Miracle-dz/UniFAR-FTUs huggingface dataset:
Evolutionary feedbacks between genes and their extended effects under limited gene flow and biased ecological inheritance

Organisms continuously modify their living conditions via extended genetic effects on their environment, microbiome, and in some species culture. These effects can impact the fitness of current but also future conspecifics due to non-genetic ecological inheritance. As previously established, biased ecological inheritance towards offspring or spatial structure are relevant to the evolution of extended genetic effects as each leads to kin selection. However the combined effects of these two factors remain unexplored. Here, we mathematically investigate selection on a genetic trait with extended effects in a patch-structured population, when extended effects experience biased transmission within patches and dispersal between patches is limited. Our analysis reveals that the interaction between these two factors opens previously undescribed pathways for nongenetic modifications to feed back on relatives. By disentangling these feedbacks, our results help understand adaptation via non-genetic modifications. As an illustration, we apply our analysis to a gene-culture coevolution scenario in which genetically-determined learning strategies coevolve with adaptive knowledge. We show that vertical cultural transmission combined with limited dispersal favour strategies that generate significant levels of knowledge. More broadly, our theory yields insights into the interplay between genetic and non-genetic inheritance, with implications for how organisms evolve to transform their environments.
True S-cones are concentrated in the ventral mouse retina for color detection in the upper visual field

Color, an important visual cue for survival, is encoded by comparing signals from photoreceptors with different spectral sensitivities. The mouse retina expresses a short wavelength-sensitive and a middle/long wavelength-sensitive opsin (S- and M-opsin), forming opposing, overlapping gradients along the dorsal-ventral axis. Here, we analyzed the distribution of all cone types across the entire retina for two commonly used mouse strains. We found, unexpectedly, that ‘true’ S-cones (S-opsin only) are highly concentrated (up to 30% of cones) in ventral retina. Moreover, S-cone bipolar cells (SCBCs) are also skewed towards ventral retina, with wiring patterns matching the distribution of true S-cones. In addition, true S-cones in the ventral retina form clusters, which may augment synaptic input to SCBCs. Such a unique true S-cone pattern forms a basis for mouse color vision, likely reflecting evolutionary adaption to enhance color coding for the upper visual field suitable for mice’s habitat and behavior.
Genomic landscape of tumor-host interactions with differential prognostic and predictive connotations

An immune active cancer phenotype typified by a T helper 1 (Th-1) immune response has been associated with increased responsiveness to immunotherapy and favorable prognosis in some but not all cancer types. The reason of this differential prognostic connotation remains unknown. Through a multi-modal Pan-cancer analysis among 31 different histologies (9,282 patients), we demonstrated that the favorable prognostic connotation conferred by the presence of a Th-1 immune response was abolished in tumors displaying specific tumor-cell intrinsic attributes such as high TGF-ß signaling and low proliferation capacity. This observation was validated in the context of immune-checkpoint inhibition. WNT-ß catenin, barrier molecules, Notch, hedgehog, mismatch repair, telomerase activity, and AMPK signaling were the pathways most coherently associated with an immune silent phenotype together with mutations of driver genes including IDH1/2, FOXA2, HDAC3, PSIP1, MAP3K1, KRAS, NRAS, EGFR, FGFR3, WNT5A, and IRF7. Our findings could be used to prioritize hierarchically relevant targets for combination therapies and to refine stratification algorithms.
L(3)mbt and the LINT complex safeguard tissue identity in the Drosophila ovary

Maintenance of cellular identity is essential for tissue development and homeostasis. At the molecular level, cell identity is determined by the coordinated activation and repression of defined sets of genes. Defects in the maintenance of the genetic programs required for identity can have dire consequences such as organ malformation and cancer. The tumor suppressor L(3)mbt was shown to secure cellular identity in Drosophila larval brains by repressing germline-specific genes. Here we interrogate the temporal and spatial requirements for L(3)mbt in the Drosophila ovary, and show that it safeguards the integrity of both somatic and germline tissues. L(3)mbt mutant ovaries exhibit multiple developmental defects, which we find to be largely caused by the inappropriate expression of a single gene, nanos, a key regulator of germline fate, in the somatic cells of the ovary. In the female germline, we find that L(3)mbt represses testis-specific and neuronal genes. Molecularly, we show that L(3)mbt function in the ovary is mediated through its cofactor Lint1 but independent of the dREAM complex. Together, our work uncovers a more complex role for L(3)mbt than previously understood and demonstrates that L(3)mbt secures tissue identity by preventing the simultaneous expression of original identity markers and tissue-specific misexpression signatures.
Resilience in HIV/AIDS' adolescent headed families

HIV/AIDS has presented humanity with various challenges, one of which is the manner in which it has affected family structure and patterns. Parental illness and eventual death due to the HIV/AIDS pandemic is escalating. One of the major challenges of HIV/AIDS in southern Africa is the increase in the number of orphaned and vulnerable children. As a result new family forms are emerging such as the "skip-generation" family in which children or adolescent siblings head the family. It is anticipated that HIV/AIDS in South Africa will progressively increase the number of such families. During this time of profound family change, the family as an institution has remained remarkably resilient. The present study utilised the Family Resilience Framework and the Resiliency Model of Family Stress, Adjustment and Adaptation to explore and describe the resilience of HIV/AIDS’ adolescent headed families. A qualitative, exploratory-descriptive research design, which was assessed against Guba’s (1985) model of trustworthiness, was employed and the participants were sampled using non-probability purposive sampling. The Masizakhe Community Project volunteers (an AIDS Community Project in Kwazakhele, Port Elizabeth receiving support from the iThemba AIDS Foundation) assisted in identifying participants according to the predetermined inclusion criteria. The sample consisted of four female, adolescent heads of HIV/AIDS’ affected households, who volunteered at the Masizakhe Community Project and resided in Kwazakhele. The data that was collected via audio-recorded semi structured interviews were transcribed verbatim and subjected to Interpretive Phenomenological Analysis. Family resilience factors that emerged included intrafamilial strengths (family cohesion, organisation, hardiness, and adaptability); social support resources (especially from the community project, friends, and
Massive rhizobial genomic variations associated with partner quality in Lotus–Mesorhizobium symbiosis

In diverse mutualistic relationships, genetic variations in impact on the growth of interacting partners—variations in partner quality—are common, despite the theoretical prediction that selection favoring high-quality partners should eliminate such variations. Here, we investigated how variations in partner quality could be maintained in the nitrogen-fixing mutualism between Lotus japonicus and Mesorhizobium bacteria. We reconstructed de novo assembled full-genome sequences from nine rhizobial symbionts, finding massive variations in the core genome and the contrastingly similar symbiotic islands, indicating recent horizontal gene transfer (HGT) of the symbiosis islands into diverse Mesorhizobium lineages. A cross-inoculation experiment using nine sequenced rhizobial symbionts and 15 L. japonicus accessions revealed extensive quality variations represented by plant growth phenotypes, including genotype-by-genotype interactions. Quality variations were not associated with the presence/absence variations of known symbiosis-related genes in the symbiosis island, but rather, showed significant correlations with the core genome variations, supported by SNP- and kinship matrix-based association analyses. These findings highlight the novel role of HGT of symbiosis islands, which indirectly supply mutations of core genomes into L. japonicus-associated bacteria, thereby contributing to the maintenance of variations in partner quality.
ZFP423 regulates early patterning and multiciliogenesis in the hindbrain choroid plexus

ABSTRACT The choroid plexus (ChP) is a secretory tissue that produces cerebrospinal fluid (CSF) secreted into the ventricular system. It is a monolayer of secretory, multiciliated epithelial cells derived from neuroepithelial progenitors and overlying a stroma of mesenchymal cells of mesodermal origin. Zfp423, which encodes a Kruppel-type zinc-finger transcription factor essential for cerebellar development and mutated in rare cases of cerebellar vermis hypoplasia/Joubert syndrome and other ciliopathies, is expressed in the hindbrain roof plate, from which the IV ventricle ChP arises, and, later, in mesenchymal cells, which give rise to the stroma and leptomeninges. Mouse Zfp423 mutants display a marked reduction of the hindbrain ChP (hChP), which: (1) fails to express established markers of its secretory function and genes implicated in its development and maintenance (Lmx1a and Otx2); (2) shows a perturbed expression of signaling pathways previously unexplored in hChP patterning (Wnt3); and (3) displays a lack of multiciliated epithelial cells and a profound dysregulation of master genes of multiciliogenesis (Gmnc). Our results propose that Zfp423 is a master gene and one of the earliest known determinants of hChP development. Summary: The zinc-finger protein 423, a transcription factor and protein-protein interaction hub, is identified as a master gene in hindbrain choroid plexus patterning and multiciliogenesis.
Transcriptional down-regulation of metabolic genes by Gdown1 ablation induces quiescent cell re-entry into the cell cycle

Liver regeneration and metabolism are highly interconnected. Here, we show that hepatocyte-specific ablation of RNA polymerase II (Pol II)-associated Gdown1 leads to down-regulation of highly expressed genes involved in plasma protein synthesis and metabolism, a concomitant cell cycle re-entry associated with induction of cell cycle-related genes (including cyclin D1). and up-regulation of p21 through activation of p53 signaling. In the absence of p53, Gdown1-deficient hepatocytes show a severe dysregulation of cell cycle progression, with incomplete mitoses, and a pre-malignant-like transformation. Mechanistically, Gdown1 is associated with elongating Pol II on the highly expressed genes and its ablation leads to reduced Pol II recruitment to these genes, suggesting that Pol II redistribution may facilitate hepatocyte re-entry into the cell cycle. These results establish an important physiological function for a Pol II regulatory factor (Gdown1) in the maintenance of normal liver cell transcription through constraints on cell cycle re-entry of quiescent hepatocytes.
Analysis of an experimental transition in individuality challenges the need to assign traits to levels

A major evolutionary transition in individuality, at any level of the biological hierarchy, occurs when groups become capable of participating in Darwinian processes as units of selection. Identifying transitions in individuality can be problematic because apparent selection at one level of the biological hierarchy may be a by-product of selection occurring at another level. Here we discuss various approaches to this ′levels-of-selection′ problem, drawing attention to the futility of designating traits to hierarchical levels prior to determining the level of selection. While individuals can exhibit traits that are maintained by selection at any level in the biological hierarchy, terms synonymous with ′collective (group) trait′ or ′particle trait′ are often applied prematurely. We argue that traits should not be assigned a priori to a hierarchical level, but may respond to selection at different levels depending on environmental conditions. This point is illustrated by an experiment in which groups of the bacterium Pseudomonas fluorescens reproduced via life cycles involving soma- and germline-like phases. The rate of transition between the two cell types was a focus of selection, and might be regarded as a property of groups, cells, or even genes. Philosophical analyses reveal that this trait evolved to be higher in one treatment as a result of its emergent relation to group fitness (contributing to the evolution of individuality), and lower in another treatment because of cell-level selection. An a priori designation of transition rate as either a ′group trait′ or a ′cell trait′ may have masked the true level of selection.
A gut sensor for sugar preference

Animals innately prefer caloric sugars over non-caloric sweeteners. Such preference depends on the sugar entering the intestine.1–4 Although the brain is aware of the stimulus within seconds,5–8 how the gut discerns the caloric sugar to guide choice is unknown. Recently, we discovered an intestinal transducer, known as the neuropod cell.9,10 This cell synapses with the vagus to inform the brain about glucose in the gut in milliseconds.10 Here, we demonstrate that neuropod cells distinguish a caloric sugar from a non-caloric sweetener using the electrogenic sodium glucose co-transporter 1 (SGLT1) or sweet taste receptors. Activation of neuropod cells by non-caloric sucralose leads to ATP release, whereas the entry of caloric sucrose via SGLT1 stimulates glutamate release. To interrogate the contribution of the neuropod cell to sugar preference, we developed a method to record animal preferences in real time while using optogenetics to silence or excite neuropod cells. We discovered that silencing these cells, or blocking their glutamatergic signaling, renders the animals unable to recognize the caloric sugar. And, exciting neuropod cells leads the animal to consume the non-caloric sweetener as if it were caloric. By transducing the precise identity of the stimuli entering the gut, neuropod cells guide an animal’s internal preference toward the caloric sugar.
Network structure of the mouse brain connectome with voxel resolution

Fine-grained descriptions of brain connectivity are fundamental for understanding how neural information is processed and relayed across spatial scales. Prior investigations of the mouse brain connectome have employed discrete anatomical parcellations, limiting spatial resolution and potentially concealing network attributes critical to the organization of the mammalian connectome. Here we provide a voxel-level description of the network and hierarchical structure of the directed mouse connectome, unconstrained by regional partitioning. We show that integrative hub regions can be directionally segregated into neural sinks and sources, defining a hierarchical axis. We describe a set of structural communities that spatially reconstitute previously described fMRI networks of the mouse brain, and document that neuromodulatory nuclei are strategically wired as critical orchestrators of inter-modular and network communicability. Notably, like in primates, the directed mouse connectome is organized along two superimposed cortical gradients reflecting unimodal-transmodal functional processing and a modality-specific sensorimotor axis. These structural features can be related to patterns of intralaminar connectivity and to the spatial topography of dynamic fMRI brain states, respectively. Together, our results reveal a high-resolution structural scaffold linking mesoscale connectome topography to its macroscale functional organization, and create opportunities for identifying targets of interventions to modulate brain function in a physiologically-accessible species.
A framework to identify structured behavioral patterns within rodent spatial trajectories

Animal behavior is highly structured. Yet, structured behavioral patterns—or “statistical ethograms”—are not immediately apparent from the full spatiotemporal data that behavioral scientists usually collect. Here, we introduce a framework to quantitatively characterize rodent behavior during spatial (e.g., maze) navigation, in terms of movement building blocks or motor primitives . The hypothesis that we pursue is that rodent behavior is characterized by a small number of motor primitives, which are combined over time to produce open-ended movements. We assume motor primitives to be organized in terms of two sparsity principles: each movement is controlled using a limited subset of motor primitives (sparse superposition) and each primitive is active only for time-limited, time-contiguous portions of movements (sparse activity). We formalize this hypothesis using a sparse dictionary learning method, which we use to extract motor primitives from rodent position and velocity data collected during spatial navigation, and successively to reconstruct past trajectories and predict novel ones. Three main results validate our approach. First, rodent behavioral trajectories are robustly reconstructed from incomplete data, performing better than approaches based on standard dimensionality reduction methods, such as principal component analysis, or single sparsity. Second, the motor primitives extracted during one experimental session generalize and afford the accurate reconstruction of rodent behavior across successive experimental sessions in the same or in modified mazes. Third, in our approach the number of motor primitives associated with each maze correlates with independent measures of maze complexity, hence showing that our formalism is sensitive to essential aspects of task structure. The framework introduced here can be used by behavioral scientists and neuroscientists as an aid for behavioral and neural data analysis. Indeed, the extracted motor primitives enable the quantitative characterization of the complexity and similarity between different mazes and behavioral patterns across multiple trials (i.e., habit formation). We provide example uses of this computational framework, showing how it can be used to identify behavioural effects of maze complexity, analyze stereotyped behavior, classify behavioral choices and predict place and grid cell displacement in novel environments.
Narrow oviposition preference of an insect herbivore risks survival under conditions of severe drought

Understanding species’ habitat preferences are crucial to predict organisms’ responses to the current climate crisis. In many insects, maternal habitat selection for oviposition essentially determines offspring performance. Whether changes in climatic conditions may pose future mismatches in oviposition preference and offspring performance when mothers continue to prefer microhabitats that now threaten offspring survival is an open question. To address this, we tested if oviposition preferences put offspring at risk in the Glanville fritillary butterfly (Melitaea cinxia) under drought stress. Mainly, we focus on identifying the microhabitat determinants for oviposition and the variation of conditions experienced by the sessile offspring, using field observations from 12 populations collected over 2015-2018. These data are combined with ten years of larval nest and precipitation data to understand within-population patterns of habitat selection. We tested whether the preferred microhabitats maximized the extended larval performance (i.e. overwinter survival). We found that females preferentially oviposited in microhabitats with higher host plant abundance and higher proportion of host plants with signs of drought stress. In most years, larval nests had higher survival in these drought-stressed microhabitats. However, in an extremely dry year, only two nests survived over the summer. Our results highlight that a failure to shift habitat preference under extreme climate conditions may have drastic consequences for the survival of natural populations under changing climatic conditions.
Disentangling latent representations of single cell RNA-seq experiments

Single cell RNA sequencing (scRNA-seq) enables transcriptional profiling at the resolution of individual cells. These experiments measure features at the level of transcripts, but biological processes of interest often involve the complex coordination of many individual transcripts. It can therefore be difficult to extract interpretable insights directly from transcript-level cell profiles. Latent representations which capture biological variation in a smaller number of dimensions are therefore useful in interpreting many experiments. Variational autoencoders (VAEs) have emerged as a tool for scRNA-seq denoising and data harmonization, but the correspondence between latent dimensions in these models and generative factors remains unexplored. Here, we explore training VAEs with modifications to the objective function (i.e. β-VAE) to encourage disentanglement and make latent representations of single cell RNA-seq data more interpretable. Using simulated data, we find that VAE latent dimensions correspond more directly to data generative factors when using these modified objective functions. Applied to experimental data of stimulated peripheral blood mononuclear cells, we find better correspondence of latent dimensions to experimental factors and cell identity programs, but impaired performance on cell type clustering. Publication Status This pre-print represents the final output of a preliminary research direction and will not be updated or published in an archival journal. We are happy to discuss future directions we believe to be promising with any interested researchers.
Social Competence and Obesity in Teenagers: An Analysis of the Last Ten Years of Studies

Socially competent people using better strategies for solving interpersonal problems are more readily accepted by peers and valued by adults. Obese individuals, especially teenagers, have deficits in several social skills, which lead to damage to the relationships, self-esteem and in their valuation by social agents. This study examines how the literature of the last decade associates the components of social competence to obesity in adolescents. The research was carried out in electronic databases in the period between Jan. 2005 and Dec. 2015, resulting in 329 articles. 303 were excluded as they did not meet the inclusion criteria, and 26 original articles have been analyzed. The results showed that the components of social competence were negatively associated with obesity and most studies focused on self-esteem, pattern of interaction with peers and social relationship. The social competence was highlighted as important for interventions aimed at reducing weight.