The transcription factor activity gradient (TAG) model: contemplating a contact-independent mechanism for enhancer–promoter communication

How distal cis-regulatory elements (e.g., enhancers) communicate with promoters remains an unresolved question of fundamental importance. Although transcription factors and cofactors are known to mediate this communication, the mechanism by which diffusible molecules relay regulatory information from one position to another along the chromosome is a biophysical puzzle—one that needs to be revisited in light of recent data that cannot easily fit into previous solutions. Here we propose a new model that diverges from the textbook enhancer–promoter looping paradigm and offer a synthesis of the literature to make a case for its plausibility, focusing on the coactivator p300.

Pengaruh Faktor Sosial Dan Pribadi Terhadap Minat Beli Produk Peyek Aziz Tanpa Tanggal Kedaluwarsa Dalam Perspektif Ekonomi Syariah

Carrying out economic activities based on Islam is an order and has the value of worship. According to fiqh rules, every muammalah transaction is allowed as long as it does not conflict with the basic Islamic law, namely the Qur'an and hadith, including carrying out economic activities in the field of food processing business. The purpose of this study was to determine the influence of social factors and personal factors on consumer buying interest in Peyek Aziz products. The method used is descriptive quantitative with the number of samples used as many as 33 respondents in the Kertamukti sub-district, Campaka sub-district which was determined through probability sampling with random sampling technique. The results of this study indicate that personal factors affect consumer buying interest with a significance value of 0.000 < 0.05. Social factors are declared not to affect because the significance value obtained is 0.063 > 0.05. While social and personal factors jointly affect consumer buying interest with a significance value of 0.000 < 0.05. Based on these results, it is known that social and personal factors affect consumer buying interest in food without an expiration date of 0.515 or 51%. While the remaining 49% is influenced by other factors not examined. The sharia economic review regarding food without expired labels did not find any specific regulatory information. The inclusion of an expired label is an ijtihad in providing information on the appropriate time limit for consumption on food products with the aim of benefiting in maintaining property and life.

Symmetric Inheritance of Histones H3 in Drosophila Male Germline Stem Cell Divisions

Mitotically-stable epigenetic memory requires a mechanism for the maintenance of gene-regulatory information through the cell division cycle. Typically DNA-protein contacts are disrupted by DNA replication, but in some cases locus- specific association between DNA and overlying histones may appear to be maintained, providing a plausible mechanism for the transmission of histone-associated gene-regulatory information to daughter cells. Male Drosophila melanogaster testis germ stem cell divisions seem a clear example of such inheritance, as previously chromatin-bound histone H3.2 proteins (presumably with their post-translational modifications intact) have been reported to be retained in the germ stem cell nuclei, while newly synthesized histones are incorporated exclusively into daughter spermatogonial chromosomes. To investigate the rate of errors in this selective partitioning that may lead to defects in the epigenetic identity of germ stem cells, we employed a photoswitchable Dendra2 moiety as a C-terminal fusion on Histones H3; we could thereby discriminate histones translated before photoswitching and those translated after. We found instead that male germ line stem cell divisions show no evidence of asymmetric histone partitioning, even after a single division, and thus no evidence for locus-specific retention of either Histone H3.2 or Histone H3.3. We considered alternative hypotheses for the appearance of asymmetry and find that previous reports of asymmetric histone distribution in male germ stem cells can be satisfactorily explained by asynchrony between subsequent sister stem cell and spermatogonial divisions.

Intercellular transport of RNA can limit heritable epigenetic changes

RNAs in circulation carry sequence-specific regulatory information between cells in animal, plant, and host-pathogen systems. Double-stranded RNA (dsRNA) delivered into the extracellular space of the nematode C. elegans accumulates within the germline and reaches progeny. Here we provide evidence for spatial, temporal, and substrate specificity in the transport of dsRNA from parental circulation to progeny. Temporary loss of dsRNA transport resulted in the persistent accumulation of mRNA from a germline gene. The expression of this gene varied among siblings and even between gonad arms within one animal. Perturbing RNA regulation of the gene created new epigenetic states that lasted for many generations. Thus, one role for the transport of dsRNA into the germline in every generation is to limit heritable changes in gene expression.One Sentence SummaryRNA from parental circulation reduces heritable changes in gene expression.

PmiREN2.0: from data annotation to functional exploration of plant microRNAs

Nearly 200 plant genomes have been sequenced over the last two years, and new functions of plant microRNAs (miRNAs) have been revealed. Therefore, timely update of the plant miRNA databases by incorporating miRNAs from the newly sequenced species and functional information is required to provide useful resources for advancing plant miRNA research. Here we report the update of PmiREN2.0 (https://pmiren.com/) with an addition of 19 363 miRNA entries from 91 plants, doubling the amount of data in the original version. Meanwhile, abundant regulatory information centred on miRNAs was added, including predicted upstream transcription factors through binding motifs scanning and elaborate annotation of miRNA targets. As an example, a genome-wide regulatory network centred on miRNAs was constructed for Arabidopsis. Furthermore, phylogenetic trees of conserved miRNA families were built to expand the understanding of miRNA evolution across the plant lineages. These data are helpful to deduce the regulatory relationships concerning miRNA functions in diverse plants. Beside the new data, a suite of design tools was incorporated to facilitate experimental practice. Finally, a forum named ‘PmiREN Community’ was added for discussion and resource and new discovery sharing. With these upgrades, PmiREN2.0 should serve the community better and accelerate miRNA research in plants.

When you talk, I remain silent: Spillover effects of peers' mandatory disclosures on firms' voluntary disclosures

We predict and find that regulated firms' mandatory disclosures crowd out unregulated firms' voluntary disclosures. Consistent with information spillovers from regulated to unregulated firms, we document that unregulated firms reduce their own disclosures in the presence of regulated firms' disclosures. We further find that unregulated firms reduce their disclosures more the greater the strength of the regulatory information spillovers. Our findings suggest that a substitutive relationship between regulated and unregulated firms' disclosures attenuates the effect of disclosure regulation on the market-wide information environment.

New insights into promoter–enhancer communication mechanisms revealed by dynamic single-molecule imaging

Establishing cell-type-specific gene expression programs relies on the action of distal enhancers, cis-regulatory elements that can activate target genes over large genomic distances — up to Mega-bases away. How distal enhancers physically relay regulatory information to target promoters has remained a mystery. Here, we review the latest developments and insights into promoter–enhancer communication mechanisms revealed by live-cell, real-time single-molecule imaging approaches.

The full spectrum of ethical issues in dementia research: findings of a systematic qualitative review

Background When including participants with dementia in research, various ethical issues arise. At present, there are only a few existing dementia-specific research guidelines (Committee for Medicinal Products for Human Use in Clinical investigation of medicines for the treatment Alzheimer’s disease (Internet). https://www.ema.europa.eu/en/clinical-investigation-medicines-treatment-alzheimers-disease; Food and Drug Administration, Early Alzheimer’s Disease: Developing Drugs for Treatment Guidance for Industry [Internet]. http://www.fda.gov/regulatory-information/search-fda-guidance-documents/alzheimers-disease-developing-drugs-treatment-guidance-industy), necessitating a more systematic and comprehensive approach to this topic to help researchers and stakeholders address dementia-specific ethical issues in research. A systematic literature review provides information on the ethical issues in dementia-related research and might therefore serve as a basis to improve the ethical conduct of this research. This systematic review aims to provide a broad and unbiased overview of ethical issues in dementia research by reviewing, analysing, and coding the latest literature on the topic. Methods We conducted a systematic review in PubMed and Google Scholar (publications in English between 2007 and 2020, no restrictions on the type of publication) of literature on research ethics in dementia research. Ethical issues in research were identified by qualitative text analysis and normative analysis. Results The literature review retrieved 110 references that together mentioned 105 ethical issues in dementia research. This set of ethical issues was structured into a matrix based on the eight major principles from a pre-existing framework on biomedical ethics (Emanuel et al. An Ethical Framework for Biomedical Research. in The Oxford textbook of clinical research ethics, Oxford University Press, Oxford, 2008). Consequently, subcategories were created and further categorized into dementia stages and study phases. Conclusions The systematically derived matrix helps raise awareness and understanding of the complex topic of ethical issues in dementia research. The matrix can be used as a basis for researchers, policy makers and other stakeholders when planning, conducting and monitoring research, making decisions on the legal background of the topic, and creating research practice guidelines.

Aberration of regulatory information

The article explores the question of the existence of grounds for the manifestation of such a negative phenomenon in the national legal field, which is the “aberration” of regulatory information. The term “aberration of regulatory information” in this study means a conscious, motivated or unconscious, unmotivated distortion of the content of regulatory information in comparison with its analogue text, that is, information contained in drafts or in regulatory legal acts, in court decisions and other materials that are annexed to these documents and used in their adoption. A conclusion is made about the causes of this phenomenon and the need to apply measures to minimize it.