Biology subjects

Gross, E.

Publications and source records attributed to Gross, E..

10 recordsLinked to original sources

bioRxiv2026

Depth-Dependent Alterations in Cerebral Blood and Tissue Oxygenation Associated with Tau in Alzheimer's Disease Models

Vascular dysfunction is an increasingly recognized feature of Alzheimer's disease, and inadequate oxygen delivery may contribute to neuronal death. However, how cerebral oxygenation relates to neuronal pathology remains unclear. Here, we used two-photon phosphorescence lifetime microscopy with Oxyphor2P to measure intravascular and tissue partial pressure of oxygen (pO2) at 0, 100 and 200 um cortical depth in awake rTg4510 and THY-Tau22 mice. Relative to WT, capillary and venular pO2 in rTg4510 mice were elevated at 6 months but reduced at 9 months, mainly in deeper layers, with increased oxygen extraction fraction. Suppressing the tau transgene with doxycycline for three months did not restore vascular pO2. THY-Tau22 mice, despite limited tangle pathology, showed even greater reductions in capillary pO2 at every depth. In 6-month-old rTg4510 mice, tissue pO2 trended lower than in WT, and the fraction of low pO2 values (< 18 mmHg) increased with depth, reaching 33% at 200 um versus 4% in WT. Labeling neurofibrillary tangles with the tau-binding dye HS84 revealed significantly lower tissue pO2 in tangle-positive areas at 100 and 200 um. Longitudinal imaging of 2,282 neurons showed that disappearing neurons were not located in relatively hypoxic tissue within an animal. Finally, ex vivo immunostaining revealed neuronal loss and increased astrogliosis in rTg4510 mice, with unchanged vascular architecture. These results indicate that tau disrupts cerebrovascular and tissue oxygenation in a depth- and age-dependent manner, and that neuronal loss is not explained by a neuron's local oxygen microenvironment but may reflect a global reduction in cortical oxygenation.

neuroscience↗

bioRxiv2026

Biotechnological potential of aromatic compounds utilizing bacteria from Brazilian caves, including a novel cave Nocardioides sp. SF1

From Brazilian limestone caves, we isolated 29 bacteria utilizing phenol (23 bacteria), toluene (all bacteria), and/or benzene (all bacteria) as sole carbon sources. One isolate showed phosphate solubilization, while lipase/esterase activity occurred in two isolates; no amylase activity was detected, but 16 isolates ([~]55%) exhibited protease activity. Among them, Nocardioides sp. SF1 was selected for whole-genome sequencing due to its aromatic compound tolerance and protease activity. Additionally, catechol cleavage assays yielded unexpected purple pigmentation, suggesting non-canonical aromatic metabolism. Its high-quality draft genome (4.25 Mbp, 16 contigs, N50 of 887 kb) lacks canonical phenol hydroxylase but encodes alternative oxidation systems, phenylacetyl-CoA pathway, besides, desferrioxamine siderophore, biosurfactants, and phosphate solubilization, key adaptations for oligotrophic caves and biotechnologically interesting activities. Whole-genome comparisons (TYGS/GGDC, OrthoANI and k-mer) suggest potential new species. Lacks acquired antimicrobial resistance genes (ResFinder) and pathogenicity potential (PathogenFinder). Nocardioides sp. SF1 emerges as a non-pathogenic candidate for aromatic bioremediation and plant growth promotion in contaminated, nutrient-poor environments, highlighting cave actinobacterias unexplored biotechnological potential.

microbiology↗

bioRxiv2025

Identifiability of Phylogenetic Level-2 Networks under the Jukes-Cantor Model

AO_SCPLOWBSTRACTC_SCPLOWWe investigate which evolutionary histories can potentially be reconstructed from sufficiently long DNA sequences by studying the identifiability of phylogenetic networks from sequence data generated under site independent models of molecular evolution. While previous work in the field has established the identifiability of phylogenetic trees and level-1 networks, networks with non-overlapping reticulation cycles, less is known about more complex network structures. In this work, we extend identifiability results to network classes that include pairs of tangled reticulations. Our main result shows that binary semi-directed level-2 phylogenetic networks are generically identifiable under the Jukes-Cantor model, provided they are triangle-free and strongly tree-child. We also strengthen existing identifiability results for level-1 networks, showing that the number of reticulation nodes is generically identifiable under the Jukes-Cantor model. In addition, we present more general identifiability results that do not restrict the network level at all and hold for the Jukes-Cantor as well as for the Kimura-2-parameter model. Specifically, we demonstrate that any two binary semi-directed networks that display different sets of 4-leaf subtrees (quartets) are distinguishable. This has direct implications for the identifiability of a networks reticulated components (blobs). We show that the tree-of-blobs of a network, the global branching structure of the network, is identifiable, as well as the circular ordering of the subnetworks around each blob, for networks in which edges do not cross and taxa are on the outside.

evolutionary biology↗

bioRxiv2025

How do egocentric boundary cells depend upon the coordinate system of environmental features?

Neurons in the retrosplenial (RSC) (Alexander et al 2020a, LaChance & Hasselmo 2024) and postrhinal cortex (POR) respond to environmental boundaries and configurations using egocentric coordinates relative to an animals current position. Neurons in these structures and adjacent structures also respond to spatial dimensions of self-motion such as running velocity (Carstensen et al 2021, Robinson et al 2023). Experimental and modeling data suggest that these responses could be essential for guiding behaviors such as obstacle avoidance and goal-directed navigation (Erdem & Hasselmo 2012, Erdem & Hasselmo 2014). However, these findings still leave the unanswered question: What specific features, and in what coordinate frames, drive these egocentric neural responses? Here we present models of the potential circuit mechanisms generating egocentric responses in RSC. One model posits that neurons encode internal representations of barriers in head-centered coordinates, defined by distance and angle, which are modulated by running velocity to enable trajectory planning and obstacle avoidance. We contrast this with a complementary hypothesis in which neurons respond to retinotopic features--such as the top, bottom, or edges of walls, which may serve as precursors to head-centered representations. Additional hypotheses include trajectory-based forward scanning (e.g., ray tracing) for barrier detection or comparing optic flow across the visual field. These hypotheses generate complementary modeling predictions about how changes in environmental parameters could alter the neural responses of egocentric boundary cells that are presented here.

neuroscience↗

bioRxiv2024

Mimosa species endemic to acidic soils in central Brazil are nodulated by a high diversity of Paraburkholderia genotypes, but widespread species are nodulated by Paraburkholderia, Cupriavidus or Rhizobium depending on soil characteristics

Neotropical Beta-rhizobia have a particular affinity to the large legume (Fabaceae) genus Mimosa and some of its relatives in the tribe Mimosae of the Caesalpinioideae subfamily. However, little is still known about the ecology of this interaction, especially the relationship between the rhizobia of "widespread" pan-tropical Mimosa species like M. pudica and the rhizobia that nodulate endemic Mimosa species that are very restricted in their habitats. The objective of this study was to examine the microsymbionts of Mimosa spp. and some other mimosoids in climates ranging from tropical to subtropical, humid to semi-arid, with varied soil characteristics and altitudes, with the aim of testing the hypothesis that widespread species have more cosmopolitan symbiont preferences than endemic ones. Nodules were sampled from more than 40 Mimosa spp. and related taxa in eleven Brazilian states, many endemics or biome-restricted, but particular attention was paid to sample nodules from the widespread species M. pudica at all locations. The Mimosa symbionts comprised 19 potential 16S rRNA and recA groups at the species level, with 16 belonging to the genus Paraburkholderia, including six lineages that may represent new species. The remaining genotypes consisted of 14 strains in two lineages of Cupriavidus that were mainly isolated from M. pudica growing at low altitudes, plus a single lineage of Rhizobium also from M. pudica. It is concluded that a high diversity of Paraburkholderia strains dominate as symbionts of Mimosa in the acidic soils of its main center of radiation in Central Brazil but that Cupriavidus and Rhizobium comprise a significant minority of symbionts of widespread Mimosa spp., especially M. pudica, in lowland or disturbed areas with less acidic soils. Mimosa symbiont diversity is thus driven either by edapho-climatic characteristics for widespread species and/or by co-evolution of the symbiotic partners for endemic species.

plant biology↗

bioRxiv2023

The radiation of nodulated Chamaecrista species from the rainforest into more diverse habitats has been accompanied by a reduction in growth form and a shift from fixation threads to symbiosomes

All non-mimosoid nodulated genera in the legume subfamily Caesalpinioideae confine their rhizobial symbionts within cell wall-bound "fixation threads" (FTs). The exception is the large genus Chamaecrista in which shrubs and subshrubs house their rhizobial bacteroids more intimately within symbiosomes, whereas large trees have FTs. This study aimed to unravel the evolutionary relationships between Chamaecrista growth habit, habitat, nodule bacteroid type, and rhizobial genotype. The growth habit, bacteroid anatomy, and rhizobial symbionts of 30 nodulated Chamaecrista species native to different biomes in the Brazilian state of Bahia, a major centre of diversity for the genus, was plotted onto an ITS-TrnL-F- derived phylogeny of Chamaecrista. The bacteroids from most of the Chamaecrista species examined were enclosed in symbiosomes (SYM-type nodules), but those in arborescent species in the section Apoucouita, at the base of the genus, were enclosed in cell wall material containing homogalacturonan (HG) and cellulose (FT-type nodules). Most symbionts were Bradyrhizobium genotypes grouped according to the growth habits of their hosts, but the tree, C. eitenorum, was nodulated by Paraburkholderia. Chamaecrista has a range of growth habits that allow it to occupy several different biomes and to co-evolve with a wide range of (mainly) bradyrhizobial symbionts. FTs represent a less intimate symbiosis linked with nodulation losses, so the evolution of SYM-type nodules by most Chamaecrista species may have (a) aided the genus-wide retention of nodulation, and (b) assisted in its rapid speciation and radiation out of the rainforest into more diverse and challenging habitats.

plant biology↗

bioRxiv2022

Individual differences in volitional social motivation in male and female mice following social stress.

BackgroundA key challenge in developing new treatments for neuropsychiatric illness is the disconnect between preclinical models and the complexity of human social behavior. We aimed to integrate voluntary social self-administration into a preclinical rodent stress model, as a platform for the identification of basic brain and behavior mechanisms underlying stress-induced individual differences in social motivation. Here, we introduce an operant social stress (OSS) procedure with male and female mice, where lever presses are reinforced by freely moving social interaction with a familiar social partner across social stress exposure. MethodsOSS is composed of three phases: (i) social self-administration training, (ii) social stress concurrent with daily reinforced social self-administration testing, and (iii) post-stress operant social reward testing under both non-reinforced and reinforced conditions. We resolve social stress-induced changes to social motivation behaviors using hierarchical clustering and aggregated z-scores, capturing the spectrum of individual differences that we describe with a social index score. ResultsOSS captures a range of stress-related dynamic social motivation behaviors inclusive of sex as a biological variable. Both male and female mice lever press for access to a social partner, independent of social partner coat color or familiarity. Social stress attenuates social self-administration in males and promotes social reward seeking behavior in females. Hierarchical clustering does not adequately describe the relative distributions of social motivation following stress, which we find is better described as a non-binary behavioral distribution that we define by introducing the social index score. This index is stable across individual mice. ConclusionWe demonstrate that OSS can be used to detect stable individual differences in stress-induced changes to social motivation in male and female mice. These differences may reflect unique neurobiological, cellular and circuit mechanisms not captured by preclinical models that omit voluntary social behaviors. The inclusion of volitional social procedures may enhance the understanding of behavioral adaptations promoting stress resiliency and their mechanisms under more naturalistic conditions.

neuroscience↗

bioRxiv2022

The innovation of the symbiosome has enhanced the evolutionary stability of nitrogen fixation in legumes

O_LINitrogen-fixing symbiosis is globally important in ecosystem functioning and agriculture, yet the evolutionary history of nodulation remains the focus of considerable debate. Recent evidence suggesting a single origin of nodulation followed by massive parallel evolutionary losses raises questions about why a few lineages in the N2-fixing clade retained nodulation and diversified as stable nodulators while most did not. Within legumes, nodulation is restricted to the two most diverse subfamilies, Papilionoideae and Caesalpinioideae, which show stable retention of nodulation across their core clades. C_LIO_LIWe characterize two nodule anatomy types across 128 species in 56 of the 150 genera of the legume subfamily Caesalpinioideae: 1) fixation thread nodules (FTs), where nitrogen-fixing bacteroids are retained within the apoplast in modified infection threads and 2) symbiosomes, where rhizobia are symplastically internalized in the host cell cytoplasm within membrane-bound symbiosomes. C_LIO_LIUsing a robust phylogenomic tree based on 997 genes from 146 caesalpinioid genera, we show that losses of nodulation are more prevalent in lineages with FTs. C_LIO_LIWe propose that evolution of the symbiosome allows for a more intimate and enduring symbiosis through greater compartmentalisation of their rhizobial microsymbionts, resulting in greater evolutionary stability of nodulation across this species-rich pantropical clade of legumes. C_LI

evolutionary biology↗

bioRxiv2020

A phospho-regulated ensemble signal motif of α-TAT1 drives dynamic microtubule acetylation

Spatiotemporally dynamic microtubule acetylation underlies diverse physiological events ranging from cell migration to intracellular trafficking, autophagy and viral infections. Despite its ubiquity, the molecular mechanisms that regulate the sole microtubule acetylating agent, -tubulin N-acetyltransferase 1 (-TAT1) remain obscure. Here we report that dynamic intracellular localization of -TAT1 unexpectedly determines the efficiency of microtubule acetylation. Specifically, we newly identified a conserved signal motif in the intrinsically disordered C-terminus of -TAT1, consisting of three competing regulatory elements - nuclear export, nuclear import and cytosolic retention. Their balance is tuned via phosphorylation by serine-threonine kinases including CDK1 and CK2. While the un-phosphorylated form resides both in the cytosol and nucleus, the phosphorylated form binds to specific 14-3-3 adapters and accumulates in the cytosol for maximal substrate access. Cytosolic localization of -TAT1 predominantly mediates microtubule acetylation, cell proliferation and DNA damage response. In contrast to other molecules with a similar phospho-regulated signal motif including transcription factors, -TAT1 uniquely uses the nucleus as a hideout. As amino acid mutations to the motif have been reported in cancer patients, the present mechanism of subcellular -TAT1 localization may help uncover a spatiotemporal code of microtubule acetylation in normal and aberrant cell functions.

cell biology↗

bioRxiv2020

A tyrosine kinase protein interaction map reveals targetable EGFR network oncogenesis in lung cancer

SUMMARYSignaling networks balance the activities of many physically interacting proteins and perturbations to this network influence downstream signaling, potentially leading to oncogenic states. Using affinity purification-mass spectrometry we defined this network for all 90 human tyrosine kinases revealing 1,463 mostly novel interactions between these key cancer proteins and diverse molecular complexes. Modulation of interactor levels altered growth phenotypes associated with corresponding tyrosine kinase partners suggesting that tumors may alter the stoichiometries of interactors to maximize oncogenic signaling. We show that the levels of EGFR interactors delineates this form of network oncogenesis in 19% of EGFR wild-type lung cancer patients which were mostly otherwise oncogene negative, predicting sensitivity to EGFR inhibitors in vitro and in vivo. EGFR network oncogenesis occurs through mechanistically distinct network alleles often in cooperation with weak oncogenes in the MAPK pathway. Network oncogenesis may be a common and targetable convergent mechanism of oncogenic pathway activation in cancer.HIGHLIGHTSA human tyrosine kinome protein interaction map reveals novel physical and functional associations.Dependence on oncogenic tyrosine kinases is modulated through perturbation of their interactors.EGFR network oncogenesis in up to 19% of EGFR wild-type lung cancers is targetable.EGFR network oncogenesis cooperates with weak oncogenes in the MAPK pathway.Competing Interest StatementS.L.W. is an employee of Pfizer. D.C., I.S., E.M., are employees of Champions oncology. S.B. has received funding from Clovis Oncology, Pfizer, Revolution Medicines and Ideaya Biosciences.View Full Text

cancer biology↗