Online behavioural patterns for Coronavirus disease 2019 (COVID-19) in the United Kingdom.

The current coronavirus (COVID-19) pandemic offers a unique opportunity to conduct an infodemiological study examining patterns in online searching activity about a specific disease and how this relates to news media within a specific country. Google Trends quantifies volumes of online activity. The relative search volume was obtained for 'Coronavirus', 'handwashing', 'face mask' and symptom related keywords, for the United Kingdom, from the date of the first confirmed case until numbers peaked in April. The relationship between online search traffic and confirmed case numbers was examined. Search volumes varied over time; peaks appear related to events in the progression of the epidemic which were reported in the media. Search activity on 'Coronavirus' correlated well against confirmed case number as did 'face mask' and symptom-related keywords. User-generated online data sources such as Google Trends may aid disease surveillance, being more responsive to changes in disease occurrence than traditional disease reporting. The relationship between media coverage and online searching activity is rarely examined, but may be driving online behavioural patterns.

Cognition and cerebrovascular function in primary hyperparathyroidism before and after parathyroidectomy.

PURPOSE: There are cognitive changes in primary hyperparathyroidism (PHPT) that improve with parathyroidectomy, but the mechanism of cognitive dysfunction has not been delineated. We assessed if cerebrovascular function is impaired in PHPT, improves post-parathyroidectomy and is associated with PTH level and cognitive dysfunction. METHODS: This is an observational study of 43 patients with mild hypercalcemic or normocalcemic PHPT or goiter. At baseline, cerebrovascular function (dynamic cerebral autoregulation and vasomotor reactivity) by transcranial Doppler and neuropsychological function were compared between all three groups. A subset underwent parathyroidectomy or thyroidectomy, and was compared 6 months post-operatively. RESULTS: Mean cerebrovascular and neuropsychological function was normal and no worse in PHPT compared to controls preoperatively. Higher PTH was associated with worse intracerebral autoregulation (r = - 0.43, p = 0.02) and worse cognitive performance on some tests. Post-parathyroidectomy, mood improved significantly, but changes did not differ compared to those having thyroidectomy (p = 0.84). There was no consistent improvement in cognition or change in vascular function in either surgical group. CONCLUSIONS: Although higher PTH was associated with worse intracerebral autoregulation, cerebrovascular function, cognition and mood were normal in mild PHPT. PTX did not improve vascular or cognitive function. The observed improvement in mood cannot be clearly attributed to PTX. Notwithstanding the small sample size, the results do not support changing current criteria for parathyroidectomy to include cognitive complaints. However, the associations between PTH, cognition and cerebral autoregulation merit future studies in those with more severe hyperparathyroidism.

Biochemical markers of bone turnover and risk of incident hip fracture in older women: the Cardiovascular Health Study.

The relationships of osteocalcin (OC) and C-telopeptide of type I collagen (CTX) with long-term incidence of hip fracture were examined in 1680 post-menopausal women from a population-based study. CTX, but not OC, levels were associated with incident hip fracture in these participants, a relationship characterized by an inverted U-shape. INTRODUCTION: We sought to investigate the relationships of OC, a marker of bone formation, and CTX, a marker of bone resorption, with long-term incidence of hip fracture in older women. METHODS: We included 1680 women from the population-based Cardiovascular Health Study (mean [SD] age 74.5 [5.0] years). The longitudinal association of both markers with incidence of hip fracture was examined using multivariable Cox models. RESULTS: During a median follow-up of 12.3 years, 288 incident hip fractures occurred. Linear spline analysis did not demonstrate an association between OC levels and incident hip fracture. By contrast, increasing levels of CTX up to the middle-upper range were associated with a significantly greater risk of hip fracture (HR = 1.52 per SD increment, 95% CI = 1.10-2.09), while further increases were associated with a marginally non-significant lower risk (HR = 0.80 per SD increment, 95% CI = 0.63-1.01), after full adjustment for potential confounders. In analyses of quartiles, CTX exhibited a similar inverted U-shaped relationship with incident fracture after adjustment, with a significant association observed only for the comparison of quartile 3 to quartile 1 (HR = 1.63, 95% CI = 1.10-2.43). In a subset with available measures, both OC and CTX were inversely associated with bone mineral density of the hip. CONCLUSION: CTX, but not OC, levels were associated with incident hip fracture in post-menopausal women, a relationship characterized by an inverted U-shape. These findings highlight the complex relationship of bone turnover markers with hip fracture risk.

Correction to: Differences in bone quality and strength between Asian and Caucasian young men.

The second name of the ninth author, X.E. Guo, was incorrectly coded as part of his surname. The publisher apologises for the inconvenience caused.

Cortical microstructure compensates for smaller bone size in young Caribbean Hispanic versus non-Hispanic white men.

Hispanic men have smaller bone size but thicker and denser cortices compared to white men, leading to similar mechanical competence. INTRODUCTION: The purpose of this study was to assess differences in vBMD and microarchitecture in young Caribbean Hispanic (n = 30) and non-Hispanic Caucasian (n = 30) men. METHODS: We measured areal bone mineral density (aBMD) at the spine, total hip (TH), femoral neck (FN), and forearm by dual-energy X-ray absorptiometry (DXA) and bone geometry, mass, microarchitecture, and mechanical competence by high-resolution peripheral quantitative computed tomography (HRpQCT), individual trabecula segmentation (ITS), and finite element analysis (FEA). RESULTS: Hispanic men were slightly older, shorter, and heavier and had higher BMI compared with white men. aBMD, measured by DXA, did not differ at the spine, TH, or forearm before or after adjustment for age, height, weight, and the interaction of height and weight. At the FN, marginally significant higher BMD in Hispanics prior to adjustment was attenuated and no longer differed after adjustment for covariates. Adjusted HRpQCT indices indicated smaller total and trabecular area at the radius but greater total volumetric density and cortical thickness in Hispanic versus white men. The adjusted difference in cortical density at the radius was of borderline significance. Trabecular and ITS microstructure tended not to differ at the radius. At the tibia, results were similar. Bone size tended to be smaller and covariate-adjusted cortical density and cortical thickness were greater in Hispanic versus white men. Additionally, cortical porosity was lower at the tibia in Hispanic compared to white men. Stiffness and failure load did not differ at either skeletal site by ethnicity. CONCLUSION: In conclusion, greater cortical thickness and density as well as lower cortical porosity tend to compensate for smaller bone size in Hispanic men, leading to similar mechanical competence compared with white men.

Differences in bone quality and strength between Asian and Caucasian young men.

This is a cross-sectional study to assess differences in bone quality in young Asian and Caucasian (n = 30/group) men between 25 and 35 years. We found that Asians had smaller bones, thicker and denser cortices, and more plate-like trabeculae, but stiffness did not differ between groups. INTRODUCTION: We conducted a cross-sectional study to assess differences in bone quality in young Asian and Caucasian (n = 30/group) men between 25 and 35 years. METHODS: We measured bone mineral density (BMD) at the spine, total hip (TH), femoral neck (FN), and forearm by dual energy X-ray absorptiometry (DXA), and bone geometry, density, microarchitecture, and mechanical competence at the radius and tibia by high-resolution peripheral quantitative computed tomography (HR-pQCT) with application of individual trabecula segmentation (ITS) and trabecular and whole bone finite element analysis (FEA). We measured load-to-strength ratio to account for differences in bone size and height, respectively. We used Wilcoxon rank sum and generalized linear models adjusted for height, weight, and their interaction for comparisons. RESULTS: Asians were 3.9 % shorter and weighed 6.5 % less than Caucasians. In adjusted models: by DXA, there were no significant race-based differences in areal BMD; by HR-pQCT, at the radius, Asians had smaller total and trabecular area (p = 0.003 for both), and denser (p = 0.01) and thicker (p = 0.04) cortices at the radius; by ITS, at the radius Asians, had more plate-like than rod-like trabeculae (PR ratio p = 0.01), greater plate trabecular surface (p = 0.009) and longer rod length (p = 0.002). There were no significant race-based differences in FEA or the load-to-strength ratio. CONCLUSIONS: Asians had smaller bones, thicker and denser cortices, and more plate-like trabeculae, but biomechanical estimates of bone strength did not differ between groups. Studies are needed to determine whether these differences persist later in life.

Effect of concomitant vitamin D deficiency or insufficiency on lumbar spine volumetric bone mineral density and trabecular bone score in primary hyperparathyroidism.

UNLABELLED: Lower vitamin D and higher parathyroid hormone (PTH) levels are associated with higher volumetric BMD and bone strength at the lumbar spine as measured by central quantitative computed tomography in primary hyperparathyroidism (PHPT), but there are no differences in bone microarchitecture as measured by trabecular bone score (TBS). INTRODUCTION: The purpose of this study was to evaluate the association between 25-hydroxyvitamin D (25OHD) and volumetric bone mineral density (vBMD) and the TBS at the lumbar spine (LS) in PHPT. METHODS: This is a cross-sectional analysis of PHPT patients with and without low 25OHD. We measured vBMD with quantitative computed tomography (cQCT) and TBS by dual-energy X-ray absorptiometry (DXA) at the LS in 52 and 88 participants, respectively. RESULTS: In the cQCT cohort, those with lower vitamin D (<20 vs. 20-29 vs. ≥30 ng/ml) tended to be younger (p = 0.05), were less likely to use vitamin D supplementation (p < 0.01), and had better renal function (p = 0.03). Those with 25OHD <20 ng/ml had 80 and 126 % higher serum PTH levels respectively vs. those with 25OHD 20-29 ng/ml (p = 0.002) and 25OHD ≥30 ng/ml (p < 0.0001). Covariate-adjusted integral and trabecular vBMD were higher in those with 25OHD 20-29 vs. those with 25OHD ≥30 ng/ml, but those with 25OHD <20 did not differ. Because there were few participants with 25OHD deficiency, we also compared those with vitamin D <30 vs. ≥30 ng/ml. Covariate-adjusted integral and trabecular vBMD were 23 and 30 % higher respectively (both p < 0.05) in those with vitamin D <30 vs. ≥30 ng/ml. TBS was in the partially degraded range but did not differ by vitamin D status. CONCLUSION: In mild PHPT, lower 25OHD is associated with higher PTH, but vitamin D deficiency and insufficiency using current clinical thresholds did not adversely affect lumbar spine skeletal health in PHPT. Further work is needed to determine if higher vBMD in those with lower vitamin D is due to an anabolic effect of PTH.

Low vitamin D levels have become less common in primary hyperparathyroidism.

UNLABELLED: We compared temporal trends in serum 25-hydroxyvitamin D and parathyroid hormone (PTH) in two primary hyperparathyroidism (PHPT) cohorts recruited 20 years apart. The prevalence of 25-hydroxyvitamin D levels <20 and <30 ng/mL declined by 30-50 %, respectively, and was accompanied by lower PTH. In the older cohort, higher PTH may be due to lower 25-hydroxyvitamin D. INTRODUCTION: Vitamin D deficiency may exacerbate PHPT. Whether there have been temporal trends in 25-hydroxyvitamin D (25OHD) levels in PHPT is unclear. The prevalence of low vitamin D levels (25OHD <20 and <30 ng/mL) and associated biochemical and bone mineral density (BMD) profiles were assessed in two PHPT cohorts recruited over 20 years apart. METHODS: This is a cross-sectional comparison of serum 25OHD levels, calciotropic hormones, and BMD between two PHPT cohorts recruited at the same hospital: the "old" (N = 103) and "new" (N = 100) cohorts were enrolled between 1984 and 1991 and between 2010 and 2014, respectively. RESULTS: Mean 25OHD levels were 26 % higher in the new cohort (23 ± 10 vs. 29 ± 10 ng/mL, p < 0.0001). Levels of 25OHD <20 and <30 ng/mL declined from 46 and 82 %, respectively, to 19 and 54 % (both p < 0.0001). Supplemental vitamin D use was common in the new (64 %) but not the old cohort (0 %). The new cohort demonstrated 33 % lower serum PTH levels (p < 0.0001). Neither serum nor urine calcium differed. BMD was higher in the new cohort at all skeletal sites (all p < 0.001). CONCLUSION: With the rise in vitamin D supplementation over the last two decades, low 25OHD levels are no longer common in PHPT patients in the New York area. Those with 25OHD <20 and <30 ng/mL have declined by over 50 and 30 %, respectively. The lower mean PTH levels in the new cohort are most likely accounted for by higher vitamin D intake. Whether improved vitamin D status also underlies the relatively higher BMD in the more vitamin D replete cohort of PHPT patients is unknown.

A trabecular plate-like phenotype is overrepresented in Chinese-American versus Caucasian women.

UNLABELLED: This study used extreme phenotype selection to define two trabecular bone phenotypes in a cohort of Chinese-American and Caucasian women. A trabecular plate-predominant phenotype is more common in Chinese-Americans while the rod-predominant phenotype is more typical of Caucasians. The robustness of these phenotypic associations with respect to lifestyle factors suggests that this trait may have a genetic basis and that these phenotypes can be utilized in future genetic studies. INTRODUCTION: Compared to Caucasians, Chinese-Americans have more plate-like trabecular bone when measured by individual trabecula segmentation (ITS). These findings suggest a phenotypic difference between the races, which may be amenable to genetic analysis. We sought to identify a single ITS plate trait to pursue in genetic studies by conducting an extreme phenotype selection strategy to numerically define two distinct phenotypes-plate-like and rod-like-and determine whether the selected phenotypic associations were independent of lifestyle factors in order to conduct future genetic studies. METHODS: A previously described cohort of 146 Chinese-American and Caucasian women with high-resolution peripheral quantitative computed tomography imaging and ITS analyses were studied with logistic regression and receiver operator characteristic analyses. RESULTS: The tibial plate-to-rod (TPR) ratio was the best ITS discriminator of race. Using extreme phenotypic selection, two TPR ratio phenotypes were defined numerically: plate-like as a TPR ratio value in the highest quartile (≥1.336) and rod-like as a TPR ratio value in the lowest quartile (≤0.621). Women with a plate-like phenotype were 25.7 times more likely (95 % CI 7.3-90.1) to be Chinese-American than women with rod-like morphology. After controlling for constitutional and lifestyle covariates, women in the highest vs. lowest TPR ratio quartile were 85.0 times more likely (95 % CI 12.7-568.0) to be Chinese-American. CONCLUSION: Using extreme phenotype selection, we defined a plate- and rod-like trabecular bone phenotype for the TPR ratio trait. The former phenotype is more common in Chinese-American women, while the latter is more typical of Caucasian women. The robustness of these phenotypic associations after controlling for differences in constitution and lifestyle suggest that the TPR ratio may have a genetic basis and that the extreme phenotypes defined in this analysis can be utilized for future studies.

Endothelial function in mild primary hyperparathyroidism.

BACKGROUND: It is not known if endothelial dysfunction, an important early event in the pathogenesis of atherosclerosis, is present in mild primary hyperparathyroidism (PHPT) and if so, whether it improves following parathyroidectomy. DESIGN: We measured flow-mediated vasodilation (FMD), which estimates endothelial function by ultrasound imaging, in patients prior to and 6 and 12 months after parathyroidectomy. RESULTS: Forty-five patients with mild PHPT [80% female, 61 ± 1 (mean ± SE) years, serum calcium 2·65 ± 0·03 mm (10·6 ± 0·1 mg/dl), PTH 10·5 ± 0·7 pm (99 ± 7 pg/ml), 25-hydroxyvitamin D (25OHD) 70·3 ± 3·7 nm (28·2 ± 1·5 ng/ml)] were studied. Baseline FMD was normal (4·63 ± 0·51%; reference mean: 4·4 ± 0·1%) and was not associated with serum calcium, PTH or 25OHD levels. In the group as a whole, FMD did not change after surgery (6 months: 4·38 ± 0·83%, P = 0·72; 12 months: 5·07 ± 0·74%, P = 0·49). However, in those with abnormal baseline FMD (<2·2%; n = 15), FMD increased by 350%, normalizing by 6 months after surgery (baseline: 0·81± 0·19%; 6 months: 3·18 ± 0·79%, P = 0·02 vs baseline; 12months: 3·68 ± 1·22%, P = 0·04 vs baseline). Baseline calcium, PTH and 25OHD levels did not differ between those with abnormal vs normal FMD, nor did these indices predict postoperative change in FMD. CONCLUSIONS: FMD is generally normal in patients with mild PHPT and is unchanged 1 year after parathyroidectomy. Although FMD may normalize after surgery in patients with baseline abnormalities, data do not support using endothelial dysfunction as an indicator for parathyroidectomy.

Volumetric bone mineral density at the spine and hip in Chinese American and White women.

UNLABELLED: This study evaluated racial differences in bone size and volumetric density at the spine and hip in pre- and postmenopausal Chinese American and White women. Compared with White women, Chinese American women have greater cortical volumetric bone density (vBMD) at the hip, congruent with the results at the peripheral skeleton. INTRODUCTION: Chinese American women have lower rates of fracture than White women despite lower areal bone density. At the forearm and tibia, however, Chinese American women have higher cortical vBMD as well as greater trabecular and cortical thickness, but smaller bone area as measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) compared with White women. Since HR-pQCT data are obtained at peripheral sites, it is unclear whether these differences are relevant to the clinically important lumbar spine and hip. This study assesses racial differences in bone size and vBMD at the spine and hip in Chinese American and White women. METHODS: QCT of the spine and hip was measured to assess racial differences in bone size, structure, and vBMD in pre- (n = 83) and postmenopausal (n = 50) Chinese American and White women. Data were adjusted for weight, height, physical activity, total calcium intake, parathyroid hormone, and 25-hydroxyvitamin D levels. RESULTS: Among premenopausal women, lumbar spine trabecular vBMD was 5.8% greater in Chinese American versus White women (p = 0.01). At the hip, cortical vBMD was 3% greater at the femoral neck (p = 0.05) and 3.6% greater at the total hip (p = 0.01) in premenopausal Chinese American compared with White women. Among postmenopausal women, there was no difference in lumbar spine trabecular vBMD. Cortical vBMD was 4% greater at the total hip (p = 0.02) and tended to be greater at the femoral neck (p = 0.058) in Chinese American versus White women. CONCLUSIONS: Consistent with earlier findings in the peripheral skeleton, cortical vBMD is greater at the hip in Chinese American versus White women.

Characteristics of Crataerina pallida (Diptera: Hippoboscidae) populations; a nest ectoparasite of the common swift, Apus apus (Aves: Apodidae).

An essential pre-requisite to understanding the nature of a host-parasite relationship is a good knowledge of the parasite's ecology, including its life history. Despite removing a significant amount of blood from their common swift (Apus apus) hosts, no detrimental effect of parasitism by the louse fly (Crataerina pallida) has been found. This may be because little is known of the characteristics of the populations of this parasite. We studied the structure of louse fly populations that may influence its pathogenicity. High levels of prevalence were seen, with 100% of nests being parasitized during 2007 and 2008. Louse fly pupae were found to be aggregated, with a frequency distribution best described by the negative binomial model in 2006-2008. The mean parasitic load per nest was 3.72±2.65 in 2007 and 4.21±3.09 in 2008, much higher than that found in comparative studies. Louse fly numbers declined throughout the swift breeding season. Parasite populations were heavily female biased, except for at the initial and final stages of the nestling period.

Cell-specific expression of the rat insulin gene: evidence for role of two distinct 5' flanking elements.

The 5' flanking DNA of the rat insulin I gene contains sequences controlling cell-specific expression. Analysis of this region by replacement of specific portions with nondiscriminatory control elements from viral systems shows that a transcriptional enhancer is located in the distal portion of the 5' flanking DNA; its position has been mapped by deletion analysis. Additional experiments suggest that another distinct regulatory element is located more proximal to the transcription start site. The activity of both elements is restricted to pancreatic B cells. The combinatorial effect of multiple control elements could explain the cell-specific expression of insulin genes.

Cumulative impacts of oil fields on northern alaskan landscapes.

Proposed further developments on Alaska's Arctic Coastal Plain raise questions about cumulative effects on arctic tundra ecosystems of development of multiple large oil fields. Maps of historical changes to the Prudhoe Bay Oil Field show indirect impacts can lag behind planned developments by many years and the total area eventually disturbed can greatly exceed the planned area of construction. For example, in the wettest parts of the oil field (flat thaw-lake plains), flooding and thermokarst covered more than twice the area directly affected by roads and other construction activities. Protecting critical wildlife habitat is the central issue for cumulative impact analysis in northern Alaska. Comprehensive landscape planning with the use of geographic information system technology and detailed geobotanical maps can help identify and protect areas of high wildlife use.

Cardiovascular aspects of primary hyperparathyroidism.

Data concerning the cardiovascular manifestations of primary hyperparathyroidism (PHPT) are inconsistent, which is due, in part, to the decrease in disease severity over the last several decades. In areas where patients tend to be more symptomatic, data support the presence of cardiovascular findings including myocardial and vascular calcification as well as increased cardiovascular mortality. Data from the cohorts in whom the disease is characterized by mild hypercalcemia, suggest that clinically overt cardiovascular manifestations are unusual in PHPT. Recent data, however, support the presence of subtle cardiovascular manifestations in mild disease, such as changes in endothelial function as well as increased vascular stiffness and perhaps diastolic dysfunction. Left ventricular hypertrophy is a more consistent finding across a spectrum of disease severity, though this finding may be related to hypertension, which has long been associated with PHPT.

Non classical complications of primary hyperparathyroidism.

Several studies suggested that the condition of primary hyperparathyroidism (PHPT) may be associated not only with the classical bone, kidney and gastrointestinal consequences, but also with cardiovascular, neuromuscular and articular complications, impaired quality of life and increased cancer risk. However, the only cardiovascular complications associated with PHPT, which seems to improve after parathyroidectomy, is left ventricular hypertrophy, while, data regarding the reversibility of hypertension, valve calcifications and increased vascular stiffness are inconsistent. Parathyroidectomy seems to ameliorate neuropsychological, cognitive disturbances and quality of life in moderate-severe PHPT, while data in mild PHPT are less clear. At variance, the effect of parathyroidectomy on neuromuscular and articular complications is still unknown, and no studies demonstrated a reduction of cancer risk after recovery from PHPT. Overall, to date, cardiovascular and neuropsychological evaluation are not recommended solely because of PHPT, nor cardiovascular disease, muscle weakness, and neuropsychological complications are indication for parathyroidectomy.

Extinction of insulin gene expression in hybrids between beta cells and fibroblasts is accompanied by loss of the putative beta-cell-specific transcription factor IEF1.

Insulin-producing cells and fibroblasts were fused to produce hybrid lines. In hybrids derived from both hamster and rat insulinoma cells, no insulin mRNA could be detected in any of seven lines examined by Northern (RNA) analysis despite the presence in each line of the insulin genes of both parental cells. Hybrid cells were transfected with recombinant chloramphenicol acetyltransferase plasmids containing defined segments of the rat insulin I gene 5' flank. We observed no transcriptional activity of the intact insulin enhancer or of IEB2, a critical cis-acting element of the insulin enhancer. IEB2 has previously been shown to interact in vitro with IEF1, a DNA-binding activity observed selectively in insulin-producing cells. Hybrid cells showed no detectable IEF1 activity. Furthermore, the insulin enhancer was unable to reduce transcription directed by the Moloney sarcoma virus enhancer in a double-enhancer construct. Thus, extinction of insulin gene expression in the hybrids apparently does not operate through a direct action of repressors on the insulin enhancer; rather, extinction is accompanied by, and may be caused by, reduced DNA-binding activity of the putative transcriptional activator IEF1.

An activation domain of the helix-loop-helix transcription factor E2A shows cell type preference in vivo in microinjected zebra fish embryos.

The E2A protein is a mammalian transcription factor of the helix-loop-helix family which is implicated in cell-specific gene expression in several cell lineages. Mouse E2A contains two independent transcription activation domains, ADI and ADII; whereas ADI functions effectively in a variety of cultured cell lines, ADII shows preferential activity in pancreatic beta cells. To analyze this preferential activity in an in vivo setting, we adapted a system involving transient gene expression in microinjected zebra fish embryos. Fertilized one- to four-cell embryos were coinjected with an expression plasmid and a reporter plasmid. The expression plasmids used encode the yeast Gal4 DNA-binding domain (DBD) alone, or Gal4 DBD fused to ADI, ADII, or VP16. The reporter plasmid includes the luciferase gene linked to a promoter containing repeats of UASg, the Gal4-binding site. Embryo extracts prepared 24 h after injection showed significant luciferase activity in response to each of the three activation domains. To determine the cell types in which the activation domains were functioning, a reporter plasmid encoding beta-galactosidase and then in situ staining of whole embryos were used. Expression of ADI led to activation in all major groups of cell types of the embryo (skin, sclerotome, myotome, notochord, and nervous system). On the other hand, ADII led to negligible expression in the sclerotome, notochord, and nervous system and much more frequent expression in the myotome. Parallel experiments conducted with transfected mammalian cells have confirmed that ADII shows significant activity in myoblast cells but little or no activity in neuronal precursor cells, consistent with our observations in zebra fish. This transient-expression approach permits rapid in vivo analysis of the properties of transcription activation domains: the data show that ADII functions preferentially in cells of muscle lineage, consistent with the notion that certain activation domains contribute to selective gene activation in vivo.

B-cell factor 1 is required for optimal expression of the DRA promoter in B cells.

The X box in the DRA promoter of the human histocompatibility complex is required for expression of the DRA gene in B cells. We show that a B-cell factor binds to a sequence that is clearly distinguishable from binding sites for the previously described X box binding nuclear proteins RF-X, NF-X, NF-Xc, NF-S, hXBP, and AP-1. Mutations in the DRA X box that disrupt the binding of this factor result in a lower level of gene expression, as does the presence of Id (a trans-dominant regulatory protein that negatively regulates helix-loop-helix proteins). Furthermore, this factor is recognized by antibodies directed against the helix-loop-helix protein A1, a mouse homolog of the immunoglobulin enhancer binding proteins E12/E47, and it binds to sequences in other genes that were previously shown to bind these proteins. By these criteria, this factor is BCF-1.

Individual protein-binding domains of the insulin gene enhancer positively activate beta-cell-specific transcription.

A beta-cell-specific enhancer is located in the 5'-flanking DNA of the rat insulin 1 gene. Two homologous 8-base-pair sequences in the enhancer (IEB1 and IEB2) significantly stimulated transcription from a heterologous promoter (two- to fourfold) in a cell-specific fashion. When the elements were combined or duplicated, more than 50% of the activity of the intact enhancer was obtained. These two cis-acting elements appear to play a dominant role in the positive control of beta-cell-specific transcription of the insulin gene.