Biology subjects

Katz, C.

Publications and source records attributed to Katz, C..

6 recordsLinked to original sources

bioRxiv2024

Precise Timing Matters: Modulating Human Memory by Synchronizing Hippocampal Stimulation to Saccadic Event Related Potentials

Episodic memory, the ability to record and relive experiences, is intricately connected to visual exploration in most humans. This study explores the possibility that eye movements create physiological states relevant for memory, analogous to those associated with hippocampal theta. Previous work has demonstrated that saccadic eye movements, which occur roughly at theta frequency, elicit hippocampal event-related potentials (ERPs). Building on the Separate Phases of Encoding and Retrieval (SPEAR) model, we asked if the peaks and troughs of this saccadic ERP are differentially important for memory formation. Specifically, we applied saccade-contingent hippocampal electrical stimulation at estimated ERP peaks and troughs while individuals with epilepsy visually explored natural scenes across 59 sessions. We subsequently assessed their recognition memory for scenes and their recall of associated targets. Results indicate that memory is robust when stimulation precisely targets the peak or trough, contrasting with impairments observed with random stimulation. Moreover, memory impairment is prominent when stimulation is applied within 100 ms of saccade initiation, a time that reflects high medial temporal lobe inhibition. Our findings suggest that the hippocampus rapidly evolves through memory-relevant states following each eye movement, while also challenging the assumption that human saccadic ERP peaks and troughs mirror the encoding and retrieval phases of theta rhythms studied in rodents. The study sheds light on the dynamic interplay between eye movements, hippocampal activity, and memory formation, offering theoretical insights with potential applications for memory modulation in neurological disorders. Significance StatementWhy do eye-movements enhance memory formation? Here, we causally tested if eye-movements initiate short-lived states critical for memory formation within the hippocampus, a brain region known to support memory. We built a system that could precisely apply hippocampal electrical stimulation at key moments after eye-movements to test how the timing of this stimulation influenced peoples ability to form memories. We found that stimulation was particularly disruptive to memory formation when applied within 100 ms of initiating an eye movement. By contrast, memory was robust to stimulation precisely timed to the peak and trough of hippocampal eye-movement responses. We interpret this temporal evolution of memory-relevant states within a prominent model of how theta phases relate to rodent memory.

neuroscience↗

bioRxiv2024

Curing of a field strain of Salmonella enterica serovar Infantis isolated from poultry from its highly stable pESI like plasmid

Salmonella enterica serovar Infantis (S. Infantis) is an important emerging pathogen, associated with poultry and poultry products and related to an increasing number of human infections in many countries. A concerning trend among S. Infantis isolates is the presence of plasmid-mediated multi-drug resistance. In many instances, the genes responsible for this resistance are carried on a megaplasmid known as the plasmid of emerging S. Infantis (pESI) or pESI like plasmids. Plasmids can be remarkably stable due to the presence of multiple replicons and post-segregational killing systems (PSKs), which contribute to their maintenance within bacterial populations. To enhance our understanding of S. Infantis and its multidrug resistance determinants toward the development of new vaccination strategies, we have devised a method for targeted plasmid curing. This approach effectively overcomes plasmid addiction by leveraging the temporal overproduction of specific antitoxins coupled with the deletion of the partition region. By employing this strategy, we successfully generated a plasmid-free strain from a field isolate derived from S. Infantis 119944. This method provides valuable tools for studying S. Infantis and its plasmid-borne multidrug resistance mechanisms.

microbiology↗

bioRxiv2023

A non-canonical Hippo pathway represses the expression of deltaNp63

The p63 transcription factor, a member of the p53 family, plays an oncogenic role in squamous cancers, while in breast cancers its expression is often repressed. In the canonical conserved Hippo pathway, known to play a complex role in regulating growth of cancer cells, the protein kinases MST1/2 and LATS1/2 act sequentially to phosphorylate and inhibit the YAP/TAZ transcription factors. We found that in the MCF10A mammary epithelial cell line as well as in squamous and breast cancer cell lines, expression of {Delta}Np63 RNA and protein is strongly repressed by inhibition of the Hippo pathway protein kinases in a manner that is independent of p53. While MST1/2 and LATS1 are required for p63 expression, the next step of the pathway, namely phosphorylation and degradation of the YAP/TAZ transcriptional activators is not required for repression of p63. This suggests that regulation of p63 expression occurs by a non-canonical version of the Hippo pathway. We additionally identified additional genes that were similarly regulated suggesting the broader importance of this pathway. Interestingly, we observed that experimentally lowering p63 expression leads to increased YAP protein levels, thereby constituting a feedback loop. These results, which reveal the intersection of the Hippo and p63 pathways, may prove useful for the control of their activities in cancer cells. One Sentence SummaryRegulation of p63 expression occurs by a non-canonical version of the Hippo pathway in mammary epithelial, breast carcinoma and head and neck squamous carcinoma cells

cancer biology↗

bioRxiv2021

Protection against avian coronavirus conferred by oral vaccination with live bacteria secreting LTB-fused viral proteins

The devastating impact of infectious bronchitis (IB) triggered by the IB virus (IBV), on poultry farms is generally curbed by livestock vaccination with live attenuated or inactivated vaccines. Yet, this approach is challenged by continuously emerging variants and by time limitations of vaccine preparation techniques. This work describes the design and evaluation of an anti-IBV vaccine comprised of E. coli expressing and secreting viral spike 1 subunit (S1) and nucleocapsid N-terminus and C-terminus polypeptides fused to heat-labile enterotoxin B (LTB) (LS1, LNN, LNC, respectively). Following chicken oral vaccination, anti-IBV IgY levels and cellular-mediated immunity as well as protection against virulent IBV challenge, were evaluated 14 days following the booster dose. Oral vaccination induced IgY levels that exceeded those measured following vaccination with each component separately. Following exposure to inactivated IBV, splenocytes isolated from chicks orally vaccinated with LNN or LNC -expressing bacteria, showed a higher percentage of CD8+ cells as compared to splenocytes isolated from chicks vaccinated with wild type or LTB-secreting E. coli and to chicks subcutaneously vaccinated. Significant reduction in viral load and percent of shedders in the vaccinated chicks was evident starting 3 days following challenge with 107.5 EID50/ml virulent IBV. Taken together, orally delivered LTB-fused IBV polypeptide-expressing bacteria induced virus-specific IgY antibody production and was associated with significantly shorter viral shedding on challenge with a live IBV. The proposed vaccine design and delivery route promise an effective and rapidly adaptable means of protecting poultry farms from devastating IB outbreaks. HighlightsO_LIMucosal vaccination was shown particularly beneficial against respiratory viruses. C_LIO_LIAn anti-IBV vaccine composed of three IBV polypeptides fused to LTB was designed. C_LIO_LIVaccine composed of bacteria secreting polypeptides was orally delivered. C_LIO_LIVaccine induced specific immune responses and shortened viral shedding duration. C_LI

immunology↗

bioRxiv2021

Oral subunit SARS-CoV-2 vaccine induces systemic neutralizing IgG, IgA and cellular immune responses and can boost neutralizing antibody responses primed by an injected vaccine

The rapid spread of the COVID-19 pandemic, with its devastating medical and economic impacts, triggered an unprecedented race toward development of effective vaccines. The commercialized vaccines are parenterally administered, which poses logistic challenges, while adequate protection at the mucosal sites of virus entry is questionable. Furthermore, essentially all vaccine candidates target the viral spike (S) protein, a surface protein that undergoes significant antigenic drift. This work aimed to develop an oral multi-antigen SARS-CoV-2 vaccine comprised of the receptor binding domain (RBD) of the viral S protein, two domains of the viral nucleocapsid protein (N), and heat-labile enterotoxin B (LTB), a potent mucosal adjuvant. The humoral, mucosal and cell-mediated immune responses of both a three-dose vaccination schedule and a heterologous subcutaneous prime and oral booster regimen were assessed in mice and rats, respectively. Mice receiving the oral vaccine compared to control mice showed significantly enhanced post-dose-3 virus-neutralizing antibody, anti-S IgG and IgA production and N-protein-stimulated IFN-{gamma} and IL-2 secretion by T cells. When administered as a booster to rats following parenteral priming with the viral S1 protein, the oral vaccine elicited markedly higher neutralizing antibody titres than did oral placebo booster. A single oral booster following two subcutaneous priming doses elicited serum IgG and mucosal IgA levels similar to those raised by three subcutaneous doses. In conclusion, the oral LTB-adjuvanted multi-epitope SARS-CoV-2 vaccine triggered versatile humoral, cellular and mucosal immune responses, which are likely to provide protection, while also minimizing technical hurdles presently limiting global vaccination, whether by priming or booster programs. HighlightsO_LIMigVax-101 is a multi-epitope oral vaccine for SARS-CoV-2. C_LIO_LIMigVax-101 elicits neutralizing IgG and IgA production and cellular responses in mice C_LIO_LIMigVax-101 serves as an effective booster in rats to a parenteral anti-S1 vaccine. C_LI

immunology↗

bioRxiv2018

Differential generation of saccade, fixation and image onset event-related potentials in the human mesial temporal lobe

The electrophysiological signatures of encoding and retrieval recorded from mesial temporal lobe (MTL) structures are observed as event related potentials (ERPs) during visual memory tasks. The waveforms of the ERPs associated with the onset of visual stimuli (image-onset) and eye movements (saccades and fixations) provide insights into the mechanisms of their generation. We hypothesized that since eye movements and image-onset (common methods of stimulus presentation when testing memory) provide MTL structures with salient visual information, that perhaps they both engage similar neural mechanisms. To explore this question, we used intracranial electroencephalographic (iEEG) data from the MTLs of 11 patients with medically refractory epilepsy who participated in a visual search task. We sought to characterize electrophysiological responses of MTL structures to saccades, fixations and image onset. We demonstrate that the image-onset response is an evoked/additive response with a low-frequency power increase and post-stimulus phase clustering. In contrast, ERPs following eye movements appeared to arise from phase resetting of higher frequencies than the image onset ERP. Intriguingly, this reset was associated with saccade onset and not saccade termination (fixation), suggesting it is likely the MTL response to a corollary discharge, rather than a response to visual stimulation - in stark contrast to the image onset response. The distinct mechanistic underpinnings of these two ERP may help guide future development of visual memory tasks.

neuroscience↗