Biology subjects

Carvalho, L.

Publications and source records attributed to Carvalho, L..

10 recordsLinked to original sources

bioRxiv2024

Dachsous is a key player in epithelial wound closure by modulating cell shape changes and cytoskeleton dynamics

Epithelia are vital tissues in multicellular organisms, acting as barriers between external and internal environments. Simple epithelia, such as those in embryos and the adult gut, have the remarkable ability to repair wounds efficiently, making them ideal for studying epithelial repair mechanisms. In these tissues, wound closure involves the coordinated action of a contractile actomyosin cable at the wound edge and collective cell movements around the wound. However, the dynamics of cell-cell interactions during this process remain poorly understood. Here, we demonstrate that Dachsous (Ds), an atypical cadherin associated with Planar Cell Polarity, is crucial for efficient epithelial repair in the Drosophila embryonic epidermis. We show that the absence of Ds leads to delayed wound closure, impaired actomyosin cable formation, and altered cell shape changes. Additionally, we reveal that Occluding Junctions are necessary for the proper apical localization of Ds, suggesting an unanticipated interaction between these two molecular complexes. This study identifies Ds as a novel player in epithelial repair and highlights the need for further investigating the molecular mechanisms by which Ds modulates cell shape and tissue morphogenesis. Summary statementThis study shows that the atypical cadherin Dachsous is essential for epithelial wound closure, influencing cytoskeletal dynamics and cell morphology, with Occluding Junctions regulating its subcellular localization.

cell biology↗

bioRxiv2023

Bipartite left-right sided endocrine system: processing of contralateral effects of brain injury

The crossed descending neural tracts set a basis for contralateral effects of brain injury. In addition, the left-right side-specific effects of the unilateral brain lesions may be mediated by neurohormones through the humoral pathway as discovered in animals with disabled descending motor tracts. We here examined if counterparts of the endocrine system that convey signals from the left and right brain injuries differ in neural and molecular mechanisms. In rats with completely transected cervical spinal cords a unilateral injury of the hindlimb sensorimotor cortex produced hindlimb postural asymmetry with contralateral hindlimb flexion, a proxy for neurological deficit. The effects of the left and right side brain lesions were differently inhibited by antagonists of the {delta}-, {kappa}- and {micro}-opioid receptors suggesting differential neuroendocrine control of the left-right side-specific hormonal signaling. Bilateral deafferentation of the lumbar spinal cord eliminated hormone-mediated effects of the left-side brain injury but not the right-side lesion suggesting their afferent and efferent mechanisms, respectively. Analysis of gene-gene co-expression patterns identified the left and right side-specific gene regulatory networks that were coordinated across the hypothalamus and lumbar spinal cord through the humoral pathway. The coordination was ipsilateral and perturbed by brain injury. These findings suggest that the neuroendocrine system that conveys left-right side-specific hormonal messages from injured brain is bipartite, contributes to contralateral neurological deficits through asymmetric neural mechanisms, and enables ipsilateral coordination of molecular processes across neural areas along the neuraxis. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=173 HEIGHT=200 SRC="FIGDIR/small/546857v2_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@1d0ad6org.highwire.dtl.DTLVardef@b273f8org.highwire.dtl.DTLVardef@1dbac79org.highwire.dtl.DTLVardef@118599c_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

RAMZIS: a bioinformatic toolkit for rigorous assessment of the alterations to glycoprotein structure that occur during biological processes

MotivationGlycosylation elaborates the structures and functions of glycoproteins; glycoproteins are common post-translationally modified proteins and are heterogeneous and non-deterministically synthesized as an evolutionarily driven mechanism that elaborates the functions of glycosylated gene products. While glycoproteins account for approximately half of all proteins, their macro- and micro-heterogeneity requires specialized proteomics data analysis methods as a given glycosite can be divided into several glycosylated forms, each of which must be quantified. Sampling of heterogeneous glycopeptides is limited by mass spectrometer speed and sensitivity, resulting in missing values. In conjunction with the low sample size inherent to glycoproteomics, this necessitated specialized statistical metrics to identify if observed changes in glycopeptide abundances are biologically significant or due to data quality limitations. ResultsWe developed an R package, Relative Assessment of m/z Identifications by Similarity (RAMZIS), that uses similarity metrics to guide biomedical researchers to a more rigorous interpretation of glycoproteomics data. RAMZIS uses contextual similarity to assess the quality of mass spectral data and generates graphical output that demonstrates the likelihood of finding biologically significant differences in glycosylation abundance dataset. Investigators can assess dataset quality, holistically differentiate glycosites, and identify which glycopeptides are responsible for glycosylation pattern expression change. Herein RAMZIS approach is validated by theoretical cases and by a proof-of-concept application. RAMZIS enables comparison between datasets too stochastic, small, or sparse for interpolation while acknowledging these issues in its assessment. Using our tool, researchers will be able to rigorously define the role of glycosylation and the changes that occur during biological processes. Availabilityhttps://github.com/WillHackett22/RAMZIS ContactJoseph Zaia, Boston University Medical Campus, 670 Albany St., rm 509, Boston, MA 02118 USA, (e) jzaia@bu.edu, (v) 1-617-358-2429 Supplementary informationSupplementary data are available

bioinformatics↗

bioRxiv2021

16S rRNA Gene Amplicon Profiling of the New Zealand parasitic blowfly Calliphora vicina.

Here, we present a 16S rRNA gene amplicon sequence data set and profiles demonstrating the bacterial diversity of larval and adult Calliphora vicina, collected from Ashhurst, New Zealand (May 2020). The three dominant genera among adult male and female C. vicina were Serratia and Morganella (phylum Proteobacteria) and Carnobacterium (phylum Firmicutes), while the larvae were also dominated by the genera Lactobacillus (phylum Firmicutes).

molecular biology↗

bioRxiv2021

Expanding N-Glycopeptide Identifications by Fragmentation Prediction and Glycome Network Smoothing

Accurate glycopeptide identification in mass spectrometry-based glycoproteomics is a challenging problem at scale. Recent innovation has been made in increasing the scope and accuracy of glycopeptide identifications, with more precise uncertainty estimates for each part of the structure. We present a layered approach to glycopeptide fragmentation modeling that improves N-glycopeptide identification in samples without compromising identification quality, and a site-specific method to increase the depth of the glycoproteome confidently identifiable even further. We demonstrate our techniques on a pair of previously published datasets, showing the performance gains at each stage of optimization, as well as its flexibility in glycome definition and search space complexity. These techniques are provided in the open-source glycomics and glycoproteomics platform GlycReSoft available at https://github.com/mobiusklein/glycresoft.

bioinformatics↗

bioRxiv2020

Characterization of the complete mitochondrial genome of the New Zealand parasitic blowfly Calliphora vicina (Insecta: Diptera: Calliphoridae).

In the present study, the complete mitochondrial genome of the New Zealand parasitic blowfly Calliphora vicina (blue bottle blowfly) field strain NZ_CalVic_NP was generated using next-generation sequencing technology and annotated. The 16,518 bp mitochondrial genome consists of 13 protein-coding genes, two ribosomal RNAs, 22 transfer RNAs, and a 1,689 bp non-coding region, similar to most metazoan mitochondrial genomes. Phylogenetic analysis showed that C. vicina NZ_CalVic_NP does not form a monophyletic cluster with the remaining three Calliphorinae species. The complete mitochondrial genome sequence of C. vicina NZ_CalVic_NP is a resource to facilitate future species identification research within the Calliphoridae.

zoology↗

bioRxiv2020

Endocrine signaling mediates asymmetric motor deficits after unilateral brain injury

A paradigm in neurology is that brain injury-induced motor deficits (e.g. hemiparesis and hemiplegia) arise due to aberrant activity of descending neural pathways. We discovered that a unilateral injury of the hindlimb sensorimotor cortex of rats with completely transected thoracic spinal cord produces hindlimb postural asymmetry with contralateral flexion, and asymmetric changes in nociceptive hindlimb withdrawal reflexes and gene expression patterns in lumbar spinal cord. The injury-induced postural effects were abolished by prior hypophysectomy and were mimicked by transfusion of serum from animals with unilateral brain injury. Antagonists of the opioid and vasopressin receptors blocked formation of hindlimb postural asymmetry suggesting that these neurohormones mediate effects of brain injury on lateralized motor responses. Our data indicate that descending neural control of spinal circuits is complemented by a previously unknown humoral signaling from injured brain to the contra- and ipsilesional hindlimbs, and suggest the existence of a body side-specific neuroendocrine regulation in bilaterally symmetric animals.

neuroscience↗

bioRxiv2019

Drp1-mediated mitochondrial fission regulates calcium and F-actin dynamics during wound healing

Mitochondria adapt to cellular needs by changes in morphology through fusion and fission events, referred to as mitochondrial dynamics. Mitochondrial function and morphology are intimately connected and the dysregulation of mitochondrial dynamics is linked to several human diseases. In this work, we investigated the role of mitochondrial dynamics in wound healing in the Drosophila embryonic epidermis. Mutants for mitochondrial fusion and fission proteins fail to close their wounds, indicating that the regulation of mitochondrial dynamics is required for wound healing. By live-imaging, we found that loss of function of the mitochondrial fission protein Dynamin-related protein 1 (Drp1) compromises the increase of cytosolic and mitochondrial calcium upon wounding and leads to F-actin defects at the wound edge, culminating in wound healing impairment. Our results highlight a new role for mitochondrial dynamics in the regulation of calcium and F-actin during epithelial repair.\n\nSummaryWe show that mitochondrial dynamics proteins are required for epithelial repair. In particular, Drp1 loss-of-function leads to defects in the dynamics of cytosolic and mitochondrial calcium and F-actin upon wounding.

cell biology↗

bioRxiv2019

Shared mechanisms between coronary heart disease and depression: findings from a large UK general population-based cohort

While comorbidity between coronary heart disease (CHD) and depression is evident, it is unclear whether the two diseases have shared underlying mechanisms. We performed a range of analyses in 367,703 unrelated middle-aged participants of European ancestry from UK Biobank, a population based cohort study, to assess whether comorbidity is primarily due to genetic or environmental factors, and to test whether cardiovascular risk factors and CHD are likely to be causally related to depression using Mendelian randomization. We showed family history of heart disease was associated with a 20% increase in depression risk (95% confidence interval [CI] 16% to 24%, p<0.0001), but a genetic risk score that is strongly associated with CHD risk was not associated with depression. An increase of one standard deviation in the CH D genetic risk score was associated with 71% higher CHD risk, but 1% higher depression risk (95% CI 0% to 3%; p=0.11). Mendelian randomization analyses suggested that triglycerides, interleukin-6 (IL-6), and C-reactive protein (CRP) are likely causal risk factors for depression. The odds ratio for depression per standard deviation increase in genetically-predicted triglycerides was 1.18 (95% CI 1.09 to 1.27; p=2x10-5); per unit increase in genetically-predicted log-transformed I L-6 was 0.74 (95% CI 0.62 to 0.89; p=0.0012); and per unit increase in genetically-predicted log-transformed CRP was 1.18 (95% CI 1.07 to 1.29; p=0.0009). Our analyses suggest that comorbidity between depression and CHD arises largely from shared environmental factors. I L-6, CRP and triglycerides, are likely to be causally linked with depression, so could be targets for treatment and prevention of depression.

genetics↗

bioRxiv2017

MERS-CoV spillover at the camel-human interface

Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus from camels causing significant mortality and morbidity in humans in the Arabian Peninsula. The epidemiology of the virus remains poorly understood, and while case-based and seroepidemiological studies have been employed extensively throughout the epidemic, viral sequence data have not been utilised to their full potential. Here we use existing MERS-CoV sequence data to explore its phylodynamics in two of its known major hosts, humans and camels. We employ structured coalescent models to show that long-term MERS-CoV evolution occurs exclusively in camels, whereas humans act as a transient, and ultimately terminal host. By analysing the distribution of human outbreak cluster sizes and zoonotic introduction times we show that human outbreaks in the Arabian peninsula are driven by seasonally varying zoonotic transfer of viruses from camels. Without heretofore unseen evolution of host tropism, MERS-CoV is unlikely to become endemic in humans.

epidemiology↗