Biology subjects

Delgado, M.

Publications and source records attributed to Delgado, M..

At least 19 recordsLinked to original sources

bioRxiv2026

KobA mediates kinesin-1-dependent transport of dynein-dynactin to microtubule plus ends

Cytoplasmic dynein transports diverse cargoes toward microtubule minus ends following activation by the dynactin complex and cargo adapters. In elongated cells such as fungal hyphae and neurons, dynein must first undergo kinesin-1-dependent transport to microtubule plus ends to engage cargoes, but the mechanism linking these opposing motors remains poorly understood. Here, we identify KobA in the filamentous fungus Aspergillus nidulans as a kinesin-1-binding, coiled-coil protein essential for kinesin-1 (KinA)-mediated plus-end transport of dynein and dynactin. KobA binds the C-terminal cargo-binding domain of KinA. Interestingly, KobA is not required for the general function of KinA in supporting hyphal growth alongside myosin-V, but is specifically required for the microtubule plus-end accumulation of dynein-dynactin even when KinA is activated. Mechanistically, KobA enhances the interaction between KinA and dynactin-dynein. Within its disordered N-terminal region, KobA harbors a Spindly motif typically present in dynein-activating cargo adapters that engage the dynactin pointed end. AlphaFold-3 predictions suggest that the Spindly motif of KobA also binds the dynactin pointed end, and in support of this notion, point mutations within the KobA Spindly motif disrupt the KinA-dynactin association, causing dynein to decorate microtubules rather than accumulate at plus ends. Together, our findings establish KobA as a novel adapter that utilizes a classic cargo adapter Spindly motif to link kinesin-1 to dynein-dynactin, ensuring targeted plus-end delivery of the minus-end motor.

cell biology↗

bioRxiv2026

Daylight, Daily Rhythms, and Downstream Physiology: A Translational Study in Diurnal Nile Grass Rats (Arvicanthis niloticus)

The circadian system evolved under natural light-dark cycles, while modern humans spend much of their time indoors under electric lighting that differs substantially from daylight in intensity, spectral composition, and temporal structure. How such lighting environments influence circadian system has not been systematically examined in a diurnal animal model under ecologically relevant conditions. In this study, we used the diurnal Nile grass rat (Arvicanthis niloticus) to assess daily locomotor rhythms across four lighting conditions designed to approximate common human exposure scenarios: rectangular daylight (D65-R; [~]5,600 lux), semi-sigmoidal daylight mimicking natural intensity dynamics (D65-S; matched peak intensity with [~]50% lower cumulative energy), fluorescent indoor light (F12; [~]150 lux), and fluorescent light supplemented with a one-hour midday daylight pulse (F12+D65-P). Using a within-subject design (n = 8), male grass rats were housed under each condition for two weeks. D65-R produced the highest daytime activity levels and the strongest day/night activity ratio, consistent with robust circadian entrainment. Despite matching peak intensity, D65-S did not yield comparable circadian outcomes, indicating that cumulative photon exposure, rather than peak intensity alone, contributes to entrainment strength. Notably, the addition of a one-hour midday daylight pulse (D65-P) partially increased circadian amplitude under otherwise fluorescent conditions, with higher periodogram amplitude relative to F12 alone. A separate cohort of males was exposed to D65-R or F12 for six weeks (n = 10/condition) to assess physiological outcomes, including metabolic and reproductive measures. Compared with the D65-R group, F12 group showed higher diabetic rate (10% vs. 40%) and reduced sperm mobility (45{+/-}6 vs. 19{+/-}1 %), consistent with potential downstream correlates of circadian rhythm disruption. Together, these findings demonstrate that lighting conditions characteristic of indoor environments produce weaker circadian organization than daylight-equivalent lighting in a diurnal rodent, which underscore the importance of light quality in shaping circadian rhythms and downstream physiological processes.

animal behavior and cognition↗

bioRxiv2026

DeMoDa: A global open access database for comparative research in human dental morphological variation

Human dental morphology is diverse and varies both within and between populations worldwide. Common variants include different numbers of cusps and roots, as well as different configurations in the fissures, ridges, and grooves on tooth crowns. Because teeth preserve well in taphonomic contexts and retain strong genetic signatures in their morphology, researchers across disciplines use dental form for research ranging from population affinity identification in forensic cases to the reconstruction of population history in archaeological and paleontological studies, and to explore the genetic underpinnings of dental development. However, these analyses are limited, as no publicly available comprehensive database of human dental morphological variation currently exists. Data are typically shared only within professional networks, excluding scientists outside those circles. Information is dispersed across repositories and the supplementary materials that accompany peer-reviewed publications, creating a fragmented and difficult-to-navigate data landscape. Although numberous dental anthropologists devoted their careers to collecting extensive datasets from thousands of individuals worldwide, their data have not yet been published in raw form nor made compatible. Here, we introduce the Dental Morphological Database (DeMoDa), an open access repository comprising 246 dental traits for 17,308 individuals across 32 major geographic regions worldwide spanning the past several thousand years. These data are from the legacy datasets of Turner, Hanihara, Scott, and Irish. Because these researchers used different scoring systems, we developed a scoring system with two steps that enables the three most-common scoring systems to be combined. We provide two versions of the data that correspond to these two steps: one with more nuanced trait scores at the cost of a smaller sample size, and another with less nuanced trait scores but broader sample coverage. We discuss the implications of publishing these legacy data and outline our decision-making process that guided their release in accordance with both the FAIR and CARE principles of open science.

evolutionary biology↗

bioRxiv2026

Subsistence transition preceded population turnover in the eastern Colombian Andes

Northwest South America was a pivotal region for human dispersals and cultural exchange during the Holocene. The Altiplano Cundiboyacense, a high-altitude plateau in the Eastern Cordillera of the Northern Andes of Colombia, preserves one of the most continuous archaeological sequences in the Americas, spanning from late Pleistocene hunter-gatherer groups to final late Holocene Muisca chiefdoms. Increasing the regional ancient DNA sample size 11-fold, we report genome-wide data from 209 individuals who lived over a period of more than 7000 years. This includes hunter-gatherers from the early-middle (10,000-7000 BP) and middle (7000-4000 BP) Holocene, initial late Holocene people (4000-2500 BP) who have the first isotopic evidence of C-enriched diets (attributed to maize), and populations associated with increasing sedentism and food production in the Herrera (2200-1300 BP) and Muisca (1200-500 BP) Periods. Previous work identified a major population turnover distinguishing earlier groups from Herrera-Muisca Period populations, but the absence of individuals dating 6000-2000 BP in that study left unresolved whether this ancestry shift was gradual or abrupt and whether it accompanied the earliest isotopic evidence of dietary input from maize or coincided with the later emergence of Herrera culture. We show that individuals predating the Herrera Period form a lineage that persisted for over five millennia, with population structure driven by drift in small groups and no detectable external gene flow. Two individuals who lived [~]2800 years ago - one directly dated to 983-835 calBCE - exhibit genetic profiles entirely consistent with hunter-gatherer ancestry yet have isotopic values consistent with the incorporation of maize into their diets, indicating subsistence change without population replacement. The emergence of Herrera culture [~]2200 BP coincided with a sharp genetic break, reflecting the migration of people carrying ancestry diverged by up to ten millennia into the Sabana de Bogota and displacing previously established peoples. By co-analyzing ancient data with modern Native Americans, we show these later populations derived from a mixture [~]4000 years ago of groups related to Chibchan language speakers of lower Central America and ones related to present-day people at the Amazonian-Andean interface who may have lived along the Chibchan expansion route. In the Herrera and Muisca Periods, genetic substructure distinguishes people from the southern and northern Altiplano, consistent with the cultural differentiation of these regions in the archaeological record. IN BRIEFAncient DNA data from the eastern Colombian Andes reveal five millennia of population continuity during which C plants were incorporated into subsistence systems without population replacement, followed later by a major ancestry turnover involving a population with ancestry admixed between that found in Chibchan-related groups and at the Amazonian-Andean interface.

genetics↗

bioRxiv2026

Aberrant expression of the testis kinase TSSK6 activates FAK-STAT3 signaling to promote tumorigenic growth

Cancer-testis antigens (CTAs) are germ cell-restricted proteins aberrantly expressed in diverse malignancies, yet whether these proteins contribute to tumor progression remains poorly defined. The CTA Testis-Specific Serine Kinase 6 (TSSK6) is frequently expressed in colorectal cancer (CRC), where it promotes key hallmarks of tumor progression, including anchorage-independent growth, invasion, and in vivo tumor formation. However, the signaling network by which ectopic TSSK6 drives these phenotypes has not been established. Here, we define the signaling pathways regulated by TSSK6 in CRC cells. We demonstrate that TSSK6 promotes focal adhesion kinase (FAK) activation, leading to enhanced STAT3 Ser727 phosphorylation and increased STAT3-dependent transcription. Transcriptomic analyses revealed induction of gene programs enriched for extracellular matrix remodeling, cytoskeletal organization, adhesion, and motility in a STAT3-dependent manner. Disruption of the FAK-STAT3 signaling axis abrogated anchorage-independent growth and invasive outgrowth in a spheroid model. Collectively, these findings demonstrate that aberrant expression of a germline-restricted kinase promotes focal adhesion signaling, which activates STAT3-dependent transcriptional programs that promote anoikis resistance and invasive behavior in CRC.

cancer biology↗

bioRxiv2026

The biogeography of the stripped Venus clam, Chamelea gallina, in the Mediterranean Sea indicates limited gene flow and shows evidence of local adaptation.

AimTo assess how biogeographic barriers and environmental heterogeneity shape connectivity and local adaptation in the striped Venus clam (Chamelea gallina), a commercially exploited bivalve in the Mediterranean Sea. LocationNortheast Atlantic (Gulf of Cadiz) and Mediterranean Sea (Alboran, Balearic, Tyrrhenian and Adriatic regions). TaxonChamelea gallina (Bivalvia: Veneridae). MethodsWe analysed genome-wide single nucleotide polymorphisms (SNPs) from 226 individuals sampled across six regions (Gulf of Cadiz, Alboran Sea, Balearic Sea, Ebro Delta, Tyrrhenian Sea and Adriatic Sea) using a seascape genomic framework. Population structure was inferred using both putatively neutral and adaptive loci. Genotype-environment associations were tested against key oceanographic variables, including sea surface temperature, salinity and nutrient availability. ResultsNeutral loci revealed weak genetic differentiation, consistent with substantial gene flow across most of the species range. In contrast, putatively adaptive loci uncovered pronounced genetic structure that corresponded closely to major Mediterranean biogeographic regions, particularly the Adriatic Sea, the Gulf of Cadiz and western-central Mediterranean basins. Significant associations were detected between genetic variation and environmental gardients, with several candidate adaptive SNPs located within coding regions, suggesting functional responses to spatially heterogeneous conditions. Main conclusionsOur results demonstrate that local adaptation can generate biologically meaningful population structure in C. gallina despite high levels of connectivity inferred from neutral markers. This decoupling between neutral and adaptive variation highlights the importance of integrating adaptive genomic information into biogeographic inference. Recognizing environmentally driven genetic differentiation is essential for defining robust management units and for improving the long-term sustainability and resilience of C. gallina fisheries under increasing anthropogenic pressure and climate change.

evolutionary biology↗

bioRxiv2026

Lessons from local ecological knowledge: cumulative stressors and governance constraints in Spanish clam fisheries

Spanish clam fisheries have contracted sharply over the past two decades, with repeated closures and declining landings affecting coastal livelihoods. Using local ecological knowledge (LEK), we examine how fishers, fishers guild leaders and regional managers interpret (i) ecological change and (ii) the institutional conditions shaping management outcomes in Spains main clam fisheries, focusing on wedge clam (Donax trunculus), striped venus clam (Chamelea gallina) and smooth clam (Callista chione). We conducted 94 semi-structured interviews (April 2024-August 2025) across the Spanish Mediterranean and the south Atlantic coast (Catalonia, Valencian Community, Balearic Islands, Murcia and Andalusia). Stakeholders characterised declines as a cumulative process driven by interacting stressors: climate variability and extremes, coastal habitat alteration, pollution, episodic disease events and fishing pressure intensified by illegal extraction and informal marketing. Governance assessments were predominantly negative, emphasising fragmented authority across administrative scales, delayed or reactive measures, uneven rules among gears exploiting shared stocks, limited user influence in decision-making, and chronic monitoring and enforcement gaps, especially for shore-based fisheries operating outside port-based control points. Overall, LEK closely aligns with scientific evidence on cumulative stressors, suggesting that persistent declines reflect less a lack of ecological understanding than institutional constraints that hinder timely, legitimate and enforceable responses. Policy priorities include climate-adaptive harvest rules linked to environmental indicators, co-produced monitoring, strengthened traceability and compliance, harmonised rules across gears and management units, and improved cross-sector coordination to reduce conflict and safeguard nearshore habitats. HighlightsO_LIStakeholders across Spain describe clam declines as the outcome of interacting ecological, climatic, and governance stressors rather than as the consequence of isolated drivers. C_LIO_LIPerceived drivers differ regionally: climate- and habitat-related pressures dominate the Mediterranean, while effort, illegal fishing, and market dynamics are more salient in the Gulf of Cadiz. C_LIO_LIMost interviewees view management and governance as ineffective, citing fragmented authority, uneven rules among gears and regions, and weak enforcement. C_LIO_LIInformal practices (off-auction sales and poaching) are repeatedly identified as mechanisms undermining legitimacy, traceability, and effort controls--particularly in nearshore wedge clam fisheries. C_LIO_LIPolicy pathways include harmonising cross-scale rules, strengthening monitoring and compliance, and institutionalising co-management that integrates LEK with science. C_LI

ecology↗

bioRxiv2025

Governing the decline: clam fisheries and the challenges of decentralized management across the western Mediterranean and Gulf of Cadiz (Spain).

Over the past four decades, clam fisheries along the Mediterranean and Atlantic coasts of Spain have exhibited significantly different ecological and governance trajectories. This study synthesises long-term landing data from 1993 to 2024 with a systematic review of regional legislation to explore how management frameworks influence the resilience of fisheries. In the northwest Mediterranean, which includes Catalonia, the Valencian Community, the Balearic Islands, and Murcia, fisheries have experienced synchronous declines, a consequence of overexploitation, fragmented governance, and reactive, top-down regulation. In contrast, Andalusia, encompassing both the Atlantic and Alboran Sea coasts, has demonstrated more resilient trajectories, bolstered by greater ecological productivity and the adoption of adaptive governance strategies since the 2010s. In this region, the implementation of gear-specific management plans, rigorous scientific monitoring (including satellite tracking), and prompt administrative responses has facilitated more sustainable exploitation. Our findings highlight the necessity of aligning governance with ecological connectivity and integrating adaptive co-governance structures that engage fishers to safeguard the future of small-scale fisheries. More broadly, this research emphasises the need for coordinated superregional or national management frameworks that incorporate ecological knowledge, promote stakeholder participation, and allow for timely regulatory adaptation.

ecology↗

bioRxiv2025

Temporal seascape genomics identifies evolutionary significant units in a highly exploited marine resource, the wedge clam Donax trunculus.

Clam fisheries along the Spanish coast have declined unevenly, while stock management often follows political rather than biological boundaries. To inform conservation and fishery management, this study used temporal seascape genomics to assess population structure, genetic diversity and effective population size (Ne) in the wedge clam Donax trunculus across approximately 2,000 km of the Iberian coast. Using 7,830 putatively neutral and 649 candidate outlier SNPs from 331 individuals, the analyses confirmed broad Atlantic-Mediterranean differentiation, identified the Alboran Sea as a distinct genetic unit, and revealed finer-scale Atlantic substructure. Temporal genomic comparisons showed that population structure remained largely stable over the study period, although genetic diversity changed in a site-specific manner across fishing areas. Genotype-environment analyses indicated that spatial structure explained more genomic variation than environmental predictors, especially after accounting for spatial- environmental collinearity. Overall, the results show that temporal seascape genomics can distinguish persistent biogeographic structure from short-term, local genomic change in exploited marine invertebrates, providing a robust framework for biologically informed stock delineation. The genetically distinct groups identified here should therefore be considered separately in conservation, fishery management and any future reinforcement planning.

evolutionary biology↗

bioRxiv2025

Engineering a perfusion bioreactor system for hiPSC-derived progenitor co-culture capturing microglial features in CNS development

Microglia are critical regulators of brain homeostasis and immune responses in the central nervous system (CNS). However, existing human-based models fail to reproduce the early and complex microglia-neural cell interactions. The differentiation of human induced pluripotent stem cells (hiPSCs) into specialized cell types offers promising avenues for understanding human development and disease modeling. Herein, we explore the differentiation of hiPSC-derived erythromyeloid progenitors (iEMPs) and their 3D co-culture with hiPSC-derived neurospheres, utilizing the Ambr(R) 250 Modular system. The aim of this research was to build a complex co-culture model between iEMP and neurospheres in a scalable and controlled environment. Our results demonstrate that the Ambr(R) 250 Modular system effectively supports the co-culture process, with iEMPs integration into the neurospheres, exhibiting cell density, aggregate morphology and concentration similar to the neurosphere monocultures. The co-culture environment induced the upregulation of transcription factors critical for microglial lineage commitment. iEMP-neurospheres displayed a unique secretory profile, releasing proteins involved in extracellular matrix remodeling and neuronal differentiation, essential for microenvironment remodeling. In conclusion, this study underscores the role of iEMPs in CNS development and presents a robust platform for preclinical research.

bioengineering↗

bioRxiv2025

CrisprBuildr: an open-source application for CRISPR-mediated genome engineering in Drosophila melanogaster

CRISPR/Cas9 is a powerful tool for targeted genome engineering experiments. With CRISPR/Cas9, genes can be deleted or modified by inserting small peptides, fluorescent proteins or other tags for protein labelling experiments. Such experiments are important for detailed protein characterization in vivo. However, designing and cloning the corresponding constructs can be repetitive, time consuming and laborious. To aid users in CRISPR/Cas9-based genome engineering experiments, we built CrisprBuildr, a web-based application that allows users to delete genes or insert fluorescent proteins at the N- or C-terminus of their gene of choice. The application is built on the Drosophila melanogaster genome but can be used as a template for other available genomes. We have also generated new tagging vectors, using EGFP and mCherry combined with the small peptide SspB-Q73R for use in iLID-based optogenetic experiments. CrisprBuildr guides users through the process of designing guide RNAs and repair template vectors. CrisprBuildr is an open-source application and future releases could incorporate additional tagging or deletion vectors, genomes or CRISPR applications.

genomics↗

bioRxiv2025

The actin module of endocytic internalization in Aspergillus nidulans: a critical role of the WISH/DIP/SPIN90 family protein Dip1

Using fluorescent protein-tagged F-actin reporters we studied the actin cytoskeleton in Aspergillus nidulans. F-actin probes labeled endocytic patches, contractile actin rings and the Spitzenkorper (SPK), but not exocytic cables generated by the SPK-associated formin, illuminated only by tropomyosin. The SPK actin mesh contains tropomyosin and capping protein, but not fimbrin or Arp2/3, showing that it does not involve branched actin. Arp2/3 and fimbrin are recruited to endocytic patches at the end of their lifecycle, staying in them for 12-14 sec, coinciding with the burst of branched actin polymerization that powers vesicle internalization, whereas verprolin stays only during the first half of this actin phase. Hyphal growth requires endocytic recycling, which we exploited to assess the efficiency of endocytosis following genetic interventions. Ablation of SlaBSla2, Arp2/3, cofilin and fimbrin is lethal, whereas that of Srv2, verprolin and capping protein are debilitating, with the lifetime of actin in mutant patches roughly correlating with the extent of growth and endocytic defects. An outstanding problem is the origin of seed filaments required to prime Arp2/3 during endocytosis. Actin patches associate with cortical cables that give rise to long distance-moving "actin worms" that are different from tropomyosin-containing cables emanating from the SPK. Cables and worms are dependent on formin, yet inactivation of formin does not affect the F-actin patch lifecycle, arguing against formin playing an endocytic role. Ablation of the WISH/DIP/SPIN90 protein Dip1 priming Arp2/3 for the synthesis of linear actin delocalizes the endocytic machinery and severely impairs, but does not preclude, endocytosis. This establishes the existence of Dip1-independent mechanism(s) that synthesize seed filaments. Our data negate the possibility that this alternative mechanism results from a priming role of formin that is unmasked in dip1{Delta} cells, but do not exclude that cofilin-mediated filament severing could produce seed microfilaments for Arp2/3, as suggested for Schizosaccharomyces pombe. Authors summaryFilamentous fungi have a deep impact in our lives as friends and foes. Certain species are used as cell factories for the production of proteins or biopharmaceuticals. In contrast, phytopathogenic species, cause important losses in crops whereas those able to infect humans represent serious risks for global health. Filamentous fungi form tubular cells, denoted hyphae, that grow by apical extension. This requires the coupling between exocytosis and endocytosis in the so-called endocytic recycling pathway, which is needed, for example, to maintain the polarization of enzymes which synthesize the cell wall as growth proceeds. Remarkably, detailed studies on endocytosis in filamentous fungi are wanting. Here we report the characterization of the endocytic pathway in the genetic model Aspergillus nidulans, a filamentous ascomycete which is well-suited for genetic manipulation and in vivo fluorescence microscopy. Our study demonstrates that endocytosis is essential for filamentous fungal life and provides significant insight on how F-actin powers the internalization of endocytic vesicles, including an important physiological role of Dip1, a protein required to provide seed filaments for the formation of F-actin branching networks. Importantly, as yet unidentified Dip1-independent mechanisms that synthesize these seeds must exist, opening new avenues for future research.

cell biology↗

bioRxiv2024

Differential representations for affective and informative components of reward in the striatum and hippocampus

Receipt of a reward is composed of affective and informative components, which are often intertwined in most reward-processing and decision-making tasks. Our previous work allowed us to identify regions that were more strongly engaged for the affective and informative components of reward upon receipt (Smith et al., 2016) and showed that the ventral striatum responds to both affective and informative components of reward processing. However, the limited spatial resolution and coarse analytical approaches made it hard to understand how these different components of reward were represented in the brain, wherein similar engagement may not necessitate similar representations. In our current study, we used high-resolution functional magnetic resonance imaging (voxel size: 1.75 mm3) and representational similarity analysis to investigate the representation of affective and informative components of reward receipt in the striatum and the hippocampus, another region that is sensitive to reward information. We found a differential representation of affective and informative components of reward receipt in the striatum and the hippocampus, with no difference in representation between the two structures. However, in the dorsal striatum, we found that representations were stronger for affective rather than the informative components of reward receipt. Finally, we observed that the ventral striatum was sensitive to the predictiveness of information, such that across-run pattern similarity in the ventral striatum increased with the predictiveness of information. In sum, our results provide evidence of how affective and informative components of rewards are represented in the striatum and the hippocampus, potentially indicating a differential coding schema for the dorsal and the ventral striatum.

neuroscience↗

bioRxiv2024

Robust Methods For Quantifying Neuronal Morphology And Molecular Signaling Reveal That Psychedelics Do Not Induce Neuroplasticity

Induction of neuroplasticity has become the dominant explanatory framework for the rapid and sustained therapeutic effects of classic psychedelics. Within this broad concept, examination of morphological neuronal plasticity, such as dendritic arbor growth, is widely used to assess the neuroplasticity effects of classic and novel psychedelics. At the molecular level, it has been reported that serotonergic psychedelic compounds mediate dendritogenesis via the master molecular regulator of plasticity, TrkB, either directly via BDNF/TrkB signaling potentiation or indirectly through 5-HT2A receptor. To examine these hypotheses in detail, we developed a robust multimodal screening platform for unbiased, semi-automated quantification of cellular morphology and multiplex molecular signaling in the same cortical neurons. We found that in widely used primary neuronal cultures psychedelics do not directly modulate TrkB receptor or BDNF-TrkB signaling. We also found 5HT2a receptor gene expression and functional receptor levels are low, and psychedelics do not induce morphological growth, in contrast to significant dendritogenesis elicited by BDNF. Our results challenge recently published results in the field and indicate a need for rigorous experimental methods to study morphological manifestations of neuroplasticity effects induced by clinically used and experimental therapeutics.

neuroscience↗

bioRxiv2024

The Cancer Testis Antigen Testis Specific Serine Kinase 6 (TSSK6) is abnormally expressed in colorectal cancer and is essential for oncogenic behaviors

Cancer testis antigens (CTAs) are a collection of proteins whose expression is normally restricted to the gamete, but abnormally activated in a wide variety of tumors. The CTA, Testis specific serine kinase 6 (TSSK6), is essential for male fertility in mice. Functional relevance of TSSK6 to cancer, if any, has not previously been investigated. Here we find that TSSK6 is frequently anomalously expressed in colorectal cancer and patients with elevated TSSK6 expression have reduced relapse free survival. Depletion of TSSK6 from colorectal cancer cells attenuates anchorage independent growth, invasion and growth in vivo. Conversely, overexpression of TSSK6 enhances anchorage independence and invasion in vitro as well as in vivo tumor growth. Notably, ectopic expression of TSSK6 in semi-transformed human colonic epithelial cells is sufficient to confer anchorage independence and enhance invasion. In somatic cells, TSSK6 co-localizes with and enhances the formation of paxillin and tensin positive foci at the cell periphery, suggesting a function in focal adhesion formation. Importantly, TSSK6 kinase activity is essential to induce these tumorigenic behaviors. Our findings establish that TSSK6 exhibits oncogenic activity when abnormally expressed in colorectal cancer cells. Thus, TSSK6 is a previously unrecognized intervention target for therapy, which could exhibit an exceptionally broad therapeutic window.

cancer biology↗

bioRxiv2023

reanalyzerGSE: tackling the everlasting lack of reproducibility and reanalyses in transcriptomics

SummaryIn the current context of transcriptomics democratization, there is an unprecedented surge in the number of studies and datasets. However, advances are hampered by aspects such as the reproducibility crisis, and lack of standardization, in particular with scarce reanalyses of secondary data. reanalyzerGSE, is a user-friendly pipeline that aims to be an all-in-one automatic solution for locally available transcriptomic data and those found in public repositories, thereby encouraging data reuse. With its modular and expandable design, reanalyzerGSE combines cutting-edge software to effectively address simple and complex transcriptomic studies ensuring standardization, up to date reference genome, reproducibility, and flexibility for researchers. Availability and implementationThe reanalyzerGSE open-source code and test data are freely available at both https://github.com/BioinfoIPBLN/reanalyzerGSE and 10.5281/zenodo.XXXX under the GPL3 license. Supplementary data are available.

bioinformatics↗

bioRxiv2023

A potential patient stratification biomarker for Parkinson's disease based on LRRK2 kinase-mediated centrosomal alterations in peripheral blood-derived cells

Parkinsos disease (PD) is a common neurodegenerative movement disorder and leucine-rich repeat kinase 2 (LRRK2) is a promising therapeutic target for disease intervention. However, the ability to stratify patients who will benefit from such treatment modalities based on shared etiology is critical for the success of disease-modifying therapies. Ciliary and centrosomal alterations are commonly associated with pathogenic LRRK2 kinase activity and can be detected in many cell types. We previously found centrosomal deficits in immortalized lymphocytes from G2019S-LRRK2 PD patients. Here, to investigate whether such deficits may serve as a potential blood biomarker for PD which is susceptible to LRKK2 inhibitor treatment, we characterized patient-derived cells from distinct PD cohorts. We report centrosomal alterations in peripheral cells from a subset of early-stage idiopathic PD patients which is mitigated by LRRK2 kinase inhibition, supporting a role for aberrant LRRK2 activity in idiopathic PD. Centrosomal defects are detected in R1441G-LRRK2 and G2019S-LRRK2 PD patients and in non-manifesting LRRK2 mutation carriers, indicating that they acumulate prior to a clinical PD diagnosis. They are present in immortalized cells as well as in primary lymphocytes from peripheral blood. These findings indicate that analysis of centrosomal defects as a blood-based patient stratification biomarker may help nominate PD patients who will benefit from LRRK2-related therapeutics. One-sentence summaryPeripheral blood-derived cells can be employed to stratify Parkinsos disease patients most likely to respond to LRRK2-related therapeutics.

neuroscience↗

bioRxiv2022

Multi-lingual multi-platform investigations of online trade in jaguar parts

We conducted research to understand online trade in jaguar parts and develop tools of utility for jaguars and other species. Our research took place to identify potential trade across 31 online platforms in Spanish, Portuguese, English, Dutch, French, Chinese, and Vietnamese. We identified 230 posts from between 2009 and 2019. We screened the images of animal parts shown in search results to verify if from jaguar; 71 posts on 12 different platforms in four languages were accompanied by images identified as definitely jaguar, including a total of 125 jaguar parts (50.7% posts in Spanish, 25.4% Portuguese, 22.5% Chinese and 1.4% French). Search effort varied among languages due to staff availability. Standardizing for effort across languages by dividing number of posts advertising jaguars by search time and number individual searches completed via term/platform combinations, the adjusted rankings of posts were: Portuguese #1, Chinese 2 (time) & 3 (searches), Spanish 3 & 4; French 5 & 4; English 5 & 2, and Dutch 6. Teeth were most common; 156 posts offered at least 367 apparent teeth. From these, 95 teeth were assessed as definitely jaguar; 71 jaguar teeth could be linked to a location, with the majority of the 71 offered for sale from Mexico, China, Bolivia, and Brazil (26.8, 25.4, 16.9, and 12.7% respectively). Ranking of number of teeth was Mexico (19), China (18), Bolivia (12), Brazil (9), Peru/Ecuador (most accurate probable location) (8), Venezuela (3), Guadeloupe (1), and Uruguay (1). The second most traded item, skins and derivative items were only identified from Latin America: Brazil (7), was followed by Peru (6), Bolivia (3), Mexico (2 and 1 skin piece), and Nicaragua and Venezuela (1 each). Whether by number of posts or pieces, the ranking of parts was teeth, skins/pieces of skins, heads, and bodies. Our research presents a snapshot of online jaguar trade and methods that may have utility for many species now traded online. Our research took place within a longer-term project to assist law enforcement in host countries to better identify potential illegal trade online, with research findings informing hubs in Latin America for building such capacity.

ecology↗