Biology subjects

Rosa, C.

Publications and source records attributed to Rosa, C..

13 recordsLinked to original sources

bioRxiv2026

Nuclear acetyl-CoA production by acetyl-CoA synthetase enables dynamic histone acetylation and gene expression in Plasmodium falciparum

A complex transcriptional cascade drives the two-day intraerythrocytic developmental cycle of the most virulent human malaria parasite, Plasmodium falciparum, in the human host. Genes are rapidly activated at specific times, then silenced as quickly. Transcriptional activity correlates with histone acetylation, which is modulated by acetyltransferases that use acetyl-CoA and deacetylases that produce acetate. Acetyl-CoA synthetase (ACAS) uses acetate to produce acetyl-CoA and has been implicated in histone acetylation, providing an interesting link between parasite metabolism and transcription. Here, we show that ACAS becomes enriched in the nucleus at a time during the life cycle when the parasite undergoes rapid growth and increased levels of transcription. We use mass spectrometry to show that ACAS inhibition results in a rapid and global depletion of histone acetylation, which leads to a general decrease in chromatin accessibility at gene promoters. These widespread alterations in chromatin composition disrupted the transcriptional cascade, resulting in cell cycle arrest. Our study provides evidence that ACAS plays an important nuclear role in the histone acetylation cycle and insight into the dynamic nature and essentiality of histone acetylation in the parasites complex transcriptional program driving infection of the human host.

molecular biology↗

bioRxiv2026

Forest degradation reshapes trophic functioning in vertebrate food webs across Amazonian forests

The Amazon is a mosaic of ecosystems, accounting for 13% of all known species globally, and responsible for providing a variety of ecosystem services, including a key role in global climate regulation. However, 18% of the Amazon forest cover has been lost completely and a further 38% degraded, threatening biodiversity and millions of local livelihoods. Currently, little is known about how this impacts the functioning of ecological communities. Here, we combine an energetic approach with biodiversity metrics to quantify ecosystem functioning in mammal and bird food webs across Amazonia, along a gradient of forest degradation linked to road proximity. We show that even under relatively low disturbance, ecosystem functions shift: carnivory increases closer to roads, driven by generalist species that persist under these conditions, whereas herbivory declines mainly due to reduced herbivore biomass and species richness. This suggests that processes associated with forest degradation can alter energy flow even where biodiversity metrics remain relatively unchanged, highlighting energetic approaches as sensitive indicators of ecosystem disruption.

ecology↗

bioRxiv2026

The emergence of bacterial blight pathogen followed the dispersal pattern of rice in Asia

Crop domestication has a significant effect on the evolutionary trajectory of plant pathogens by providing new ecological niches and abundant resources. The domestication of Asian rice (Oryza sativa) in Asia, approximately 9,000 years ago, might have shaped the genetic makeup of associated microbes into modern threats. In this study, we provide insight into the evolutionary history and dispersal pattern of the rice bacterial blight (BB) pathogen, Xanthomonas oryzae pv. oryzae (Xoo), one of the most destructive rice pathogens in the last century. The analysis of 433 Asian Xoo (AXoo) genomes identified twelve modern populations derived from three ancestral lineages (AXooL). Each population emerged with a unique genetic composition including the combination of pathogenicity factors. Bayesian reconstruction suggests that Xoo lineages emerged alongside O. sativa domestication hotspots and followed the dispersal pattern of rice across the continent. An ancient Xoo lineage (AXooL1) emerged in China and was likely dispersed with japonica rice. A second lineage (AXooL2) which could have turned up from China and spread across India, then evolved due to the domestication and spread of indica rice, and later on expanded eastward of Asia.. We also showed that recombination played a significant role in the emergence of AXooL3, which appeared more recently and might have spread with the rice trading routes. Our study aligns the evolution and dissemination of the phylogroup AXoo with the history of O. sativa, offering valuable insights for the formulation of precise disease management strategies. AUTHOR SUMMARYRice domestication was a crucial step in the development of Asian civilization. However, this process also affected the evolution of an associated pathogen, leading to its emergence as a global threat. Rice bacterial blight (BB), caused by the pathogen Xanthomonas oryzae pv. oryzae (Xoo), has been a scourge in many Asian countries. Using population genomics, we explored the diversity and evolutionary history of Xoo in Asia (AXoo). Here we show that two ancestral pathogen lineages emerged in rice domestication centers (China and India) and dispersed with rice across the continent. More recently, recombination played a crucial role in the appearance of a third lineage that spread through trading activity. This study provides the implications of the adaptation of AXoo in Oryza sativa, and might be valuable in forecasting BB outbreaks.

genomics↗

bioRxiv2025

Defective But Promising: Evaluating Bioinformatic Pipelines for Utility of Defective Interfering RNA Discovery in Plant Viral Infections

We explored the utility of the currently available bioinformatics programs ViReMa, DI-tector, DVGfinder, DG-Seq, and VODKA2 for identifying junction points in plant virus high-throughput sequencing (HTS) data that could be tested downstream for antiviral capacity. Specifically, we looked at whether the outputs from these bioinformatic tools generally agree and whether the most frequently identified "defective viral genomes" (DVGs) from these programs are promising defective interfering RNA (DI) candidates for downstream validation. We also explored the possibility of these tools helping us address a larger research question of whether DI RNA are consistently generated and maintained in a specific virus-host combination when conditions are permissive for their replication and accumulation, our "DI prevalence" hypothesis. This was conducted by running eight previously published RNAseq datasets through all five programs and comparing degree of output overlap, most common junction point identified, and whether previously published DI junction points were found. Our results demonstrate a low degree of agreement regarding identified junction points between programs, promise regarding looking at the most commonly occurring junction for DI candidates, and support for our DI prevalence hypothesis. We conclude that bioinformatics workflows have a place in the toolbox of DI and DVG research, but they should not be used alone. We suggest the use of multiple programs on a dataset to better inform decisions regarding deletions to re-create and screen downstream and reiterate the importance of other avenues of evidence in DVG/DI characterization.

bioinformatics↗

bioRxiv2024

Micro-C reveals MORC/ApiAP2-mediated links between distant, functionally related genes in the human malaria parasite

Genome organization plays a significant role in silencing heterochromatinized genes in the most virulent human malaria parasite, Plasmodium falciparum. However, it remains unclear how heterochromatinized genes spatially cluster or if active genes are also organized in a specific manner. We used Micro-C to achieve a near-nucleosome resolution DNA-DNA contact map, which revealed new inter- and intrachromosomal heterochromatic and euchromatic structures in the blood stage parasite. We observed subtelomeric fold structures that facilitate interactions amongst heterochromatinized genes involved in antigenic variation. In addition, we identified long-range intra- and interchromosomal interactions amongst active, stage-specific genes. Both structures are mediated by AP2-P, an ApiAP2 transcription factor, and a putative MORC chromatin remodeler, and functional specificity is achieved via combinatorial binding with other sequence-specific DNA-binding factors. This study provides unprecedented insight into the organizational machinery used by this medically important eukaryotic parasite to spatially coordinate genes underlying antigenic variation and to co-activate stage-specific genes.

molecular biology↗

bioRxiv2024

Infected grapevines are poor hosts but can serve as source of pathogen transmission for SLF

The potential of the invasive spotted lanternfly (Lycorma delicatula White; SLF) to serve as vector of plant pathogens is especially a concern for grapevine growers, as SLF are known to invade and can heavily infest vineyards, where the insects may encounter grapevines with multiple diseases. In this study, we have found that, when given the choice, SLF preferentially fed on healthy vines and that, when forced, feeding on Pierces disease (PD)-infected vines had negative effects on nymph development. Upon transmission trials, most of the recipient vines showed scorching symptoms typical of PD and one of the recipient vines resulted positive by qPCR. Our study suggests that SLF could be a vector of PD, however further experiments are needed to determine if transmission would occur under field conditions.

plant biology↗

bioRxiv2023

Small RNA Analysis of Virus-virus Interaction between Two Orthotospoviruses

Mixed infections of plant viruses are commonly found in natural patho-systems and pre-sent a valuable opportunity to understand how multiple viruses can co-infect the same host. Tomato spotted wilt orthotospovirus (TSWV) and impatiens necrotic spot orthotospovirus (INSV) are pre-sent in the same geographic areas and are closely related. More mixed infections of TSWV and INSV have been reported in recent years, and the INSV host range has been reported to be increasing. In a previous study, we have isolated one strain of INSV and one of TSWV and showed that they have an antagonistic relationship in their vectors, but we were unable to determine, the underlying mech-anisms governing their antagonism in planta and the contribution of the host to this. Here, we used small RNA sequencing to study TSWV-INSV antagonistic interaction and showed that INSV alters plant responses and the processing of TSWV.

plant biology↗

bioRxiv2023

Coordinated Rho1-dependent mechanical cell-to-cell interactions and medioapical contractile pulsing regulate morphogenesis in the Drosophila retina

Lattice cells (LCs) in the developing Drosophila retina constantly move and change shape before attaining final forms. Previously we showed that repeated contraction and expansion of apical cell contacts affect these dynamics. Here we describe a second contributing factor, the assembly of a medioapical actomyosin ring composed of nodes linked by filaments that attract each other, fuse, and contract the LCs apical area. This medioapical actomyosin network is dependent on Rho1 and its known effectors. Apical cell area contraction alternates with relaxation, generating pulsatile changes in apical cell area. Strikingly, cycles of contraction and relaxation of cell area are reciprocally synchronized between adjacent LCs. Further, in a genetic screen, we identified RhoGEF2 as an activator of these Rho1 functions and RhoGAP71E/C-GAP as an inhibitor. Thus, Rho1 signaling regulates pulsatile medioapical actomyosin contraction exerting force on neighboring cells, coordinating cell behavior across the epithelium. This ultimately serves to control cell shape and maintain tissue integrity during epithelial morphogenesis of the retina. Short summaryRosa et. al. describe a Rho1-dependent pulsatile medioapical actomyosin network that couples neighboring retina lattice cells biomechanically, creating an adaptive supracellular actomyosin network that coordinates the mechanical behavior of neighboring cells and regulates cell shape and tissue integrity.

developmental biology↗

bioRxiv2022

Cohesin is involved in transcriptional repression of stage-specific genes in the human malaria parasite

The most virulent human malaria parasite, Plasmodium falciparum, has a complex life cycle between its human host and mosquito vector. Each stage is driven by a specific transcriptional program, but with a relatively high ratio of genes to specific transcription factors, it is unclear how genes are activated or silenced at specific times. The P. falciparum genome is relatively euchromatic compared to the mammalian genome, except for specific genes that are uniquely heterochromatinized via HP1. There seems to be an association between gene activity and spatial organization; however, the molecular mechanisms behind genome organization are unclear. While P. falciparum lacks key genome-organizing proteins found in metazoans, it does have all core components of the cohesin complex. In other eukaryotes, cohesin is involved in sister chromatid cohesion, transcription, and genome organization. To investigate the role of cohesin in P. falciparum, we combined genome editing, mass spectrometry, chromatin immunoprecipitation and sequencing (ChIP-seq), and RNA sequencing to functionally characterize the cohesin subunit Structural Maintenance of Chromosomes protein 3 (SMC3). SMC3 knockdown in early stages of the intraerythrocytic developmental cycle (IDC) resulted in significant upregulation of a subset of genes involved in erythrocyte egress and invasion, which are normally expressed at later stages. ChIP-seq of SMC3 revealed that over the IDC, enrichment at the promoter regions of these genes inversely correlates with their expression and chromatin accessibility levels. These data suggest that SMC3 binding helps to repress specific genes until their appropriate time of expression, revealing a new mode of stage-specific, HP1-independent gene repression in P. falciparum.

molecular biology↗

bioRxiv2020

Anodal transcranial direct-current stimulation over the left dorsolateral prefrontal cortex and perception of emotional faces

The prefrontal cortices have been shown to be engaged in the perception of emotional faces, and imaging studies correlate activation of the left dorsolateral prefrontal cortex (l-DLPFC) with correct identification of emotional expressions. Transcranial direct current stimulation (tDCS)has been shown to modulate cortical function and might influence the perception of emotional faces. Our aim was to evaluate the possible effects of tDCS on a task that required correct identification of emotions represented by human faces presented on a screen. Ten volunteers (ages 18-30; mean = 23.2; SD = 4.3) were evaluated. The experiments were carried out in two 20 minutes stimulation sessions (real and sham tDCS) 4 days apart, at least, to avoid carryover effects, and session orders were randomized. The anode was placed over the l-DLPFC (F3 of the international 10-20 EEG electrode positioning system) and the cathode over the contralateral supraorbital region. Emotional stimuli were 120 consecutive human faces to be verbally classified as "happy", "surprised", "neutral", "angry" or "sad". Real anodal tDCS over the l-DLPFC resulted in significantly longer response times with a trend towards increased error rates, compared to the sham condition.

neuroscience↗

bioRxiv2019

The role of post-Golgi transport pathways and sorting motifs in the plasmodesmal targeting of the movement protein (MP) of Ourmia melon virus (OuMV)

Plants have a highly sophisticated endomembrane system targeted by plant viruses for cell-to-cell movement. The movement protein (MP) of ourmia melon virus (OuMV) is delivered to plasmodesmata (PD) and forms tubules to facilitate cell-to-cell movement. Although several functionally important regions for correct subcellular localization of OuMV MP have been identified, little is known about the pathways OuMV MP hijacks to reach the PD. Here, we demonstrate that OuMV MP localizes to the trans-Golgi network (TGN), but not to the multivesicular body/prevacuolar compartment or Golgi, and carries two putative sorting motifs, a tyrosine (Y) and a dileucine (LL) motif, near its N-terminus. Glycine substitutions in these motifs result in loss of OuMV infectivity in Nicotiana benthamiana and Arabidopsis. Live cell imaging of GFP-labeled sorting motif mutants shows that Y motif mutants fail to localize to the TGN, plasma membrane, and PD. Mutations in the LL motif do not impair plasma membrane targeting of MP but affect its ability to associate with callose deposits at the PD. Taken together, these results suggest that both motifs are indispensable for targeting OuMV MP to PD and for efficient systemic infection but show differences in functionality. Co-immunoprecipitation assays coupled with mass spectrometry identified a series of host factors that could interact with the OuMV MP and link the MP with various pathways, in particular vesicle trafficking and membrane lipids. This study provides new insights into the intracellular targeting of MPs and pathways that plant viruses hijack for cell-to-cell movement.

plant biology↗

bioRxiv2019

In-situ detection of Tomato spotted wilt orthotospovirus from crude plant extracts using Reverse Transcriptase- Recombinase Polymerase Amplification (RT-RPA) in endpoint and real-time.

Virus detection in early stages of infection could prove useful for identification and isolation of foci of inoculum before its spread to the rest of susceptible individuals via vectoring insects. However, the low number of viruses present at the beginning of infection renders their detection and identification difficult and requires the use of highly sensitive laboratory techniques that are often incompatible with a field application. To obviate this challenge, we designed a Recombinase Polymerase Amplification, a molecular technique that makes millions of copies of a predefined region in the genome, in this case of Tomato spotted wilt orthotospovirus. The reaction occurs at 39 and can be used directly from crude plant extracts without nucleic acid extraction. Notably, positive results can be seen with the naked eye as a flocculus made of newly synthesized DNA and metallic beads. The objective of the procedure is to create a portable and affordable system that can isolate and identify viruses in the field, from infected plants and suspected insect vectors, and can be used by scientists and extension managers for making informed decisions for viral management. Results can be obtained in situ without the need of sending the samples to a specialized lab.

plant biology↗

bioRxiv2017

A toolbox of immunoprecipitation-grade monoclonal antibodies against human transcription factors.

A key component to overcoming the reproducibility crisis in biomedical research is the development of readily available, rigorously validated and renewable protein affinity reagents. As part of the NIH Protein Capture Reagents Program (PCRP), we have generated a collection of 1406 highly validated, immunoprecipitation (IP) and/or immunoblotting (IB) grade, mouse monoclonal antibodies (mAbs) to 736 human transcription factors. We used HuProt human protein microarrays to identify mAbs that recognize their cognate targets with exceptional specificity. Using an integrated production and validation pipeline, we validated these mAbs in multiple experimental applications, and have distributed them to the Developmental Studies Hybridoma Bank (DSHB) and several commercial suppliers. This study allowed us to perform a meta-analysis that identified critical variables that contribute to the generation of high quality mAbs. We find that using full-length antigens for immunization, in combination with HuProt analysis, provides the highest overall success rates. The efficiencies built into this pipeline ensure substantial cost savings compared to current standard practices.

biochemistry↗