Loop Catalog: a comprehensive HiChIP database of human and mouse samples.

HiChIP enables cost-effective and high-resolution profiling of regulatory and structural loops. To leverage the increasing number of publicly available HiChIP datasets from diverse cell lines and primary cells, we developed the Loop Catalog (https://loopcatalog.lji.org), a web-based database featuring HiChIP loop calls for 1319 samples across 133 studies and 44 high-resolution Hi-C loop calls. We demonstrate its utility in interpreting fine-mapped GWAS variants (SNP-to-gene linking), in identifying enriched sequence motifs and motif pairs at loop anchors, and in network-level analysis of loops connecting regulatory elements (community detection). Our comprehensive catalog, spanning over 4M unique 5kb loops, along with the accompanying analysis modalities constitutes an important resource for studies in gene regulation and genome organization.

LIGHT signaling through LTßR and HVEM in keratinocytes promotes psoriasis and atopic dermatitis-like skin inflammation.

Psoriasis (PS) and atopic dermatitis (AD) are common skin inflammatory diseases characterized by hyper-responsive keratinocytes. Although, some cytokines have been suggested to be specific for each disease, other cytokines might be central to both diseases. Here, we show that Tumor necrosis factor superfamily member 14 (TNFSF14), known as LIGHT, is required for experimental PS, similar to its requirement in experimental AD. Mice devoid of LIGHT, or deletion of either of its receptors, lymphotoxin ß receptor (LTßR) and herpesvirus entry mediator (HVEM), in keratinocytes, were protected from developing imiquimod-induced psoriatic features, including epidermal thickening and hyperplasia, and expression of PS-related genes. Correspondingly, in single cell RNA-seq analysis of PS patient biopsies, LTßR transcripts were found strongly expressed with HVEM in keratinocytes, and LIGHT was upregulated in T cells. Similar transcript expression profiles were also seen in AD biopsies, and LTßR deletion in keratinocytes also protected mice from allergen-induced AD features. Moreover, in vitro, LIGHT upregulated a broad spectrum of genes in human keratinocytes that are clinical features of both PS and AD skin lesions. Our data suggest that agents blocking LIGHT activity might be useful for therapeutic intervention in PS as well as in AD.

Lineage-specific 3D genome organization is assembled at multiple scales by IKAROS.

A generic level of chromatin organization generated by the interplay between cohesin and CTCF suffices to limit promiscuous interactions between regulatory elements, but a lineage-specific chromatin assembly that supersedes these constraints is required to configure the genome to guide gene expression changes that drive faithful lineage progression. Loss-of-function approaches in B cell precursors show that IKAROS assembles interactions across megabase distances in preparation for lymphoid development. Interactions emanating from IKAROS-bound enhancers override CTCF-imposed boundaries to assemble lineage-specific regulatory units built on a backbone of smaller invariant topological domains. Gain of function in epithelial cells confirms IKAROS' ability to reconfigure chromatin architecture at multiple scales. Although the compaction of the Igκ locus required for genome editing represents a function of IKAROS unique to lymphocytes, the more general function to preconfigure the genome to support lineage-specific gene expression and suppress activation of extra-lineage genes provides a paradigm for lineage restriction.

Cellulosic and microplastic fibers in the Antarctic fish Harpagifer antarcticus and Sub-Antarctic Harpagifer bispinis.

Human settlements within the Antarctic continent have caused significant coastal pollution by littering plastic. The present study assessed the potential presence of microplastics in the gastrointestinal tract of the Antarctic fish Harpagifer antarcticus, endemic to the polar region, and in the sub-Antarctic fish Harpagifer bispinis. H. antarcticus. A total of 358 microfibers of multiple colors were found in 89 % of H. antarcticus and 73 % of H. bispinis gastrointestinal track. A Micro-FTIR analysis characterized a sub-group (n = 42) of microfibers. It revealed that most of the fibers were cellulose (69 %). Manmade fibers such as microplastics polyethylene terephtalate, acrylics, and semisynthetic/natural cellulosic fibers were present in the fish samples. All the microfibers extracted were textile fibers of blue, black, red, green, and violet color. Our results suggest that laundry greywater discharges of human settlements near coastal waters in Antarctica are a major source of these pollutants in the Antarctic fish.

Rewiring of the 3D genome during acquisition of carboplatin resistance in a triple-negative breast cancer patient-derived xenograft.

Changes in the three-dimensional (3D) structure of the genome are an emerging hallmark of cancer. Cancer-associated copy number variants and single nucleotide polymorphisms promote rewiring of chromatin loops, disruption of topologically associating domains (TADs), active/inactive chromatin state switching, leading to oncogene expression and silencing of tumor suppressors. However, little is known about 3D changes during cancer progression to a chemotherapy-resistant state. We integrated chromatin conformation capture (Hi-C), RNA-seq, and whole-genome sequencing obtained from triple-negative breast cancer patient-derived xenograft primary tumors (UCD52) and carboplatin-resistant samples and found increased short-range (< 2 Mb) interactions, chromatin looping, formation of TAD, chromatin state switching into a more active state, and amplification of ATP-binding cassette transporters. Transcriptome changes suggested the role of long-noncoding RNAs in carboplatin resistance. Rewiring of the 3D genome was associated with TP53, TP63, BATF, FOS-JUN family of transcription factors and led to activation of aggressiveness-, metastasis- and other cancer-related pathways. Integrative analysis highlighted increased ribosome biogenesis and oxidative phosphorylation, suggesting the role of mitochondrial energy metabolism. Our results suggest that 3D genome remodeling may be a key mechanism underlying carboplatin resistance.

A double-negative thymocyte-specific enhancer augments Notch1 signaling to direct early T cell progenitor expansion, lineage restriction and ß-selection.

T cell differentiation requires Notch1 signaling. In the present study, we show that an enhancer upstream of Notch1 active in double-negative (DN) mouse thymocytes is responsible for raising Notch1 signaling intrathymically. This enhancer is required to expand multipotent progenitors intrathymically while delaying early differentiation until lineage restrictions have been established. Early thymic progenitors lacking the enhancer show accelerated differentiation through the DN stages and increased frequency of B, innate lymphoid (IL) and natural killer (NK) cell differentiation. Transcription regulators for T cell lineage restriction and commitment are expressed normally, but IL and NK cell gene expression persists after T cell lineage commitment and T cell receptor ß VDJ recombination, Cd3 expression and ß-selection have been impaired. This Notch1 enhancer is inactive in double-positive (DP) thymocytes. Its aberrant reactivation at this stage in Ikaros mutants is required for leukemogenesis. Thus, the DN-specific Notch1 enhancer harnesses the regulatory architecture of DN and DP thymocytes to achieve carefully orchestrated changes in Notch1 signaling required for early lineage restrictions and normal T cell differentiation.

The link between agriculture and rural food security in the ecoregions of Mexico: path diagrams and underlying dataset.

In this research, we build two food systems datasets in Mexico; The first one describes the structure of agricultural production units and the second one describes food security aspects of the rural population in these agricultural production units. We also build a third dataset, consisting of path diagrams and path coefficients (derived from Structural Equation Modeling) that relate the first dataset to the second dataset in the four most populated ecoregions of Mexico. The description of the path models and the insights they bring to the current state of food security in Mexican rural households are detailed in an associated article entitled "Is food security primarily associated with smallholder agriculture or with commercial agriculture?: An approach to the case of Mexico using structural equation modeling" (https://doi.org/10.1016/j.agsy.2021.103091). The agricultural variables (in the first dataset) include farm size, destination of the farmer's production, cultivation practice / water management, predominant source of income of the household, land tenure type, crop diversity, agricultural surface expansion, and the presence of forest cover. They are based on the primary data of the full, latest available agricultural census in Mexico and corresponding official land use / land cover data. The second dataset consists of four food security indicators designed and built for the first food security model in Mexico that incorporates food availability, food accessibility and food utilization aspects. They include the Food Self-sufficiency Index (the balance between food production and food consumption), the Food Access Index (inversely related to marginalization), the Entitlement to Public Health Care index, and the Undernutrition Infrequency index (related to hospital sickness records). We provide the path tables and diagrams that describe the links between the agricultural structure and food security. These diagrams provide the first nationwide statistical evidence for the prominent role of smallholder agriculture in rural food security at the national level and at ecoregion scale for a country of the global South. In order to further investigate the structure of the agricultural production units and their relationships with socio-economic, territorial and landscape data, artificial intelligence (i.e. data mining and machine learning) techniques could be performed on this compendium of datasets. The food security data may stir the development of more food security models in Mexico in relation to other drivers such as consumption habits and non-agricultural activities of rural households.

Spatiotemporal patterns of mortality associated with chronic non-communicable diseases and child malnutrition at the municipal level in Mexico.

Malnutrition is one of the main risk factors related to chronic non-communicable diseases and child undernourishment on a planetary scale. Mexico is one of the countries with the highest levels of malnutrition, but there is also an accelerated increase in overweight or obesity. This study explored the spatiotemporal behaviour of mortality associated with chronic non-communicable diseases such as type II diabetes mellitus, hypertension, ischemic heart disease and cerebrovascular disease. The analysis was carried out at the municipality level for the 2000-2020 period targeting two age groups: ≥60-year olds and 20-59-year olds. In addition, 0-4-year olds were investigated with respect to undernourishment. National databases were gathered and standardized for each disease and SaTScan spatiotemporal cluster analyses were performed. We found that mortality associated with most of the diseases evaluated has increased since 2016 except for mortality caused by child undernourishment, which showed a downward trend during the study period. To focus on active conglomerates of diseases is important as they currently represent a threat to public health. Our results contribute to the potential spatial prioritization of the allocation of resources and campaigns for prevention and treatment of chronic non-communicable diseases and child undernourishment. Generally, geographical studies are fundamental for the discovery of disease aetiology and they provide valuable and timely information to multiple stakeholders.

Pluripotency exit is guided by the Peln1-mediated disruption of intrachromosomal architecture.

The molecular circuitry that causes stem cells to exit from pluripotency remains largely uncharacterized. Using chromatin RNA in situ reverse transcription sequencing, we identified Peln1 as a novel chromatin RNA component in the promoter complex of Oct4, a stem cell master transcription factor gene. Peln1 was negatively associated with pluripotent status during somatic reprogramming. Peln1 overexpression caused E14 cells to exit from pluripotency, while Peln1 downregulation induced robust reprogramming. Mechanistically, we discovered that Peln1 interacted with the Oct4 promoter and recruited the DNA methyltransferase DNMT3A. By de novo altering the epigenotype in the Oct4 promoter, Peln1 dismantled the intrachromosomal loop that is required for the maintenance of pluripotency. Using RNA reverse transcription-associated trap sequencing, we showed that Peln1 targets multiple pathway genes that are associated with stem cell self-renewal. These findings demonstrate that Peln1 can act as a new epigenetic player and use a trans mechanism to induce an exit from the pluripotent state in stem cells.

Needs for a Curricular Change in Primary and Secondary Education From the One Health Perspective: A Pilot Study on Pneumonia in Schools.

This is the first pilot study on alternative conceptions and obstacles pertaining to pneumonia in adolescents of different school vulnerability indexes. Countries with low socioeconomic levels are disproportionately affected, with Latin America and the Caribbean (LAC) being the second-most affected area in the world, after sub-Saharan Africa. In spite of this fact, pneumonia is not included as an important component within the contents of the microbiology curriculum unit in the natural science school program. Therefore, we wanted to study how students knew about this topic by putting One Health into action by building and validating qualitative and quantitative questionnaires, put together by different experts in pedagogy, didactics, microbiology, and veterinary to find out what students knew about pneumonia and their misconceptions about it. A total of 148 students (in 8th and 9th grade) participated in this survey. The results reveal that no statistically significant differences between the different scholar grades (p = 0.3360 Pearson chi∧2) or genders (p = 0.8000 Fisher's exact test) presented higher or lower School Vulnerability Index (SVI). Regardless of the social stratum or the level of vulnerability of the students, they have heard about this disease primarily through their family/relatives, maintaining a superficial notion of the disease, learning wrong ideas about microorganisms and treatments that can contribute to the risk to public health.

TWEAK functions with TNF and IL-17 on keratinocytes and is a potential target for psoriasis therapy.

TNF and IL-17 are two cytokines that drive dysregulated keratinocyte activity, and their targeting is highly efficacious in patients with psoriasis, but whether these molecules act with other inflammatory factors is not clear. Here, we show that mice having a keratinocyte-specific deletion of Fn14 (Tnfrsf12a), the receptor for the TNF superfamily cytokine TWEAK (Tnfsf12), displayed reduced imiquimod-induced skin inflammation, including diminished epidermal hyperplasia and less expression of psoriasis signature genes. This corresponded with Fn14 being expressed in keratinocytes in human psoriasis lesions and TWEAK being found in several subsets of skin cells. Transcriptomic studies in human keratinocytes revealed that TWEAK strongly overlaps with IL-17A and TNF in up-regulating the expression of CXC chemokines, along with cytokines such as IL-23 and inflammation-associated proteins like S100A8/9 and SERPINB1/B9, all previously found to be highly expressed in the lesional skin of patients with psoriasis. TWEAK displayed strong synergism with TNF or IL-17A in up-regulating messenger RNA for many psoriasis-associated genes in human keratinocytes, including IL23A, IL36G, and multiple chemokines, implying that TWEAK acts with TNF and IL-17 to enhance feedback inflammatory activity. Correspondingly, therapeutic treatment of mice with anti-TWEAK was equally as effective as antibodies to IL-17A or TNF in reducing clinical and immunological features of psoriasis-like skin inflammation and combination targeting of TWEAK with either cytokine had no greater inhibitory effect, reinforcing the conclusion that all three cytokines function together. Thus, blocking TWEAK could be comparable to targeting TNF or IL-17 and might be considered as an alternate therapeutic treatment for psoriasis.

From the Approach to the Concept: One Health in Latin America-Experiences and Perspectives in Brazil, Chile, and Colombia.

Professionals throughout the world have been working to assess the interdisciplinary interaction and interdependence between health and wellbeing in a constantly changing environment. The One Health concept was developed to encourage sustainable collaborative partnerships and to promote optimal health for people, animals, plants, the environment, and the whole planet. The dissemination of scientific discoveries and policies, by working directly with diverse communities, has been one of the main goals for Global One Health. The One Health concept has also been referred or related to as "One Medicine, One Medicine-One Health, One World-One Health, EcoHealth," and Planetary Health," depending on each fundamental view and approach. In Latin America, despite the concept still being discussed among health professionals and educators, several One Health initiatives have been used daily for more than decades. One Health action has been applied especially in rural and underserved urban areas where low socioeconomic status, lack of health professionals, and scarcity of medical resources may require professionals to work together. Local communities from diverse social and economic statuses, including indigenous populations have been working with institutions and social organizations for many years, accomplishing results through grassroots movements. These "bottom-up" socio-community approaches have also been tools for the prevention and control of diseases, such practice has preceded the One Health concepts in Latin American countries. It is strongly believed that collaborative, multidisciplinary, political, and economic initiatives with prosocial focus may become investments toward obtaining significant results in the face of global, economic and health challenges; working for a healthier world with inclusivity, equity, and equality. In this study, it is briefly presented how the One Health approach has been initiated and developed in Latin America, highlighting the events and actions taken in Brazil, Chile, and Colombia.

Chromatin lncRNA Platr10 controls stem cell pluripotency by coordinating an intrachromosomal regulatory network.

BACKGROUND: A specific 3-dimensional intrachromosomal architecture of core stem cell factor genes is required to reprogram a somatic cell into pluripotency. As little is known about the epigenetic readers that orchestrate this architectural remodeling, we used a novel chromatin RNA in situ reverse transcription sequencing (CRIST-seq) approach to profile long noncoding RNAs (lncRNAs) in the Oct4 promoter. RESULTS: We identify Platr10 as an Oct4 - Sox2 binding lncRNA that is activated in somatic cell reprogramming. Platr10 is essential for the maintenance of pluripotency, and lack of this lncRNA causes stem cells to exit from pluripotency. In fibroblasts, ectopically expressed Platr10 functions in trans to activate core stem cell factor genes and enhance pluripotent reprogramming. Using RNA reverse transcription-associated trap sequencing (RAT-seq), we show that Platr10 interacts with multiple pluripotency-associated genes, including Oct4, Sox2, Klf4, and c-Myc, which have been extensively used to reprogram somatic cells. Mechanistically, we demonstrate that Platr10 helps orchestrate intrachromosomal promoter-enhancer looping and recruits TET1, the enzyme that actively induces DNA demethylation for the initiation of pluripotency. We further show that Platr10 contains an Oct4 binding element that interacts with the Oct4 promoter and a TET1-binding element that recruits TET1. Mutation of either of these two elements abolishes Platr10 activity. CONCLUSION: These data suggest that Platr10 functions as a novel chromatin RNA molecule to control pluripotency in trans by modulating chromatin architecture and regulating DNA methylation in the core stem cell factor network.

Terrestrial dissolved organic matter inflow drives temporal dynamics of the bacterial community of a subarctic estuary (northern Baltic Sea).

Climate change is projected to cause increased inflow of terrestrial dissolved organic matter to coastal areas in northerly regions. Estuarine bacterial community will thereby receive larger loads of organic matter and inorganic nutrients available for microbial metabolism. The composition of the bacterial community and its ecological functions may thus be affected. We studied the responses of bacterial community to inflow of terrestrial dissolved organic matter in a subarctic estuary in the northern Baltic Sea, using a 16S rRNA gene metabarcoding approach. Betaproteobacteria dominated during the spring river flush, constituting ~ 60% of the bacterial community. Bacterial diversity increased as the runoff decreased during summer, when Verrucomicrobia, Betaproteobacteria, Bacteroidetes, Gammaproteobacteria and Planctomycetes dominated the community. Network analysis revealed that a larger number of associations between bacterial populations occurred during the summer than in spring. Betaproteobacteria and Bacteroidetes populations appeared to display similar correlations to environmental factors. In spring, freshly discharged organic matter favoured specialists, while in summer a mix of autochthonous and terrestrial organic matter promoted the development of generalists. Our study indicates that increased inflows of terrestrial organic matter-loaded freshwater to coastal areas would promote specialist bacteria, which in turn might enhance the transformation of terrestrial organic matter in estuarine environments.

Phenotypic plasticity is not a cline: Thermal physiology of an intertidal barnacle over 20° of latitude.

Our understanding of the plastic and evolutionary potential of ectothermic organisms and their populational impacts in the face of rapid global change remains limited. Studies attempting on the relationship between the magnitude of thermal variability across latitude and the degree of phenotypic plasticity exhibited by marine ectotherms are inconclusive. We state that the latter arises from the narrow range of thermal variability captured by the limited span of the latitudinal gradients studied to date. Using a mechanistic ecophysiological approach and a satellite-based assessment of the relevant environmental variables (i.e. temperature and food availability), we studied individuals of the intertidal barnacle Jehlius cirratus from seven local populations widely spread along the Humboldt current system that spanning two biogeographic regions. At the same time, we synthesized published information on the local abundance of our study species across a total of 76 sites representing 20° of latitude, and spanning from 18 to 42°S. We examined the effects of latitude and environmental variability on metabolic rate plasticity, thermal tolerance (thermal breadth and thermal safety margins) and their impacts on the abundance of this widespread marine invertebrate. We demonstrate that the phenotypic plasticity of metabolic rate in J. cirratus populations is not related to latitude. In turn, thermal breadth is explained by the temperature variability each population experiences. Furthermore, we found clinal variation with a poleward decrease of the critical thermal minimum, suggesting that episodic extreme low temperatures represent a ubiquitous selective force on the lower thermal limit for ectotherms. Across our study gradient, plasticity patterns indicate that populations at the equatorial extreme are more vulnerable to a warming climate, while populations located in the biogeographic transitional zone (i.e. high environmental heterogeneity), on the centre of the gradient, display higher levels of phenotypic plasticity and may represent a genetic buffer for the effects of ocean warming. Together, our results suggest the existence of a fitness trade-off involving the metabolic cost of plasticity and population density that is evident only across the vast latitudinal gradient examined.

Nuestro conocimiento del potencial plástico y evolutivo de organismos ectotérmicos y de los posibles impactos poblacionales a la luz del rápido cambio global sigue siendo limitado. Los estudios que relacionan la magnitud de la variabilidad térmica y el grado de plasticidad fenotípica a través de la latitud realizados en organismos ectotérmicos marinos no son concluyentes. Lo anterior creemos que es consecuencia del estrecho rango latitudinal y por consecuencia el menor rango de variabilidad térmica abarcado por los estudios previos. Utilizando un enfoque ecofisiológico mecanicista e información satelital de las variables ambientales relevantes (i.e., temperatura y disponibilidad de alimento), estudiamos individuos del cirripedio intermareal Jehlius cirratus a lo largo de siete poblaciones locales que se distribuyen ampliamente a lo largo del Sistema de la corriente de Humboldt abarcando dos regiones biogeográficas. Al mismo tiempo, sintetizamos la información publicada sobre la abundancia local de nuestro modelo de estudio en un total de 76 sitios que representan 20 grados de latitud y abarcan desde los 18° a los 42°S. Examinamos los efectos de la latitud y la variabilidad ambiental en la plasticidad de la tasa metabólica, la tolerancia térmica (i.e. amplitud térmica y márgenes de seguridad térmica) y los impactos en la abundancia de este invertebrado marino con amplia distribución geográfica. Demostramos que la plasticidad fenotípica de la tasa metabólica en poblaciones de J. cirratus no está relacionada con la latitud. A su vez, la amplitud térmica se explica por la variabilidad térmica que cada población experimenta. Además, encontramos un patrón de variación clinal con una disminución hacia los polos del crítico térmico mínimo, lo que sugiere que las temperaturas episódicas extremadamente bajas representan una fuerza selectiva ubicua en el límite térmico inferior para los ectotermos. A lo largo de nuestro gradiente estudiado, los patrones de plasticidad indican que las poblaciones en el extremo ecuatorial son más vulnerables al calentamiento, mientras que las poblaciones ubicadas en la zona de transición biogeográfica (i.e., alta heterogeneidad ambiental), en el centro del gradiente, muestran mayores niveles de plasticidad fenotípica, lo que puede representar un reservorio genético para los efectos del calentamiento de los océanos. Nuestros resultados sugieren la existencia de un compromiso en la adecuación biológica que involucra el costo metabólico de la plasticidad y la densidad de población que es sólo evidente dado el vasto gradiente latitudinal examinado.