Biology subjects

Jimenez, J. C.

Publications and source records attributed to Jimenez, J. C..

6 recordsLinked to original sources

bioRxiv2022

Viroscope: plant viral diagnosis from NGS data using biologically-informed genome assembly coverage

Next-generation sequencing (NGS) methods are transforming our capacity to detect pathogens and perform disease diagnosis. Although sequencing advances have enabled accessible and point-of-care NGS, data analysis pipelines have yet to provide robust tools for precise and certain diagnosis, particularly in cases of low sequencing coverage. Lack of standardized metrics and harmonized detection thresholds confound the problem further, impeding the adoption and implementation of these solutions in real-world applications. In this work, we tackle these issues and propose biologically-informed viral genome assembly coverage as a method to improve diagnostic certainty. We use the identification of viral replicases, an essential function of viral life cycles, to define genome coverage thresholds in which biological functions can be described. We validate the analysis pipeline, Viroscope, using field samples, synthetic and published datasets and demonstrate that it provides sensitive and specific viral detection. Furthermore, we developed Viroscope.io a web-service to provide on-demand NGS data viral diagnosis to facilitate adoption and implementation by phytosanitary agencies to enable precise viral diagnosis.

microbiology↗

bioRxiv2021

ACUTE FOOD DEPRIVATION DECREASES THE EXPRESSION OF METHAMPHETAMINE-INDUCED LOCOMOTOR SENSITIZATION IN RATS

INTRODUCTIONAMPH and METH are known to increase DAergic signaling in the brain reward system by stimulating the release of DA through the reversal of DAT function. However, there is evidence that insulin signaling pathways have the ability to modulate DAT functions. Some studies have reported that hypoinsulinemia attenuates DAT functions, and as a consequence, psychostimulant-induced behaviors are reduced. In the present study, we examined the effects of acute food deprivation, which also reduces insulin levels, on METH-induced locomotor sensitization. METHODSSeparate groups of rats were treated with METH (1 mg/kg i.p.) or saline for 5 days (development phase). On the test day (expression phase), the groups were treated with METH or saline after food deprivation for 24 h. Furthermore, in separate groups of rats, levels of glucose, insulin, and phosphorylation of Akt at Ser473 were also examined after food deprivation for 24 h. RESULTSThe results showed that repeated administration of METH induced a progressive increase in locomotor activity in rats during the development phase. However, METH administration in the expression phase produced a decrease in locomotor activity after 24 h of food deprivation. In addition, the results showed that a reduction in glucose, insulin, and Akt levels occurred as a result of food deprivation. CONCLUSIONThese results are in line with previous studies and suggest that food deprivation reduces some behavioral effects of psychostimulants such as AMPH and METH. HighlightsAdministration of METH increases DAergic neurotransmission by interfering with proper DA transporter (DAT) function Some evidence suggests that insulin signaling pathways modulate the DAT in the brain reward system Acute food deprivation reduces glucose and insulin levels This study examined the effects of acute food deprivation on METH-induced locomotor sensitization Present study showed that food deprivation for 24 h reduced METH-induced locomotor sensitization Plain Language SummaryThe dopamine transporter (DAT) is responsible for the reuptake of dopamine (DA) and the termination of DA neurotransmission. DAT is also the target for psychostimulant drugs such as cocaine, amphetamine, and methamphetamine. These drugs produce an increase of DA neurotransmission in the reward system. It is now well established that insulin levels modulate DAT function. Several studies have reported that hypoinsulinemia attenuates DAT function, and as a consequence, psychostimulant-induced behaviors are reduced. Food deprivation reduces glucose and insulin levels. In the present study we evaluated the effects of food deprivation on methamphetamine-induced locomotor sensitization. This behavior reflects brain neuroadaptations that contribute to drug addiction. Rats of the main experimental group were treated with methamphetamine for 5 days (development phase). On the test day (expression phase) the rats were treated with methamphetamine after food deprivation for 24 h. In separated groups of rats levels of glucose and insulin were evaluated after food deprivation for 24 h. The results showed that acute food deprivation reduced methamphetamine-induced locomotor sensitization. It was also observed that insulin and glucose levels were reduced after food deprivation. The results of the present study suggest that food deprivation can modulate some behavioral effects of methamphetamine.

neuroscience↗

bioRxiv2020

Distinct VIP interneurons in the cingulate cortex encode anxiogenic and social stimuli

A hallmark of higher-order cortical regions is their functional heterogeneity, but it is not well understood how these areas encode such diverse information. The anterior cingulate cortex (ACC), for example, is important in both emotional regulation and social cognition. Previous work shows activation of the ACC to anxiety-related and social stimuli, but it is unknown how subpopulations or microcircuits within the ACC simultaneously encode these distinct stimuli. One type of inhibitory interneuron, which is positive for vasoactive intestinal peptide (VIP), is known to alter the activity of many cells in local cortical microcircuits, but it is unknown whether the activity of VIP cells in the ACC (VIPACC) encodes anxiety-related or social information. Using in vivo calcium imaging and miniscopes in freely behaving mice to monitor VIPACC activity, we identified distinct, non-overlapping subpopulations of VIPACC that preferentially activated to either anxiogenic, anxiolytic, social, or non-social stimuli. We determined that stimulus-selective cells encode the animals behavioral states and VIP interneuron clusters may co-activate, improving this encoding. Finally, we used trans-synaptic tracing to show that VIPACC receive widespread inputs from regions implicated in emotional regulation and social cognition. These findings demonstrate not only that the ACC is not homogeneous in its function, but also that there is marked functional heterogeneity even within disinhibitory interneuron populations. This work contributes to our understanding of how the cortex encodes information across diverse contexts and provides insight into the complexity of neural processes involved in anxiety and social behavior.

neuroscience↗

bioRxiv2020

Deep learning enables the design of functional de novo antimicrobial proteins

Protein sequences are highly dimensional and present one of the main problems for the optimization and study of sequence-structure relations. The intrinsic degeneration of protein sequences is hard to follow, but the continued discovery of new protein structures has shown that there is convergence in terms of the possible folds that proteins can adopt, such that proteins with sequence identities lower than 30% may still fold into similar structures. Given that proteins share a set of conserved structural motifs, machine-learning algorithms can play an essential role in the study of sequence-structure relations. Deep-learning neural networks are becoming an important tool in the development of new techniques, such as protein modeling and design, and they continue to gain power as new algorithms are developed and as increasing amounts of data are released every day. Here, we trained a deep-learning model based on previous recurrent neural networks to design analog protein structures using representations learning based on the evolutionary and structural information of proteins. We test the capabilities of this model by creating de novo variants of an antifungal peptide, with sequence identities of 50% or lower relative to the wild-type (WT) peptide. We show by in silico approximations, such as molecular dynamics, that the new variants and the WT peptide can successfully bind to a chitin surface with comparable relative binding energies. These results are supported by in vitro assays, where the de novo designed peptides showed antifungal activity that equaled or exceeded the WT peptide.

bioengineering↗

bioRxiv2019

A neuronal signature for monogamous reunion

Pair bond formation depends vitally on neuromodulatory signaling within the nucleus accumbens, but the neuronal dynamics underlying this behavior remain unclear. Using in vivo Ca2+ imaging in monogamous prairie voles, we found that pair bonding does not elicit differences in overall nucleus accumbens Ca2+ activity. Instead, we identified distinct neuronal ensembles in this region recruited during approach to either a partner or novel vole. The partner-approach neuronal ensemble increased in size following bond formation and differences in the size of approach ensembles for partner and novel voles predicts bond strength. In contrast, neurons comprising departure ensembles do not change over time and are not correlated with bond strength indicating that ensemble plasticity is specific to partner approach. Further, the neurons comprising partner and novel approach ensembles are non-overlapping while departure ensembles are more overlapping than chance, which may reflect another key feature of approach ensembles. We posit that the features of the partner approach ensemble and its expansion upon bond formation make it a potential key substrate underlying bond formation and maturation.\n\nHighlightsO_LIWe performed in vivo Ca2+ in the nucleus accumbens of pair bonded prairie voles\nC_LIO_LIOverall nucleus accumbens activity did not differ during partner versus stranger interaction\nC_LIO_LIDistinct approach neurons exist for the partner and for the stranger\nC_LIO_LIPartner-approach ensemble increases as partner preference emerges\nC_LIO_LIWe identify a putative neuronal substrate underlying bond formation and maturation\nC_LI

neuroscience↗

bioRxiv2017

A new sequencing-based women’s health assay combining self-sampling, HPV detection and genotyping, STI detection, and vaginal microbiome analysis

The composition of the vaginal microbiome, including both the presence of pathogens involved in sexually transmitted infections (STI) as well as commensal microbiota, has been shown to have important associations for a womans reproductive and general health. Currently, healthcare providers cannot offer comprehensive vaginal microbiome screening, but are limited to the detection of individual pathogens, such as high-risk human papillomavirus (hrHPV), the predominant cause of cervical cancer. There is no single test on the market that combines HPV, STI, and microbiome screening. Here, we describe a novel inclusive womens health assay that combines self-sampling with sequencing-based HPV detection and genotyping, vaginal microbiome analysis, and STI-associated pathogen detection. The assay includes genotyping and detection of 14 hrHPV types, 5 low-risk HPV types (lrHPV), as well as the relative abundance of 32 bacterial taxa of clinical importance, including Lactobacillus, Sneathia, Gardnerella, and 4 pathogens involved in STI, with high sensitivity, specificity, and reproducibility. For each of these taxa, healthy ranges were determined in a group of 50 self-reported healthy women. The hrHPV portion of the test was evaluated against the Digene High-Risk HPV HC2 DNA test with vaginal samples obtained from 185 women. Results were concordant for 181/185 of the samples (overall agreement of 97.83%, Cohens kappa = 0.93), with sensitivity and specificity values of 94.74% and 98.64%, respectively. Two discrepancies were caused by the Digene assays known cross-reactivity with low-risk HPV types, while two additional samples were found to contain hrHPV not detected by Digene. This novel assay could be used to complement conventional cervical cancer screening, because its self-sampling format can expand access among women who would otherwise not participate, and because of its additional information about the composition of the vaginal microbiome and the presence of pathogens.

microbiology↗