Biology subjects

Bianchi, D.

Publications and source records attributed to Bianchi, D..

10 recordsLinked to original sources

bioRxiv2026

SMIM1 drives an alternative iron uptake pathway

Iron is essential for numerous biological processes, and its abundance is critical in human cells to prevent anemia or toxic overload. Although transferrin receptor-mediated iron uptake is the canonical route, human cells also possess an unstudied alternative pathway. To reveal this missing mechanism, we developed a large-scale, gain-of-function approach to assign genes to a catalogue of quantitative cellular traits. Applying this genetic strategy, we identified SMIM1, the antigen responsible for the rare Vel blood group and a transmembrane protein with unknown function, as a key regulator of iron homeostasis. We found that SMIM1 expression completely suppresses the iron deficiency caused by transferrin receptor loss. Mechanistically, SMIM1 mediates iron uptake through clathrin-dependent endocytosis of hemoglobin (Hb). SMIM1 directly binds Hb via its extracellular HKCK motif, leading to its transport to lysosomes and subsequent iron release. In the human population, genetic variants in SMIM1 influence Hb levels and erythrocyte traits. SMIM1-deficient mice display iron deficiency in early erythroid precursors in response to erythropoietic stress, underscoring the physiological relevance of this process.

cell biology↗

bioRxiv2026

Epipelagic to mesopelagic variability of acoustic backscatter in the California Current

Mid-Trophic Level (MTL) organisms--including krill, forage fish, and mesopelagic fish-- are abundant in the California Current System (CCS) and play an essential role in transferring energy and biomass from primary producers to top predators. However, their spatiotemporal distribution and variability remain poorly understood, particularly with respect to vertical structure across epipelagic and mesopelagic habitats and coastal-offshore gradients. This lack of understanding emerges from both the complexity of MTL interactions with a heterogeneous environment and the challenges associated with sampling these organisms at high spatial and temporal resolution. To address this gap, we analyze 11 years of fisheries acoustic observations in the CCS (2006-2016) to characterize the spatiotemporal dynamics of MTLs as inferred from acoustic backscatter. Acoustic observations at 38 and 120 kHz, collected during day and night across depth strata from 15 to 495 m, reveal consistent cross-shore, seasonal, and latitudinal patterns in the backscatter of acoustically defined zooplankton, epipelagic fish, and mesopelagic fish communities. These patterns include: (1) weaker cross-shore gradients in mesopelagic relative to epipelagic communities; (2) a temporal succession among communities associated with seasonal upwelling; and (3) a multimodal latitudinal distribution with distinct coastal backscatter peaks. We further investigate relationships between acoustic backscatter and co-located environmental variables from in situ, remote sensing, and reanalysis products to elucidate plausible mechanisms underlying MTL dynamics. HighlightsO_LIFisheries acoustics resolve variability in mid-trophic communities C_LIO_LIEleven years of backscatter reveal consistent patterns in the California Current C_LIO_LIEpipelagic backscatter declines faster from the coast to offshore than mesopelagic C_LIO_LISeasonal changes in community composition are linked to upwelling dynamics C_LIO_LIBackscatter exhibits multimodal latitudinal distributions with distinct peaks C_LI

ecology↗

bioRxiv2026

Anti-inflammatory and pro-proliferative effects of fasudil in human trisomy 21 neural progenitor cells

Down syndrome (DS) results from trisomy for human chromosome 21 and is the most frequent genetic cause of intellectual disability. No effective treatments currently exist that improve neurodevelopment and cognition. Atypical brain development in individuals with DS is apparent before birth, which suggests that the optimal time to begin administration of therapies is prenatally. Human neural progenitor cell (NPC) cultures provide a tractable in vitro model system to examine the effects of trisomy 21 (T21) on neurodevelopment and to measure the effects of pharmacological interventions. Here we report the results of preclinical studies evaluating 24 candidate therapies. RNA-Seq analyses found that euploid and T21 NPCs showed different transcriptomic responses to five candidate pharmacotherapies. The Rho-associated coiled-coil kinase (ROCK) inhibitor fasudil increased proliferation of T21 NPCs, reduced expression of inflammatory pathway genes in T21 NPCs, and reduced markers of inflammation in LPS-stimulated microglia model systems. These results demonstrate that fasudil can alter multiple T21-associated abnormalities in a beneficial manner, suggesting that fasudil warrants further study as a candidate prenatal pharmacotherapy for DS.

pharmacology and toxicology↗

bioRxiv2026

Bacteroides intestinalis-Driven Arabinoxylan Fermentation Mitigates Inflammatory and Metabolic Dysfunction

Insufficient dietary fiber intake is closely linked to gut microbiome dysfunction and increased risk of noncommunicable diseases. Synergistic synbiotics, pairing defined microbes with their dietary substrates, offer a precise strategy to restore microbiome function. Here, we show that pairing the human colonic commensal Bacteroides intestinalis with insoluble wheat arabinoxylan (inWAX) yields pronounced metabolic and anti-inflammatory benefits. Using mono-associated gnotobiotic mice and high-fat diet-induced obese mice, we demonstrate that this synbiotic enhances resistance to intestinal inflammation and improves glucose homeostasis. Mechanistically, this synbiotic increases production of 6-hydroxylated bile acids with anti-diabetic and anti-steatotic effects. It also promotes microbial transformation of phenolic compounds and redirects protein metabolism toward neuroactive metabolites. These metabolic shifts are accompanied by transcriptional remodeling in the colon, spleen and liver, involving induction of genes essential for circadian rhythm, lipid metabolism, immune defense, and bile acid 6-hydroxylation. Notably, Y chromosome-linked genes associated with epigenetic regulation and protein turnover are also induced, suggesting a potential sex-specific response to synbiotics. Together, our findings establish a mechanistic framework for targeted synbiotic interventions to combat inflammatory and metabolic disorders.

microbiology↗

bioRxiv2025

The ecology of carbon sequestration in coastal upwelling ecosystems

The biological carbon pump (BCP) transports carbon fixed by phytoplankton into the deep ocean via multiple pathways and leads to net carbon dioxide sequestration. The BCP is very active in highly productive eastern boundary upwelling systems (EBUSs), however, the extent to which climate change will impact this key ecosystem service remains uncertain. While this review and synthesis focuses on results from the California Current Ecosystem (the most extensively studied EBUS), similarities and differences are also noted with the Benguela, Canary, and Humboldt ecosystems. We focus on vertical carbon export mediated by sinking particles (responsible for >half of the BCP in EBUSs), as well as subduction of organic matter and vertically migrating zooplankton and fish. We suggest that a plug-flow-reactor conceptual model can be used to link BCP results with physical circulation changes within EBUSs to predict whether climate change will lead to increased or decreased biologically mediated CO2 uptake.

ecology↗

bioRxiv2025

WEE1 inhibitors trigger GCN2-mediated activation of the integrated stress response

The WEE1 kinase negatively regulates CDK1/2 to control DNA replication and mitotic entry. Genetic factors that determine sensitivity to WEE1 inhibitors (WEE1i) are largely unknown. A genome-wide insertional mutagenesis screen revealed that mutation of EIF2A, a translation regulator, sensitized to WEE1i. Mechanistically, WEE1i treatment triggers a translational shut-down, which is lethal in combination with the reduced translation of EIF2AKO cells. A genome-wide CRISPR-Cas9 screen revealed that inactivation of integrated stress response (ISR) kinases GCN1/2 rescued WEE1i-mediated cytotoxicity. WEE1i induced GCN2 activation, ATF4 upregulation, and altered ribosome dynamics. Loss of the collided ribosome sensor ZNF598 conversely increased sensitivity to WEE1i. Notably, the ISR was not required for WEE1i to induce DNA damage, premature mitotic entry or sensitization to DNA-damaging chemotherapeutics. ISR activation was independent of CDK1/2 activation. Importantly, WEE1i-mediated ISR activation was independent of WEE1 presence, pointing at off-target effects, which are shared by multiple chemically distinct WEE1i. This response was also observed in peripheral blood mononuclear cells. Importantly, low-dose WEE1 inhibition did not induce ISR activation, while it still synergized with PKMYT1 inhibition. Taken together, WEE1i triggers toxic ISR activation and translational shutdown, which can be prevented by low-dose or combination treatments, while retaining the cell cycle checkpoint-perturbing effects.

cancer biology↗

bioRxiv2022

Patterns and drivers of the diving behavior of large pelagic predators

Many large pelagic predators, including shark, tuna, and billfish, periodically dive to deep oceanic layers, connecting the surface and mesopelagic ecosystems. However, the patterns and drivers of deep dives across species remain poorly understood. To close this gap, we conduct a meta-analysis of the diving behavior of 24 pelagic predator species from the global ocean, resulting in 671 independent diving depth estimates from 87 tagging studies. Our analysis reveals consistent large-scale patterns in diving depths, with predators diving deeper offshore and during the day, and shallower closer to the coast and during the night. Deep diving species show similar diving depths during the night, with deeper dives for sharks, and shallower dives for tuna and swordfish. These patterns are reversed during the day, widening the gap between day and night vertical ranges for these groups. In contrast, shallow diving species show smaller variations between day and night dives, with sharks diving slightly deeper on average, followed by tuna and billfish. Correlations with co-located environmental variables suggest an important predictive role for proxies of prey abundance and light availability, as well as variables that influence physiology, such as oxygen and temperature. These relationships are more robust for deep divers during the day, and shallow divers at night. Our analysis highlights the value of tagging observations for the development of a mechanistic, quantitative characterization of vertical habitat use of large marine predators and its environmental constraints.

ecology↗

bioRxiv2021

Movement shapes the structure of fish communities along a cross-shore section in the California Current

Pelagic fish communities are shaped by bottom-up and top-down processes, transport by currents, and active swimming. However, the interaction of these processes remains poorly understood. Here, we use a regional implementation of the APex ECOSystem Model (APECOSM), a mechanistic model of the pelagic food web, to investigate these processes in the California Current, a highly productive upwelling system characterized by vigorous mesoscale circulation. The model is coupled with an eddy-resolving representation of ocean currents and lower trophic levels, and is tuned to reproduce observed fish biomass from fisheries independent trawls. Several emergent properties of the model compare realistically with observations. First, the epipelagic community accounts for one order of magnitude less biomass than the vertically migratory community, and is composed by smaller species. Second, the abundance of small fish decreases from the coast to the open ocean, while the abundance of large fish remains relatively uniform. This in turn leads to flattening of biomass size-spectra away from the coast for both communities. Third, the model reproduces a cross-shore succession of small to large sizes moving offshore, consistent with observations of species occurrence. These cross-shore variations emerge in the model from a combination of: (1) passive offshore advection by the mean current, (2) active swimming towards coastal productive regions to counterbalance this transport, and (3) mesoscale heterogeneity that reduces the ability of organisms to return to coastal waters. Our results highlight the importance of passive and active movement in structuring the pelagic food web, and suggest that a correct representation of these processes is needed for realistic simulations with marine ecosystem models.

ecology↗

bioRxiv2020

Biogeochemical variability in the California Current System

The biological productivity and diversity of the California Current System (CCS) is at the leading edge of major emerging climate trends, including hypoxia and acidification. We present results from a hindcast simulation (reanalysis) of an eddy-resolving oceanic physical-biogeochemical model of the CCS, to characterize its mean state and its patterns and drivers of variability in marine biogeochemical and ecosystem processes from 1995-2010. This is a companion paper to a physical analysis in Renault et al. (2021). The model reproduces long-term mean distributions of key ecosystem metrics, including surface nutrients and productivity and subsurface O2 and carbonate undersaturation. The spatial patterns of Net Primary Productivity (NPP) are broadly consistent with measured and remotely sensed rates, and they reflect a predominant limitation by nitrogen, with seasonal and episodic limitation by Fe nearshore in the central CCS, and in the open ocean northern CCS. The vertical distribution of NPP is governed by the trade-off between nutrient and light limitation, a balance that reproduces and explains the observed spatial variations in the depth of the deep Chl maximum. The seasonal to interannual variability of biogeochemical properties and rates is also well captured by model simulations. Because of the prevailing nutrient limitation, fluctuations in the depth of the pycnocline and associated nutricline are the leading single factor explaining interannual variability in the interior biogeochemical state, and the relationships between density and biogeochemical rates and tracers are consistent between model and observations. The magnitude and relationship between density structure and biogeochemical processes is illustrated by the 1997-98 El Nino event, which faithfully reproduces the single largest deviation from the mean state in the simulated period. A slower decadal shoaling of the pycnocline also accounts for the concomitant trends in hypoxic and corrosive conditions on the shelf. The resulting variability is key to understanding the vulnerability of marine species to oceanic change, and to the detection of such changes, soon projected to exceed the range of conditions in the past century.

ecology↗

bioRxiv2018

Ensemble projections of global ocean animal biomass with climate change

Climate change is shifting the abundance and distribution of marine species with consequences for ecosystem functioning, seafood supply, management and conservation. Several approaches for future projection exist but these have never been compared systematically to assess their variability. We conducted standardized ensemble projections including 6 global fisheries and marine ecosystem models, forced with 2 Earth-system models and 4 emission scenarios in a fished and unfished ocean, to derive average trends and associated uncertainties. Without fishing, mean global animal biomass decreased by 5% ({+/-}4%) under low and 17% ({+/-}11%) under high emissions by 2100, primarily driven by increasing temperature and decreasing primary production. These climate-change effects were slightly weaker for larger animals and in a fished ocean. Considerable regional variation ranged from strong biomass increases in high latitudes to strong decreases in mid-low latitudes, with good model agreement on the direction of change but variable magnitude. Uncertainties due to differences among ecosystem or Earth-system models were similar, suggesting equal need for model improvement. Our ensemble projections provide the most comprehensive outlook on potential climate-driven ecological changes in the ocean to date. Realized future trends will largely depend on how fisheries and management adapt to these changes in a changing climate.

ecology↗