Biology subjects

Anderson, K. L.

Publications and source records attributed to Anderson, K. L..

5 recordsLinked to original sources

bioRxiv2026

Engineering a Hyper-Adherent E. coli Nissle Probiotic Strain that Reduces Intestinal Carriage of SalmonellaPathogens in Poultry

Salmonellosis continues to be one of the most important causes of food-borne illness in the U.S. An additional concern with this bacterial pathogen is that infections with multiple-antibiotic-resistant Salmonella strains are becoming untreatable infectious diseases. Poultry meat and eggs are major sources of Salmonella food-borne illness, due to carriage of these bacterial pathogens in the intestinal microbiome of chickens. A food safety priority, as stated by the USDA, is a significant reduction in carriage of pathogenic Salmonella species in poultry which would significantly improve food safety and reduce cases of human salmonellosis contracted from consumption of contaminated poultry. While this goal has been a priority for many years, basic research and animal management efforts have not achieved significant control of Salmonella carriage. This study represents an alternative approach to reduce or eliminate carriage of Salmonella in poultry flocks. We characterized a type 1 fimbrial allele of Salmonella that confers high levels of adherence to various host cells. We then engineered an E. coli Nissle 1917 probiotic strain that expresses this Salmonella adherence factor at high levels. The E. coli Nissle 1917 is used as the scaffold strain for this work since this E. coli strain has received the FDA designation of Generally Regarded As Safe (GRAS) and has been used for many years as a probiotic to treat human intestinal disorders. Our E. coli Nissle strain was engineered to use an in vivo selection system for a plasmid carrying the cloned Salmonella type 1 fimbrial genes, so that the strain can be used as a probiotic without any antibiotic resistance-encoding genes requiring antibiotic selection for maintenance of the desired phenotype. Our probiotic strain displays high levels of adherence to host cells, in fact higher levels of adherence than a Salmonella strain carrying the same type 1 fimbrial genes. We demonstrate that the probiotic strain significantly outcompetes pathogenic Salmonella strains for adherence to tissue culture cells and in vivo experimental challenges revealed that the probiotic strain mediates a significant exclusion of Salmonella from the intestines of broilers, layers, and turkeys.

microbiology↗

bioRxiv2025

Neural dynamics of proactive and reactive cognitive control in medial and lateral prefrontal cortex

Goal-directed behavior requires adjusting cognitive control to both react to and prepare for conflict. Previous work indicates theta oscillations and population activity in dorsomedial prefrontal cortex (dmPFC) and dorsolateral prefrontal cortex (dlPFC) are critical for reactive control. However, the neural mechanisms supporting proactive control are less clear. Here, we investigated the neural basis of behavioral adaptations when control is prepared in anticipation of conflict using intracranial EEG (iEEG) in dmPFC and dlPFC during a Stroop task where conflict frequency was manipulated across blocks. We observed canonical conflict-driven increases in dmPFC theta and in dmPFC and dlPFC local population activity, as indexed by high frequency activity (HFA). Conflict also suppressed theta power in both regions after the response, accentuated a pre-response beta desynchronization selectively in dlPFC, and increased a post-response beta rebound in both regions. Importantly, we identified a pre-trial marker of proactive control where dmPFC theta power increased before trials when conflict was expected, and theta, beta, and HFA conflict signals in both regions were enhanced when conflict was rare and diminished when conflict was common. These findings reveal shared HFA but dissociable oscillatory dynamics in dmPFC and dlPFC during reactive conflict processing, highlight pre-trial dmPFC theta as a potential substrate for proactive control, and refine the roles of dmPFC and dlPFC in control adaptations.

neuroscience↗

bioRxiv2020

Identification of Bovine Genotypes Conferring Diminished Susceptibility to Salmonellosis and Colonization by Salmonella and E. coli O157:H7

ABSTRACTSalmonella and E. coli O157:H7 are two of the most important problems for the beef industry. Cattle can develop salmonellosis and persistently harbor Salmonella, or they can asymptomatically shed Salmonella and/or E. coli O157:H7 resulting in contamination of the hide and carcass surfaces during processing. Additionally, Salmonella infiltrates lymph nodes that get incorporated into ground beef. In this study, we investigated the possibility of identifying cattle with reduced susceptibility to one or both of these infections. Empirical observations from previous studies suggested that a diminished susceptibility was possible in amelanotic cattle, i.e., cattle bearing the mcr1/mcr1 genotype and lacking overt black pigmentation. By searching for single nucleotide polymorphisms (SNP) present in the 34 genes encoding the Salmonella interactome, we identified a SNP that was consistently present in amelanotic cattle with diminished susceptibility to Salmonella. Specifically, we used an ex vivo assay to screen 500 cattle blood samples for the diminished ability of Salmonella to penetrate peripheral leukocytes. Diminished Salmonella penetration was observed in 150 of these blood samples and 147 of these samples harbored two alleles bearing a SNP that introduces a miRNA cleavage site (bta-let-7b) in the 3’UTR of the bsynJ1 gene, which we designate as the SYNJ1/SNYJ1 genotype. Further ex vivo studies revealed a decreased expression of SYNJ1 in leukocytes bearing the SYNJ1/SNYJ1 genotype. In vivo experimental challenge studies revealed a diminished susceptibility to salmonellosis in cattle with the SYNJ1/SNYJ1::mcr1/mcr1 genotype. Additional in vivo challenge studies revealed that SYNJ1/SNYJ1::mcr1/mcr1 cattle have a decreased susceptibility to lymph node infiltration by two Salmonella serotypes (S. Anatum and S. Montevideo) implicated in this lymph node problem, and a decreased susceptibility to E. coli O157:H7 colonization of the recto-anal junction. A field study revealed that the SYNJ1/SNYJ1::mcr1/mcr1 genotype was five times more prevalent, when compared to the SYNJ1/synj1::mcr1/mcr1 and synj1/ synj1::mcr1/mcr1 genotypes, in Salmonella-free lymph nodes. Small-scale genetic surveys revealed that the SYNJ1/SNYJ1 genotype was present in the following mcr1/mcr1 breeds: Akaushi, Barzona, Braunvieh, Hereford, Piedmontese, Red and White Holsteins, Red Angus, Red Poll, Shorthorn, Simmental (Red), and Tarentaise. Studies using the aforementioned ex vivo penetration assay, which putatively predicts the diminished susceptibility phenotype, revealed that the penetrance of the diminished susceptibility is >99% in SYNJ1/SNYJ1::mcr1/mcr1 cattle but only ∼1% in SYNJ1/SNYJ1 cattle with at least one MCR1 allele. Further studies with the ex vivo assay revealed that three additional SNPs are part of a genotype conferring diminished susceptibility to a broad array of Salmonella serotypes commonly associated with cattle. In summary, the studies presented herein reveal a bovine genotype associated with decreased susceptibility to Salmonella and E. coli O157:H7. PSR Genetics LLC holds a U.S. patent on testing for the SYNJ1/SNYJ1 genotype (patent number 9,049,848) while the three complementary SNPs are under further investigation.Competing Interest StatementThis study was funded by PSR Genetics LLC which included a rental agreement for laboratory space at Iowa State UniversityView Full Text

genetics↗

bioRxiv2020

Early EEG and behavioral alterations in Dravet mice

Dravet Syndrome (Dravet) is a severe childhood epileptic encephalopathy. The disease begins around the age of six months, with a febrile stage, characterized by febrile seizures with otherwise normal development. By the end of the first year of life, the disease progresses to the worsening stage, featuring recurrent intractable seizures and the appearance of additional comorbidities, including global developmental delay, cognitive deficits, hyperactivity and motor problems. Later, in early school years, Dravet reaches the stabilization stage, in which seizure burden decreases, while Dravet-associated comorbidities persist. Dravet syndrome mouse models (DS) faithfully recapitulate the three stages of the human syndrome. Here, we performed power spectral analyses of background EEG activity in DS and their wild-type (WT) littermates, demonstrating disease stage-related alterations. Specifically, while the febrile stage activity resembled that of WT mice, we observed a marked reduction in total power during the worsening stage and a smaller reduction during the stabilization stage. Moreover, low EEG power at the worsening stage correlated with increased risk for premature death, suggesting that such measurements can potentially be used as a marker for Dravet severity. With normal development at the febrile stage and the presentation of developmental delay at the worsening stage, the contribution of recurrent seizures to the emergence of Dravet-associated comorbidities is still debated. Thus, we further characterized the behavior of WT and DS mice during the different stages of Dravet. At the febrile stage, despite their normal background EEG patterns, DS mice already demonstrated motor impairment and hyperactivity in the open field, that persisted to the worsening and stabilization stages. Conversely, clear evidence for deficits in working memory emerged later in life, during the worsening stage. These results indicate that despite the mild epilepsy at the febrile stage, DS development is already altered, suggesting that the pathophysiological mechanisms governing the appearance of some Dravet behavioral comorbidities may be independent of the epileptic phenotype. HighlightsO_LIReduction in background EEG power in Dravet C_LIO_LILow EEG power correlates with the risk of premature death C_LIO_LIMotor deficits and hyperactivity are evident as early as the febrile stage C_LIO_LICognitive deficits and detection of increased anxiety begin at the worsening stage C_LI

neuroscience↗

bioRxiv2017

Accurate alignment between correlated light, cryo-light, and electron cryo-microscopy data using sample support features

Combining fluorescence microscopy with electron cryo-tomography allows, in principle, spatial localization of tagged macromolecular assemblies and structural features within the cellular environment. To allow precise localization and scale integration between the two disparate imaging modalities, accurate alignment procedures are needed. Here, we describe a marker-free method for aligning images from light or cryo-light fluorescence microscopy and from electron cryo-microscopy that takes advantage of sample support features, namely the holes in the carbon film. We find that the accuracy of this method, as judged by prediction errors of the hole center coordinates, is better than 100 nm.

biophysics↗