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Ruiz, A.

Publications and source records attributed to Ruiz, A..

At least 19 recordsLinked to original sources

Movements for Grooming in Rhesus Macaques Co-opted from Feeding Movements

Abstract Catarrhine primates exhibit a wide range of skilled hand movements, including those used for foraging and grooming, and their evolution attracts ongoing attention. Competing hypotheses are that skilled hand movements evolved for feeding, or that the hand movements of various behaviors evolved independently. The present study addressed these questions by asking whether the movements of grooming of rhesus macaques (Macaca mulatta) are co-opted from feeding movements. We video-recorded free-ranging rhesus macaques in the Cayo Santiago colony of the Caribbean Primate Research Center (CPRC), University of Puerto Rico. Allogrooming (grooming a conspecific), self-grooming, and rhythmic scratching with a hand or foot were compared with a common foraging behavior, geophagy, mining and eating soil. Allogrooming, self-grooming, and foraging occurred in visually mediated bouts that featured numerous comb and brush hand movements directed toward searching for a target in the fur or soil. Once located, the target was grasped between the thumb and index finger in a pincer grip to be placed in the mouth - or less often bitted or licked from the fur. Hand movements were generally directed toward the actor but were also influenced by object-surface features, including fur direction during grooming and the rocks and debris covering soil targets during geophagy. The grooming movements of comb, brush, and grasp were recognizably those used during foraging. Rhythmic scratching with a hand or foot was not visually guided but did employ a comb movement of the digits of the hand or foot. Thus, with the exception of the rhythmicity of scratching, the hand movements of grooming are fundamentally foraging movements. It is proposed that grooming movements are coopted from oromanual feeding movements in macaques, a relationship that may be widespread in other species.

animal behavior and cognition↗

CB2 activation during epileptogenesis recruits immunomodulatory monocytes and mitigates cognitive, affective and seizure outcomes

Temporal lobe epilepsy (TLE) is frequently associated with severe cognitive impairment and psychiatric comorbidities that are highly disabling and not targeted by anti-seizure medications, highlighting the need for therapies that target epileptogenesis rather than merely suppress seizures. Despite strong evidence implicating neuroinflammation in this process, anti-inflammatory approaches have not yielded such therapies yet. Infiltrating peripheral monocytes are widely viewed as detrimental amplifiers of post-status epilepticus (SE) inflammation, although emerging data suggest context-dependent protective roles. The cannabinoid receptor type 2 (CB2), highly expressed in myeloid cells, represents a potential immunomodulatory target linking leukocyte recruitment and inflammatory polarization. Using a juvenile rat model of TLE, we characterized hippocampal neuroinflammation and CB2 expression during epileptogenesis and evaluated the effects of transient CB2 activation with the selective agonist GP1a. SE induced a rapid but transient inflammatory response and robust recruitment of peripheral monocytes that persisted as anti-inflammatory monocyte-derived macrophages. CB2 activation did not suppress early cytokine induction but selectively enhanced recruitment of anti-inflammatory monocytes and modestly increased anti-inflammatory signaling. Importantly, transient CB2 stimulation preserved synaptic plasticity, improved cognitive performance, reduced anxiety-like behavior, and delayed seizure onset. These findings identify CB2-dependent modulation of peripheral myeloid cells as a potential disease-modifying axis in TLE.

neuroscience↗

Mechanisms of resilience to autosomal dominant Alzheimer's disease via oligogenic modulation of rare variants in the entorhinal cortex

Two PSEN1 E280A carriers have presented extreme protection against autosomal dominant Alzheimers disease (ADAD), with over two decades of delay for dementia onset. One of them, a male heterozygous for the RELN-COLBOS protective variant showed increased neuronal density in the entorhinal cortex 1. We conducted a deep phenotyping and genotyping study of the entorhinal cortex in protected and unprotected PSEN1 E280A cases, sporadic AD, and non-demented controls. We used single nuclei and spatial transcriptomics, whole genome sequencing, and candidate genotype-associated expression changes (GAEC) analysis. Our results showed unique neuronal and oligodendrocytic populations in the male RELN-COLBOS patient. Unique RELN positive inhibitory interneurons were enriched in cortical Layer I, while unique abundant ADAMTSL1 positive excitatory neurons were distributed in Layers II/III and Layer Va. These neurons and mature myelinated oligodendrocytes benefitted from increased expression of LRP6 receptor, functioning as a non-canonical receptor for the mutated Reelin protein encoded by RELN-COLBOS. Finally, GAEC and pathway enrichment analyses suggested that other mutations enhanced RELN-COLBOS effects in oligodendrocytes in the male RELN-COLBOS patient, explaining the phenotypic differences with his sister, a RELN-COLBOS carrier with no evident protection from ADAD. Our findings suggest that extreme deviations of the PSEN1 E280A phenotype are more likely attributed to oligogenic effects, including simultaneous mutations occurring in genes including ITGA2, involved in single molecular pathways, such as the Integrins / Focal Adhesion pathway, as potential disease modifiers for Alzheimers disease (AD).

neuroscience↗

A spatially-specific pattern of cortical thickness in frontal lobe predisposes to faster future amyloid accumulation in individuals with subjective cognitive decline

The risk of developing AD is conferred through numerous genetic and environmental factors. How these risks influence brain structure prior to the onset of AD pathology is not yet known. We hypothesise that there may be specific anatomic endophenotypes that predispose to AD years before the first signs of amyloid accumulation occur. Using clinical, genetic and brain MRI data from Fundacio ACE Healthy Brain Initiative (FACEHBI) --a longitudinal cohort of individuals with Subjective Cognitive Decline aged > 50 years--, we identified a spatially-specific, fine-grained pattern of cortical thickness in frontal lobe regions among amyloid-negative individuals at baseline that holds a significant relationship with the rate of amyloid accumulation during the next five years. This pattern may represent a structural fingerprint of increased susceptibility to the initiation of the AD cascade.

neuroscience↗

Conserved Cell Type Signatures Across the Brainstem and Spinal Cord in the Mouse Central Nervous System

Understanding how cell types are organized across the central nervous system (CNS) is key to uncovering neural function. Here, we integrate single-nucleus Multiome (RNA+ATAC) sequencing, spatial transcriptomics, and computational analyses to map conserved cell type signatures in the adult mouse brainstem and spinal cord. We identify a shared core of neuronal and non-neuronal cell types, alongside region-specific specializations reflecting distinct functions. Spatial data reveal conserved cellular niches across the brainstem-spinal cord boundary, indicating a continuous organizational logic. Cross-region comparisons uncover recurrent gene expression modules and signaling programs that may support shared circuit features. Chromatin accessibility profiling highlights cell-type-specific regulatory programs and implicates Hox transcription factors in positional identity. Notably, cell-type and positional identities are largely orthogonal, with varying regional influence across neuronal classes: motor neurons show strong positional coupling, whereas glutamatergic and GABAergic interneurons show minimal entrainment. This work provides a reference for the shared molecular architecture of these CNS regions.

neuroscience↗

A consensus spinal cord cell type atlas across mouse, macaque, and human

The spinal cord contains evolutionarily conserved cell types critical for motor function, sensory processing, and autonomic regulation, many of which are implicated in diverse neurological diseases and injuries. Yet the field lacks a comprehensive molecular characterization of cellular diversity in human, macaque, and mouse spinal cord. Here, we present a unified, cross-species cell type atlas based on the integration of single-nucleus gene expression, chromatin accessibility, and spatial transcriptomic data from segments within cervical, thoracic, lumbar, and sacral regions, including motor neurons (MNs) sampled across the entire rostro-caudal axis of the macaque spinal cord. Leveraging the spatial distributions of our molecularly defined cell types, we generated a cell type-guided anatomical map of spinal cord laminae and nuclei. We identified both conserved and species-specific cellular features, including gene expression patterns across distinct MN subtypes in the primate spinal cord. Cross-species cis-regulatory analysis and deep learning sequence models dissected the enhancer logic underlying viral targeting, uncovering conserved transcription factor grammar encoding cellular identity. Together, these results establish a unifying molecular and anatomical taxonomy of spinal cord cell types across species.

neuroscience↗

The Caudate Nucleus Exhibits Distinct Pathology and Cell Type-Specific Responses Across Alzheimer's Disease

A{beta} presence in the caudate nucleus (Ca) partially defines Thal stage III in Alzheimers disease (AD), but little is known about ADs cellular impact on the region. Leveraging a public basal ganglia taxonomy of cellular populations, we generated a cellular resolution atlas of AD-associated pathological changes in Ca. Unlike cortex, we found that Ca AD pathology is dominated by two key features: phosphorylated tau (pTau)-containing neuropil threads enriched near oligodendrocytes in white matter tracts and amyloid-{beta} diffuse plaques enriched in gray matter. Although AD pathology in affected cortical regions results in neuronal loss, we find no AD-driven reductions in neuron proportions in Ca. However, there were observable changes in multiple cellular populations. Protoplasmic astrocytes and FLT1+/IL1B+ microglia increased in abundance with global pTau levels. We also observe gene expression changes in fast-spiking PTHLH-PVALB interneurons indicative of disrupted signaling pathways and altered intrinsic physiological properties. This work provides a cellular-resolution framework for understanding AD pathology in Ca.

neuroscience↗

A cross-species spatial transcriptomic atlas of the human and non-human primate basal ganglia

The basal ganglia are interconnected subcortical nuclei with complex topographical organization that orchestrate goal-directed behaviors and are implicated in neurodegenerative movement disorders. We generated a cellular-resolution, spatial transcriptomic atlas of the basal ganglia in human, rhesus macaque, and common marmoset, sampling over one million cells in each species. By integrating spatial data with a cross-species, consensus snRNA-seq cell type taxonomy, this atlas reveals conserved principles of molecular organization within and across structures. The cellular architecture is complex but highly stereotyped, with gene expression gradients superimposed onto discrete compartments. Extensive spatial sampling illuminates 3D gradients of molecular organization in the striatum and reveals cell type-specific core and shell compartments in the primate internal globus pallidus, which is conserved with mouse. This unified, cross-species spatial transcriptomic atlas will be a foundational resource for characterizing the molecular and functional organization of the basal ganglia and their roles in health and disease.

neuroscience↗

Spatial patterning of transcriptional and regulatory programs in the primate subcortex

Mammalian brain cell identity is shaped by intrinsic factors and external context. We present a spatially resolved transcriptomic and gene regulatory atlas of cell types across all subcortical regions in a primate, the common marmoset. Dense sampling and cross-species integration revealed spatially precise neuronal assemblies, including in complex midbrain and diencephalic structures. Chromatin accessibility and transcriptional identity are spatially tuned within and across subcortical structures; spatial gradients within hippocampal subfields are orchestrated by graded transcription factors acting through graded enhancers. The primate-expanded thalamic GABAergic population shares transcriptional and regulatory syntax with conserved midbrain populations, reflecting an evolutionary adaptation compared with rodents. Similar regional expression across cell types can arise by distinct regulatory architectures, as for telencephalic astrocytes and neurons. Conversely, distant cell types can share regulatory programs despite divergent identities: striatal GABAergic medium spiny neurons and telencephalic glutamatergic neurons share a postsynaptic regulatory program despite divergent lineage, region, and neurotransmitter identity.

neuroscience↗

Quantitative Fluorescence Imaging with SI-Traceable Radiance: Radiometric Fluorescence Characterization with a Calibrated Solid-State Emitter

SignificanceFluorescence imaging remains largely qualitative and device-specific, limiting reproducibility and intersystem comparisons. Advancing toward quantitative imaging requires a radiometric characterization framework that provides SI-traceable units while explicitly addressing the interdependent factors that govern image formation. AimEstablish and evaluate a radiometric characterization framework that converts device-native counts to SI-traceable imaged radiance ({micro}W{middle dot}cm-2{middle dot}sr-1) and aggregate fluorescence yield (sr-1) while accounting for interdependent factors that influence fluorescence image formation. ApproachA calibrated Lambertian solid-state radiometric emitter target (RET) was combined with a three-step radiometric framework consisting of the Radiance Transfer Curve (RTC), the Radiance Imaging Transform (RIT), and the Fluorescence Imaging Transform (FIT). The RTC establishes system responsivity as a function of radiance; the RIT applies this calibration at the pixel level to map digital counts to SI-traceable radiance; and the FIT performs pixel-wise excitation normalization of the RIT image to produce an aggregate fluorescence yield image. The framework was tested through distance and aperture invariance, digital-vs-physical ROI analyses, RTC acquisition, and application of the RIT and FIT to an ICG concentration target and a breast lumpectomy phantom. ResultsThe RET exhibited Lambertian behavior, with no significant dependence of the measured radiance on distance or aperture; imager responsivity (R{lambda}) also remained invariant within uncertainty across working distances and f-numbers. Digitally masked ROIs reproduced R{lambda} obtained with matched physical apertures, enabling ROI and pixel-level radiance transfer. RTCs acquired over 49 radiances captured sensor and processing nonlinearities. The RIT provided a per-pixel mapping from counts to radiance ({micro}W{middle dot}cm-2{middle dot}sr-1). Applying pipeline-specific RTCs, the RIT and FIT reconciled large discrepancies across RAW, 8-bit, and log10 image processing pipelines, yielding closely aligned radiance-concentration curves and improved SBR/SNR/CNR agreement. In a breast lumpectomy phantom, FIT produced SI-traceable aggregate fluorescence yield (sr-1) images and absolute contrast metrics in an anthropomorphic geometry. ConclusionsThe combined framework converts device-native counts into SI-traceable radiance and aggregate fluorescence yield at the pixel level, providing a practical basis for reproducible quantitative fluorescence imaging. The feasibility results across distance/aperture tests, ROI analyses, image pipelines, and phantom imaging indicate readiness for broader evaluation. Future work will establish formal uncertainty budgets and assess robustness across devices, geometries, and excitation conditions to support adoption as a quantitative reporting standard.

bioengineering↗

Single-cell spatial mapping reveals dynamic bone marrow microarchitectural alterations and enhances clinical diagnostics in MDS

Myelodysplastic neoplasms (MDS) disrupt bone marrow hematopoiesis, yet clinical assessment relies largely on blast enumeration and qualitative morphology, which incompletely capture marrow architecture and disease state. We applied whole-slide multiplex immunofluorescence imaging with single-cell phenotyping to map bone marrow microarchitecture in MDS. Diagnostic biopsies (n=36), longitudinal treatment samples (n=29), precursor states (n=13), and normal controls (n=21) were analyzed, comprising >5 million spatially resolved cells. MDS marrow exhibited coordinated, genotype-imprinted architectural remodeling, including altered progenitor composition and spatial patterning, disrupted erythroid island organization, and displacement of hematopoietic stem and progenitor cells from perivascular niches. Interrogation of 82 cellular and spatial features yielded a composite Microarchitectural Perturbation Score (MDS-MAPS), derived from diagnostic samples and fixed prior to longitudinal analyses. In leave-one-patient-out cross-validation, MDS-MAPS discriminated remission from active disease more accurately than blast percentage (AUC 0.883 vs 0.660) and distinguished low-blast MDS from clonal cytopenia of undetermined significance (CCUS) (AUC 0.815). Mixed-effects modeling showed MAPS decreased in remission statistically independent of blast burden, with architectural normalization during remission and re-emergence at relapse. These findings define quantitative bone marrow architecture as a dynamic tissue-state biomarker that complements molecular and blast-based assessment in MDS.

pathology↗

The Pseudomonas putida Type VI Secretion Systems Shape the Tomato Rhizosphere Microbiota

Bacterial competition mechanisms drive microbial community dynamics across diverse ecological niches. The Type VI Secretion System (T6SS) represents a sophisticated nanomachine used by Gram-negative bacteria for contact-dependent elimination of competitors through the delivery of toxic effectors. While the T6SS has been well-documented in mammalian gut microbiota development, its role in shaping plant rhizosphere communities remains poorly understood despite the ecological importance of rhizosphere microbiota. This study investigates how the three Pseudomonas putida KT2440 T6SS clusters influence the tomato rhizosphere microbiota in agricultural soil. Through comprehensive in vitro and in vivo analyses, we demonstrate that while the K2/K3-T6SSs remain inactive under standard laboratory conditions, they become specifically activated in the presence of plant pathogens, suggesting an adaptive response to competitive pressure. Our experiments with T6SS-deficient mutants reveal that the P. putida T6SSs are essential for effective rhizosphere colonisation, with mutant strains showing significantly reduced colonisation capabilities compared to wildtype strain in competitive soil environments. Most importantly, our data establish that the P. putida T6SSs directly shape the taxonomic diversity and community structure of the rhizosphere microbiota of tomato plants. These results place the T6SS as a critical factor driving the evolution of complex polymicrobial communities within the plant rhizosphere, paralleling its established role in the gut microbiota. This research advances our understanding of the ecological functions of the different T6SSs in P. putida and the molecular mechanisms underlying microbial community assembly in the rhizosphere. Thus, it offers valuable insights for agricultural applications involving beneficial microbes and plant health management strategies.

microbiology↗

Altered Gut Microbiota Mediates the Association between APOE Genotype and Amyloid-β Accumulation in Middle-Aged Adults

ImportanceThe apolipoprotein E (APOE) {varepsilon}4 allele is the strongest genetic risk factor for Alzheimers disease (AD), yet the mechanisms linking APOE to amyloid-{beta} (A{beta}) pathology remain incompletely understood. Emerging evidence suggests that the gut microbiome may modulate neurodegeneration; however, its role as a mediator in the APOE-A{beta} relationship remains unclear. ObjectiveTo evaluate whether specific microbial taxa mediate APOE-related effects on brain A{beta} burden in an established population-based study of middle-aged adults. Design, Setting, and ParticipantsThis cross-sectional study analyzed data from the Framingham Heart Study cohort. Data were collected at the third examination visit (n = 227, %Female = 58, mean age = 56.5 {+/-} 8.3), between 2016 and 2019. ExposuresGut bacterial DNA was sequenced using 16S rRNA, and amplicon sequence variants (ASVs) were agglomerated at various taxonomic levels (14 phyla, 70 families, and [~]140 genera). APOE genotypes were derived from blood DNA using PCR and restriction isotyping. Predicted microbial functional potential was based on KEGG Orthologs. Main Outcomes and MeasuresOverall and regional measures of cerebral amyloid-{beta} deposition were assessed using carbon-11 Pittsburgh (PiB) Compound-B PET scans. The global PiB deposition served as the primary outcome for "overall" amyloid burden. Regional amyloid deposition values were analyzed as secondary outcomes. ResultsA higher A{beta} burden was significantly associated with the depletion of protective genera (e.g., Faecalibacterium {beta} [95%CI],-0.35 [-0.40,-0.30]; Ruminococcus-0.25 [-0.27,-0.23]; Butyricicoccus-0.27 [-0.32,-0.22]) and the enrichment of pro-inflammatory taxa (e.g., Alistipes 0.07 [0.06, 0.08], Bacteroides 0.10 [0.07, 0.13]) and Barnesiella (0.18 [0.16, 0.20]). These associations were more pronounced in APOE {varepsilon}4 carriers, who exhibited a broader spectrum of microbial dysbiosis. Mediation analysis showed that Ruminococcus, Butyricicoccus, Clostridium, and Christensenellaceae collectively mediated [~]0.3-0.4% of the effect of APOE {varepsilon}4 on global A{beta} burden. Functional profiling revealed a reduced abundance of microbial genes involved in key metabolic pathways among individuals with higher A{beta} levels. Conclusion and RelevanceGut microbiome composition partially mediates the relationship between APOE {varepsilon}4 and cerebral amyloid burden. These findings support a gut-brain axis mechanism in AD and suggest that microbiome-targeted interventions may mitigate APOE-related risk.

neuroscience↗

Loss of meiotic double strand breaks triggers recruitment of recombination-independent pro-crossover factors in C. elegans spermatogenesis

A key event in meiosis is the conversion of a small subset of double strand breaks into interhomolog crossovers. In this study, we demonstrate that Caenorhabditis elegans male spermatogenesis has less robust mechanisms than hermaphrodite oogenesis for ensuring and limiting the conversion of double strand breaks into crossovers. This is not a consequence of differences in meiotic prophase timing, sex chromosome genotype, or the presence or absence of germline apoptosis. Using the cyclin-like crossover marker COSA-1, we show that males have a linear response in converting increasing numbers of double strand breaks into crossovers, suggesting weakened crossover homeostasis. While the topoisomerase SPO-11, responsible for initiating meiotic double strand breaks, has an extended period of activity in males as in hermaphrodites, we discovered that COSA-1 foci form at the very end of meiotic prophase in the absence of SPO-11 during spermatogenesis. These COSA-1-marked sites are also independent of homologous recombination, and Topoisomerases I and II. We find that the synaptonemal complex, which holds homologs in proximity, differently modulates COSA-1 enrichment to chromosomes in the absence of SPO-11 in males and hermaphrodites. Together, these findings suggest that males have less robust crossover control and that there are previously unrecognized lesions or structures at the end of meiotic prophase in spermatocytes that can accumulate CO markers. Author SummaryFormation of healthy gametes depends on the accurate partitioning of genetic material in the daughter cells through meiosis. A hallmark of meiosis is the establishment of crossovers, which arise from physical exchange of DNA between the parental chromosomes during homologous recombination. Recombination is initiated via the induction of physiological DNA damage by the topoisomerase SPO-11 and its auxiliary factors. Abrogating SPO-11 activity prevents crossover formation, resulting in random chromosome segregation and generation of aneuploid gametes. While the underlying mechanisms of crossover formation are conserved between the sexes, several pieces of evidence indicate extensive sexual dimorphism. In our work we describe novel features of C. elegans spermatogenesis that reveal significant differences in the regulation of recombination compared to oogenesis. We find that in spermatogenesis crossover-promoting proteins can be recruited to chromosomes even in the absence of SPO-11 activity, a phenomenon not observed in the oogenic hermaphrodite germ line. Furthermore, removal of some auxiliary factors required for physiological break formation during oogenesis does not prevent crossover designation in spermatocytes. We show that the synaptonemal complex, tasked with keeping homologous chromosomes in proximity, exerts opposing roles in males and hermaphrodites by promoting and limiting the recruitment of SPO-11-independent crossover factors, respectively.

genetics↗

OGDHL regulates nucleotide metabolism, tumor growth, and neuroendocrine marker expression in prostate cancer

As cancer cells evade therapeutic pressure and adopt alternate lineage identities not commonly observed in the tissue of origin, they likely adopt alternate metabolic programs to support their evolving demands. Targeting these alternative metabolic programs in distinct molecular subtypes of aggressive prostate cancer may lead to new therapeutic approaches to combat treatment-resistance. We identify the poorly studied metabolic enzyme Oxoglutarate Dehydrogenase-Like (OGDHL), named for its structural similarity to the tricarboxylic acid (TCA) cycle enzyme Oxoglutarate Dehydrogenase (OGDH), as an unexpected regulator of tumor growth, treatment-induced lineage plasticity, and DNA Damage in prostate cancer. While OGDHL has been described as a tumor-suppressor in various cancers, we find that its loss impairs prostate cancer cell proliferation and tumor formation. Loss of OGDHL profoundly alters Androgen Receptor inhibition-induced plasticity, including suppressing the neuroendocrine markers DLL3 and HES6, induces accumulation of the DNA damage response marker {gamma}H2AX, and reduces nucleotide synthesis. Our data suggest that OGDHL has minimal impact on TCA cycle activity, and that mitochondrial localization is not required for its regulation of prostate cancer plasticity and nucleotide metabolism. Finally, we demonstrate that OGDHL expression is tightly correlated with neuroendocrine differentiation in clinical prostate cancer. These findings underscore the importance of investigating poorly characterized metabolic genes as potential regulators of distinct molecular subtypes of aggressive cancer.

cancer biology↗

Tke5 is a novel Pseudomonas putida toxin that depolarises membranes killing plant pathogens

The soil bacterium Pseudomonas putida injects toxic proteins into neighbouring competitors, including resilient phytopathogens, using the Type VI secretion system (T6SS). The secretion of toxins endows P. putida with a significant fitness advantage, allowing this biocontrol agent to thrive in plant-related polymicrobial environments and prevent phytopathogen infections. Despite its agricultural significance, the toxin repertoire of P. putida, particularly those secreted via the K2- and K3-T6SSs, remains poorly understood. We present the first comprehensive molecular study of Tke5, a potent toxin encoded within the K3-T6SS, which represents the first comprehensive functional analysis of the BTH_I2691 protein family. Our biophysical data demonstrate that Tke5 is a pore-forming toxin that disrupts bacterial membranes through selective ion transport, inducing membrane depolarisation and cell death. Unlike conventional detergent-like pore-forming toxins, Tke5 preserves overall membrane integrity, avoiding large, non-specific disruptions. This unique mechanism offers a powerful approach to targeting resilient phytopathogens. This study reveals a previously undescribed mode of action within a widespread yet understudied toxin family. Our findings highlight the potential of P. putida as a biocontrol agent, offering alternatives to chemical pesticides by exploiting novel toxin mechanisms. Understanding these bacterial toxins is crucial for developing effective strategies to combat plant pathogens.

microbiology↗

Brain Infiltrated Monocyte-Macrophages in a rat model of Temporal Lobe Epilepsy: Revisiting the Pro-Inflammatory Paradigm

Neuroinflammation is central to temporal lobe epilepsy, yet the specific role of myeloid cells remains unclear. In status epilepticus (SE) models, circulating monocytes have been reported to infiltrate the brain, though distinguishing them from microglia remains challenging. Using a rat model, we traced infiltrating monocytes post-SE, to investigate their persistence, phenotypic evolution during epileptogenesis and contribution to neuroinflammation. By tracking phagocyted fluorescent nanoparticles and using CD68 immunohistochemistry, we confirmed that monocytes entered the brain in significant numbers 24 hours post-SE, after the inflammatory peak occurred (7h post-SE). Tracked up to 7 weeks, these cells adopted a microglia-like phenotype, contributed to the microglial scar and sustained low-grade inflammation during the chronic phase of epilepsy solely through their presence, as their expression of pro-inflammatory markers resembled that of non-activated microglia. Importantly, monocytes initially and transiently supported an anti-inflammatory response providing a unique opportunity to modulate neuroinflammation and potentially disrupt epilepsy progression, opening new avenues for therapeutic interventions.

neuroscience↗

MerQuaCo: a computational tool for quality control in image-based spatial transcriptomics

Image-based spatial transcriptomics platforms are powerful tools often used to identify cell populations and describe gene expression in intact tissue. Spatial experiments return large, high-dimensional datasets and several open-source software packages are available to facilitate analysis and visualization. The outputs of spatial transcriptomics platforms are typically imperfect. For example, local variations in transcript detection probability are common. Software tools to characterize imperfections and their impact on downstream analyses are lacking so the data quality is assessed manually, a laborious and often a subjective process. Here we describe imperfections in a dataset of 641 fresh-frozen adult mouse brain sections collected using the Vizgen MERSCOPE. Common imperfections included the local loss of tissue from the section, tissue outside the imaging volume due to detachment from the coverslip, transcripts missing due to dropped images, varying detection probability through space, and differences in transcript detection probability between experiments. We describe the incidence of each imperfection and the likely impact on the accuracy of cell type labels. We develop MerQuaCo, open-source code that detects and quantifies imperfections without user input, facilitating the selection of sections for further analysis with existing packages. Together, our results and MerQuaCo facilitate rigorous, objective assessment of the quality of spatial transcriptomics results.

bioinformatics↗