Spatial Compartments Research Articles

EBF1 nuclear repositioning instructs chromatin refolding to promote therapy resistance in T leukemic cells

Chromatin misfolding has been implicated in cancer pathogenesis; yet, its role in therapy resistance remains unclear. Here, we systematically integrated sequencing and imaging data to examine the spatial and linear chromatin structures in targeted therapy-sensitive and -resistant human Tcell acute lymphoblastic leukemia (T-ALL). We found widespread alterations in successive layers of chromatin organization including spatial compartments, contact domain boundaries, and enhancer positioning upon the emergence of targeted therapy resistance. The reorganization of genome folding structures closely coincides with the restructuring of chromatin activity and redistribution of architectural proteins. Mechanistically, the derepression and repositioning of the B-lineage-determining transcription factor EBF1 from the heterochromatic nuclear envelope to the euchromatic interior instructs widespread genome refolding and promotes therapy resistance in leukemic Tcells. Together, our findings suggest that lineage-determining transcription factors can instruct changes in genome topology as a driving force for epigenetic adaptations in targeted therapy resistance.

A spatiotemporal atlas of the lepidopteran pest Helicoverpa armigera midgut provides insights into nutrient processing and pH regulation

BackgroundCaterpillars from the insect order Lepidoptera are some of the most widespread and destructive agricultural pests. Most of their impact is at the larval stage, where the midgut epithelium mediates the digestion and absorption of an astonishing amount of food. Although this tissue has been the subject of frequent investigation in Lepidoptera, a comprehensive expression atlas has yet to be generated.ResultsHere, we perform RNA-sequencing and proteomics on the gut of the polyphagous pest Helicoverpa armigera across, life stages, diet types, and compartments of the anterior-posterior axis. A striking relationship between the structural homology and expression pattern of a group of sugar transporters was observed in the early larval stages. Further comparisons were made among the spatial compartments of the midgut, which suggested a putative role for vATPases and SLC9 transporters in the generation of alkaline conditions in the H. armigera midgut.ConclusionsThis comprehensive resource will aid the scientific community in understanding lepidopteran gut physiology in unprecedented resolution. It is hoped that this study advances the understanding of the lepidopteran midgut and also facilitates functional work in this field.

The Role of Illumination in Integration and Differential Processes of Visual Perception of Temple Interior Architecture

Despite Orthodox Christian temples have been actively being built over the last years in Moscow (as part of its programme of building 200 Orthodox churches), the problem of temple illumination is still understudied, and in view of this, the article addresses the temple interior architecture as a set of illuminated spatial compartments (temple zones) with different area lighting. A number of concepts is stated including the following: 1) a luminous environment of a temple is designed as a combined system of natural, artificial, and mixed interior lighting interacting with its architecture and decorations including light accents as well as different lighting effects within the interior; 2) temple illumination has several functions: assisting in church services, arrangement of spaces and compositions, visual and symbolic function, and utility function and, with all importance of daylight temple illumination, artificial and mixed illumination has the main semantic priority of temple lighting.

RNA promotes the formation of spatial compartments in the nucleus

RNA, DNA, and protein molecules are highly organized within three-dimensional (3D) structures in the nucleus. Although RNA has been proposed to play a role in nuclear organization, exploring this has been challenging because existing methods cannot measure higher-order RNA and DNA contacts within 3D structures. To address this, we developed RNA & DNA SPRITE (RD-SPRITE) to comprehensively map the spatial organization of RNA and DNA. These maps reveal higher-order RNA-chromatin structures associated with three major classes of nuclear function: RNA processing, heterochromatin assembly, and gene regulation. These data demonstrate that hundreds of ncRNAs form high-concentration territories throughout the nucleus, that specific RNAs are required to recruit various regulators into these territories, and that these RNAs can shape long-range DNA contacts, heterochromatin assembly, and gene expression. These results demonstrate a mechanism where RNAs form high-concentration territories, bind to diffusible regulators, and guide them into compartments to regulate essential nuclear functions.

Abstract 3137: Characterizing heterogeneity of CD8 inflammation in biopsied tumor tissues using novel image analysis techniques

Abstract Analyzing images of tissue sections stained with biomarker-specific indicators can generate quantitative, cell-specific expression data rather than relying on pathologist's ability to count cells and recapitulate confounding scoring paradigms. Beyond biomarker expression, numerous cell features can be measured such as the cell morphology, biomarker staining patterns and intensity, and localization of the cells within defined spatial compartments or relations to one another. One of the most studied immune cells in immuno-oncology (IO) is the cytotoxic T cell, whose biological function is to identify and destroy infected or dysfunctional cells; this function is complicated by numerous factors within the tumor microenvironment (TME). Tumor cells can aberrantly express immune checkpoint molecules designed to stop CD8 T cells from performing their tumor killing function. Additionally, CD8 T cell function may be perturbed by other immune modulating factors within the TME. IO drugs modulating tumor and immune cell interactions such as PD-L1 checkpoint inhibitors have shown that an inflammatory TME, represented by high CD8 presence in the tumors (inflamed tumors), is indicative of a better therapeutic response. Investigation of CD8 T cell status in biopsied tissues typically describes each tissue as one of three main phenotypes: Immune Desert, Immune Excluded, or Inflamed. Immune Desert tissues do not express appreciable levels of CD8 throughout the tissue. Immune Excluded tissues contain CD8, but the expression is almost exclusively localized to the stroma surrounding tumor nests. Inflamed tissues show higher percentages of CD8 within the tumor nests. While this phenotypic categorization is informative, CD8 expression is often calculated as a mean of expression through the tissue and does not take in to account the heterogeneous nature of tumor biology. This may result in a tumor containing one highly inflamed tumor nest being averaged out with multiple deserted tumor nests and a tissue categorized as excluded or deserted even though inflammation is present. To better represent the heterogeneity of inflammation within tumor tissues, we present an image analysis-based algorithm which not only separates out the tumor, stroma, and tumor/stroma margin, but identifies each tumor nest within the tissue as its own discrete object. This allows for the enumeration of number and size of all tumor nests within the tissue. Each tumor nest is given its own phenotypic classification (inflamed, excluded, or deserted) and the percentage of tumor nests displaying each phenotype. We demonstrate heterogeneity of inflammation assessment alongside standard mean phenotypic evaluations of CD8 expression in non-small cell lung cancer, bladder, and melanoma tumor samples. Practical use in clinical studies can help uncover response or resistance associated phenotypes related to tumor heterogeneity. Citation Format: Charles William Caldwell, Will Paces, Sofia Reitsma, Christopher Brueckner, Si T. Lee-Hoeflich, Roberto Gianani. Characterizing heterogeneity of CD8 inflammation in biopsied tumor tissues using novel image analysis techniques [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3137.

The "Genomic Code": DNA Pervasively Moulds Chromatin Structures Leaving no Room for "Junk".

The chromatin of the human genome was analyzed at three DNA size levels. At the first, compartment level, two “gene spaces” were found many years ago: A GC-rich, gene-rich “genome core” and a GC-poor, gene-poor “genome desert”, the former corresponding to open chromatin centrally located in the interphase nucleus, the latter to closed chromatin located peripherally. This bimodality was later confirmed and extended by the discoveries (1) of LADs, the Lamina-Associated Domains, and InterLADs; (2) of two “spatial compartments”, A and B, identified on the basis of chromatin interactions; and (3) of “forests and prairies” characterized by high and low CpG islands densities. Chromatin compartments were shown to be associated with the compositionally different, flat and single- or multi-peak DNA structures of the two, GC-poor and GC-rich, “super-families” of isochores. At the second, sub-compartment, level, chromatin corresponds to flat isochores and to isochore loops (due to compositional DNA gradients) that are susceptible to extrusion. Finally, at the short-sequence level, two sets of sequences, GC-poor and GC-rich, define two different nucleosome spacings, a short one and a long one. In conclusion, chromatin structures are moulded according to a “genomic code” by DNA sequences that pervade the genome and leave no room for “junk”.

In vivo evidence for the unique kinetics of evoked dopamine release in the patch and matrix compartments of the striatum

The neurochemical transmitter dopamine (DA) is implicated in a number of diseases states, including Parkinson’s disease, schizophrenia, and drug abuse. DA terminal fields in the dorsal striatum and core region of the nucleus accumbens in the rat brain are organized as heterogeneous domains exhibiting fast and slow kinetic of DA release. The rates of dopamine release are significantly and substantially faster in the fast domains relative to the slow domains. The striatum is composed of a mosaic of spatial compartments known as the striosomes (patches) and the matrix. Extensive literature exists on the spatial organization of the patch and matrix compartments and their functions. However, little is known about these compartments as they relate to fast and slow kinetic DA domains observed by fast scan cyclic voltammetry (FSCV). Thus, we combined high spatial resolution of FSCV with detailed immunohistochemical analysis of these architectural compartments (patch and matrix) using fluorescence microscopy. Our findings demonstrated a direct correlation between patch compartments with fast domain DA kinetics and matrix compartments to slow domain DA kinetics. We also investigated the kinetic domains in two very distinct sub-regions in the striatum, the lateral dorsal striatum (LDS) and the medial dorsal striatum (MDS). The lateral dorsal striatum as opposed to the medial dorsal striatum is mainly governed by fast kinetic DA domains. These finding are highly relevant as they may hold key promise in unraveling the fast and slow kinetic DA domains and their physiological significance.Graphical abstract

Dual disruption of eNOS and ApoE gene accelerates kidney fibrosis and senescence after injury

The relationship between cellular senescence and fibrosis in the kidney is being elucidated and we have identified it as therapeutic target in recent studies. Chronic kidney disease has also become a lifestyle disease, often developing on the background of hypertension and dyslipidemia. In this study, we clarify the effect of interaction between these two conditions on kidney fibrosis and senescence. Wild type mice (WT), apolipoprotein E-/- mice (ApoEKO), and endothelial nitric oxide synthase (eNOS)-/- ApoE-/- mice (DKO) were obtained by breeding. Unilateral ureteral obstruction (UUO) was performed on 8–10 week old male mice and the degree of renal tubular injury, fibrosis and kidney senescence were evaluated. DKO manifested elevated blood pressure, higher total cholesterol and lower HDL than WT. DKO showed sustained kidney injury molecule-1 protein expression. Kidney fibrosis was significantly higher in ApoEKO and DKO. mRNA expression of genes related to kidney fibrosis was the highest in DKO. The mRNA expression of Zinc-α2-Glycoprotein and heme oxygenase-1 were significantly decreased in DKO. Furthermore, mRNA expression of p53, p21 and p16 were increased both in ApoEKO and DKO, with DKO being the highest. Senescence associated β-gal positive tubule area was significantly increased in DKO. Increased DNA damage and target of rapamycin–autophagy spatial coupling compartments (TASCCs) formation was found in DKO. Mice with endothelial dysfunction and dyslipidemia developed kidney fibrosis and accelerated senescence even in young mice after injury. These data highlight the fact managing lifestyle-related diseases from a young age is important for CKD prevention.

Nanocell-mediated delivery of miR-34a counteracts temozolomide resistance in glioblastoma

BackgroundGlioblastoma is the most common primary brain tumor and remains uniformly fatal, highlighting the dire need for developing effective therapeutics. Significant intra- and inter-tumor heterogeneity and inadequate delivery of therapeutics across blood–brain barrier continue to be significant impediments towards developing therapies which can significantly enhance survival. We hypothesize that microRNAs have the potential to serve as effective therapeutics for glioblastoma as they modulate the activity of multiple signaling pathways, and hence can counteract heterogeneity if successfully delivered.MethodsUsing a computational approach, we identified microRNA-34a as a microRNA that maximally reduces the activation status of the three core signaling networks (the receptor tyrosine kinase, p53 and Rb networks) that have been found to be deregulated in most glioblastoma tumors. Glioblastoma cultures were transfected with microRNA-34a or control microRNA to assess biological function and therapeutic potential in vitro. Nanocells were derived from genetically modified bacteria and loaded with microRNA-34a for intravenous administration to orthotopic patient-derived glioblastoma xenografts in mice.ResultsOverexpression of microRNA-34a strongly reduced the activation status of the three core signaling networks. microRNA-34a transfection also inhibited the survival of multiple established glioblastoma cell lines, as well as primary patient-derived xenograft cultures representing the proneural, mesenchymal and classical subtypes. Transfection of microRNA-34a enhanced temozolomide (TMZ) response in in vitro cultures of glioblastoma cells with primary TMZ sensitivity, primary TMZ resistance and acquired TMZ resistance. Mechanistically, microRNA-34a downregulated multiple therapeutic resistance genes which are associated with worse survival in glioblastoma patients and are enriched in specific tumor spatial compartments. Importantly, intravenous administration of nanocells carrying miR-34a and targeted to epidermal growth factor receptor (EGFR) strongly enhanced TMZ sensitivity in an orthotopic patient-derived xenograft mouse model of glioblastoma.ConclusionsTargeted bacterially-derived nanocells are an effective vehicle for the delivery of microRNA-34a to glioblastoma tumors. microRNA-34a inhibits survival and strongly sensitizes a wide range of glioblastoma cell cultures to TMZ, suggesting that combination therapy of TMZ with microRNA-34a loaded nanocells may serve as a novel therapeutic approach for the treatment of glioblastoma tumors.

Connexins and the Epithelial Tissue Barrier: A Focus on Connexin 26

Simple SummaryTissues that face the external environment are known as ‘epithelial tissue’ and form barriers between different body compartments. This includes the outer layer of the skin, linings of the intestine and airways that project into the lumen connecting with the external environment, and the cornea of the eye. These tissues do not have a direct blood supply and are dependent on exchange of regulatory molecules between cells to ensure co-ordination of tissue events. Proteins known as connexins form channels linking cells directly and permit exchange of small regulatory signals. A range of environmental stimuli can dysregulate the level of connexin proteins and or protein function within the epithelia, leading to pathologies including non-healing wounds. Mutations in these proteins are linked with hearing loss, skin and eye disorders of differing severity. As such, connexins emerge as prime therapeutic targets with several agents currently in clinical trials. This review outlines the role of connexins in epithelial tissue and how their dysregulation contributes to pathological pathways.Epithelial tissue responds rapidly to environmental triggers and is constantly renewed. This tissue is also highly accessible for therapeutic targeting. This review highlights the role of connexin mediated communication in avascular epithelial tissue. These proteins form communication conduits with the extracellular space (hemichannels) and between neighboring cells (gap junctions). Regulated exchange of small metabolites less than 1kDa aide the co-ordination of cellular activities and in spatial communication compartments segregating tissue networks. Dysregulation of connexin expression and function has profound impact on physiological processes in epithelial tissue including wound healing. Connexin 26, one of the smallest connexins, is expressed in diverse epithelial tissue and mutations in this protein are associated with hearing loss, skin and eye conditions of differing severity. The functional consequences of dysregulated connexin activity is discussed and the development of connexin targeted therapeutic strategies highlighted.

Multi-Compartment Spatially-Derived Radiomics From Optical Coherence Tomography Predict Anti-VEGF Treatment Durability in Macular Edema Secondary to Retinal Vascular Disease: Preliminary Findings.

Objective: Diabetic macular edema (DME) and retinal vein occlusion (RVO) are the leading causes of visual impairments across the world. Vascular endothelial growth factor (VEGF) stimulates breakdown of blood-retinal barrier that causes accumulation of fluid within macula. Anti-VEGF therapy is the first-line treatment for both the diseases; however, the degree of response varies for individual patients. The main objective of this work was to identify the (i) texture-based radiomics features within individual fluid and retinal tissue compartments of baseline spectral-domain optical coherence tomography (SD-OCT) images and (ii) the specific spatial compartments that contribute most pertinent features for predicting therapeutic response. Methods: A total of 962 texture-based radiomics features were extracted from each of the fluid and retinal tissue compartments of OCT images, obtained from the PERMEATE study. Top-performing features selected from the consensus of different feature selection methods were evaluated in conjunction with four different machine learning classifiers: Linear Discriminant Analysis (LDA), Quadratic Discriminant Analysis (QDA), Random Forest (RF), and Support Vector Machine (SVM) in a cross-validated approach to distinguish eyes tolerating extended interval dosing (non-rebounders) and those requiring more frequent dosing (rebounders). Results: Combination of fluid and retinal tissue features yielded a cross-validated area under receiver operating characteristic curve (AUC) of 0.78±0.08 in distinguishing rebounders from non-rebounders. Conclusions: This study revealed that the texture-based radiomics features pertaining to IRF subcompartment were most discriminating between rebounders and non-rebounders to anti-VEGF therapy. Clinical Impact: With further validation, OCT-based imaging biomarkers could be used for treatment management of DME patients.

Travel restrictions during pandemics: A useful strategy?

Though carrying considerable economic and societal costs, restricting individuals’ traveling freedom appears as a logical way to curb the spreading of an epidemic. However, whether, under what conditions, and to what extent travel restrictions actually exert a mitigating effect on epidemic spreading are poorly understood issues. Recent studies have actually suggested the opposite, i.e., that allowing some movements can hinder the propagation of a disease. Here, we explore this topic by modeling the spreading of a generic contagious disease where susceptible, infected, or recovered point-wise individuals are uncorrelated random-walkers evolving within a space comprising two equally sized separated compartments. We evaluate the spreading process under different separation conditions between the two spatial compartments and a forced relocation schedule. Our results confirm that, under certain conditions, allowing individuals to move from regions of high to low infection rates may turn out to have a positive effect on aggregate; such positive effect is nevertheless reduced if a directional flow is allowed. This highlights the importance of considering travel restriction policies alternative to classical ones.

Automated identification of the mouse brain\u2019s spatial compartments from in situ sequencing data

BackgroundNeuroanatomical compartments of the mouse brain are identified and outlined mainly based on manual annotations of samples using features related to tissue and cellular morphology, taking advantage of publicly available reference atlases. However, this task is challenging since sliced tissue sections are rarely perfectly parallel or angled with respect to sections in the reference atlas and organs from different individuals may vary in size and shape and requires manual annotation. With the advent of in situ sequencing technologies and automated approaches, it is now possible to profile the gene expression of targeted genes inside preserved tissue samples and thus spatially map biological processes across anatomical compartments.ResultsHere, we show how in situ sequencing data combined with dimensionality reduction and clustering can be used to identify spatial compartments that correspond to known anatomical compartments of the brain. We also visualize gradients in gene expression and sharp as well as smooth transitions between different compartments. We apply our method on mouse brain sections and show that a fully unsupervised approach can computationally define anatomical compartments, which are highly reproducible across individuals, using as few as 18 gene markers. We also show that morphological variation does not always follow gene expression, and different spatial compartments can be defined by various cell types with common morphological features but distinct gene expression profiles.ConclusionWe show that spatial gene expression data can be used for unsupervised and unbiased annotations of mouse brain spatial compartments based only on molecular markers, without the need of subjective manual annotations based on tissue and cell morphology or matching reference atlases.

Drug modulation by nuclear condensates.

Concentration of antineoplastic agents into spatial compartments influences activity

Novel specialized cell state and spatial compartments within the germinal center.

Within germinal centers (GCs), complex and highly orchestrated molecular programs must balance proliferation, somatic hypermutation (SHM) and selection to both provide effective humoral immunity and to protect against genomic instability and neoplastic transformation. In contrast to this complexity, GC B cells are canonically divided into two principal populations, dark zone (DZ) and light zone (LZ) cells. We now demonstrate that following selection in the LZ, B cells migrated to specialized sites within the canonical DZ that contained tingible body macrophages (TBMs) and were sites of ongoing cell division. Proliferating DZ (DZp) cells then transited into the larger DZ to become differentiating DZ (DZd) cells before re-entering the LZ. Multidimensional analysis revealed distinct molecular programs in each population commensurate with observed compartmentization of non-compatable functions. These data provide a new three-cell population model that both orders critical GC functions and reveals essential molecular programs of humoral adaptive immunity.

Calibration of the Welding Advanced REACH Tool (weldART).

This paper reports a study to develop and calibrate a deterministic model of welding fume exposure based on a four-compartment mass-balance model - The Welding Advanced REACH Tool (weldART). To achieve this aim, measurements of welding fume exposure were collected along with data on exposure determinants needed in the modelling. The welding fume exposure data was obtained from workers in a structural steel fabrication plant. Welders were engaged in three processes: flux-cored arc welding (FCAW), shielded metal arc welding (SMAW) and gas tungsten arc welding (GTAW). Aerosol concentration was measured using 13mm diameter Swinnex sampling heads and MicroPEM direct-reading aerosol monitors. The model was initially developed with three spatial compartments (near-field (NF), far-field (FF), and welding plume (WP)). However, in the welding scenario investigated the FF had a very large volume and it was necessary to subdivide the room volume into an intermediate zone representing the FF along with the remaining room zone (RM). We fitted linear equations forced through the origin to the gravimetric concentrations measured inside the welders' visor and the weldART model estimates. The flowrates between the model compartments were adjusted by trial and error to obtain proportionate concentrations in each compartment. The FCAW process generated higher welding fume particulate concentrations than SMAW and GTAW. The MicroPEM monitors considerably underestimated and were poorly correlated with the corresponding data from the Swinnex samplers. It was concluded that the MicroPEM data were unreliable. The model calibration showed a strong association between the personal exposure measurement and the weldART model values (R2=0.94), with the average estimated value 1.3 times the measurements. The NF and the FF model estimates were poorly correlated with the corresponding compartment measurements (R2=0.37 and 0.35, respectively), although on average the model estimates were close to the measurement data (ratio of modelled to measured 0.9, and 1.0, respectively). The calibration shows that the weldART model is able to predict the exposure of welding fume particulate.

Tetrapod Polymersomes.

Hollow nanoparticles such as polymersomes have promising potentials in many fields. However, the design and construction of higher-order polymersomes with precisely controlled spatial compartments is still very challenging. Herein, we report a unique tetrapod polymersome that is assembled by the controlled fusion of four traditional spherical polymersomes. This original species was prepared from poly(ethylene oxide)113-b-poly[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl methacrylate61-stat-2-(diethylamino)ethyl methacrylate23] [PEO113-b-P(TBA61-stat-DEA23)] in DMF/water at lower water content (Cw), where PEO acts as corona forming block. To unravel the secret behind the tetrapod polymersomes, a series of block copolymers with various comonomer types and degrees of polymerization were synthesized and self-assembled. PEO113-b-PTBA80 self-assembles into spherical micelles in DMF/water, and the subsequent evolution into tripod and multipod micelles and finally micelle clusters was achieved by increasing Cw. This suggests that relatively rigid TBA is a "pro-fusion" component that facilitates particle-particle fusion due to its providential hydrophobicity and chain mobility. When one-fourth of TBA of PEO113-b-PTBA80 is substituted by DEA, spherical polymersomes of PEO113-b-P(TBA61-stat-DEA23) are born in DMF/water and then fused into dipod, tripod (Cw = 95%), and finally tetrapod polymersomes (Cw = 100%) upon increasing Cw, suggesting that flexible DEA is not only a promoter for hollow pods but also an "anti-fusion" component that can compromise with pro-fusion force for its high chain mobility. The formation of either tetrapod polymersomes or micelle clusters is a matter of balance between pro-fusion and anti-fusion forces. Overall, we provide a fresh insight for the preparation of tetrapod polymersomes as well as other higher-order structures with precisely defined spatial compartments by fusion-induced particle assembly (FIPA).

Isoform‐resolved correlation analysis between mRNA abundance regulation and protein level degradation

Profiling of biological relationships between different molecular layers dissects regulatory mechanisms that ultimately determine cellular function. To thoroughly assess the role of protein post‐translational turnover, we devised a strategy combining pulse stable isotope‐labeled amino acids in cells (pSILAC), data‐independent acquisition mass spectrometry (DIA‐MS), and a novel data analysis framework that resolves protein degradation rate on the level of mRNA alternative splicing isoforms and isoform groups. We demonstrated our approach by the genome‐wide correlation analysis between mRNA amounts and protein degradation across different strains of HeLa cells that harbor a high grade of gene dosage variation. The dataset revealed that specific biological processes, cellular organelles, spatial compartments of organelles, and individual protein isoforms of the same genes could have distinctive degradation rate. The protein degradation diversity thus dissects the corresponding buffering or concerting protein turnover control across cancer cell lines. The data further indicate that specific mRNA splicing events such as intron retention significantly impact the protein abundance levels. Our findings support the tight association between transcriptome variability and proteostasis and provide a methodological foundation for studying functional protein degradation.

Towards an integrative understanding of soil biodiversity.

ABSTRACTSoil is one of the most biodiverse terrestrial habitats. Yet, we lack an integrative conceptual framework for understanding the patterns and mechanisms driving soil biodiversity. One of the underlying reasons for our poor understanding of soil biodiversity patterns relates to whether key biodiversity theories (historically developed for aboveground and aquatic organisms) are applicable to patterns of soil biodiversity. Here, we present a systematic literature review to investigate whether and how key biodiversity theories (species–energy relationship, theory of island biogeography, metacommunity theory, niche theory and neutral theory) can explain observed patterns of soil biodiversity. We then discuss two spatial compartments nested within soil at which biodiversity theories can be applied to acknowledge the scale‐dependent nature of soil biodiversity.

The Genomic Code: A Pervasive Encoding/Molding of Chromatin Structures and a Solution of the “Non‐Coding DNA” Mystery

Recent investigations have revealed 1) that the isochores of the human genome group into two super-families characterized by two different long-range 3D structures, and 2) that these structures, essentially based on the distribution and topology of short sequences, mold primary chromatin domains (and define nucleosome binding). More specifically, GC-poor, gene-poor isochores are low-heterogeneity sequences with oligo-A spikes that mold the lamina-associated domains (LADs), whereas GC-rich, gene-rich isochores are characterized by single or multiple GC peaks that mold the topologically associating domains (TADs). The formation of these "primary TADs" may be followed by extrusion under the action of cohesin and CTCF. Finally, the genomic code, which is responsible for the pervasive encoding and molding of primary chromatin domains (LADs and primary TADs, namely the "gene spaces"/"spatial compartments") resolves the longstanding problems of "non-coding DNA," "junk DNA," and "selfish DNA" leading to a new vision of the genome as shaped by DNA sequences.