Biology subjects

Hou, X.

Publications and source records attributed to Hou, X..

At least 55 records · Page 3Linked to original sources

bioRxiv2025

A pancrustacean brain and its visual systems define a Cambrian great appendage arthropod.

Early Cambrian fossils from the Chengjiang biota demonstrate that over half a billion years ago early stem euarthropods existed coevally with representatives of already recognizable crown groups. Prominent stem taxa were Fuxianhuia protensa and Alalcomenaeus whose cerebral and ganglionic traits identify them as, respectively, stem mandibulates and stem chelicerates. Here we report features of the visual systems and brain of the enigmatic lower Cambrian stem euarthropod Jianfengia multisegmentalis, which despite the absence of trunk tagmatization reveals neural traits that justify its inclusion within stem Pancrustacea also known as Tetraconata. The sutured eyestalks of Jianfengia, typifying crown Malacostraca, terminate as compound eyes populated by ommatidia that reveal tetradic structures indicative of cone-building Semper cells. Preserved neuropils and tracts in the eyestalks of Jianfengia resolve nested optic neuropils as occur in eucrustaceans. The nauplius-like eyes of Jianfengia and their associated nerves supply a discrete forebrain region, as they do in pancrustaceans. These attributes distinguish Pancrustacea from stem Chelicerata and extant Myriapoda as does the organization of the jianfengiid deutocerebrum and tritocerebrum. In the absence of external traits that differentiate identities amongst stem euarthropods, neuroanatomical traits provide a powerful tool for discerning characteristic distinctions and correspondences for elucidating euarthropod relationships. Here, we demonstrate that cerebral arrangements in Jianfengia correspond to those of pancrustaceans existing today.

evolutionary biology↗

bioRxiv2025

Role of drug induced nuclear CTSL (nCTSL) in DNA damage response in cancer- therapeutic implications

ABSTRACT Background: Despite treatment advances, ovarian cancer (OC) remains the deadliest gynecological cancer, with a ~70% mortality rate. OCs initially respond to platinum chemotherapy but often develop resistance. While PARP inhibitors improve relapse-free survival in responsive cases, they do not extend overall survival. This underscores the need for effective combination therapies beyond BRCA status. The lysosomal protein cathepsin L (CTSL) can traffic to the nucleus, where it can regulate DNA repair and serve as a chromatin modifier. Here, we tested the hypothesis that nucleoside analog clofarabine (CLF) induced nuclear CTSL (nCTSL) serves as a biomarker of sensitivity to DNA-damaging agents in ovarian cancer. Methods: Role of nuclear CTSL in DNA damage, synergy with PARPis and CRM1 inhibitor, tumor regression was analyzed by 3D-spheroid culture, colony forming assay, subcellular fractions, comet assay, and IFC/ western-blotting using PARP inhibitor-sensitive and -resistant OC cell lines, ex vivo cultures of patient-derived OC ascites cells (OVA), primary OCs, and patient-derived xenografts (PDXs). Results: In OC cell lines, treatment with CLF induced nCTSL in a subset of models-designated CLF-responsive (CLF-r)-and sensitized them to the PARP inhibitors olaparib and rucaparib. In CLF-non-responsive (CLF-nr) models, nCTSL trafficking and drug synergy were achieved with the CLF+olaparib combination. Synergy was observed in 47% of CLF-r and 24% of CLF-nr OVA samples. Mechanistically, CLF monotherapy induced nuclear import of CTSL via KPNB1 in CLF-r cells, while combination treatment with CLF+olaparib was required in CLF-nr cells. CLF also downregulated the nuclear export protein CRM1 in both CLF-r and CLF-nr models. CTSL knockdown conferred resistance to CLF+olaparib in both cohorts, supporting a functional role for nCTSL in therapeutic response. Notably, in a subset of OVAs (29%) classified as CLF-resistant (CLF-Res), CLF failed to downregulate CRM1; however, pharmacological inhibition of CRM1 with KPT8602 restored sensitivity to CLF+PARP inhibitor treatment. In vivo, CLF+olaparib treatment in CLF-r and CLF-nr PDX models led to enhanced DNA damage, reduced tumor burden, and prolonged survival. Conclusion: Collectively, these findings identify nCTSL as a predictive marker of response to DNA-damaging therapies and support the CLF+olaparib combination as a promising strategy for overcoming drug resistance in OC via CTSL-mediated DNA damage.

cancer biology↗

bioRxiv2025

Comprehensive Infectome Analysis Reveals Diverse Infectious Agents with Zoonotic Potential in Wildlife

Understanding wildlife-pathogen interactions is crucial for mitigating zoonotic risk. Through meta-transcriptomic sequencing we profiled the infectomes of 1,922 samples from 67 mammalian species across China, uncovering a remarkable diversity of viral, bacterial, fungal, and parasitic pathogens. Of the 195 pathogens identified, 62 were novel, including a bi- segmented coronavirus in diseased lesser pandas, which we propose represents a new genus - Zetacoronavirus. The orders Carnivora and Rodentia exhibited the highest pathogen diversity and were implicated in numerous host-jumping events. Comparative analysis of diseased versus healthy animals revealed a trend of higher pathogen loads in the former, with possible differences in tissue tropisms. In total, 48 zoonotic and 17 epizootic pathogens were identified, with frequent cross-species transmission, emphasizing the potential for emerging public health threats. This study highlights the urgent need for wildlife pathogen surveillance to inform proactive disease management strategies.

microbiology↗

bioRxiv2025

HD2Net: A Deep Learning Framework for Simultaneous Denoising and Deaberration in Fluorescence Microscopy

Fluorescence microscopy is essential for biological research, offering high-contrast imaging of microscopic structures. However, the quality of these images is often compromised by optical aberrations and noise, particularly in low signal-to-noise ratio (SNR) conditions. While adaptive optics (AO) can correct aberrations, it requires costly hardware and slows down imaging; whereas current denoising approaches boost the SNR but leave out the aberration compensation. To address these limitations, we introduce HD2Net, a deep learning framework that enhances image quality by simultaneously denoising and suppressing the effect of aberrations without the need for additional hardware. Building on our previous work, HD2Net incorporates noise estimation and aberration removal modules, effectively restoring images degraded by noise and aberrations. Through comprehensive evaluation of synthetic phantoms and biological data, we demonstrate that HD2Net outperforms existing methods, significantly improving image resolution and contrast. This framework offers a promising solution for enhancing biological imaging, particularly in challenging aberrating and low-light conditions.

bioengineering↗

bioRxiv2024

Genomic Insights into Hybridization and Speciation of Mitten Crabs in the Eriocheir Genus

Hybridization is a prominent and influential phenomenon with significant implications for adaptive evolution, species distribution and biodiversity. However, the intricacies of how hybridization influences genomic structure and facilitates adaptive evolution still elude our full understanding. Analyzing whole genome data from seven populations within Eriocheir genus across diverse geographic regions, we have validated a complex hybridization history between Chinese and Japanese mitten crabs. This hybridization gave rise to two distinct ecological species: Hepu and Russian mitten crabs with unique genomic architectures and adaptations. Genes related to reproduction, development, and temperature adaptation exhibit divergent selection signals, potentially contributing to their phenotypic diversity and ecological niches. Meanwhile, genes associated with reproduction, namely Birc6, Bap31, and Poxn, displayed robust evidence of selective sweeps in Hepu mitten crab. Notably, the favored alleles for these genes originated from the parental lineages during the hybridization process. Furthermore, Hepu mitten crab is a homoploid hybrid species that originated from an ancient hybridization event, resolving its longstanding taxonomic controversy. Our study sheds light on the evolutionary history of mitten crabs and highlights the crucial role of hybridization in driving adaptation, range expansion, and diversification within the Eriochier genus.

genomics↗

bioRxiv2024

Speech motor cortex enables BCI cursor control and click

Decoding neural activity from ventral (speech) motor cortex is known to enable high-performance speech brain-computer interface (BCI) control. It was previously unknown whether this brain area could also enable computer control via neural cursor and click, as is typically associated with dorsal (arm and hand) motor cortex. We recruited a clinical trial participant with ALS and implanted intracortical microelectrode arrays in ventral precentral gyrus (vPCG), which the participant used to operate a speech BCI in a prior study. We developed a cursor BCI driven by the participants vPCG neural activity, and evaluated performance on a series of target selection tasks. The reported vPCG cursor BCI enabled rapidly-calibrating (40 seconds), accurate (2.90 bits per second) cursor control and click. The participant also used the BCI to control his own personal computer independently. These results suggest that placing electrodes in vPCG to optimize for speech decoding may also be a viable strategy for building a multi-modal BCI which enables both speech-based communication and computer control via cursor and click.

neuroscience↗

bioRxiv2024

The phosphatase PP2C12 is a negative player in LRX-RALF-FER-mediated cell wall integrity sensing

Plants have evolved an elaborate cell wall integrity (CWI) sensing system to monitor and modify cell wall formation. LRR-extensins (LRXs) are cell wall-anchored proteins that bind RAPID ALKALINIZATION FACTOR (RALF) peptide hormones and induce compaction of cell wall structures. At the same time, LRXs form a signaling platform with RALFs and the transmembrane receptor kinase FERONIA (FER) as a means to relay changes in CWI to the protoplast. LRX1 of Arabidopsis thaliana is predominantly expressed in root hairs and lrx1 mutants develop defective root hairs. Here, we identify a regulator of LRX1-RALF-FER signaling as a suppressor of the lrx1 root hair phenotype. The repressor of lrx1_23 (rol23) gene encodes PP2C12, a type 2C phosphatase of clade H that interacts with FER and dephosphorylates Thr696 in the FER activation loop in vitro. The LRX1-related function of PP2Cs appears clade H-specific and was not observed for other PP2Cs investigated. Collectively, our data suggest that LRX1 acts upstream of the RALF1-FER signaling module and PP2C12 has an inhibitory activity via modulating FER activity to fine-tune CWI signaling.

plant biology↗

bioRxiv2024

Computational Microbiome Pharmacology Analysis Elucidates the Anti-Cancer Potential of Vaginal Microbes and Metabolites

The vaginal microbiomes role in risk, progression, and treatment of female cancers has been widely explored. Yet, there remains a need to develop methods to understand the interaction of microbiome factors with host cells and to characterize their potential therapeutic functions. To address this challenge, we developed a systems biology framework we term the Pharmacobiome for microbiome pharmacology analysis. The Pharmacobiome framework evaluates similarities between microbes and microbial byproducts and known drugs based on their impact on host transcriptomic cellular signatures. Here, we apply our framework to characterization of the Anti-Gynecologic Cancer Vaginal Pharmacobiome. Using published vaginal microbiome multi-omics data from the Partners PrEP clinical trial, we constructed vaginal epithelial gene signatures associated with each profiled vaginal microbe and metabolite. We compared these microbiome-associated host gene signatures to post-drug perturbation host gene signatures associated with 35 FDA-approved anti-cancer drugs from the Library of Integrated Network-based Cellular Signatures database to identify vaginal microbes and metabolites with high statistical and functional similarity to these drugs. We found that Lactobacilli and their metabolites can regulate host gene expression in ways similar to many anti-cancer drugs. Additionally, we experimentally tested our model prediction that taurine, a metabolite produced by L. crispatus, kills cancerous breast and endometrial cancer cells. Our study shows that the Pharmacobiome is a powerful framework for characterizing the anti-cancer therapeutic potential of vaginal microbiome factors with generalizability to other cancers, microbiomes, and diseases.

systems biology↗

bioRxiv2024

Efficacy and Safety of a novel virulent phage against acute pulmonary infection of Acinetobacter baumanniii in mice

Acinetobacter baumannii (A.baumannii) is a notable opportunistic pathogen responsible for severe hospital-acquired infections, with multidrug-resistant strains posing significant treatment challenges. Phage therapy, which employs bacteriophages as natural bacterial antagonists, has gained renewed attention as a promising solution to combat antibiotic-resistant infections. In this study, we isolated and characterized a novel virulent phage, vB_AbaS_qsb1, which specifically lyses A.baumannii. Phylogenetic and genomic analyses indicate that vB_AbaS_qsb1 is the founding member of a previously unreported genus, which we have named as Acinibactriovirus, with Acinibactriovirus lysinus as the type species. vB_AbaS_qsb1 demonstrated robust stability across diverse temperature and pH ranges, a short latent period, and no known virulence or antibiotic resistance genes within its 54,713 bp dsDNA genome. Safety assessments showed that high-dose vB_AbaS_qsb1 induced no adverse effects in mice, with histopathology confirming its safety profile. Therapeutic experiments further indicated that vB_AbaS_qsb1 provided at least 50% protection against A.baumannii-induced pneumonia, significantly reducing bacterial loads and inflammation markers, while maintaining high phage titers in lung tissue.This study introduces vB_AbaS_qsb1 as a promising candidate for phage therapy against A.baumannii, offering both innovative insights and a valuable framework for future isolation, genomic characterization, and efficacy evaluation of phages targeting antibiotic-resistant bacteria. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/617119v3_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@17bf4cdorg.highwire.dtl.DTLVardef@104c49eorg.highwire.dtl.DTLVardef@89e1dorg.highwire.dtl.DTLVardef@1c4b018_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2024

An instantaneous voice synthesis neuroprosthesis

Brain computer interfaces (BCIs) have the potential to restore communication to people who have lost the ability to speak due to neurological disease or injury. BCIs have been used to translate the neural correlates of attempted speech into text1-3. However, text communication fails to capture the nuances of human speech such as prosody, intonation and immediately hearing ones own voice. Here, we demonstrate a "brain-to-voice" neuroprosthesis that instantaneously synthesizes voice with closed-loop audio feedback by decoding neural activity from 256 microelectrodes implanted into the ventral precentral gyrus of a man with amyotrophic lateral sclerosis and severe dysarthria. We overcame the challenge of lacking ground-truth speech for training the neural decoder and were able to accurately synthesize his voice. Along with phonemic content, we were also able to decode paralinguistic features from intracortical activity, enabling the participant to modulate his BCI-synthesized voice in real-time to change intonation, emphasize words, and sing short melodies. These results demonstrate the feasibility of enabling people with paralysis to speak intelligibly and expressively through a BCI.

neuroscience↗

bioRxiv2024

SlNAP2 promoted fruit ripening by directly binding the ACS2 promoter and interacting with EIL3

The ripening process of tomato fruit is affected by a variety of environmental factors and genetic regulators. NAC transcription factors (TFs) function in a multitude of biological processes, while the current knowledge on the participation of NAC TFs in the regulatory network of fruit ripening is relatively limited. In this study, we isolated a NAC TFs, NAP2, which acts as a positive transcription activator in tomato fruit ripening. We also observed a notable delay in the ripening process of SlNAP2 silenced and knockout mutant fruit. In particular, ethylene production was obviously inhibited in SlNAP2 mutant fruit. Y1H and DLR assays showed that SlNAP2 directly binds to the promoter of SlACS2 and activates its transcriptional activity. Furthermore, SlNAP2 and SlEIL3 physically interaction was demonstrated by yeast two-hybrid (Y2H), luciferase complementation (LUC), bimolecular fluorescence complementation (BiFC) and coimmunoprecipitation analysis (CoIP) assays. Meanwhile, the pigment content, firmness and the transcript levels of genes associated with carotenoid and chlorophyll metabolism and cell wall metabolism were also potentially affected by the SlNAP2 deletion; however, it has remained unclear whether these genes are also directly regulated by SlNAP2. Therefore, our findings indicate that SlNAP2 directly binds to SlACS2 promoter to activate its expression and promote ethylene generation, which in turn interacts with EIL3 to enhance the function of ethylene in tomato fruit ripening. Collectively, our data contribute to understanding the interaction of NAC TFs and ethylene in tomato fruit ripening, thereby enhancing our knowledge of the ripening regulatory network that governs tomato fruit maturation.

biochemistry↗

bioRxiv2024

Ventral Morphology and Ecological Implications of Cindarella eucalla (Artiopoda, Xandarellida) from Chengjiang Biota, China

Artiopoda, an early arthropod group, displays post-antennal appendages resembling trilobite limbs, but relationships with other ealy arthropods remain enigmatic. Limited studies and morphological details hinder the understanding of internal relationships within Artiopoda. Recently, exceptionally well preserved arthropod fossils from the Chengjiang Biota were studied using X-ray computed tomography, revealing detailed morphologies. In this study, Cindarella eucalla, a xandarellid from the Chengjiang Biota, was re-investigated using X-ray computed tomography and fluorescent microscopy to reconstruct its morphology and understand its phylogeny and ecology. This study successfully reconstructed a three-dimensional model of Cindarella eucalla, revealing features, such as spindle-shaped trunk tergites with the anterior six covered by the head shield and axial spines extending from the last four, natant hypostome, four post-antennal cephalic appendage pairs, dorsoventral mismatch existed between trunk tergites and limb pairs. This research suggests that Cindarella eucalla could escape in a very short time when it encounters an enemy, and it probably lived in muddy environments with ample light. Phylogenetic analysis indicates that Xandarellids may have close relationship with concililiterga or a clade composed of Nektaspida + (Conciliterga + (Phytophilaspis pergamena + Trilobita)).

evolutionary biology↗

bioRxiv2024

Histidine limitation causes alteration in the TOR network and plant development

Plant growth depends on growth regulators, nutrient availability, and amino acids levels. The TOR (Target of Rapamycin) network senses these parameters and influences cell wall formation and expansion accordingly. Cell wall integrity and structures are surveyed and modified by a complex array of cell wall integrity sensors, including LRR-extensins (LRXs), that function as hormone receptors and help to compact cell walls. Expressing the Arabidopsis root-hair specific LRX1 without the extensin domain, which anchors the protein to the cell wall, has a negative effect on root hair development. The mechanism of this negative effect was investigated by a suppressor screen, which led to the identification of a sune (suppressor of dominant-negative LRX1) mutant collection. The sune82 mutant was identified as an allele of HISN2 which encodes an enzyme essential for histidine biosynthesis. The sune82 mutation leads to reduced accumulation of histidine, and this influences the TOR network. The sune82 mutant reflects the impact of the TOR network on cell wall formation processes involving LRX proteins. It also represents an excellent tool to study the effects of reduced histidine levels on plant development, as it is a rare example of a viable partial loss-of-function allele in an essential biosynthetic pathway. HighlightPartial loss of function of HISN2 in sune82 results in a significant reduction in histidine content, which subsequently alters the TOR network.

cell biology↗

bioRxiv2024

Lestaurtinib's antineoplastic activity converges on JAK/STAT signaling to inhibit advanced forms of therapy resistant ovarian cancer

Ovarian cancer is the deadliest gynecological malignancy, owing to its late-stage diagnosis and high rates of recurrence and resistance following standard-of-care treatment, highlighting the need for novel treatment approaches. Through an unbiased drug screen, we identified the kinase inhibitor, lestaurtinib, as a potent antineoplastic agent for chemotherapy- and PARP-inhibitor (PARPi)-sensitive and -resistant ovarian cancer cells and patient derived xenografts (PDXs). RNA-sequencing revealed that lestaurtinib potently suppressed JAK/STAT signaling and lestaurtinib efficacy was shown to be directly related to JAK/STAT pathway activity in cell lines and PDX models. Most ovarian cancer cells exhibited constitutive JAK/STAT pathway activation and genetic loss of STAT1 and STAT3 resulted in growth inhibition. Lestaurtinib also displayed synergy when combined with cisplatin and olaparib, including in a model of PARPi resistance. In contrast, the most well-known JAK/STAT inhibitor, ruxolitinib, lacked antineoplastic activity against all ovarian cancer cell lines and PDX models tested. This divergent behavior was reflected in the ability of lestaurtinib to block both Y701/705 and S727 phosphorylation of STAT1 and STAT3, whereas ruxolitinib failed to block S727. Consistent with these findings, lestaurtinib additionally inhibited JNK and ERK activity, leading to more complete suppression of STAT phosphorylation. Concordantly, combinatorial treatment with ruxolitinib and a JNK or ERK inhibitor resulted in synergistic antineoplastic effects at dose levels where single agents were ineffective. Taken together, these findings indicate that lestaurtinib, and other treatments that converge on JAK/STAT signaling, are worthy of further pre-clinical and clinical exploration for the treatment of highly aggressive and advanced forms of ovarian cancer. Statement of significanceLestaurtinib is a novel inhibitor of ovarian cancer, including chemotherapy- and PARPi-resistant models, that acts through robust inhibition of the JAK/STAT pathway and synergizes with standard-of-care agents at clinically relevant concentrations.

cancer biology↗

bioRxiv2024

Alterations of PINK1-PRKN signaling in mice during normal aging

The ubiquitin kinase-ligase pair PINK1-PRKN identifies and selectively marks damaged mitochondria for elimination via the autophagy-lysosome system (mitophagy). While this cytoprotective pathway has been extensively studied in vitro upon acute and complete depolarization of mitochondria, the significance of PINK1-PRKN mitophagy in vivo is less well established. Here we used a novel approach to study PINK1-PRKN signaling in different energetically demanding tissues of mice during normal aging. We demonstrate a generally increased expression of both genes and enhanced enzymatic activity with aging across tissue types. Collectively our data suggest a distinct regulation of PINK1-PRKN signaling under basal conditions with the most pronounced activation and flux of the pathway in mouse heart compared to brain or skeletal muscle. Our biochemical analyses complement existing mitophagy reporter readouts and provide an important baseline assessment in vivo, setting the stage for further investigations of the PINK1-PRKN pathway during stress and in relevant disease conditions.

neuroscience↗

bioRxiv2024

Gut Microbiome-Driven Metabolites Influence Skin Pigmentation in TYRP1 Mutant Oujiang Color Common Carp

The gut microbiome is one of the major regulators of the gut-skin axis and is partly regulated by host genetics. In the present study, using comparative high-throughput omics data on CRISPR/Cas9-mediated TYRP1 mutant and wild-color common carp populations, we quantified the proportion of inter-individual variation in the skin transcriptome and blood metabolome by genetic architecture and gut microbiomes. We found 525 differential metabolites (DMs) and 45 differential gut microbial genera in TYRP1 mutant fishes relative to the wild type. Through interaction analysis and causal mediation analyses, we revealed that the TYRP1-mutant derived genetic background may exert an inflammatory Acinetobacter - Leukotrience-C4 and - Spermine metabolic pathway under the regulation of an anti-inflammatory cardio-vascular genetic network underlying the upregulating expression of COMT, PLG, C2, C3, F10, TDO2, MHC1, and SERPINF2 gene for evolving unusual coffee-like color phenotype. This unique network appears to underlie the "coffee-like" color phenotype. We propose that the COMT-mediated causal effect of the unusual gut microbiome on the atypical skin gene expression patterns through the gut-skin metabolic pathway. Article SummaryR.N. Mandal et al. report on the causal effect of gut microbiome-driven metabolites on the expression pattern of regulatory genes underlying an unusual color phenotype. It suggests that TYRP1 Mutation may rise an unusual inflammatory gut microbiome-skin metabolic pathway that may be balanced by an anti-inflammatory cardio-vascular genetic network leading to unique coloration in Oujiang Color Common Carp.

genetics↗

bioRxiv2024

The Interplay Between Nutrition and the Midgut Microbiome of the Mosquito Aedes aegypti Reveals Putative Symbionts.

Blood meals are crucial for the reproductive cycle of Aedes aegypti and represent the means by which arboviruses are transmitted to its hematophagy hosts. It also has been postulated that feeding on blood may modulate the mosquito microbiome, but the compositional shifts in microbial diversity and function remain elusive. In this paper, we analyzed the modulation of the midgut microbiome in 60 females of Aedes aegypti throughout the digestive period, 12, 24, and 48 hours after blood or sugar meals using whole-genome shotgun sequencing. Microbial transstadial transmission between larvae and adults was also assessed. This approach provided a high coverage of the midgut metagenome, allowing microbial taxonomic assignments at the species level and gene-based functional profiling. Females at later hours post-feeding and larvae display low microbiome diversities and little evidence of transstadial transmission. However, a striking proliferation of Enterobacterales was observed during early hours of digestion in blood-fed mosquitoes. The compositional shift was concomitant with a predicted functional change in genes associated with carbohydrate and protein metabolism. The observed shifts in blood-fed females midguts are restored to a sugar-fed-like microbial profile after 48h, when blood digestion is completed. Conversely, as in all blood-fed females, a high abundance of the opportunistic human pathogen Elizabethkingia anophelis (Flavobacteriales) takes place in this post-digestion stage. This bacterial species has also been described as a symbiont of mosquitoes of the genus Anopheles (Culicidae). This work is the first report of the adaptation of the midgut microbiome of A. aegypti to a digestive role after a blood meal, at the expense of the proliferation of potential symbionts. Significance statementThe findings in this paper can contribute to a better understanding of the dynamics of the mosquito microbiome during digestion and its potential implications for host physiology and metabolism, also informing the future development of sustainable methods for insect-borne diseases control based on microbial components that might influence vectorial capacity and pathogen transmission by A. aegypti.

microbiology↗

bioRxiv2024

Development and characterization of phospho-ubiquitin antibodies to monitor PINK1-PRKN signaling in cells and tissue

The selective removal of dysfunctional mitochondria, a process termed mitophagy, is critical for cellular health and impairments have been linked to aging, Parkinson disease, and other neurodegenerative conditions. A central mitophagy pathway is orchestrated by the ubiquitin (Ub) kinase PINK1 together with the E3 Ub ligase PRKN/Parkin. The decoration of damaged mitochondrial domains with phosphorylated Ub (p-S65-Ub) mediates their elimination though the autophagy system. As such p-S65-Ub has emerged as a highly specific and quantitative marker of mitochondrial damage with significant disease relevance. Existing p-S65-Ub antibodies have been successfully employed as research tools in a range of applications including western blot, immunocytochemistry, immunohistochemistry, and ELISA. However, physiological levels of p-S65-Ub in the absence of exogenous stress are very low, therefore difficult to detect and require reliable and ultrasensitive methods. Here we generated and characterized a collection of novel recombinant, rabbit monoclonal p-S65-Ub antibodies with high specificity and affinity in certain applications that allow the field to better understand the molecular mechanisms and disease relevance of PINK1-PRKN signaling. These antibodies may also serve as novel diagnostic or prognostic tools to monitor mitochondrial damage in various clinical and pathological specimens.

neuroscience↗