Miracle-dz/UniFAR-FTUs huggingface dataset:
A lipid-associated macrophage lineage rewires the spatial landscape of adipose tissue in early obesity

Objective Obesity-induced metabolic dysfunction, tissue remodelling, and chronic inflammation in visceral white adipose-tissue (WAT) are correlated with insulin resistance, type II diabetes, and metabolic disease pathogenesis [1]. In this work, we sought to establish spatio-temporal context of adipose tissue macrophage (ATM) reprogramming during obesity. Methods We captured single-cell RNA-sequencing, spatial transcriptomics, and histological imagining of murine WAT over the course of diet-induced obesity to study macrophage phenotype dynamics. We developed a straightforward mathematical approach to integrating multi-modal data to quantify obesityinduced changes to WAT organization. We aligned ATM phenotypes with crown-like structures (CLS) in early obesity and used spatial network analysis to uncover signalling mechanisms implicated in CLS formation. Results We identified novel diversity of the lipid-associated macrophage (LAM) phenotype, whose transcriptional profile, signaling mechanisms, and spatial context serve as indicators of CLS formation in early obesity. We demonstrated that dysregulation of lipid-metabolic signalling is a critical turning point in the monocyte-LAM lineage and identified novel ligand-receptor mechanisms including Apoe, Lrp1, Lpl and App that serve as hallmarks of nascent CLS in WAT. Conclusions Multi-modal spatio-temporal profiling demonstrates that LAMs disproportionately accumulate in CLS and are preceded by a transition-state macrophage phenotype with monocytic origins. We identified novel ligand-receptor interactions implicated in nascent CLS regions which may guide future cellular-reprogramming interventions for obesity-related sequelae. Graphical Abstract Highlights - We characterize a novel lipid-associated macrophage (LAM) phenotype along the monocyte-LAM lineage - Integrated imaging, single-cell sequencing and spatial transcriptomics data show that LAMs accumulate at nascent CLS - Analysis of spatial transcriptomics data reveals a novel set of ligands and receptors that implicate immature LAMs in shaping the CLS microenvironment in early obesity - We present a simple mathematical framework for studying dynamics of tissue-structure over time
Epistasis facilitates functional evolution in an ancient transcription factor

A protein’s genetic architecture – the set of causal rules by which its sequence produces its functions – also determines its possible evolutionary trajectories. Prior research has proposed that genetic architecture of proteins is very complex, with pervasive epistatic interactions that constrain evolution and make function difficult to predict from sequence. Most of this work has analyzed only the direct paths between two proteins of interest – excluding the vast majority of possible genotypes and evolutionary trajectories – and has considered only a single protein function, leaving unaddressed the genetic architecture of functional specificity and its impact on the evolution of new functions. Here we develop a new method based on ordinal logistic regression to directly characterize the global genetic determinants of multiple protein functions from 20-state combinatorial deep mutational scanning (DMS) experiments. We use it to dissect the genetic architecture and evolution of a transcription factor’s specificity for DNA, using data from a combinatorial DMS of an ancient steroid hormone receptor’s capacity to activate transcription from two biologically relevant DNA elements. We show that the genetic architecture of DNA recognition consists of a dense set of main and pairwise effects that involve virtually every possible amino acid state in the protein-DNA interface, but higher-order epistasis plays only a tiny role. Pairwise interactions enlarge the set of functional sequences and are the primary determinants of specificity for different DNA elements. They also massively expand the number of opportunities for single-residue mutations to switch specificity from one DNA target to another. By bringing variants with different functions close together in sequence space, pairwise epistasis therefore facilitates rather than constrains the evolution of new functions.
Sensitivity of Diagnosed Convective Fluxes to Model Assumptions

Abstract The sensitivity of diagnosed cloud mass and heat fluxes over tropical oceans to assumptions about cumulus-scale updrafts and downdrafts is tested. The ensemble of clouds investigated is the population of precipitating clouds observed in GATE. The basic input to the calculations is radar data. However, a previous paper shows that the same sensitivity is involved in diagnostic calculations based on large-scale heat and moisture budgets. The assumptions investigated include the relationship between entrainment rate and cloud size, thermodynamic conditions at the base of convective updrafts. thermodynamic properties of entrained air, thermodynamic conditions at the tops of convective downdrafts. and the mass flux profiles in the updrafts and downdrafts. Diagnostic results are most sensitive to the relation between cloud size and entrainment rate and the thermodynamic conditions at the base of the updraft. It is found that assumed mass flux profiles that do not concentrate all of the detrainment from .
Wing morphology variations in Culicoides circumscriptus from France

The biting midge Culicoides circumscriptus Kieffer, 1918 is a European widespread vector of avian malaria throughout the continent and is a possible vector of Akabane virus and Bluetongue virus. This species populates a wide range of environments in contrasting ecological settings often exposed to strong seasonal fluctuations. The main goals of this study were to investigate C. circumscriptus phenotypic variation at three departments in France (Corsica Island, Moselle and Var) and to determine if its phenotypes vary with the environment. Culicoides circumscriptus wing phenotypes were analyzed using a geometric morphometric approach based on anatomical landmarks and outlines of the wing. Dendogram trees based on landmarks and the outlines-2 set (cell m4) showed similar topologies and separated populations of C. circumscriptus. In contrast, another set of outlines-1 (covering the r-m cross vein, M, radiale and arculus) presented a different hierarchical clustering tree. The phenotypic variation observed in C. circumscriptus indicated that these populations are exposed to environmental and ecological pressures. Our results suggest the presence of phenotypic plasticity in this species.
Good, quarrelsome, bad: animal agency and human-elephant interactions in the Western Ghats, India

Ecological breakdowns are posing many serious threats to the lives of both humans and wild animals in the spaces where those lives are shared. Today the intensification of conservation-related conflict is one of the main ecological challenges faced in the Western Ghats of India. This article explores some of the complex interactions between different groups of people, such as wealthy farmers, small-scale farmers, and Adivasi (indigenous) people, and Asian elephants and suggests potentially non-conflictual approaches to sharing spaces with these elephants. The study used a multispecies ethnographic approach as a primary research method and focused on detailed stories and anecdotes narrated by the inhabitants of the study area who had long experience of living with these elephants and who frequently encountered them. Based on insights offered by the stories and anecdotes, the article argues that the lives of elephants and those of people are deeply and intimately interconnected and co-constructed in the study area; such ‘naturecultures’ of elephants and humans constitute a complex whole. The stories highlight that most people in the study area know that elephants have agency and are intelligent, emotional beings, and can subvert human attempts to control them. According to local people, each individual elephant possesses a distinct personality: some are good, some are quarrelsome, and some are bad. People believe that, just as human beings do, elephants also perceive and respond to individual humans differently; such beliefs, and the stories created out of them, are non-anthropocentric in nature. Overall, this article explores how understanding, and treating seriously, the concepts, beliefs, and experiences of multidimensional elephant agency can be beneficial for envisioning possible new ways for human-elephant coexistence.
miRNome of Child A hepatocellular carcinoma in Egyptian patients

Introduction Hepatocellular carcinoma (HCC) has different etiologies that contribute to its heterogeneity. In regards to the number of HCC patients, Egypt ranks third in Africa and fifteenth worldwide. Despite significant advancements in HCC diagnosis and treatment, the precise biology of the tumor is still not fully understood, which has a negative impact on patient outcomes. Methods Advances in next-generation sequencing (NGS) have increased our knowledge of the molecular complexity of HCC. Results & discussion In this research, 16 HCC and 6 tumor adjacent tissues (control) of Child A Egyptian patients were successfully profiled for the expression profile of miRNAs by NGS. Forty-one differentially expressed miRNAs (DEMs) were found by differential expression analysis, with 31 being upregulated and 10 being downregulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was then conducted on these differentially expressed miRNAs revealing that Sensitivity and specificity analysis showed that hsa-miR-4488, hsa-miR-3178, and hsa-miR-3182 were unique miRNAs as they are expressed in HCC tissues only. These miRNAs were all highly involved in AMPK signaling pathways. However, hsa-miR-214-3p was expressed in control tissues about eight times higher than in cancer tissues and was most abundant in “pathways in cancer and PI3K-Akt signaling pathway” KEGG terms. As promising HCC diagnostic markers, we here suggest hsa-miR-4488, hsa-miR-3178, hsa-miR-3182, and hsa-miR-214-3p. We further urge future research to confirm these markers' diagnostic and prognostic potential as well as their roles in the pathophysiology of HCC.
Conditional deletion of KCC2 impairs synaptic plasticity and both spatial and nonspatial memory

The postsynaptic inhibition through GABAA receptors (GABAAR) relies on two mechanisms, a shunting effect due to an increase in the postsynaptic membrane conductance and, in mature neurons, a hyperpolarization effect due to an entry of chloride into postsynaptic neurons. The second effect requires the action of the K+–Cl− cotransporter KCC2 which extrudes Cl− from the cell and maintains its cytosolic concentration very low. Neuronal chloride equilibrium seems to be dysregulated in several neurological and psychiatric conditions such as epilepsy, anxiety, schizophrenia, Down syndrome, or Alzheimer’s disease. In the present study, we used the KCC2 Cre-lox knockdown system to investigate the role of KCC2 in synaptic plasticity and memory formation in adult mice. Tamoxifen-induced conditional deletion of KCC2 in glutamatergic neurons of the forebrain was performed at 3 months of age and resulted in spatial and nonspatial learning impairment. On brain slices, the stimulation of Schaffer collaterals by a theta burst induced long-term potentiation (LTP). The lack of KCC2 did not affect potentiation of field excitatory postsynaptic potentials (fEPSP) measured in the stratum radiatum (dendrites) but increased population spike (PS) amplitudes measured in the CA1 somatic layer, suggesting a reinforcement of the EPSP-PS potentiation, i.e., an increased ability of EPSPs to generate action potentials. At the cellular level, KCC2 deletion induced a positive shift in the reversal potential of GABAAR-driven Cl− currents (EGABA), suggesting an intracellular accumulation of chloride subsequent to the downregulation of KCC2. After treatment with bumetanide, an antagonist of the Na+-K+-Cl− cotransporter NKCC1, spatial memory impairment, chloride accumulation, and EPSP-PS potentiation were rescued in mice lacking KCC2. The presented results emphasize the importance of chloride equilibrium and GABA-inhibiting ability in synaptic plasticity and memory formation.
Horse domestication as a multi-centered, multi-stage process: Botai and the role of specialized Eneolithic horse pastoralism in the development of human-equine relationships

For over a decade there has been general, but not universal, consensus that the earliest known evidence for horse husbandry was at Eneolithic Botai, Kazakhstan, circa 3,500 BCE. Recent ancient genomic analyses, however, indicate that Botai is not the source of modern domestic horse stock (DOM2 lineage), but is instead related to the Przewalski clade of horses. DOM2 appears to instead to have emerged in early Bronze Age (mid 3rd Mill. BCE) in the Pontic-Caspian steppe, and spread quickly replacing other horse lineages after approximately 2,000 BCE. Whilst the specific evidence for earlier husbandry at Botai is not diminished by this evidence, it has broken the consensus regarding the early stages of horse domestication, with some now viewing it as a later event. This paper argues that domestication is rarely an event, but instead a process that is ongoing. The case is made for a “prey pathway” initial phase of domestication in multiple localities during the Eneolithic, which was based around local subsistence pastoralist niche construction. This took different forms due to the presence or absence of ruminant domestic stock in the Eastern European or Central Asian steppes, respectively. Whilst “push” factors likely played a part in the development of horse specialist pastoralism at Botai, it is suggested that “pull” factors accelerated the spread of DOM2 lineages, replacing others, in the later Bronze Age. The DOM2 spread was principally driven, not by local subsistence needs, but wider social, economic and military desirability of equestrianism. The long-term process of horse domestication continues in modernity with major breed changes caused first by the post-medieval agricultural revolution and, more currently, the desire for sporting achievement.
Case Report: Step-by-step procedures for total intracorporeal laparoscopic kidney autotransplantation in a patient with distal high-risk upper tract urothelial carcinoma

A 47-year-old man presented to the emergency department with right abdominal pain and a new onset of painless haematuria two weeks earlier. Urine cytology test results suggested urothelial carcinoma. Computed tomography urography (CTU) showed a filling defect in the lower right ureter with right hydronephrosis. Lymphadenopathy and any signs of metastatic disease were absent on CTU. Cystoscopy appeared normal. Creatinine level was also normal before surgery. After the treatment options were discussed, the patient chose to undergo 3D total intracorporeal laparoscopic kidney autotransplantation, bladder cuff excision, and segmental resection of the proximal two-thirds of the ureter based on the membrane anatomy concept. After more than one year of follow-up, the patient was in good health and showed no signs of haematuria. Surveillance cystoscopy and CTU examination showed no evidence of disease recurrence. Therefore, it is reasonable to assume that kidney-sparing surgery may be considered for carefully selected patients with high-grade upper tract urothelial carcinoma.
Exploring the plankton bacteria diversity and distribution patterns in the surface water of northwest pacific ocean by metagenomic methods

The study of marine microbial communities is crucial for comprehending the distribution patterns, adaptations to the environment, and the functioning of marine microorganisms. Despite being one of the largest biomes on Earth, the bacterioplankton communities in the Northwest Pacific Ocean (NWPO) remain understudied. In this research, we aimed to investigate the structure of the surface bacterioplankton communities in different water masses of the NWPO. We utilized metagenomic sequencing techniques and cited previous 16S rRNA data to explore the distribution patterns of bacterioplankton in different seasons. Our results revealed that Cyanobacteria, Proteobacteria, Bacteroidetes, and Actinobacteria dominated the microbial communities, accounting for over 95% of the total. During spring, we observed significant differentiation in community structure between the different water masses. For instance, Prochlorococcus and Pseudoalteromonas were primarily distributed in the nutrient-deficient subtropical countercurrent zone, while Flavobacteriaceae and Rhodobacteraceae were found in the Kuroshio-Oyashio mixing zone. During summer, the surface planktonic bacteria communities became homogenized across regions, with Cyanobacteria becoming the dominant group (68.6% to 84.9% relative abundance). The metabolic processes of the microorganisms were dominated by carbohydrate metabolism, followed by amino acid transport and metabolism. However, there was a low relative abundance of functional genes involved in carbohydrate metabolism in the Kuroshio-Oyashio mixing zone. The metagenomic data had assembled 37 metagenomic-assembled genomes (MAGs), which belong to Proteobacteria, Bacteroidetes, and Euryarchaeota. In conclusion, our findings highlight the diversity of the surface bacterioplankton community composition in the NWPO, and its distinct geographic distribution characteristics and seasonal variations.
Myography of isolated blood vessels: Considerations for experimental design and combination with supplementary techniques

The study of the mechanisms of regulation of vascular tone is an urgent task of modern science, since diseases of the cardiovascular system remain the main cause of reduction in the quality of life and mortality of the population. Myography (isometric and isobaric) of isolated blood vessels is one of the most physiologically relevant approaches to study the function of cells in the vessel wall. On the one hand, cell-cell interactions as well as mechanical stretch of the vessel wall remain preserved in myography studies, in contrast to studies on isolated cells, e.g., cell culture. On the other hand, in vitro studies in isolated vessels allow control of numerous parameters that are difficult to control in vivo. The aim of this review was to 1) discuss the specifics of experimental design and interpretation of data obtained by myography and 2) highlight the importance of the combined use of myography with various complementary techniques necessary for a deep understanding of vascular physiology.
Selection on Visual Opsin Genes in Diurnal Neotropical Frogs and Loss of the SWS2 Opsin in Poison Frogs

Amphibians are ideal for studying visual system evolution because their biphasic (aquatic and terrestrial) life history and ecological diversity expose them to a broad range of visual conditions. Here we evaluate signatures of selection on visual opsin genes across Neotropical anurans and focus on three diurnal clades that are well-known for the concurrence of conspicuous colors and chemical defense (i.e., aposematism): poison frogs (Dendrobatidae), Harlequin toads (Bufonidae: Atelopus), and pumpkin toadlets (Brachycephalidae: Brachycephalus). We found evidence of positive selection on 44 amino acid sites in LWS, SWS1, SWS2, and RH1 opsin genes, of which one in LWS and two in RH1 have been previously identified as spectral tuning sites in other vertebrates. Given that anurans have mostly nocturnal habits, the patterns of selection revealed new sites that might be important in spectral tuning for frogs, potentially for adaptation to diurnal habits and for color-based intraspecific communication. Furthermore, we provide evidence that SWS2, normally expressed in rod cells in amphibians, has likely been lost in the ancestor of Dendrobatidae, suggesting that under low-light levels, dendrobatids have inferior wavelength discrimination compared to other frogs. This loss might follow the origin of diurnal activity in dendrobatids and could have implications for their chemical ecology, biodiversity, and behavior. Our analyses show that assessments of opsin diversification in understudied groups could expand our understanding of the role of sensory system evolution in ecological adaptation.
Modeling spatial batting ability using a known covariance matrix

In baseball, heat maps, which visualize a batter’s ability across regions in and around the strike zone, play an important role in baseball commentary and scouting reports. We represent the stochastic process underlying these heat maps as a spatial Gaussian field with isotropic covariance. Spatial interpolation (kriging) relies on the assumption of a known covariance function, but in reality the parameters of the covariance are typically estimated from the data. Our simulation study, based on a known covariance function, helps to understand and explain the spatial dependence of the process and allows us to produce improved heat maps.
Analysis of Radiative Transport in a 2-D Cylindrical Participating Medium Subjected to Collimated Radiation

This article deals with the numerical analysis of radiative transport in a 2-D axisymmetric cylindrical enclosure containing absorbing, emitting, and scattering medium. The participating medium receives collimated radiation from the top boundary of the enclosure. Attenuation of the collimated radiation in the medium gives rise to the diffuse radiation. Thus, the governing radiative transfer equation accounts for both collimated and diffuse radiation. The radiative transfer equation is solved using the modified discrete ordinate method. Effects of extinction coefficient, scattering albedo, and aspect ratio on radial and axial distributions of heat flux and incident radiation are studied. In all cases, results are validated against those available in the literature. Modified discrete ordinate method has been found to provide accurate results.
Nonlinear Elasticity: Strain-energy Functions with Multiple Local Minima: Modeling Phase Transformations Using Finite Thermo-elasticity

This chapter provides a brief introduction to the following basic ideas pertaining to thermoelastic phase transitions: the lattice theory of martensite, phase boundaries, energy minimization, WeierstrassErdmann corner conditions, phase equilibrium, nonequilibrium processes, hysteresis, the notion of driving force, dynamic phase transitions, nonuniqueness, kinetic law, nucleation condition, and microstructure.
Amovingboundaryproblemmotivatedbyelectricbreakdown,I:Spectrumof linearperturbations

a b s t r a c t Aninterfacialapproximationofthestreamerstageintheevolutionofsparksandlightningcanbewritten as a Laplacian growth model regularized by a ‘kinetic undercooling’ boundary condition. We study the linear stability of uniformly translating circles that solve the problem in two dimensions. In a space of smoothperturbationsofthecircularshape,thestabilityoperatorisfoundtohaveapurepointspectrum. Exceptfortheeigenvalue 0D0forinfinitesimaltranslations,alleigenvaluesareshowntohavenegative real part. Therefore perturbations decay exponentially in time. We calculate the spectrum through a combination of asymptotic and series evaluation. In the limit of vanishing regularization parameter, all eigenvaluesarefoundtoapproachzeroinasingularfashion,andthisasymptoticbehaviorisworkedout indetail.Aconsiderationoftheeigenfunctionsindicatesthatastrongintermediategrowthmayoccurfor genericinitialperturbations.Boththelinearandthenonlinearinitialvalueproblemareconsideredina secondpaper. ’2009ElsevierB.V. Allrightsreserved.