Biology subjects

Rubin, C.

Publications and source records attributed to Rubin, C..

4 recordsLinked to original sources

bioRxiv2023

Low intensity mechanical signals promote proliferation in a cell-specific manner: Tailoring a non-drug strategy to enhance biomanufacturing yields.

Biomanufacturing relies on living cells to produce biotechnology-based therapeutics, tissue engineering constructs, vaccines, and a vast range of agricultural and industrial products. With the escalating demand for these bio-based products, any process that could improve yields and shorten outcome timelines by accelerating cell proliferation would have a significant impact across the discipline. While these goals are primarily achieved using biological or chemical strategies, harnessing cell mechanosensitivity represents a promising - albeit less studied - physical pathway to promote bioprocessing endpoints, yet identifying which mechanical parameters influence cell activities has remained elusive. We tested the hypothesis that mechanical signals, delivered non-invasively using low-intensity vibration (LIV; <1g, 10-500Hz), will enhance cell expansion, and determined that any unique signal configuration was not equally influential across a range of cell types. Varying frequency, intensity, duration, refractory period, and daily doses of LIV increased proliferation in CHO-adherent cells (+79% in 96h) using a particular set of LIV parameters (0.2g, 500Hz, 3x30 min/d, 2h refractory period), yet this same mechanical input suppressed proliferation in CHO-suspension cells (-13%). Exposing these same CHO-suspension cells to distinct LIV parameters (30Hz, 0.7g, 2x60 min/d, 2h refractory period) increased proliferation by 210%. Particle image velocimetry combined with finite element modeling showed high transmissibility of these signals across fluids (>90%), and LIV effectively scaled up to T75 flasks. Ultimately, when LIV is tailored to the target cell population, its highly efficient transmission across media represents a means to non-invasively augment biomanufacturing endpoints for both adherent and suspended cells, and holds immediate applications, ranging from small-scale, patient-specific personalized medicine to large-scale commercial bio-centric production challenges.

bioengineering↗

bioRxiv2021

CytoPro: A computational platform for accurate and robust assessment of cell contributions in bulk expression from diverse tissues and conditions

Cells are the quanta unit of biology and their relative composition in a tissue is the prime driver of bulk tissue gene expression variation. When there is no cell information, deconvolution is an effective tool to achieve cell resolution, which provides important information for learning disease complexity and its interactions with treatments, drugs and/or the environment in a wide variety of contexts. Here we present CytoPro, a production-level tissue and condition-specific deconvolution platform, based on a large collection of human tissue-specific signatures derived from single and sorted cells. CytoPro infer per-sample multiple cell-type composition, given input bulk gene expression. CytoPro includes a rigorous QC pipeline for learning, generating and selecting signatures and performs internal automated validation using multiple QC test criteria including: Comparison to ground truth cytometry and pure sorted cells data, performance evaluation using simulated data including robustness to noise as well as agreement with biological expectations in validation datasets regarding genes and cells. We demonstrate that CytoPro outperforms existing deconvolution tools, in both accuracy and robustness. By exploring multiple datasets with predefined disease phenotypes, and analyzing a use-case of biological treatment response, we show the ability of CytoPro to flush out relevant cell biology in real pathological conditions.

bioinformatics↗

bioRxiv2019

Patterns and predictors of Staphylococcus aureus carriage during the first year of life; a longitudinal study

ObjectivesTo determine the patterns of S. aureus carriage in the first year of life, its determinants and dynamics of transmission between mothers and infants.\n\nMethodsProspective longitudinal cohort study of S. aureus carriage among mothers and their infants. Monthly screenings from pregnancy/birth through the first year of the infants life. Medical and lifestyle data was collected. Infant S. aureus carriage was detected by rectal and nasal swabs and maternal carriage by nasal swabs. Multivariate analysis and an NLMixed model were used to determine predictors of carriage and S. aureus persistence.\n\nResults130 S. aureus carrier women and their 132 infants were included in the study. 93% of the infants acquired S. aureus sometime during the first year of life, 64% of them acquired the maternal strain, mostly (66%) during the first month of life. 70 women (52.50%) and 17 infants (14%) carried S. aureus persistently. Early acquisition of S. aureus carriage was associated with longer duration of initial carriage and was the most significant predictor of S. aureus persistence, while day-care center attendance was negatively associated with persistent carriage.\n\nConclusionsEarly acquisition of S. aureus, mostly from the mother, is an important determinant of carriage persistence in infancy.

epidemiology↗

bioRxiv2018

Comparison of early effects of PCV7, PCV10 and PCV13 on S. pneumoniae (SP) nasopharyngeal carriage in a population based study; the Palestinian-Israeli Collaborative Research (PICR)

BackgroundPneumococcal conjugate vaccines (PCVs), PCV10 and PCV13, are currently used in different countries. We have previously reported the effectiveness of PCV7, following its introduction in Israel and before PCVs were introduced in Palestine. Here, we extended the study and compared the initial impact of PCV10 to that of PCV7/13.\n\nMethodsFour cross-sectional surveys of S. pneumoniae carriage among children <5y through 2009-2014 were preformed among two proximate populations, living under two distinct health authorities, with different vaccination policies. In East-Jerusalem (EJ), PCV7 was implemented in 2009 and replaced by PCV13 in late 2010, while in Palestine (PA), PCV10 was implemented in 2011.\n\nResultsA total of 1267 and 2414 children from EJ and PA were screened. Implementation of both PCV7 (in EJ) and PCV10 (in PA) did not affect overall S. pneumoniae carriage ([~]30%), but resulted in a significant decrease in carriage of VT7 strains. In the pre-vaccine era, VT7/VT13 strains consisted 47.0%/62.0% and 41.2%/54.8% of pneumococci in EJ and PA, respectively. A 48.6% and 53.9% decrease was observed within 3 years of PCV7 implementation in EJ (p= 0.001) and PCV10 in PA (p<0.0001), respectively. These vaccination policies also resulted in [~]50% reduction in VT13-added serotypes especially 6A (from 11.0% to 0.0% (EJ) and 9.5% to 4.9% (PA)). Three years after PCV13 implementation in EJ, an additional 67% decrease in VT13 strains was observed, yet an increase in serotype 3 was observed (0.0% to 3.4%, p=0.056). The prevalence of non-VT13 strains increased during the study period from 38% and 45.3% to 89.8% and 70.7%, in EJ and in PA respectively.\n\nConclusionsWithin the first three years following PCV implementation, we observed similar reductions in carriage of VT10 and VT13 strains with either vaccination policies, with no effect on overall carriage. Further follow-up is needed to compare the long-term effects.

microbiology↗