Biology subjects

Israel, A.

Publications and source records attributed to Israel, A..

11 recordsLinked to original sources

bioRxiv2026

Optical Spectral Fingerprinting Enables Sensitive Detection of Anthracycline Chemotherapeutics in Synthetic Clinical Biofluids

Anthracycline chemotherapeutics are commonly used as frontline treatments for a wide array of cancers. However, their administration to patients results in substantial side effects, primarily cardiotoxicity, as well as myelosuppression and gastrointestinal toxicity. Current clinical management of such side effects is solely based on a lifetime dosage limit, which inhibits their anti-tumor efficacy. Many individualized factors, including age, family history of cardiovascular disease, treatment regimen, and other co-morbidities influence drug pharmacology. Despite this heterogeneity, there is no method for determining actual organ or tumor exposure to the treatment in an individual. Here, we developed an optical nanosensor array for four anthracyclines--doxorubicin, daunorubicin, epirubicin, and idarubicin. We used single-walled carbon nanotubes as the signal transducer due to their tunable near-infrared fluorescence. We screened twelve distinct ssDNA sequences paired with seven SWCNT (n,m) species at increasing concentrations of each of the four anthracyclines. The spectral responses were then used to develop machine learning-based classification models to identify different anthracycline types and concentrations. The optimized extreme gradient boosting model was able to classify high levels of each anthracycline with 100% accuracy. Concentration-based classification by PCA was performed for each anthracycline, distinguishing low ([≤] 5 {micro}M) and high (> 5 {micro}M) concentrations. Finally, we validated the sensor performance using synthetic urine and sweat. Our findings demonstrate the potential of carbon nanotube-based sensor array to measure the pharmacokinetics of anthracyclines in patients with the goal of enhancing anti-tumor efficacy and monitoring off-target toxicities.

bioengineering↗

bioRxiv2026

Selective and robust dopamine detection is enabled by aptamer-SWCNT optical sensors in physiological media

Monitoring dopamine in complex biological environments is essential for understanding neurological disorders and disease diagnosis, though it presents a unique chemical challenge. In this work, we rationally designed several single-walled carbon nanotube (SWCNT)-based near-infrared fluorescent sensors for dopamine using ssDNA aptamers as selective molecular recognition elements. The performance of three dopamine-selective aptamer-SWCNT hybrids and sensitive but non-selective (GT)10-SWCNT constructs were evaluated and compared for their magnitude of response, sensitivity, and selectivity to dopamine. We performed these studies in buffer, in complex media with noradrenaline and serotonin, and in synthetic cerebrospinal fluid. We evaluated sensor constructs alone, with heat + divalent cation addition, and with four different molecular passivation agents. Ultimately, sensors passivated with bovine serum albumin (BSA) demonstrated strong selectivity for dopamine relative to noradrenaline, serotonin, and ascorbic acid, with a greater magnitude of response compared to (GT)10-SWCNT. Concentration-response curves in PBS, in a serotonin and noradrenaline solution, and artificial cerebrospinal fluid (aCSF) revealed dynamic ranges between 30 and 200 nM, and we found that the response occurs within five minutes. Together, these results demonstrate that dopamine aptamer-SWCNT sensors enable more selective and robust optical detection in complex biological environments.

bioengineering↗

bioRxiv2026

High-throughput SWCNT NIR-II screening enables cell and in vivo applications

Diagnostic sensor development and clinical translation lag, in part, due to a lack of rapid, high-throughput screening methodology. Optimization of high-throughput sensor development and deployment will likely help in expediting tools toward the clinic. To address this issue, we optimized high-throughput screening parameters using a near-infrared (NIR-II) plate reader attached to an external probe for in vivo testing. We assessed spectroscopy parameters to improve speed and precision in screening a single-walled carbon nanotube (SWCNT)-based optical sensor. To do so, we assessed the appropriate well plate specifications, including laser power, excitation wavelength, exposure time, and focal height parameters for SWCNT-based optical sensor development. We also used the plate reader to screen fluorescent SWCNT which were endocytosed by a macrophage cell line. We then performed NIR probe spectroscopy to assess SWCNT embedded within a methylcellulose hydrogel. Finally, we used the NIR probe to measure SWCNT center wavelength and intensity from live immunocompetent mice. We anticipate that this framework may be broadly applicable to the development of near infrared nanosensors with the potential for more rapid clinical diagnostic translation.

bioengineering↗

bioRxiv2026

Screening Molecular Recognition Element-Based SWCNT Optical Sensors for the Inflammatory Cytokine TNF-α

TNF- (Tumor Necrosis Factor) is a proinflammatory cytokine that amplifies inflammatory response and promotes leukocyte recruitment. TNF- is primarily produced by activated macrophages, among others, in response to infection, inflammation, or tissue damage. Given its central role in normal and abnormal immune responses, it is the target of several therapeutics, such as adalimumab and etanercept. TNF- is also a prognostic and diagnostic biomarker associated with Rheumatoid Arthritis, Alzheimers disease, Multiple Sclerosis, several kidney diseases, several cancers, Type 2 diabetes, sepsis, and others. Spatial quantification of TNF- in disease models can also be a powerful tool to understand the contributions of inflammatory processes to disease progression. Single-walled carbon nanotubes (SWCNT) are cylindrical carbon lattices that emit distinct near-infrared bandgap photoluminescence. In this work, we evaluated three aptamer-based sensor constructs, plus an additional two iterations of one aptamer sequence, and two antibody-based sensor constructs for TNF- that use SWCNT near-infrared photoluminescence signal transduction. Several, but not all, of these aptamer and antibody-based sensors sensitively and selectively detected TNF- in serum in a physiologically relevant range, and we found that their sensing was improved by both passivation and incorporating an exogenous quencher onto the aptamer sequence. Specifically, we found that modification of one aptamer sequence with a Black Hole Quencher induced selective detection in serum when passivated with poly-L-Lysine. This study highlights the importance, and challenges, of translating previously-validated molecular recognition elements to new detection conditions, in this case on the surface of SWCNT and in challenging serum conditions. It also validated a lead sensor construct that builds upon constructs that failed in serum. We anticipate that the sensors evaluated here will have utility in both the diagnosis and study of inflammation-driven chronic disease, while the sensor assessment framework will help drive the broader field of molecularly specific diagnostics.

bioengineering↗

bioRxiv2025

Multiplexed Molecularly-Specific SWCNT Cytokine Sensing is Enabled and Enhanced by Amine-Functionalized DNA Aqueous Two-Phase Extraction

Single-walled carbon nanotubes (SWCNT) are versatile building blocks for optical sensors. Their carbon lattice structure, denoted by chiral (n,m) indices, determines the wavelength of their near infrared fluorescence emission. Commercially available SWCNT are polydisperse, containing many (n,m) species with overlapping fluorescence peaks, leading to spectral congestion. Aqueous two-phase extraction (ATPE) has emerged as a valuable tool to sort SWCNT according to their chiral structure and promises improved nanosensor performance as well as unique opportunities for multiplexing. Previous applications of ATPE have enabled ratiometric sensors, but simultaneous detection of multiple analytes using distinct SWCNT chiralities has yet to be realized. This hurdle is largely due to the contrasting surface chemistries needed for ATPE sorting and those needed for biosensing applications. In this work, we introduce a method for purifying multiple chiralities of SWCNT which can be functionalized with molecularly specific antibodies to create a multiplexed sensor platform. We utilize aminated DNA (DNA-NH2), which serves as both a conduit for ATPE sorting and an intermediate linker for later antibody conjugation, to realize this goal. We demonstrate that chemically modified DNA enables ATPE sorting, supporting the broad future utility of the technique. We further show that chirality-sorted SWCNT-DNA-NH2 serve as excellent base constructs for antibody conjugation, forming highly specific sensors with enhanced optical properties (compared to unsorted SWCNT sensors). Importantly, one batch of monochiral base constructs can be functionalized with different antibodies towards different biological applications. Finally, we show that we can sort and functionalize two separate SWCNT chiralities and combine them together to create a multiplexed sensor platform where each peak responds distinctly to its target. There are vast opportunities for expansion of this work through the use of alternative DNA sequences to enable sorting, various SWCNT chiralities, and virtually any commercially available antibody for molecular recognition.

bioengineering↗

bioRxiv2023

Non-indigenous seaweeds in the Northeast Atlantic Ocean, the Mediterranean Sea and Macaronesia: a critical synthesis of diversity, spatial and temporal patterns

Effective monitoring and combatting the effect of non-indigenous seaweeds relies on a solid confirmation of the non-indigenous status of the species. We critically analysed the status of presumed non-indigenous seaweed species reported from the Mediterranean Sea, the Northeast Atlantic Ocean and Macaronesia, resulting in a list of 140 species whose non-indigenous nature is undisputed. For an additional 87 species it is unclear if they are native or non-indigenous (cryptogenic species) or their identity requires confirmation (data deficient species). We discuss the factors underlying both taxonomic and biogeographic uncertainties and outline recommendations to reduce uncertainty about the non-indigenous status of seaweeds. Our dataset consisted of over 19,000 distribution records, half of which can be attributed to only five species (Sargassum muticum, Bonnemaisonia hamifera, Asparagopsis armata, Caulerpa cylindracea and Colpomenia peregrina), while 56 species (40%) are recorded no more than once or twice. In addition, our analyses revealed considerable variation in the diversity of non-indigenous species between the geographic regions. The Eastern Mediterranean Sea is home to the largest fraction of non-indigenous seaweed species, the majority of which have a Red Sea or Indo-Pacific origin and have entered the Mediterranean Sea mostly via the Suez Canal. Non-indigenous seaweeds with native ranges situated in the Northwest Pacific make up a large fraction of the total in the Western Mediterranean Sea, Lusitania and Northern Europe, followed by non-indigenous species with a presumed Australasian origin. Uncertainty remains, however, regarding the native range of a substantial fraction of non-indigenous seaweeds in the study area. In so far as analyses of first detections can serve as a proxy for the introduction rate of non-indigenous seaweeds, these do not reveal a decrease in the introduction rate, indicating that the current measures and policies are insufficient to battle the introduction and spread of non-indigenous species in the study area. HighlightsO_LINon-indigenous seaweed species in the Northeast Atlantic Ocean, the Mediterranean Sea and Macaronesia are critically reanalysed. C_LIO_LI>19,000 distribution records revealed considerable variation in diversity of non-indigenous seaweed species in the study area. C_LIO_LITaxonomic and biogeographic uncertainties hamper a critical evaluation of the non-indigenous status of many seaweed species. C_LI

plant biology↗

bioRxiv2022

Reduced fibrous capsule elastic fibers of biologic ECM-enveloped CIEDs in minipigs fitted with a compression mechanics model

BACKGROUNDFibrous capsules (Fb) in response to cardiovascular implantable electronic devices (CIEDs), including a pacemaker (P) system, can produce patient discomfort and difficulties in revision surgery due partially to their increased compressive strength, previously linked to elevated tissue fibers. OBJECTIVETo quantify structural proteins, determine if biologic extracellular matrix-enveloped CIEDs (PECM) caused differential Fb properties, and to implement a realistic mechanical model. METHODSRetrieved Fb (-P and -PECM) from minipigs were subjected to biomechanical (shear oscillation and uniaxial compression) and histological (collagen I and elastin) analyses. RESULTSFb-PECM showed significant decreases compared to Fb-P in: low strain-loss modulus (390 vs. 541 Pa) across angular frequencies, high strain-compressive elastic modulus (1043 vs. 2042 kPa), and elastic fiber content (1.92 vs. 3.15 g/mg tissue). Decreases in elastin were particularly noted closer to the implants surface (Fb-PECM = 71% vs. Fb-P = 143% relative to dermal elastin at mid-tangential sections) and verified with a solid mechanics hyperelasticity with direction-dependent fiber viscoelasticity compression simulation (r2 [≥] 98.9%). CONCLUSIONSThe biologic envelope composed of decellularized porcine small intestine submucosa ECM for CIEDs promoted fibrous tissues with less elastic fibers. Novel compression modeling analyses directly correlated this singular reduction to more desirable subcutaneous tissue mechanics.

bioengineering↗

bioRxiv2022

Phenotyping technology for assessing protein content in seaweed by field spectroscopy and a machine learning algorithm

Determining seaweed protein concentration and the associated phenotype is critical for food industries that require precise tools to moderate concentration fluctuations and attenuate risks. Algal protein extraction and profiling have been widely investigated, but content determination involves a costly, time-consuming, and high-energy, laboratory-based fractionation technique. The present study examines the potential of field spectroscopy technology as a precise, high-throughput, non-destructive tool for on-site detection of red seaweed protein concentration. By using information from a large dataset of 144 Gracilaria sp. specimens, studied in a land-based cultivation set-up, under six treatment regimes during two cultivation seasons, and an artificial neural network, machine learning algorithm and diffuse visible-near infrared reflectance spectroscopy, predicted protein concentrations in the algae were obtained. The prediction results were highly accurate (R2 = 0.95; RMSE = 0.84), exhibiting a high correlation with the analytically determined values. External validation of the model derived from a separate trial, exhibited even better results (R2 = 0.99; RMSE = 0.45). This model, trained to convert phenotypic spectral measurements and pigment intensity into accurate protein content predictions, can be adapted to include diversified algae species and usages. HighlightNon-destructive determination of protein content in the edible red seaweed Gracilaria sp. by in-situ, VIS-NIR spectroscopy and a machine learning algorithm.

biochemistry↗

bioRxiv2021

RNA-sequencing reveals a gene expression signature in skeletal muscle of a mouse model of age-associated post-operative functional decline

This study aimed to characterize the effects of laparotomy on post-operative physical function and skeletal muscle gene expression in C57BL/6N mice at 3, 20 and 24 months of age to investigate late-life vulnerability and resiliency to acute surgical stress. Pre- and post-operative physical functioning were assessed by forelimb grip strength and motor coordination. Laparotomy induced an age-associated post-operative decline in forelimb grip strength that was greatest in the oldest mice. In contrast, while motor coordination declined with increasing age at baseline, it was unaffected by laparotomy. Moreover, baseline physical function as stratified by motor coordination performance (low vs. high functioning) in 24-month-old mice did not differentially affect post-laparotomy reduction in grip strength. RNA sequencing of soleus muscles showed that laparotomy induced age-associated differential gene expression and canonical pathway activation with the greatest effects in the youngest mice. Examples of such age-associated, metabolically important pathways that were only activated in the youngest mice after laparotomy included oxidative phosphorylation and NRF2-mediated oxidative stress response. Analysis of lipid mediators in serum and gastrocnemius muscle showed alterations in profiles of these mediators during aging and confirmed an association between such changes and functional status in gastrocnemius muscle. These findings demonstrate a mouse model of laparotomy which recapitulated some features of post-operative skeletal muscle decline in older adults following surgery, and identified age-associated, laparotomy-induced molecular signatures in skeletal muscles. Future research can build upon this mouse model to study molecular mechanisms of late-life vulnerability to acute surgical stress and resiliency to counter surgery-induced physical decline.

molecular biology↗

bioRxiv2021

Bioelectricity generation from live marine photosynthetic macroalgae

Conversion of solar energy into electrical current by photosynthetic organisms has the potential to produce clean energy. Previously reported bio-photoelectrochemical cells (BPECs) have utilized unicellular photosynthetic microorganisms. In this study, we describe for the first time BPECs that utilize intact live marine macroalgae (seaweeds) in natural seawater or saline buffer or natural seawater. The BPECs produce electrical currents from of >50mA/cm2, from both light-dependent (photosynthesis) and light independent processes. These values are significantly greater than the current densities that have been reported for single-cell microorganisms. The photocurrent is inhibited by the Photosystem II inhibitor DCMU, indicating that the source of light-driven electrons is from water oxidation via NADPH and other reduced molecules. We show here that intact seaweed cultures can be used in a large-scale BPEC containing seawater that produces bias-free photocurrent. The ability to produce bioelectricity from intact seaweeds may pave the way to future development of a low-cost energy technology using BPECs.

bioengineering↗

bioRxiv2020

Identification and characterization of distinct murine brown adipocyte lineages

Brown adipose tissue (BAT) plays an important role in the regulation of body weight and glucose homeostasis. While increasing evidence supports white adipose tissue heterogeneity, little is known about heterogeneity within murine BAT. Using single cell RNA sequencing of the stromal vascular fraction of murine BAT and analysis of 67 brown preadipocyte and adipocyte clones we unravel heterogeneity within brown preadipocytes. Statistical analysis of gene expression profiles from these clones identifies markers distinguishing brown adipocyte lineages. We confirm the presence of distinct brown adipocyte populations in vivo using three identified markers; Eif5, Tcf25, and Bin1. Functionally, we demonstrate that loss of Bin1 enhances UCP1 expression and mitochondrial respiration, suggesting that Bin1 marks a dormant brown adipocyte type. The existence of multiple brown adipocyte lineages suggests distinct functional properties of BAT depending on its cellular composition, with potentially distinct function in thermogenesis and the regulation of whole body energy homeostasis.

cell biology↗