The Applicability of the ADA to Private Internet Web Sites

This article proposes that private commercial web sites are considered places of public accommodation; consequently, private Internet web sites must be accessible to people with disabilities under the Americans with Disabilities Act. Part I introduces the thesis of this article. Part II sets out the historical inception of the legal rights of accessibility for people with disabilities in public and private entities. Additionally, Part II describes recent federal actions mandating accessibility of government related web sites. Part III addresses the question of whether Internet web sites are considered places of public accommodation under the ADA, including an analysis of supporting and defensive arguments. Part IV addresses the National Federation for the Blind v. America On Line class action lawsuit. Part V evaluates concerns related to the First Amendment. Finally, Part VI states the conclusion of the article summarizing significant points and advocating that private Internet web sites should be legally required to make their sites accessible to people with disabilities

Parents’ Perspectives on Variants of Uncertain Significance from Chromosome Microarray Analysis

Chromosomal microarray analysis (CMA) for unexplained anomalies and developmental delay has improved diagnosis rates, but results classified as variants of uncertain significance (VUS) may challenge both clinicians and families. We explored the impact of such results on families, including parental knowledge, understanding and interpretation. Semi‐structured telephone interviews were conducted with parents (N = 14) who received genetic counseling for a VUS in their child. Transcripts were analyzed through an iterative coding process. Participants demonstrated a range of recall and personal interpretation regarding whether test results provided a causal explanation for their children’s health issues. Participants maintained contradictory interpretations, describing results as answers while maintaining that little clarification of their child’s condition had been provided. Reported benefits included obtaining medical services and personal validation. Parents described adaptation/coping processes similar to those occurring after positive test results. Recall of terminology, including “VUS” and precise CMA abnormalities, was poor. However, most demonstrated conceptual understanding of scientific uncertainty. All participants expressed intentions to return for recommended genetics follow‐up but had misconceptions about how this would occur. These results provide insight into the patient‐and‐family experience when receiving uncertain genomic findings, emphasize the importance of exploring uncertainty during the communication process, and highlight areas for potential attention or improvement in the clinical encounter.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146918/1/jgc40101.pd

Nuclease Modulates Biofilm Formation in Community-Associated Methicillin-Resistant Staphylococcus aureus

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging contributor to biofilm-related infections. We recently reported that strains lacking sigma factor B (sigB) in the USA300 lineage of CA-MRSA are unable to develop a biofilm. Interestingly, when spent media from a USA300 sigB mutant was incubated with other S. aureus strains, biofilm formation was inhibited. Following fractionation and mass spectrometry analysis, the major anti-biofilm factor identified in the spent media was secreted thermonuclease (Nuc). Considering reports that extracellular DNA (eDNA) is an important component of the biofilm matrix, we investigated the regulation and role of Nuc in USA300. The expression of the nuc gene was increased in a sigB mutant, repressed by glucose supplementation, and was unaffected by the agr quorum-sensing system. A FRET assay for Nuc activity was developed and confirmed the regulatory results. A USA300 nuc mutant was constructed and displayed an enhanced biofilm-forming capacity, and the nuc mutant also accumulated more high molecular weight eDNA than the WT and regulatory mutant strains. Inactivation of nuc in the USA300 sigB mutant background partially repaired the sigB biofilm-negative phenotype, suggesting that nuc expression contributes to the inability of the mutant to form biofilm. To test the generality of the nuc mutant biofilm phenotypes, the mutation was introduced into other S. aureus genetic backgrounds and similar increases in biofilm formation were observed. Finally, using multiple S. aureus strains and regulatory mutants, an inverse correlation between Nuc activity and biofilm formation was demonstrated. Altogether, our findings confirm the important role for eDNA in the S. aureus biofilm matrix and indicates Nuc is a regulator of biofilm formation

Net neutrality discourses: comparing advocacy and regulatory arguments in the United States and the United Kingdom

Telecommunications policy issues rarely make news, much less mobilize thousands of people. Yet this has been occurring in the United States around efforts to introduce "Net neutrality" regulation. A similar grassroots mobilization has not developed in the United Kingdom or elsewhere in Europe. We develop a comparative analysis of U.S. and UK Net neutrality debates with an eye toward identifying the arguments for and against regulation, how those arguments differ between the countries, and what the implications of those differences are for the Internet. Drawing on mass media, advocacy, and regulatory discourses, we find that local regulatory precedents as well as cultural factors contribute to both agenda setting and framing of Net neutrality. The differences between national discourses provide a way to understand both the structural differences between regulatory cultures and the substantive differences between policy interpretations, both of which must be reconciled for the Internet to continue to thrive as a global medium

Net neutrality discourses: comparing advocacy and regulatory arguments in the United States and the United Kingdom

Telecommunications policy issues rarely make news, much less mobilize thousands of people. Yet this has been occurring in the United States around efforts to introduce "Net neutrality" regulation. A similar grassroots mobilization has not developed in the United Kingdom or elsewhere in Europe. We develop a comparative analysis of U.S. and UK Net neutrality debates with an eye toward identifying the arguments for and against regulation, how those arguments differ between the countries, and what the implications of those differences are for the Internet. Drawing on mass media, advocacy, and regulatory discourses, we find that local regulatory precedents as well as cultural factors contribute to both agenda setting and framing of Net neutrality. The differences between national discourses provide a way to understand both the structural differences between regulatory cultures and the substantive differences between policy interpretations, both of which must be reconciled for the Internet to continue to thrive as a global medium

Templated Synthesis of Peptide Nucleic Acids via Sequence-Selective Base-Filling Reactions

The templated synthesis of nucleic acids has previously been achieved through the backbone ligation of preformed nucleotide monomers or oligomers. In contrast, here we demonstrate templated nucleic acid synthesis using a base-filling approach in which individual bases are added to abasic sites of a peptide nucleic acid (PNA). Because nucleobase substrates in this approach are not self-reactive, a base-filling approach may reduce the formation of nontemplated reaction products. Using either reductive amination or amine acylation chemistries, we observed efficient and selective addition of each of the four nucleobases to an abasic site in the middle of the PNA strand. We also describe the addition of single nucleobases to the end of a PNA strand through base filling, as well as the tandem addition of two bases to the middle of the PNA strand. These findings represent an experimental foundation for nonenzymatic information transfer through base filling.Chemistry and Chemical Biolog

Perception and Impact of COVID-19 Pandemic in Psoriasis Patients: Data from the German PsoBest and the CoronaBest Registries

María José Valencia López,1,* Brigitte Stephan,1,* Anna Meineke,1 Sandra Wolf,1 Diamant Thaci,2 Ulrich Mrowietz,3 Valerie Andrees,1 Stephan Jeff Rustenbach,1 Kristian Reich,1 Linus Thalmann,1 Henriette Bogena,1 Petra Staubach,4 Ralph Michael von Kiedrowski,5 Matthias Augustin1 1Institute for Health Services Research in Dermatology and Nursing (IVDP), University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany; 2Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany; 3Psoriasis-Center, Department of Dermatology, University Medical Center Schleswig-Holstein, Kiel, Germany; 4Department of Dermatology and Allergy, University Medical Center Mainz, Mainz, Germany; 5Dermatological Practice Selters, Selters, Germany*These authors contributed equally to this workCorrespondence: Matthias Augustin, Institute for Health Services Research in Dermatology and Nursing (IVDP), University Medical Center Hamburg-Eppendorf (UKE), Martinistraße 52, Hamburg, 20246, Germany, Tel +49 040 7410 55428, Fax +49 040 7410 55348, Email [email protected]: Limited data are available characterizing the impact of the SARS-CoV-2 pandemic on psoriasis care for patients in Germany.Objective: To analyze patient perception and impact of the pandemic on well-being and psoriasis management of German patients with moderate-to-severe psoriasis or psoriasis arthritis under systemic therapies.Methods: The CoronaBest registry captures events of SARS-CoV-2 infections and analyzes the impact of the pandemic on patients with psoriasis or psoriasis arthritis. In June 2020, and independently in February 2022, patients with psoriasis or psoriasis arthritis received a standardized questionnaire for current treatment, protective measures, well-being, and individual risks for COVID-19, among others.Results: Included were 4,194 patients in 2020 (mean age of 47.7 years and 41.8% women) and 4,818 patients in 2022 (mean age of 56.4 and 42.9% women). Treatment discontinuations were observed in 2.7% and 1.7% of patients in 2020 and 2022, respectively. In the vast majority of the cases (> 92%), no additional measures were taken concerning the management of psoriasis treatments in either 2020 or 2022. Those patients with changes reported most frequently: telephone calls instead of face-to-face visits (80.2%, in 2020 vs 40.5% in 2022) or more frequent controls (27.1%, 2020 vs 22.0%, 2022). A majority (66.7%, 2020, and 70.6%, 2022) did not perceive the virus as a considerable threat. The proportion of patients feeling well informed about COVID-19 by physicians increased from 42.6% in 2020 to 51.8% in 2022. About 81.1% of patients in 2020 and 67.5% in 2022 stated that their overall personal condition was not affected due to the pandemic. Physicians attributed no special risk of contracting SARS-CoV-2 in most of the patients.Conclusion: A high rate of systemic treatment persistence and awareness of risks and protective measures indicate that health care for psoriasis largely followed current national and international recommendations during the COVID-19 pandemic.Keywords: psoriasis, COVID-19, SARS-CoV-2, pandemic, patient perception, risk factor

A genome-wide association study of severe asthma exacerbations in Latino children and adolescents

Severe asthma exacerbations are a major cause of school absences and healthcare costs in children, particularly those in high-risk racial/ethnic groups. To identify susceptibility genes for severe asthma exacerbations in Latino children and adolescents, we conducted a meta-analysis of genome-wide association studies (GWAS) in 4010 Latino youth with asthma in four independent cohorts, including 1693 Puerto Ricans, 1019 Costa Ricans, 640 Mexicans, 256 Brazilians, and 402 members of other Latino subgroups. We then conducted methylation quantitative trait locus (mQTL), expression quantitative trait locus (eQTL), and expression quantitative trait methylation (eQTM) analyses to assess whether the top SNP in the meta-analysis is linked to DNA methylation and gene expression in nasal (airway) epithelium in separate cohorts of Puerto Rican and Dutch children and adolescents. In the meta-analysis of GWAS, a SNP in FLJ22447 (rs2253681) was significantly associated with 1.55 increased odds of severe asthma exacerbations (95% confidence interval=1.34 to 1.79, p=6.3×10-9). This SNP was significantly associated with DNA methylation of a CpG site (cg25024579) at the FLJ22447 locus, which was in turn associated with increased expression of KCNJ2-AS1 in nasal airway epithelium from Puerto Rican children and adolescents (β=0.10, p=2.18×10-7). Thus, SNP rs2253681 was significantly associated with both DNA methylation of a cis-CpG in FLJ22447 and severe asthma exacerbations in Latino youth. This may be partly explained by changes in airway epithelial expression of a gene recently implicated in atopic asthma in Puerto Rican children and adolescents (KCNJ2-AS1)

Transcriptional regulation of the cinnamyl alcohol dehydrogenase gene from sweetpotato in response to plant developmental stage and environmental stress

Cinnamyl alcohol dehydrogenase (CAD) is a key enzyme in the biosynthesis of lignin. We have isolated full length of a cDNA encoding CAD (IbCAD1) that was previously identified as the most abundant gene in an EST library of sweetpotato suspension cells. Phylogenetic analysis revealed that IbCAD1 belongs to the family of defense-related CADs. High levels of IbCAD1 mRNA were found in the roots of sweetpotato, but not in the leaves and petioles. The IbCAD1 gene transcripts were highly induced by cold, wounding, and reactive oxygen species. Analyses of transcriptional regulation of the IbCAD1 gene in transgenic tobacco plants carrying the IbCAD1 promoter–GUS revealed that IbCAD1 promoter expression was strong in the roots, but barely detectable in the cotyledons. IbCAD1 promoter activity increased with increasing root age, and strong promoter expression was observed in the lateral root emergence sites and in root tips. Weak GUS expression was observed in lignified tissues of vascular system of mature leaves and stems. IbCAD1 promoter activity was strongly induced in response to the biotic and abiotic stresses, with the strongest inducer being wounding, and was also induced by salicylic acid (SA) and jasmonic acid (JA) as well as by abscisic acid (ABA) and 6-benzylaminopurine. Taken together, our data suggest that IbCAD1 can be involved in JA- and SA-mediated wounding response and ABA-mediated cold response, respectively. The IbCAD1 gene may play a role in the resistance mechanism to biotic and abiotic stresses as well as in tissue-specific developmental lignification

Prebiotically plausible mechanisms increase compositional diversity of nucleic acid sequences

During the origin of life, the biological information of nucleic acid polymers must have increased to encode functional molecules (the RNA world). Ribozymes tend to be compositionally unbiased, as is the vast majority of possible sequence space. However, ribonucleotides vary greatly in synthetic yield, reactivity and degradation rate, and their non-enzymatic polymerization results in compositionally biased sequences. While natural selection could lead to complex sequences, molecules with some activity are required to begin this process. Was the emergence of compositionally diverse sequences a matter of chance, or could prebiotically plausible reactions counter chemical biases to increase the probability of finding a ribozyme? Our in silico simulations using a two-letter alphabet show that template-directed ligation and high concatenation rates counter compositional bias and shift the pool toward longer sequences, permitting greater exploration of sequence space and stable folding. We verified experimentally that unbiased DNA sequences are more efficient templates for ligation, thus increasing the compositional diversity of the pool. Our work suggests that prebiotically plausible chemical mechanisms of nucleic acid polymerization and ligation could predispose toward a diverse pool of longer, potentially structured molecules. Such mechanisms could have set the stage for the appearance of functional activity very early in the emergence of life