Biology subjects

Smith, J.

Publications and source records attributed to Smith, J..

At least 163 records · Page 9Linked to original sources

bioRxiv2019

Preparation and pharmacokinetics of genistein MePEG-PLGA copolymer micelles

In this report, we demonstrated a novel technique to prepare genistein (GEN) MePEG-PLGA copolymer micelles. Initial stability and pharmacokinetic behavior in rats after intravenous administration were investigated. The micelles were prepared by modified self-emulsifying solvent evaporation method. The morphology, encapsulation efficiency, drug loading, particle size and Zeta potential were investigated. The release behavior was investigated by dynamic membrane dialysis technique. The micelles were stored in a refrigerator at 4 {degrees}C, and samples were taken after 1 d, 10 d, 1 month, 3 months, and 6 months, and the encapsulation efficiency and drug loading were examined. The GEN micelles were injected into the tail vein of healthy rats. The blood concentration of GEN in rats was determined by HPLC. The plasma concentration data was processed by DAS 2.0 software. The main pharmacokinetic parameters were statistically analyzed by SPSS 17.0 software. Results The encapsulation efficiency of the prepared micelles was (84.43+/-2.93) %, the drug loading was (2.63+/-0.91) %, and the particle size was (63.75+/-4.12) nm. The release behavior of GEN micelles was in line with the Weibull model. The 6-month leakage rate of GEN micelles was 2.45%, and the drug loading decreased by 0.18%. The main pharmacokinetic parameters AUC0-t after GEN micelles and GEN emulsion 40 mg{middle dot}kg-1 were injected into the tail vein of rats. They were (99.46+/- 4.77) mg {middle dot} L-1 {middle dot}h and (57.51+/-1.37) mg{middle dot}L-1 {middle dot}h, and t1/2 were (7.48+/-1.15)h and (4.95+/- 1.15)h, respectively, and Cmax was (16.03+/-1.20) mg{middle dot}L-1 and (16.73+/-1.10) mg{middle dot}L-1, CL are (0.36+/-0.02) L{middle dot}h-1 {middle dot}kg-1 and (0.67+/-0.02)L{middle dot}h-1 {middle dot}kg-1.

bioengineering↗

bioRxiv2019

Effect of mannose modified chitosan on uptake of nanoparticles by macrophages

This report provided a new method to prepare and evaluate mannose-modified chitosan-coated lactic acid-glycolic acid copolymer (PLGA) nanoparticles, and to investigate their effects on macrophage toxicity and macrophage uptake. The PLGA nanoparticles loaded with ovalbumin (OVA) were prepared by double emulsion method. The size and zeta potential of the nanoparticles were determined by laser granulometry after mannose-modified chitosan coating. The nanoparticles were observed by transmission electron microscopy. The appearance of the form, the BCA method to determine the OVA content, calculate the drug loading and release. The OVA nanoparticles labeled with fluorescein isothiocyanate (FITC) were co-incubated with macrophages (RAW 264. 7), cell viability was determined by MTT assay, and uptake was examined by fluorescence microscopy. Results The size and {zeta} potential of OVA-PLGA nanoparticles increased with the increase of chitosan coating concentration (P < 0.05), and OVA drug loading range was 7. 2% to 8. 4%. Chitosan and mannose modified chitosan coating FITC-OVAPLGA nanoparticles and RAW 264. 7 After incubation, there was little effect on cell viability (P > 0.05), but it significantly promoted macrophage uptake by FITC-OVA-PLGA nanoparticles (P < 0.05).

bioengineering↗

bioRxiv2019

Preparation of anti-HER-2 antibody PLGA polymer nano-ultrasound contrast agent In vitro targeting experiment

In this report, we demonstrated a novel method to prepare a hollow nano-targeted ultrasound contrast agent carrying anti-HER-2 antibody with high molecular weight polylactic acid-glycolic acid (PLGA) as a film-forming material, and to investigate in vitro targeting and imaging effects. We utilized the camphor as porogen, PLGA nano-ultrasound contrast agent was prepared by modified double emulsion solvent evaporation method. The general characteristics were characterized by scanning electron microscope, transmission electron microscope and laser particle size analyzer. The angiography was performed by carbodiimide method. The anti-HER-2 antibody was used to prepare the PLGA-targeted nano-ultrasound contrast agent with anti-HER-2 antibody. The in-situ imaging ability was evaluated by laser confocal scanning microscopy. Results indicate that the average particle size of PLGA nano-ultrasound contrast agent was (152.00{+/-} 58.08) nm. The particles were regular spherical, uniform in size and good in dispersion. In vitro targeting experiments showed that PLGA-targeted contrast agents with anti-HER-2 antibodies were more strongly aggregated on the surface of breast cancer cells. In vitro imaging experiments showed that the PLGA-targeted nano-ultrasound contrast imaging showed a fine and uniform point-like hyperechoic echo, and no significant attenuation of the posterior echo. This study successfully produced a PLGA-targeted nano-ultrasound contrast agent with anti-HER-2 antibody, which can specifically bind to breast cancer cells with high expression of HER-2 receptor in vitro, and the imaging effect in vitro is better.

bioengineering↗

bioRxiv2019

pH-responsive nano-vaccines as antigen and adjuvant carrier that improve vaccine immunogenicity

Here, we report a novel method to establish an effective antigen and immunoagonist co-vector to solve the problems of low antigenic endocytosis efficiency, low immunological activity and easy degradation of antigen by antigen presenting cells. Mesoporous silica was selected as the nucleus. After loading the model antigen chicken egg albumin (OVA), the metal organic framework (MOF) formed by Eu 3+ and guanine mononucleotide (GMP) was coated on the mesoporous silicon surface. The immunostimulant CpG nucleic acid is adsorbed on the surface to construct a co-carrier system of pH-sensitive antigen and immunostimulant. The antigen loading rate of mesoporous silicon was 20%, and the protein release amount reached 55% after incubation for 24 h under acidic conditions. Transmission electron microscopy showed that the conjugated polymer was uniformly coated on the surface of the material; It was found that the adsorption capacity of the carrier for CpG nucleic acid was 8 x10-6 mol per gram of carrier-adsorbing nucleic acid; MTT results showed that the vector had low toxicity.

bioengineering↗

bioRxiv2019

Preparation of PLGA Nanoparticles Encapsulated with Fluorescent Probe Coumarin-6

In this report, we provided a novel platform to prepare fluorescent probe coumarin-6 nanoparticles by using biodegradable material polylactic acid-glycolic acid copolymer (PLGA) as material. The coumarin-6-PLGA nanoparticles were prepared by double emulsion and solvent evaporation. The encapsulation efficiency and releasing kinetics were also investigated. Results indicate that the encapsulation efficiency of coumarin-6 nanoparticles was 51.6%, the utilization rate was 81.9%, the average particle size was 135 nm, and the leakage rate of coumarin-6 in vitro was lower than 72 h. 2%. Our experimental results provide evidence that PLGA nanoparticles can effectively encapsulate fluorescent probe Coumarin-6 and release the probe in a controlled manner.

bioengineering↗

bioRxiv2019

Meningeal Worm Infection in Central Iowa Goat Herds II: Individual Cases and Treatment Using a Camelid Therapeutic Protocol

Summary and ImplicationsMeningeal worm (Paralaphostrongylus tenuis) infection, also known as cerebrospinal nematodiasis, is a common parasitic infection in New World Camelids in the United States. There is also a considerable risk for this disease in the Boer goat population. Despite the rapidly increasing size of the national goat herd, there are no treatment protocols reported in the literature for goats with this disease. This study describes a successful clinical approach and treatment of 3 Boer goat cases with therapy previously reported for use in New World Camelids. The clinical presentation, diagnosis, and long-term outcome of P. tenuis infections in these goats presented to ISU Food Animal and Camelid Hospital (FACH) is reported here within. Practitioners should be aware that clinical presentation and diagnosis are similar for goats as reported for camelids with cerebrospinal nematodiasis. Additionally, the described treatment protocols for camelids appear to demonstrate a comparative efficacy in goats.

pharmacology and toxicology↗

bioRxiv2019

Behavioral flexibility is associated with changes in structure and function distributed across a frontal cortical network in macaques

One of the most influential accounts of central orbitofrontal cortex- that it mediates behavioral flexibility - has been challenged by the finding that discrimination reversal in macaques -the classic test of behavioral flexibility -is unaffected when lesions are made by excitotoxin injection rather than aspiration. This suggests the critical brain circuit mediating behavioral flexibility in reversal tasks lies beyond the central orbitofrontal cortex. To determine its identity a group of nine macaques were taught discrimination reversal learning tasks and its impact on grey matter was measured. Magnetic resonance imaging scans were taken before and after learning and compared with scans from two control groups each comprising ten animals. One control group learned similar discrimination tasks but which lacked any reversal component and the other control group engaged in no learning. Grey matter changes were prominent in posterior orbitofrontal cortex/anterior insula but also were found in three other frontal cortical regions: lateral orbitofrontal cortex (12o), cingulate cortex, and lateral prefrontal cortex. In a second analysis, neural activity in posterior orbitofrontal cortex/anterior insula was measured at rest and its pattern of coupling with the other frontal cortical regions was assessed. Activity coupling increased significantly in the reversal learning group in comparison to controls. In a final set of experiments we used similar structural imaging procedures and analyses to demonstrate that aspiration lesion of central orbitofrontal cortex, of the type known to affect discrimination learning, affected structure and activity in the same frontal cortical circuit. The results identify a distributed frontal cortical circuit associated with behavioral flexibility.

neuroscience↗

bioRxiv2019

A Membrane-Bound Cytochrome Enables Methanosarcina acetivorans to Conserve Energy to Support Growth from Extracellular Electron Transfer

Conservation of energy to support growth solely from extracellular electron transfer was demonstrated for the first time in a methanogen. Methanosarcina acetivorans grew with methanol as the sole electron donor and the extracellular electron acceptor anthraquione-2,6-disulfonate (AQDS) as the sole electron acceptor when methane production was inhibited with bromoethanesulfonate. Transcriptomics revealed that transcripts for the gene for the transmembrane, multi-heme, c-type cytochrome MmcA were 4-fold higher in AQDS-respiring cells versus methanogenic cells. A strain in which the gene for MmcA was deleted failed to grow via AQDS reduction whereas strains in which other cytochrome genes were deleted grew as well as the wild-type strain. The MmcA-deficient strain grew with the conversion of methanol or acetate to methane, suggesting that MmcA has a specialized role as a conduit for extracellular electron transfer. Enhanced expression of genes for methanol conversion to methyl-coenzyme M and components of the Rnf complex suggested that methanol is oxidized to carbon dioxide in AQDS-respiring cells through a pathway that is similar to methyl-coenezyme M oxidation in methanogenic cells. However, during AQDS respiration the Rnf complex and reduced methanophenazine probably transfer electrons to MmcA, which functions as the terminal reductase for AQDS reduction. Extracellular electron transfer may enable survival of methanogens in dynamic environments in which oxidized humic substances and Fe(III) oxides are intermittently available. The availability of tools for genetic manipulation of M. acetivorans makes it an excellent model microbe for evaluating c-type cytochrome-dependent extracellular electron transfer in Archaea.\n\nImportanceExtracellular electron exchange in Methanosarcina species and closely related Archaea plays an important role in the global carbon cycle and can enhance the speed and stability of anaerobic digestion, an important bioenergy strategy. The potential importance of c-type cytochromes for extracellular electron transfer to syntrophic bacterial partners and/or Fe(III) minerals in some Archaea has been suspected for some time, but the studies with Methanosarcina acetivorans reported here provide the first genetic evidence supporting this hypothesis. The results suggest parallels with Gram-negative bacteria, such as Shewanella and Geobacter species, in which outer-surface c-type cytochromes are an essential component for electrical communication with the extracellular environment. M. acetivorans offers an unprecedented opportunity to study mechanisms for energy conservation from the anaerobic oxidation of one-carbon organic compounds coupled to extracellular electron transfer in Archaea with implications not only for methanogens, but possibly also for anaerobic methane oxidation.

microbiology↗

bioRxiv2019

The quail as an avian model system: its genome provides insights into social behaviour, seasonal biology and infectious disease response

The Japanese quail (Coturnix japonica) is a popular domestic poultry species and an increasingly significant model species in avian developmental, behavioural and disease research. We have produced a high-quality quail genome sequence, spanning 0.93 Gb assigned to 33 chromosomes. In terms of contiguity, assembly statistics, gene content and chromosomal organization, the quail genome shows high similarity to the chicken genome. We demonstrate the utility of this genome through three diverse applications. First, we identify selection signatures and candidate genes associated with social behaviour in the quail genome, an important agricultural and domestication trait. Second, we investigate the effects and interaction of photoperiod and temperature on the transcriptome of the quail medial basal hypothalamus, revealing key mechanisms of photoperiodism. Finally, we investigate the response of quail to H5N1 influenza infection. In quail lung, many critical immune genes and pathways were downregulated, and this may be key to the susceptibility of quail to H5N1. This genome will facilitate further research into diverse research questions using the quail as a model avian species.

genomics↗

bioRxiv2019

Transfer of Xanthomonas campestris pv. arecae, and Xanthomonas campestris pv. musacearum to Xanthomonas vasicola (Vauterin) as Xanthomonas vasicola pv. arecae comb. nov., and Xanthomonas vasicola pv. musacearum comb. nov. and description of Xanthomonas vasicola pv. vasculorum pv. nov.

LETTER TO THE EDITOR LETTER TO THE EDITOR EMENDED DESCRIPTION OF... REFERENCES Members of the genus Xanthomonas, within the gamma-Proteobacteria, collectively cause disease on more than 400 plant species (Hayward 1993), though some members are apparently non-pathogenic (Vauterin et al. 1996) and some have been isolated from clinical samples such as skin microbiota (Seite, Zelenkova, and Martin 2017). Historically, taxonomy of Xanthomonas was tied to the host of isolation (Starr 1981; Wernham 1948), with the genus being split into large numbers of species, each defined by this single phenotypic feature (Dye 1962). Subsequently, most of the species were transferred (lumped) into a single species, X. campestris, and designated as nomenspec ...

microbiology↗

bioRxiv2019

Robustness of respiratory rhythm generation across dynamic regimes

A central issue in the study of the neural generation of respiratory rhythms is the role of the intrinsic pacemaking capabilities that some respiratory neurons exhibit. The debate on this issue has occurred in parallel to investigations of interactions among respiratory network neurons and how these contribute to respiratory behavior. In this computational study, we demonstrate how these two issues are inextricably linked. We use simulations and dynamical systems analysis to show that once a conditional respiratory pacemaker, which can be tuned across oscillatory and non-oscillatory dynamic regimes in isolation, is embedded into a respiratory network, its dynamics become masked: the network exhibits similar dynamic properties regardless of the conditional pacemaker nodes tuning, and that nodes outputs are dominated by network influences. Furthermore, the outputs of the respiratory central pattern generator as a whole are invariant to these changes of dynamical properties, which ensures flexible and robust performance over a wide dynamic range. Author summaryBreathing movements in mammals are generated by brainstem respiratory central pattern generator (CPG) networks, which incorporate an excitatory oscillator located in the pre-Botzinger Complex (preBotC) that can exhibit autorhythmic behavior. To understand how these autorhythmic properties impact CPG network dynamical performance, we performed computational studies with an established modeling framework to systematically analyze network behavior when the preBotC excitatory neurons intrinsic dynamics are tuned to operate in autorhythmic versus non-autorhythmic regimes. Both of these regimes enable rhythmic activity of the CPG network, and we show that the rhythm and its responses to various manipulations are preserved across the tunings of intrinsic properties of the preBotC component. Correspondingly, the emergence of behaviorally appropriate rhythmic patterns of network activity is maintained across preBotC regimes, accompanied by an expansion of the ranges of network output frequencies and amplitudes beyond those attainable with either preBotC regime alone. These results lead to the novel conclusion and concept that the dynamical operation of the CPG is functionally highly robust with respect to the rhythmogenic state of the preBotC excitatory circuits, which could represent a key property for preserved respiratory function across varying conditions and demands on network performance.

neuroscience↗

bioRxiv2018

Genetic dissection of a Leishmania flagellar proteome demonstrates requirement for directional motility in sand fly infections

The protozoan parasite Leishmania possesses a single flagellum, which is remodelled during the parasites life cycle from a long motile flagellum in promastigote forms in the sand fly to a short immotile flagellum in amastigotes residing in mammalian phagocytes. This study examined the protein composition and in vivo function of the promastigote flagellum. Protein mass spectrometry and label free protein enrichment testing of isolated flagella and deflagellated cell bodies defined a flagellar proteome for L. mexicana promastigote forms (available via ProteomeXchange with identifier PXD011057). This information was used to generate a CRISPR-Cas9 knockout library of 100 mutants to screen for flagellar defects. This first large-scale knockout screen in a Leishmania sp. identified 56 mutants with altered swimming speed (52 reduced and 4 increased) and defined distinct mutant categories (faster swimmers, slower swimmers, slow uncoordinated swimmers and paralysed cells, including aflagellate promastigotes and cells with curled flagella and disruptions of the paraflagellar rod). Each mutant was tagged with a unique 17-nt barcode, providing a simple barcode sequencing (bar-seq) method for measuring the relative fitness of L. mexicana mutants in vivo. In mixed infections of the permissive sand fly vector Lutzomyia longipalpis, paralysed promastigotes and uncoordinated swimmers were severely diminished in the fly after defecation of the bloodmeal. Subsequent examination of flies infected with a single mutant lacking the central pair protein PF16 showed that these paralysed promastigotes did not reach anterior regions of the fly alimentary tract. These data show that L. mexicana need directional motility for successful colonisation of sand flies.\n\nAuthor SummaryLeishmania are protozoan parasites, transmitted between mammals by the bite of phlebotomine sand flies. Promastigote forms in the sand fly have a long flagellum, which is motile and used for anchoring the parasites to prevent clearance with the digested blood meal remnants. To dissect flagellar functions and their importance in life cycle progression, we generated here a comprehensive list of >300 flagellar proteins and produced a CRISPR-Cas9 gene knockout library of 100 mutant Leishmania. We studied their behaviour in vitro before examining their fate in the sand fly Lutzomyia longipalpis. Measuring mutant swimming speeds showed that about half behaved differently compared to the wild type: a few swam faster, many slower and some were completely paralysed. We also found a group of uncoordinated swimmers. To test whether flagellar motility is required for parasite migration from the fly midgut to the foregut from where they reach the next host, we infected sand flies with a mixed mutant population. Each mutant carried a unique tag and tracking these tags up to nine days after infection showed that paralysed and uncoordinated Leishmania were rapidly lost from flies. These data indicate that directional swimming is important for successful colonisation of sand flies.

cell biology↗

bioRxiv2018

Spatial relationships between white matter degeneration, amyloid load and cortical volume in amnestic mild cognitive impairment

The spatial-temporal relationships between gray and white matter (WM) degeneration during preclinical and early symptomatic Alzheimers disease are poorly understood. We characterized {beta}-amyloid deposition, cortical volume and WM degeneration in 44 subjects including healthy control (N=23), amnestic mild cognitive impairment (aMCI) (N=19), and early Alzheimers subjects (N=2). Integrated PET-MRI provided simultaneous measurement of 18F-Florbetapir uptake in cortical areas, regional brain volumes from structural MRI, and WM tract integrity metrics from diffusion MRI using biophysical modeling.\n\nAcross the cohort of healthy control and aMCIs, cortical volumes correlated poorly with {beta}-amyloid deposition in the same area (p < 0.05 only in the posterior cingulate and parietal lobe). WM degeneration correlated significantly with both amyloid and volume of connected cortical areas, but more strongly with volume. Diffusion MRI metrics for WM demyelination and/or axonal loss could therefore provide new biomarkers associated with clinical Alzheimers conversion. These WM changes may represent sequential propagation of Alzheimers neurodegeneration between functionally connected regions, and/or evidence of direct WM injury during the Alzheimers pathology cascade.

neuroscience↗

bioRxiv2018

Mining unknown porcine protein isoforms by tissue-based map of proteome enhances the pig genome annotation

A lack of the complete pig proteome has left a gap in our knowledge of the pig genome and has restricted the feasibility of using pigs as a biomedical model. We developed the tissue-based proteome maps using 34 major normal pig tissues. A total of 7,319 unknown protein isoforms were identified and systematically characterized, including 3,703 novel protein isoforms, 669 protein isoforms from 460 genes symbolized beginning with LOC, and 2,947 protein isoforms without clear NCBI annotation in current pig reference genome. These newly identified protein isoforms were functionally annotated through profiling the pig transcriptome with high-throughput RNA sequencing (RNA-seq) of the same pig tissues, further improving the genome annotation of corresponding protein coding genes. Combining the well-annotated genes that having parallel expression pattern and subcellular witness, we predicted the tissue related subcellular components and potential function for these unknown proteins. Finally, we mined 3,656 orthologous genes for 49.95% of unknown protein isoforms across multiple species, referring to 65 KEGG pathways and 25 disease signaling pathways. These findings provided valuable insights and a rich resource for enhancing studies of pig genomics and biology as well as biomedical model application to human medicine.

genomics↗

bioRxiv2018

Expected patterns of local ancestry in a hybrid zone

1The initial drivers of reproductive isolation between species are poorly characterized. In cases where partial reproductive isolation exists, genomic patterns of variation in hybrid zones may provide clues about the barriers to gene flow which arose first during the early stages of speciation. Purifying selection against incompatible substitutions that reduce hybrid fitness has the potential to distort local patterns of ancestry relative to background patterns across the genome. The magnitude and qualitative properties of this pattern are dependent on several factors including migration history and the relative fitnesses for different combinations of incompatible alleles. We present a model which may account for these factors and highlight the potential for its use in verifying the action of natural selection on candidate loci implicated in reducing hybrid fitness.

evolutionary biology↗

bioRxiv2018

Bangers and cash: Baiting efficiency in a heterogeneous population.

O_LIContext: The uptake of baits is a key variable in management actions aimed at the vaccination, training, or control of many vertebrate species. Increasingly, however, it is appreciated that individuals of the target species vary in their likelihood of taking baits. To optimise a baiting program, then, we require knowledge, not only on the rate of bait uptake, and how this changes with bait availability, but also knowledge on the proportion of the target population that will take a bait.\nC_LIO_LIThe invasive cane toad (Rhinella marina) is a major threat to northern quolls (Dasyurus hallucatus), which are poisoned when they attack this novel toxic prey item. Conditioned taste aversion baits (cane toad sausages) can be delivered in the field to train individual northern quolls to avoid toads.\nC_LIO_LIMethods: Here we report on a large-scale field trial across eleven sites across one large property in Western Australia. Camera trapping and statistical modelling was used to estimate the proportion of baitable animals in the population, and the proportion of these that were baited at varying bait availabilities.\nC_LIO_LIResults: Population estimates varied at each site from 3.5 ({+/-}0.76 SD) to 18 ({+/-} 1.58 SD) individual quolls per site, resulting in a range across sites of 0.6-4 baits available per individual. Bait uptake increased with increasing bait availability.\nC_LIO_LIWe also estimate that only 62% of individual quolls are baitable, and that a baiting rate of 3 baits per individual (rather than per area) will result in almost all of these baitable individuals being treated.\nC_LIO_LIWe compared our statistical method with prior data informing the probability of being baitable; and with probability of being baitable set to 1; this resulted in largely differing estimates in relation to an appropriate baiting rate.\nC_LIO_LISynthesis and applications: Data and models such as ours provide wildlife managers with information critical to informed decision making and are fundamental to estimate the cost-efficiency of any baiting campaign.\nC_LI

ecology↗

bioRxiv2018

Genetic risk for schizophrenia and developmental delay is associated with shape and microstructure of midline white matter structures

Genomic copy number variants (CNVs) are amongst the most highly penetrant genetic risk factors for neuropsychiatric disorders. The scarcity of carriers of individual CNVs and their phenotypical heterogeneity limits investigations of the associated neural mechanisms and endophenotypes. We applied a novel design based on CNV penetrance for schizophrenia and developmental delay that allows us to identify structural sequelae that are most relevant to neuropsychiatric disorders. Our focus on brain structural abnormalities was based on the hypothesis that convergent mechanisms contributing to neurodevelopmental disorders would likely manifest in the macro- and microstructure of white matter and cortical and subcortical grey matter. 21 adult participants carrying neuropsychiatric risk CNVs (including those located at 22q11.2, 15q11.2, 1q21.1, 16p11.2, and 17q12) and 15 age- and gender matched controls underwent T1-weighted structural, diffusion and quantitative T1 relaxometry MRI.\n\nThe macro- and microstructural properties of the cingulum bundles were associated with penetrance for both developmental delay and schizophrenia, in particular curvature along the anterior-posterior axis (Sz: pcorr=0.026; DD: pcorr=0.035) and intracellular volume fraction (Sz: pcorr=0.019; DD: pcorr=0.064) Further principal component analysis showed alterations in the interrelationships between the volumes of several mid-line white matter structures (Sz: pcorr=0.055; DD, pcorr=0.027). In particular, the ratio of volumes in the splenium and body of the corpus callosum was significantly associated with both penetrance scores (Sz: p=0.037; DD; p=0.006). Our results are consistent with the notion that a significant alteration in developmental trajectories of mid-line white-matter structures constitutes a common neurodevelopmental aberration contributing to risk for schizophrenia and intellectual disability.

neuroscience↗

bioRxiv2018

Brucella Peptide Cross-Reactive MHC I Presentation Activates SIINFEKL-Specific TCR Expressing T Cells

Brucella spp are intracellular pathogenic bacteria remarkable in their ability to escape immune surveillance and therefore inflict a state of chronic disease within the host. To enable further immune response studies, Brucella were engineered to express the well characterized chicken ovalbumin (OVA). Surprisingly, we found that CD8 T cells bearing T cell receptors (TCR) nominally specific for the OVA peptide SIINFEKL (OT-1) reacted to parental Brucella-infected targets as well as OVA-expressing Brucella variants in cytotoxicity assays. Furthermore, splenocytes from Brucella immunized mice produced IFN-{gamma} and exhibited cytotoxicity in response to SIINFEKL-pulsed target cells. To determine if the SIINFEKL-reactive OT-1 TCR could be cross-reacting to Brucella peptides, we searched the Brucella proteome using an algorithm to generate a list of near-neighbor nonamer peptides that would bind to H2Kb. Selecting five Brucella peptide candidates, along with controls, we verified that several of these peptides mimicked SIINFEKL resulting in T cell activation through the \"SIINFEKL-specific\" TCR. Activation was dependent on peptide concentration as well as sequence. Our results underscore the complexity and ubiquity of cross-reactivity in T cell recognition. This cross-reactivity may enable microbes such as Brucella to escape immune surveillance by presenting peptides similar to the host, and may also lead to the activation of autoreactive T cells.

immunology↗