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Functional photoacoustic imaging: from nano- and micro- to macro-scale
No full textFunctional photoacoustic imaging is a promising biological imaging technique that offers such unique benefits as scalable resolution and imaging depth, as well as the ability to provide functional information. At nanoscale, photoacoustic imaging has provided super-resolution images of the surface light absorption characteristics of materials and of single organelles in cells. At the microscopic and macroscopic scales. photoacoustic imaging techniques have precisely measured and quantified various physiological parameters, such as oxygen saturation, vessel morphology, blood flow, and the metabolic rate of oxygen, in both human and animal subjects. This comprehensive review provides an overview of functional photoacoustic imaging across multiple scales, from nano to macro, and highlights recent advances in technology developments and applications. Finally, the review surveys the future prospects of functional photoacoustic imaging in the biomedical field
D-SPIN constructs gene regulatory network models from multiplexed scRNA-seq data revealing organizing principles of cellular perturbation response
No full textGene regulatory networks within cells modulate the expression of the genome in response to signals and changing environmental conditions. Reconstructions of gene regulatory networks can reveal the information processing and control principles used by cells to maintain homeostasis and execute cell-state transitions. Here, we introduce a computational framework, D-SPIN, that generates quantitative models of generegulatory networks from single-cell mRNA-seq data sets collected across thousands of distinct perturbation conditions. D-SPIN models the cell as a collection of interacting gene-expression programs, and constructs a probabilistic model to infer regulatory interactions between gene-expression programs and external perturbations. Using large Perturb-seq and drug-response datasets, we demonstrate that D-SPIN models reveal the organization of cellular pathways, sub-functions of macromolecular complexes, and the logic of cellular regulation of transcription, translation, metabolism, and protein degradation in response to gene knockdown perturbations. D-SPIN can also be applied to dissect drug response mechanisms in heterogeneous cell populations, elucidating how combinations of immunomodulatory drugs can induce novel cell states through additive recruitment of gene expression programs. D-SPIN provides a computational framework for constructing interpretable models of gene-regulatory networks to reveal principles of cellular information processing and physiological control
Complexities of the Turkey-Syria doublet earthquake sequence
No full textIn the early morning of February 6th, 2023, an M7.8 earthquake occurred in southeastern Türkiye near the northern border of Syria. The event initiated a complex sequence of aftershocks, including an M7.6 earthquake about 9 h later and 90 km to the north (Figures 1A and 1B). The earthquake sequence is also referred to as a strong doublet earthquake sequence. Aftershocks of the two strong earthquakes occurred along two separate branches of the East Anatolia Fault, with lengths of up to 300 km, and some aftershocks occurred in Syria (NEIC/USGS, 2023). The earthquake sequence caused significant losses to Türkiye and Syria, including over fifty thousand human lives and tens of billions of US dollars in damage to the economy, social infrastructure, and valuable historical sites,1 along with abundant evidence of surface ruptures, ground deformation and liquefied soils. The earthquake sequence also triggered extensive subaerial landslides, with about 100 identified by NASA from Planet Lab’s high-resolution satellite imagery, including several in the valley near Sarıseki. Very strong ground motion was observed at station 3126 in Antakya during the M7.8 earthquakes (Figure 1D), with horizontal acceleration greater than 1 g (normal gravitational value)
Targeting Sex Determination to Suppress Mosquito Populations
No full textEach year, hundreds of millions of people are infected with arboviruses such as dengue, yellow fever, chikungunya, and Zika, which are all primarily spread by the notorious mosquito Aedes aegypti. Traditional control measures have proven insufficient, necessitating innovations. In response, here we generate a next generation CRISPR-based precision-guided sterile insect technique (pgSIT) for Aedes aegypti that disrupts genes essential for sex determination and fertility, producing predominantly sterile males that can be deployed at any life stage. Using mathematical models and empirical testing, we demonstrate that released pgSIT males can effectively compete with, suppress, and eliminate caged mosquito populations. This versatile species-specific platform has the potential for field deployment to control wild populations, safely curtailing disease transmission
Hyperconnectivity of Two Separate Long-Range Cholinergic Systems Contributes to the Reorganization of the Brain Functional Connectivity during Nicotine Withdrawal in Male Mice
No full textChronic nicotine results in dependence with withdrawal symptoms on discontinuation of use, through desensitization of nicotinic acetylcholine receptors and altered cholinergic neurotransmission. Nicotine withdrawal is associated with increased whole-brain functional connectivity and decreased network modularity; however, the role of cholinergic neurons in those changes is unknown. To identify the contribution of nicotinic receptors and cholinergic regions to changes in the functional network, we analyzed the contribution of the main cholinergic regions to brain-wide activation of the immediate early-gene Fos during withdrawal in male mice and correlated these changes with the expression of nicotinic receptor mRNA throughout the brain. We show that the main functional connectivity modules included the main long-range cholinergic regions, which were highly synchronized with the rest of the brain. However, despite this hyperconnectivity, they were organized into two anticorrelated networks that were separated into basal forebrain-projecting and brainstem-thalamic-projecting cholinergic regions, validating a long-standing hypothesis of the organization of the brain cholinergic systems. Moreover, baseline (without nicotine) expression ofChrna2,Chrna3,Chrna10, andChrndmRNA of each brain region correlated with withdrawal-induced changes in Fos expression. Finally, by mining the Allen Brain mRNA expression database, we were able to identify 1755 gene candidates and three pathways (Sox2-Oct4-Nanog, JAK-STAT, and MeCP2-GABA) that may contribute to nicotine withdrawal-induced Fos expression. These results identify the dual contribution of the basal forebrain and brainstem-thalamic cholinergic systems to whole-brain functional connectivity during withdrawal; and identify nicotinic receptors and novel cellular pathways that may be critical for the transition to nicotine dependence
Vanadium oxide and a sharp onset of cold-trapping on a giant exoplanet
No full textThe abundance of refractory elements in giant planets can provide key insights into their formation histories. Owing to the low temperatures of the Solar System giants, refractory elements condense below the cloud deck, limiting sensing capabilities to only highly volatile elements. Recently, ultra-hot giant exoplanets have allowed for some refractory elements to be measured, showing abundances broadly consistent with the solar nebula with titanium probably condensed out of the photosphere. Here we report precise abundance constraints of 14 major refractory elements on the ultra-hot giant planet WASP-76b that show distinct deviations from proto-solar and a sharp onset in condensation temperature. In particular, we find nickel to be enriched, a possible sign of the accretion of the core of a differentiated object during the evolution of the planet. Elements with condensation temperatures below 1,550 K otherwise closely match those of the Sun before sharply transitioning to being strongly depleted above 1,550 K, which is well explained by nightside cold-trapping. We further unambiguously detect vanadium oxide on WASP-76b, a molecule long suggested to drive atmospheric thermal inversions, and also observe a global east–west asymmetry in its absorption signals. Overall, our findings indicate that giant planets have a mostly stellar-like refractory elemental content and suggest that temperature sequences of hot Jupiter spectra can show abrupt transitions wherein a mineral species is either present or completely absent if a cold trap exists below its condensation temperature
Evaluating the evidence for exponential quantum advantage in ground-state quantum chemistry
No full textDue to intense interest in the potential applications of quantum computing, it is critical to understand the basis for potential exponential quantum advantage in quantum chemistry. Here we gather the evidence for this case in the most common task in quantum chemistry, namely, ground-state energy estimation, for generic chemical problems where heuristic quantum state preparation might be assumed to be efficient. The availability of exponential quantum advantage then centers on whether features of the physical problem that enable efficient heuristic quantum state preparation also enable efficient solution by classical heuristics. Through numerical studies of quantum state preparation and empirical complexity analysis (including the error scaling) of classical heuristics, in both ab initio and model Hamiltonian settings, we conclude that evidence for such an exponential advantage across chemical space has yet to be found. While quantum computers may still prove useful for ground-state quantum chemistry through polynomial speedups, it may be prudent to assume exponential speedups are not generically available for this problem
Probing the nature of the low state in the extreme ultraluminous X-ray pulsar NGC 5907 ULX1
No full textNGC 5907 ULX1 is the most luminous ultra-luminous X-ray pulsar (ULXP) known to date, reaching luminosities in excess of 10⁴¹ erg s⁻¹. The pulsar is known for its fast spin-up during the on-state. Here, we present a long-term monitoring of the X-ray flux and the pulse period between 2003 and 2022. We find that the source was in an off- or low-state between mid-2017 to mid-2020. During this state, our pulse period monitoring shows that the source had spun down considerably. We interpret this spin-down as likely being due to the propeller effect, whereby accretion onto the neutron star surface is inhibited. Using state-of-the-art accretion and torque models, we use the spin-up and spin-down episodes to constrain the magnetic field. For the spin-up episode, we find solutions for magnetic field strengths of either around 10¹² G or 1013 G, however, the strong spin-down during the off-state seems only to be consistent with a very high magnetic field, namely, > 10¹³ G. This is the first time a strong spin-down is seen during a low flux state in a ULXP. Based on the assumption that the source entered the propeller regime, this gives us the best estimate so far for the magnetic field of NGC 5907 ULX1
Calcium signaling in chemotherapy-induced neuropathy
No full textAlterations in calcium (Ca²⁺) signaling is a major mechanism in the development of chemotherapy-induced peripheral neuropathy (CIPN), a side effect caused by multiple chemotherapy regimens. CIPN is associated with numbness and incessant tingling in hands and feet which diminishes quality of life during treatment. In up to 50% of survivors, CIPN is essentially irreversible. There are no approved, disease-modifying treatments for CIPN. The only recourse for oncologists is to modify the chemotherapy dose, a situation that can compromise optimal chemotherapy and impact patient outcomes. Here we focus on taxanes and other chemotherapeutic agents that work by altering microtubule assemblies to kill cancer cells, but also have off-target toxicities. There have been many molecular mechanisms proposed to explain the effects of microtubule-disrupting drugs. In neurons, an initiating step in the off-target effects of treatment by taxane is binding to neuronal calcium sensor 1 (NCS1), a sensitive Ca²⁺ sensor protein that maintains the resting Ca²⁺ concentration and dynamically enhances responses to cellular stimuli. The taxane/NCS1 interaction causes a Ca²⁺ surge that starts a pathophysiological cascade of consequences. This same mechanism contributes to other conditions including chemotherapy-induced cognitive impairment. Strategies to prevent the Ca²⁺ surge are the foundation of current work
Mantle-crust-interaction and subduction dynamics in Central Cameroon: Evidence from the Pan-African Linté microgranular magmatic enclaves (MMEs) and host syenite
No full textThe Central African Fold Belt (CAFB) in Cameroon is characterized by voluminous intrusive rocks hosting microgranular magmatic enclaves (MMEs) whose petrogenesis and tectonic implications remain unclear. Here, we present detailed geochronological and geochemical data of the host rocks and their MMEs from the Linté pluton in central Cameroon. The MMEs are finer-grained than their host syenite and both rocks are composed of alkali feldspar, plagioclase, biotite, amphibole and pyroxenes as main mineral phases. The enclaves show lower Mg#, total alkalis and transition elements contents, and are more HFSEs depleted than the host syenite. Both rocks are characterized by high-K, metaluminous I-type, alkaline to sub-alkaline and magnesian affinities. The Ti-in-zircon thermometer suggests crystallization temperatures of 615–1080 °C and 613–1008 °C for syenites and MMEs, respectively. Their zircon trace element distribution and patterns coupled with whole-rock geochemical features indicate that the Linté intrusive rocks were most likely originated from interaction of mantle-derived magma with crustal material. LA-ICP-MS U-Pb zircon analyses yield emplacement age of 599 ± 3 Ma and 597 ± 4 Ma for the host syenite and MMEs, respectively, indicating coeval crystallization date. Integrated whole rock geochemistry, U-Pb dating and Ti-in-zircon thermometry data indicate that the Linté syenite were probably formed from a mantle-derived ultrapotassic alkaline melt with significant crustal contribution, while MMEs are likely derived from a similar but separate melt with more fractionation and crustal contamination. The genesis of the host syenite and MMEs magmas started with break-off of the Congo plate after subduction and collision. This initiated an upwelling thermal pulse and underplating of mafic magma which led to partial melting of the Paleoproterozoic crust of the Central Cameroon