Biology subjects

Mohammadi, A.

Publications and source records attributed to Mohammadi, A..

10 recordsLinked to original sources

bioRxiv2026

Millisecond-scale detection of mouse ultrasonic vocalizations enables closed-loop experiments

Mouse ultrasonic vocalizations (USVs) provide a rapidly evolving readout of social interaction but are typically analysed only after acquisition. Here we introduce DeepFisFis, a waveform-based neural network that detects USVs while they are being produced. DeepFisFis classifies consecutive 5 ms audio segments directly from the waveform with high accuracy, processing each segment in approximately 2.5 ms and therefore faster than the incoming audio stream. This enables ongoing vocalizations to guide experimental interventions in real time. In a deployed closed-loop system, detections triggered an external stimulus, demonstrating online control of ongoing vocal behaviour. DeepFisFis also enables event-triggered data acquisition: gating storage around detected calls preserved more than 99% of vocalization time while retaining only approximately 22% of the continuous recording. DeepFisFis thus transforms USVs from a retrospective behavioural readout into a real-time experimental signal for selective acquisition and closed-loop causal interrogation of vocal communication and its underlying neural circuits.

neuroscience↗

bioRxiv2026

Population-specific drivers of reproductive phenology in a widespread large carnivore, the gray wolf

Animals often rely on cues from the environment to time reproduction with optimal conditions. However, for most species, which environmental cues are used and how their use varies across a species distribution remains poorly understood. The gray wolf (Canis lupus) is found across a broad latitudinal range (12{degrees}N to 83{degrees}N) and diverse natural habitats, making them an ideal study species to explore these questions. Using 1,261 estimated birth dates of wild and captive wolves across their global range, we investigated how environmental variables influence reproductive phenology in this widespread large carnivore. Birth dates for wild wolves ranged from November 22nd for Indian wolves (18{degrees}N) to June 15th for Arctic wolves (80{degrees}N). The best predictor of timing of birth was increasing daylength during the mating season, followed by precipitation variability during the year. The timing of birth in captive wolves was highly similar to wild wolves at same latitudes, suggesting they use similar environmental cues to time reproduction. Near the equator where photoperiod is more stable, wolves remained seasonal and likely use climatic cues to time reproduction. Our work reveals populations may use different environmental cues to time reproduction, a characteristic that likely facilitates adaptation to diverse environments.

ecology↗

bioRxiv2025

Ultrasensitive proteomics uncovers nociceptor diversity and novel pain targets

The richness of our somatosensory experience is reflected in the functional diversity of somatic sensory neurons. Single-cell sequencing (scRNA) of sensory neurons has revealed a molecular basis for such diversity1-3. However, sensory neuron diversity has yet to be captured at the level of the proteome. Here, we combined electrophysiology with deep visual proteomics (DVP)4 to quantify over 6,000 proteins from phenotypically-defined sensory neurons and identified novel proteomic markers of sensory neuron subtypes. Comparative analysis revealed both concordance and meaningful divergence between transcriptomes and proteomes. We further show that up to 3,000 proteins can be quantified from one-fourth of a single neuron, demonstrating subset-specific protein signatures. In culture, nociceptive neurons can be acutely sensitized to mechanical stimuli by nerve growth factor (NGF) which normally drives inflammatory pain in vivo5. Indeed, overnight exposure of peptidergic nociceptors to NGF and a protein kinase C (PKC) activator produced functional sensitization associated with proteome changes. Functional knockdown experiments identified the up-regulated B3GNT2 enzyme as a potential effector of nociceptor sensitization. In summary, we present a high-resolution proteomic resource linking molecular identity to function, enabling the discovery of novel mechanisms underlying somatic sensation and pain sensitization.

systems biology↗

bioRxiv2025

A New Type of Nonsuppressible Viremia Produced by HIV-Infected Macrophage

BackgroundHIV-1 RNA typically declines rapidly after initiation of antiretroviral therapy (ART); often reaching undetectable levels within a few weeks and remaining undetectable by standard assays. However, some patients on ART have persistent nonsuppressible viremia (NSV) that does not respond to treatment optimization or intensification. NSV can emerge at the time of ART initiation (primary NSV) or after being ART-suppressed (secondary NSV). Here, we examine mechanisms producing primary NSV in four people on ART. MethodsBlood samples were collected from four participants who, despite being adherent to ART, required approximately a year or more to become virologically suppressed. Viral RNA and proviral DNA genomes were sequenced to examine HIV-1 drug resistance, genome intactness and genetic diversity. The ability of HIV-1 Envs to facilitate efficient entry into cells expressing low levels of CD4 (a proxy for macrophage tropism) was assessed. ResultsBefore ART, the blood contained HIV-1 RNA genomes that were adapted to replication in CD4+ T cells and rapidly decayed after ART initiation. During ART, the blood contained HIV-1 genomes that were drug sensitive, genetically diverse, macrophage-tropic, not evolving and often had defects in vpr. ConclusionsOur results suggest that in individuals with primary NSV, ART stopped virus replication, but large pools of long-lived, HIV-infected macrophage continued to produce virus. This is mechanistically distinct from secondary NSV produced by CD4+ T cell clones. In addition, defects in vpr independently accumulation in macrophage-tropic lineages found in three participants, suggesting that vpr may impact survival of, or virus production from, HIV-infected macrophage. SUMMARYPeople with HIV-1 on ART can experience persistent, nonsuppressible viremia (NSV). We identified four people with a previously uncharacterized form of NSV that emerged at the time of ART initiation (primary NSV) and is notable for its genetic diversity, drug sensitivity, and macrophage tropism. This is mechanistically distinct from previously described cases of NSV produced by CD4+ T cells in people who were previously ART-suppressed (secondary NSV).

microbiology↗

bioRxiv2024

Multipath projection stereolithography (MPS) for 3D printing microfluidic devices

Although many lab-on-chip applications require inch-sized devices with microscale feature resolution, achieving this via current 3D printing methods remains challenging due to inherent tradeoffs between print resolution, design complexity, and build sizes. Inspired by microscopes that can switch objectives to achieve multiscale imaging, we report a new optical printer coined as Multipath Projection Stereolithography (MPS) specifically designed for printing microfluidic devices. MPS is designed to switch between high-resolution (1xmode, [~]10{micro}m) and low-resolution (3x mode, [~]30{micro}m) optical paths to generate centimeter sized constructs (3cm x 6cm) with a feature resolution of [~]10{micro}m. Illumination and projection systems were designed, resin formulations were optimized, and slicing software was integrated with hardware with the goal of ease of use. Using a test-case of micromixers, we show user-defined CAD models can be directly input to an automated slicing software to define printing of low-resolution features via the 3x mode with embedded microscale fins via 1x mode. A new computational model, validated using experimental results, was used to simulate various fin designs and experiments were conducted to verify simulated mixing efficiencies. New 3D out-of-plane micromixer designs were simulated and tested. To show broad applications of MPS, multi-chambered chips and microfluidic devices with microtraps were also printed. Overall, MPS can be a new fabrication tool to rapidly print a range of lab-on-chip applications.

bioinformatics↗

bioRxiv2023

Neutron capture enhances dose and reduces cancer cell viability in and out of beam during helium and carbon ion therapy.

PurposeNeutron Capture Enhanced Particle Therapy (NCEPT) is a proposed augmentation of charged particle therapy which exploits thermal neutrons generated internally, within the treatment volume via nuclear fragmentation, to deliver a biochemically targeted radiation dose to cancer cells. This work is the first experimental demonstration of NCEPT, performed using both carbon and helium ion beams with two different targeted neutron capture agents (NCAs). Materials and MethodsHuman glioblastoma cells (T98G) were irradiated by carbon and helium ion beams in the presence of NCAs, [10B]-BPA and [157Gd]-DOTA-TPP. Cells were positioned within a PMMA phantom either laterally adjacent to, or within, a 100x100x60 mm spread out Bragg peak (SOBP). The impact of NCAs and location relative to the SOBP on the cells was measured by cell growth and survival assays in six independent experiments. Neutron fluence within the phantom was characterised by quantifying the neutron activation of gold foil. ResultsCells placed inside the treatment volume reached 10% survival by 2 Gy of C or 2-3 Gy of He in the presence of NCAs compared to 5 Gy of C and 7 Gy of He with no NCA. Cells placed adjacent to the treatment volume showed a dose-dependent decrease in cell growth when treated with NCAs, reaching 10% survival by 6 Gy of C or He (to the treatment volume), compared to a no detectable effect on cells without NCA. The mean thermal neutron fluence at the centre of the SOBP was approximately 2.2x109 n/cm2/Gy(RBE) for the carbon beam and 5.8x109 n/cm2/Gy(RBE) for the helium beam and gradually decreased in all directions. ConclusionsThe addition of NCAs to cancer cells during C and He beam irradiation has a measurable impact on cell survival and growth in-vitro. Through the capture of internally generated neutrons, NCEPT introduces the concept of a biochemically targeted radiation dose to charged particle therapy. NCEPT enables the established pharmaceuticals and concepts of neutron capture therapy to be applied to a wider range of deeply situated and diffuse tumours, by targeting this dose to micro-infiltrates and cells outside of defined treatment regions. These results also demonstrate the potential for NCEPT to provide an increased dose to tumour tissue within the treatment volume, with a reduction in radiation doses to off target tissue.

biophysics↗

bioRxiv2021

Insertive vaginal sex has a profound impact on the penile immune correlates of HIV susceptibility

The penis is the primary site of HIV acquisition in heterosexual men. Elevated penile inflammatory cytokines increase sexual acquisition risk, and topically applied cytokines enhance foreskin HIV susceptibility in an explant model. However, the impact of penile-vaginal sex on these immune parameters is undefined. Heterosexual couples were recruited to the Sex, Couples and Science (SECS) Study, with the collection of penile swabs, semen, cervico-vaginal secretions, and blood after a period of abstinence, and repeated sampling up to 72 hours after either condomless (n=30) or condom-protected (n=8) penile-vaginal sex. Soluble immune parameters were quantified by multiplex immunoassay. Co-primary immune endpoints were penile levels of IL-8 and MIG, cytokines previously linked to penile HIV acquisition. One hour after sex there were dramatic increases in penile IL-8 and MIG levels, regardless of condom use, with a gradual return to baseline by 72 hours; similar patterns were observed for other chemoattractant chemokines. Penile cytokine changes were similar in circumcised and uncircumcised men, and repeated measures ANOVA and ANCOVA models demonstrated that the degree of change after condomless sex was explained by cytokine levels in their partners cervico-vaginal secretions. This may have important implications for the biology of penile HIV acquisition. Author summaryIn heterosexual men, the penis is the primary site of Human Immunodeficiency Virus (HIV) acquisition. Levels of inflammatory cytokines in the coronal sulcus are associated with an increased HIV risk, and we hypothesized that these may be altered after insertive penile sex. Therefore, we designed the Sex, Couples and Science Study (SECS study) to define the impact of penile-vaginal sex on the penile immune correlates of HIV susceptibility. We found that multiple coronal sulcus cytokines increased dramatically and rapidly after sex, regardless of condom use, with a return to baseline levels by 72 hours. The changes observed after condomless sex were strongly predicted by cytokine concentrations in the vaginal secretions of the female partner, and were similar in circumcised and uncircumcised men. We believe that these findings have important implications for understanding the immunopathogenesis of penile HIV acquisition; in addition, they have important implications for the design of clinical studies of penile HIV acquisition and prevention.

immunology↗

bioRxiv2020

A new isolated local varicella virus: isolation, identification, comparative growth characteristics and immunological evaluation on an animal model

A panel of 4 different cell lines was optimized for isolation, identification, and authentication of a VZV virus from a swab sample of an 8-year-old boy suspected to varicella zoster infection. The system enabled highly efficient and rapid isolation of viruses in 33{degrees}C by serial sub culturing to more than 25 passages. The technique relies on isolation of viral genes by increasing the number of particles that are statistically represented in cell culture and verified by CCID50, FAM-RT-PCR, and IE62 antibody in IF test. The viral genes (ORF38, ORF54) confirmed the new isolate as VZV and revealed the amino acid sequence of viral-encoded proteins after 27 passages, identical with positive control virus, in RFLP-PCR test. Utilization of successive serial passages at temperatures lower than the normal body temperature would reduce the virus virulence and directly cause virus attenuation. As a result, the attenuated virus is adapted to growth in vitro and presented higher replication at 33{degrees}C. Our goal was to determine if the targeted virus with a large double-stranded DNA genome, varicella virus, is isolated and can be attenuated by cold adapting in vitro, Using vOka as attenuated VZV golden standard, in two quantitative tests, including CCID50 and FAM-RT-PCR. Finally, when compared with the local isolated virus, these results were strongly confirmed. We recorded plaque forming assay to show phenotypic changing which encodes the attenuation regarding size of plaque. Although in plaque forming assay, the size of plaque seemed smaller at first glance, the statistical distribution of the plaque size did not show any change between the virus in the first and last passages. In cell culture, the local VZV isolated viruses formed clear plaques and grew to higher titers compared with lower passages as parental virus.Due to lack of access to human fetal lung cells (MRC-5) and an alternative to vaccine production in the future, a new authenticated local foreskin cell substrate (RFSC) was used for virus cultivation. In comparison to, MRC-5-optimized and cloned-viruses replicated in vitro with kinetics that were similar to those of the RFSC. Laboratory animals that were infected with the optimized virus fluid as vaccine showed a good neutralization antibody against local VZV isolated as compared to vOka as control positive virus. These results demonstrate that the virus isolated from swab sample was authenticated as VZV virus, and this cold adapted attenuated virus may be an applicable candidate for future plan. Author summaryWe used different cell substrates for isolation, identification, and attenuation of a new local VZV virus from vesicle swab of suspected patient to varicella zoster diseases. The technique involves serial sub culturing of virus in cell culture. Our goal was to determine if the targeted virus with a large double-stranded DNA genome, varicella virus, is isolated and can be attenuated by cold adapting in vitro, using vOka as attenuated VZV golden standard, The virus was cloned and purified by serial dilution cloning and plaque assay. Different techniques were used regarding verification as differentiation from other members in family, potency, and sterility for isolated virus. The virus can grow well in new local foreskin cell substrate and produce good titre as compared with MRC-5. The isolated VZV potentially induced neutralization antibody in animal model. The results of our study imply that local VZV might be an applicable isolate for future plan in research and developing a varicella vaccine.

microbiology↗

bioRxiv2019

Metronomic capecitabine as an immune modulator in glioblastoma patients reduces myeloid-derived suppressor cells

BackgroundMyeloid-derived suppressor cells (MDSCs) are elevated in glioblastoma (GBM) patient circulation, present in tumor tissue, and associated with poor prognosis. While low-dose chemotherapy reduces MDSCs in preclinical models, the use of this strategy to reduce MDSCs in GBM patients has yet to be evaluated. MethodsA phase 0/1 dose-escalation clinical trial was conducted in recurrent glioblastoma patients treated 5-7 days prior to surgery with low-dose chemotherapy via capecitabine followed by concomitant low-dose capecitabine and bevacizumab. Clinical outcomes, including progression-free and overall survival, were measured, along with safety and toxicity profiles. Over the treatment time course, circulating MDSC levels were measured by multi-parameter flow cytometry, and tumor tissue immune profiles were assessed via mass cytometry time-of-flight. ResultsA total of 11 patients were enrolled across escalating dose cohorts of 150, 300, and 450 mg bid, with a progression-free survival of 5.8 months (range of 1.8-27.8 months) and an overall survival of 11.5 months (range of 3->28.0 months) from trial enrollment. No serious adverse events related to the drug combination were observed. Compared to pre-treatment baseline, circulating MDSCs were found to be higher after surgery in the 150 mg treatment arm and lower in the 300 mg and 450 mg treatment arms. Increased cytotoxic immune infiltration was observed after low-dose capecitabine compared to untreated GBM patients in the 300 mg and 450 mg treatment arms. ConclusionsLow-dose, metronomic capecitabine in combination with bevacizumab is well tolerated in GBM patients and was associated with a reduction in circulating MDSC levels and an increase in cytotoxic immune infiltration into the tumor microenvironment. Trial registrationNCT02669173 FundingThis research was funded by the Cleveland Clinic, Case Comprehensive Cancer Center, Musella Foundation, and B*CURED. Capecitabine was provided in kind by Mylan Pharmaceuticals.

clinical trials↗

bioRxiv2018

Infectious bursal disease virus suppresses H9N2 avian influenza viral shedding in broiler chickens

Infectious bursal disease (Gumboro) virus causes immunosuppression in chickens, increasing their susceptibility to other viral and bacterial diseases and resulting in vaccination failure. In the present study, we investigated the immune-depressing effect of infectious bursal disease virus on H9N2 avian influenza viral infection in commercial broiler chickens. Chickens were divided into four groups. In group A, chickens were inoculated with Gumboro virus at 21 days of age and H9N2 influenza virus 5 days later. Groups B and C only received influenza virus at 26 days of age and Gumboro virus at 21 days, respectively. Chickens in the control group (D) were inoculated with normal saline at the same times.\n\nTissue samples from different organs were collected on days 1, 3, 6, 9, and 12 after H9N2 infection. Macroscopic observation showed bursal disease lesions in groups A and C, including swollen bursa with the presence of gelatinous exudates, hemorrhages in the thigh muscle, edema, and nephritis.\n\nReverse transcription polymerase chain reaction was used to study H9N2 influenza virus dissemination, and quantitative reverse transcription polymerase chain reaction to determine viral genome copy number in different organs. A considerable titer of avian influenza virus was found in the trachea, lungs, cecal tonsils, spleens, and feces of infected chickens. The genome copy number of the virus in the trachea and lungs of group A was significantly higher than that in group B on the first day after inoculation. However, our method did not detect the avian influenza virus genome in group A. In conclusion, we suggest that pre-exposure to Gumboro virus at 3 weeks of age reduces the replication and shedding of H9N2 in broiler chicken.

microbiology↗