy. This result outperforms all recent methods trained on the same dataset. Furthermore, we used our technique to build two multi-classification models (SH3 and PDZ domains) to predict the interaction preference between a peptide and every single domain in the corresponding domain family at once. Predicting the domain specificity most reliably, our proposed approach can be seen as a first step towards a complete multi-domain classification model comprised of all domains of one family. Such a comprehensive domain specificity model would benefit the quest for highly specific peptide ligands interacting solely with the domain of choice.

BACKGROUND

Supplementary data are available at Bioinformatics online.

The aim of this study was to compare tidal volume (VT) derived from the Qualitative Diagnostic Calibration (QDC) method (VT,QDC) with measurements from pneumotachography (VT,PN,T) in anaesthetized infants. Measurements were made during spontaneous (SV) and intermittent positive pressure (IPPV) ventilation, sighs and airway occlusions. The VT,DIF was the difference between VT,QDC and VT,PNT (%VT). The contribution of the ribcage (rc) to VT,QDC (%rc) and the thoracoabdominal phase lag were also derived. Twenty-eight infants, mean (SD) age 14.0 (6.2) months were studied. VT,QDC represented VT,PNT most closely when>> or = 20 breaths were analysed. There was close agreement during SV immediately after the calibration period (95% limits of agreement (LA; QDC - PNT) -23, 3.0%). The 95% LA increased to -9.6, 10.2% after 10 min. Accuracy diminished during IPPV (95% LA -38, 31%), and sighs. During airway occlusions, when VT,PNT was zero, the 95% LA were -63, 4.1 mL x kg(-1). Mean phase lag was 36 and 2%, respectively, during SV and IPPV (p<0.05). The %rc appeared to be overestimated, being in excess of 50% in infants under 12 months. The Qualitative Diagnostic Calibration method used to estimate tidal volume in anaesthetized infants was limited by the need to analyse>> or = 20 breaths and by a loss of within-subject accuracy if measurement conditions or pattern of breathing changed.

BACKGROUND

Diabetes is a serious chronic illness that disproportionately affects prevalence and comorbidity rates among Hispanic populations. Little comparative research has been conducted on the emotional distress experienced by Hispanic patients living with type 2 diabetes.

OBJECTIVE

[corrected] To conduct a psychometric examination of an established measure of emotional distress specific to diabetes and to use this tool to examine levels and predictors of distress in a comparative study of Hispanic and non-Hispanic type 2 diabetes patients.

METHODS

Psychometric analyses were conducted (skewness, kurtosis, differential item function (DIF), confirmatory factor analysis (CFA), internal consistency reliability) to examine the equivalence of U.S. English and U.S. Spanish language versions of a measure of diabetes-related distress (Problem Areas in Diabetes (PAID). Regression modeling was used to evaluate differences in distress by ethnic group, after adjusting for blood glucose control, sex, age, education, physical functioning, mental health functioning, and spirituality. Psychometric results showed that PAID had high reliability (alpha = 0.96). Skewness, kurtosis, and DIF were not present. CFA identified a large general factor, supporting use of the total PAID score. Univariate analyses found a significantly higher mean PAID score for Hispanic patients compared to non-Hispanic (45.9 +/- 28.5 vs. 35.9 +/- 26.4). A final regression model based on age, physical functioning, and mental functioning accounted for approximately 50% of PAID variance.

CONCLUSIONS

Our findings supported the reliability and unidimensionality of the U.S. Spanish and U.S. English PAID versions for comparative research. Compared to non-Hispanic patients, Hispanic patients reported higher distress, which was substantially predicted from age and physical and mental functioning.

We previously described a new variant of endemic pemphigus foliaceus in El Bagre, Colombia, South America (El Bagre-EPF). On physical examination, the palms and soles of El Bagre-EPF patients reveal an edematous texture and mild hyperkeratosis, in comparison with the non-glabrous skin of the patients where blisters, pustules or other lesions are commonly found. Based on the preceding observation, we tested the palms of 20 El Bagre-EPF cases and 20 controls from the endemic area for any pathological alterations in the samples by direct immunofluorescence (DIF). Our DIF demonstrated pathological deposits of fibrinogen and albumin, as well as IgG, IgA, IgM, IgD and C3c, at 1) the epidermal basement membrane zone; 2) around isolated areas in the epidermis, 3) within the dermal vessels and nerves, and 4) in areas surrounding dermal neurovascular structures and sweat glands. Specific markers for blood vessels, including 1) anti-intercellular adhesion molecule 1 (ICAM-1)/CD54, and 2) anti-junctional adhesion molecule (JAM-A); as well as specific markers for nerves, including 1) anti-glial fibrillary acidic protein (GFAP), and 2) anti-human neuron specific enolase (NSE) co-localized with the patients' autoantibodies. Although no blisters, ulcerations, pustules or erosions are clinically observed on the palms of El Bagre-EPF patients, our DIF detected distinct immunoreactivity in palm tissue. These alterations may contribute to the clinically edematous texture of the palms and the mild clinical hyperkeratosis found in most of these patients. We propose that normal glabrous skin and non-glabrous skin may be different with regard to the expression of selected molecules, which may vary in number, size or structural organization depending on their anatomical site. Our findings may also partially explain the hyperkeratotic palms that have been clinically well documented in the chronic phase of fogo selvagem i.e., endemic pemphigus foliaceus, in Brazil.

The mature fruiting body of Dictyostelium consists of stalk and spore cells but its construction, and the migration of the preceding slug stage, requires a number of specialized sub-types of prestalk cell whose nature and function are not well understood. The prototypic prestalk-specific gene, ecmA, is inducible by the polyketide DIF-1 in a monolayer assay and requires the DimB and MybE transcription factors for full inducibility. We perform genome-wide microarray analyses, on parental, mybE- and dimB- cells, and identify many additional genes that depend on MybE and DimB for their DIF-1 inducibility. Surprisingly, an even larger number of genes are only DIF inducible in mybE- cells, some genes are only inducible in DimB- cells and some are inducible when either transcription factor is absent. Thus in assay conditions where MybE and DimB function as inducers of ecmA these genes fall under negative control by the same two transcription factors. We have studied in detail rtaA, one of the MybE and DimB repressed genes. One especially enigmatic group of prestalk cells is the anterior-like cells (ALCs), which exist intermingled with prespore cells in the slug. A promoter fusion reporter gene, rtaA:gal(u), is expressed in a subset of the ALCs that is distinct from the ALC population detected by a reporter construct containing ecmA and ecmB promoter fragments. At culmination, when the ALC sort out from the prespore cells and differentiate to form three ancillary stalk cell structures: the upper cup, the lower cup and the outer basal disk, the rtaA:gal(u) expressing cells preferentially populate the upper cup region. This fact, and their virtual absence from the anterior and posterior regions of the slug, identifies them as a new prestalk sub-type: the pstU cells. PstU cell differentiation is, as expected, increased in a dimB- mutant during normal development but, surprisingly, they differentiate normally in a mutant lacking DIF. Thus genetic removal of MybE or DimB reveals an alternate DIF-1 activation pathway, for pstU differentiation, that functions under monolayer assay conditions but that is not essential during multicellular development.