Biology subjects

Karimi, A.

Publications and source records attributed to Karimi, A..

9 recordsLinked to original sources

bioRxiv2026

Microfluidic cultivation enables probiotic growth under thermal stress

Thermal stress tolerance is essential for preserving the viability and functionality of probiotic bacteria. Conventional batch cultures offer limited control over temperature changes across space and time. We have introduced an integrated microfluidic platform to continuously cultivate bacteria within a precisely defined and tunable thermal environment, and used Lacticaseibacillus rhamnosus as a model system. The device features serially connected microchambers with independently controlled heating zones, creating distinct and dynamic thermal profiles as the bacteria travel from one microchamber to the next. Biomass accumulation was observed at 37 {degrees}C within 48 h in all microchambers, no growth occurred at 49 {degrees}C even after 72 h. When the cells were exposed to a periodic thermal landscape, where an increase in temperature in one chamber was followed by a return to 37 {degrees}C in the next, growth was observed in the last chamber (49 {degrees}C) after three days indicating adaptation to thermal stress. Cells that grew on-chip at 49 {degrees}C showed no growth in off-chip experiments. Continuous monitoring of pH at the chip outlet confirmed ongoing metabolic activity in growing populations. Tailored microfluidic thermal environments were shown to help bacteria grow even under otherwise inhibitory conditions.

bioengineering↗

bioRxiv2026

Oculomotor dance learning task: Implications for audio-visual cued spatial learning

Motor sequence learning involves the coordination of both oculomotor and manual motor systems through the practiced repetition of a fixed sequence of actions. This study aims to address whether a sequence-based learning paradigm centered on the visual-motor system can feasibly be measured while listening to music (Bar and DeSouza 2016). It aims to develop a new visual-motor-based learning paradigm with music, potentially promoting neuroplasticity and creating new interventional tools, building upon prior research that shows behavioural and putative neural changes following dance-based neurorehabilitation in people with Parkinsons disease (Bearss et al. 2024). Eye movements of 10 participants (8 female, 2 male) were tracked using the Eyelink 1000 Plus system during a 68-second eye-dance sequence. The experiment consisted of a learning phase, where participants observed the sequence five times with 30-second breaks, and a performance phase, where they performed the sequence five times from memory on a grey screen without visual cues. Music was incorporated into both phases to aid memorization of the 4 spatial locations. After each performance, the participant was shown a visual reinforcer and asked for their thoughts on how well they executed the dance. A visual reinforcer flashes one of three different colours: red, yellow, or green. Each colour corresponds to how many steps in the dance a participant performed correctly, with key points being: under one third, between one to two thirds, and over two thirds of total steps correct. Participants were scored based on timing of the steps as well for exact (1.00), good (0.66), slightly off (0.33) or missed (0) steps. Data was analyzed using R4.3.1, MATLAB, and Experiment Builder: Data Viewer software. Results showed a significant improvement in performance accuracy between the first session (g1; M = 40%, SD = 7.2%) and the last session (g5; M = 69.7%, SD = 22.8%). A repeated-measures ANOVA revealed a significant main effect of session on performance accuracy, F(4, 36) = 6.99, p < 0.001, {superscript 2}G = 0.26, indicating that accuracy significantly improved over sessions. Post-hoc Bonferroni comparisons showed that accuracy in later sessions was significantly higher than earlier sessions, suggesting a defined learning curve and consolidation of performance pattern across repeated practice. Similarly, there was significant improvement in timing accuracy between the first session g1; M = 0.29, SD = 0.06) and the fifth session (g5; M = 0.46, SD = 0.12). A repeated-measures ANOVA revealed a significant main effect of session on timing precision, F(4, 36) = 11.67, p < 0.001, {superscript 2}G = 0.25, indicating significant improvements in temporal control and coordination over sessions. Post-hoc Bonferroni comparisons showed that timing precision significantly improved between early and late sessions (e.g, g1-g4, p <0.01; g1-g5, p < 0.001), suggesting a defined learning curve and increase in precision across repeated practice. These findings suggest that visual-motor-based interventions have the potential to enhance motor and non-motor symptoms like depression and anxiety for neurodegenerative diseases such as Parkinsons Disease (PD). The results provide a foundation for developing targeted therapies that integrate learning paradigms to improve functional outcomes, warranting further exploration of their long-term efficacy.

neuroscience↗

bioRxiv2025

Adaptive surface sensing enables mammalian sperm navigation in complex environments

During transit through the fallopian tube of the female reproductive tract, sperm encounter a structurally complex lattice-like environment characterized by confinement and curvature created by the folded epithelium of the fallopian tube. To replicate these conditions, we examined sperm scattering and migratory behavior in microfabricated obstacle lattices with varying spacing. We found a passive adaptive sensing mechanism that regulates sperm surface interactions in confined and curved environments. Specifically, scattering dynamics, including the collision angle, were impacted as sperm navigated the lattice, and surface interaction times were reduced under more confined conditions. A mathematical model was developed to describe sperm transport in these structured landscapes, predicting up to a nine-fold enhancement of diffusivity compared to free swimming sperm. Hyperactivated sperm displayed similar adaptive behavior within the lattice. We found that sperm dynamically adjust their navigation strategy in response to environmental geometry, allowing efficient migration despite confinement. More broadly, the study highlights how physical structure modulates microswimmer behavior and provides new insight into the physical processes that govern sperm navigation and the mechanisms underlying mammalian fertilization.

biophysics↗

bioRxiv2025

Memory CD4 T cells orchestrate neoadjuvant-responsive niches in colorectal cancer liver metastases

Colorectal cancer frequently progresses to liver metastases (CRLM), a stage with limited treatment options and poor prognosis. Neoadjuvant chemotherapy is used to control tumor growth and enable resection, yet many patients fail to respond, and the mechanisms underlying this variability remain unclear. To identify determinants of treatment response, we profiled T cell states and their spatial organization in CRLM. We found that spatial arrangement and polarization of CD4 memory T cell networks determine treatment outcome. In responders, Th1-like CD4 memory T cells organized with effector-memory CD8 T cells and antigen-presenting cells (APCs) into therapy-responsive immune niches (TRINs) that support CD4-mediated APC licensing and local immune engagement. Non-responders lacked such immune architecture, exhibiting myeloid-rich regions dominated by circulating-like CD4 memory and regulatory T cells. CD4-driven TRINs thus emerge as key determinants of chemotherapy efficacy and provide a rationale for developing biomarkers and strategies that enhance CD4-APC-CD8 crosstalk within organized immune niches. Statement of significanceTh1-polarized CD4 memory T cells form therapy-responsive immune niches (TRINs) that orchestrate CD4, CD8, and APC function in colorectal cancer liver metastases, a clinically challenging and immunologically cold tumor type. TRINs define chemotherapy response and provide a mechanistic foundation for biomarker development and immunotherapy strategies designed to restore anti-tumor immunity.

immunology↗

bioRxiv2025

Integration of Audiovisual Motion in Dorsolateral Prefrontal Cortical Neurons

The dorsolateral prefrontal cortex is well recognized for its role in cognitive functions and activating action plans. In contrast, the properties of prefrontal neurons with respect to multisensory processing are less well studied. To address this question, we recorded single units from areas 8a and 46 of two female rhesus macaques while they were presented with visual, auditory, and audiovisual motion stimuli. The majority of dorsolateral prefrontal neurons responded to these sensory stimuli, with similar percentages of auditory-only, visual-only and audiovisual neurons. Approximately one third of responsive neurons exhibited significant super- or sub-additive interactions in response to the pairing of auditory and visual stimuli, revealing significant nonlinearities in their response profiles. Decoding motion signals from the population activity robustly differentiated multisensory from unisensory trials and also unisensory auditory and visual trials from each other. These results demonstrate that dorsolateral prefrontal neurons integrate auditory and visual motion signals, extending multisensory computations beyond sensory cortices into prefrontal circuits that support higher-order cognition. New & NoteworthyWe recorded single neurons in macaque dorsolateral prefrontal cortex during visual, auditory, and audiovisual motion. Nearly half of responsive neurons were multisensory and a third displayed significant super- or sub-additive interactions, while ensemble activity reliably decoded stimulus modality. These findings provide the strongest evidence to date that DLPFC performs rapid, nonlinear audiovisual integration, extending multisensory computations beyond classical posterior regions into the prefrontal circuits that support cognition.

neuroscience↗

bioRxiv2025

SARS-CoV-2 causes chronic lung inflammation and impaired respiratory capacity in aged Roborovski dwarf hamsters

Roborovski dwarf hamsters are permissive for SARS-CoV-2 infection and progress to acute viral pneumonia with profound lung tissue injury, recapitulating hallmarks of severe COVID-19 in vulnerable patient groups such as older adults. In this study, we established dwarf hamster whole body plethysmography and assessed disease severity and propensity for long-term compromise of lung recovery from severe COVID-19-like disease in young, adult, and aged animals. Aged dwarf hamsters infected intranasally with variant of concern (VOC) omicron BA.4 experienced more severe clinical signs, carried a higher lung virus load, and had a greater risk of succumbing to infection. Resting airway hypersensitivity was transiently increased in aged, but not young, dwarf hamsters 3-4 days post infection (dpi). Pharmacologically induced respiratory distress revealed compromised lung capacity in animals of both age groups at peak disease. Aged animals showed impaired respiratory function for 45 days, mounted a weaker antiviral response, and developed chronic pneumonia with lasting tissue damage. Treatment of acute disease with approved antivirals, paxlovid-like nirmatrelvir+ritonavir or molnupiravir, prevented long-term respiratory sequelae in aged animals. Nirmatrelvir+ritonavir fully suppressed transient respiratory distress and mediated complete survival of aged animals. This study shows a high positive correlation between host age and SARS-CoV-2 disease severity in dwarf hamsters, establishes a model for chronic pneumonia with impaired respiratory capacity in at-risk hosts, and demonstrates benefit of antiviral therapy of acute disease for long-term respiratory health. Author SummaryIn the COVID-19 pandemic, the frequency of chronic respiratory insufficiency after acute SARS-CoV-2 infection was positively linked to patient age. Roborovski dwarf hamsters recapitulate hallmarks of life-threatening COVID-19 in at-risk patients that present with acute respiratory failure and prolonged respiratory incapacitation. In this study, we monitored disease progression and lung function in young and aged dwarf hamsters infected with a VOC omicron isolate and assessed the effect of antiviral treatment on long-term lung function. We established a strong correlation between host age and SARS-CoV-2 disease severity in dwarf hamsters, identified a high propensity of aged animals to develop chronic lung inflammation, and demonstrated a long-term loss of respiratory capacity in the subset of aged animals that survived the acute infection. Antiviral treatment suppressed the development of late sequelae and preserved lung function. These results have important implications for effective SARS-CoV-2 management in aged hosts at high risk of developing severe viral pneumonia with long-term impaired lung function.

microbiology↗

bioRxiv2022

Paxlovid-like nirmatrelvir/ritonavir fails to block SARS-CoV-2 transmission in ferrets

Despite the continued spread of SARS-CoV-2 and emergence of variants of concern (VOC) that are capable of escaping preexisting immunity, therapeutic options are underutilized. In addition to preventing severe disease in high-risk patients, antivirals may contribute to interrupting transmission chains. The FDA has granted emergency use authorizations for two oral drugs, molnupiravir and paxlovid. Initial clinical trials suggested an efficacy advantage of paxlovid, giving it a standard-of-care-like status in the United States. However, recent retrospective clinical studies suggested a more comparable efficacy of both drugs in preventing complicated disease and case-fatalities in older adults. For a direct efficacy comparison under controlled conditions, we assessed potency of both drugs against SARS-CoV-2 in two relevant animal models; the Roborovski dwarf hamster model for severe COVID-19 in high-risk patients and the ferret model of upper respiratory tract disease and transmission. After infection of dwarf hamsters with VOC omicron, paxlovid and molnupiravir were efficacious in mitigating severe disease and preventing death. However, a pharmacokinetics-confirmed human equivalent dose of paxlovid did not significantly reduce shed SARS-CoV-2 titers in ferrets and failed to block virus transmission to untreated direct-contact ferrets, whereas transmission was fully suppressed in a group of animals treated with a human-equivalent dose of molnupiravir. Prophylactic administration of molnupiravir to uninfected ferrets in direct contact with infected animals blocked productive SARS-CoV-2 transmission, whereas all contacts treated with prophylactic paxlovid became infected. These data confirm retrospective reports of similar therapeutic benefit of both drugs for older adults, and reveal that treatment with molnupiravir, but not paxlovid, may be suitable to reduce the risk of SARS-CoV-2 transmission.

microbiology↗

bioRxiv2019

Cell-type specific innervation of cortical pyramidal cells at their apical tufts

We investigated the synaptic innervation of apical tufts of cortical pyramidal cells in a region between layers 1 and 2 using 3-D electron microscopy (3D-EM) applied to four cortical regions in mouse. Across all cortices, we found the relative inhibitory input at the apical dendrites main bifurcation to be more than 3-fold stronger for layer 2 pyramidal cells than for all other pyramidal cells. Towards the distal tuft dendrites in upper layer 1, however, the relative inhibitory input was about 2-fold stronger for L5 pyramidal cells than for all others. Only L3 pyramidal cells showed homogeneous inhibitory input density. The inhibitory to excitatory synaptic balance is thus specific for the types of pyramidal cells. Inhibitory axons preferentially innervated either layer 2 or L3/5 apical dendrites, but not both. These findings describe connectomic principles for the control of pyramidal cells at their apical dendrites in the upper layers of the cerebral cortex and point to differential computational properties of layer 2, layer 3 and layer 5 pyramidal cells in cortex.

neuroscience↗

bioRxiv2018

FluoEM: Virtual labeling of axons in 3-dimensional electron microscopy data for long-range connectomics

Volume electron microscopy (3D EM) has enabled the dense reconstruction of neuronal circuits in datasets that are so far about a few hundred micrometers in extent. In mammalian brains, most neuronal circuits are however highly non-local, such that a large fraction of the synapses in such a volume of neuropil originates from distant projection sources. The labeling and identification of such long-range axonal inputs from multiple sources within a densely reconstructed EM dataset has been notoriously difficult because of the limited color label space of EM. Here, we present FluoEM, a set of experimental and computational methods that allows the identification of multi-color fluorescently labeled axons in dense EM data without the need for artificially introduced fiducial marks or direct label conversion for EM. The approach is based on correlated imaging of the tissue and computational matching of neurite reconstructions, amounting to a virtual color labeling of axons in dense EM circuit data. We show that the identification of fluorescent light-microscopically (LM) imaged axons in 3D EM data from mouse cortex is faithfully possible as soon as the EM dataset is about 40-50 m in extent, relying on the unique trajectories of axons in dense mammalian neuropil. The method is exemplified for the identification of longdistance axonal input into layer 1 of the mouse cerebral cortex.

neuroscience↗