bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbial Assemblages and Metabolic Activity in Organic‐Rich Subterranean Estuaries: Impact of Climate and Land Use Changes
Authors: Adyasari Dini , Dimova Natasha T. , Ní Chadhain Sinéad M. , Waska Hannelore 
Published: March 2024

AbstractMicrobial communities in subterranean estuaries mediate biogeochemical reactions of coastal groundwater discharging into the oceans; however, studies on their response to abrupt environmental changes caused by climate and land use alterations are still limited. In this study, we conducted a controlled laboratory study using combined geochemical and metagenomic approaches to investigate microbial structures and their metabolic pathways under a wide range of nitrate () inputs, saline solutions, and incubation times. These factors served as proxies for land use, salinization of the shallow aquifer, and climate changes. We found a highly reducing habitat and an amplification of genes related to denitrification, sulfate reduction, and methanogenesis processes. Core communities consisting of Clostridia, Bacilli, Alphaproteobacteria, Gammaproteobacteria, and Desulfobaccia were observed across all treatments. The metabolic prediction of plant‐derived organic matter (i.e., tannin and lignin) degradation was not affected by inputs or salinity because of it being implemented by core communities and the abundance of electron donors and acceptors. Quantification of denitrification genes shows that they are susceptible to inputs and seawater ions. Long‐term incubation allowed sufficient time for microbes to degrade less labile DOM, promoting the re‐release of buried solid phase organic matter into the active carbon cycle and increasing the relative abundance of biofilm or spore‐forming taxa while decreasing that of rare taxa. Our results illustrate the sensitivity of microbial assemblages to environmental changes and their capacity to altering the C and N cycles in coastal areas, further affecting coastal water quality and ecosystem‐scale biogeochemistry.
Millennial‐Scale Carbon Flux Variability in the Subantarctic Pacific During Marine Isotope Stage 3 (57–29 ka)
Authors: Anderson H. J. , Chase Z. , Bostock H. C. , Noble T. L. , Shuttleworth R. , Taiapa B. , Chen W. H. , Ren H. , Jacobsen G. E. 
Published: March 2024

AbstractAntarctic ice cores reveal a glacial climate state during Marine Isotope Stage 3 (MIS‐3; 57–29 ka) punctuated by millennial‐scale warming events and pulses of CO2. This study further explores how changes in Southern Ocean carbon cycling contributed to these millennial‐scale fluctuations in climate. Evidence from South Atlantic sediment cores suggests that warming events were associated with decreased dust‐borne iron flux, reduced export production, and increased upwelling from the deep Southern Ocean (SO). These processes are considered to have contributed to rising atmospheric CO2 during periods of rapid warming. Here we investigate whether the same processes occurred in the southwest Pacific sector of the SO at TAN1106‐28. We show that reduced New Zealand glaciation and localized iron limitation in the southwest Pacific led to reduced export production during millennial‐scale warming events. Decreases in foraminifera‐bound δ15N during all MIS‐3 warming events may reflect increased nutrient supply by upwelling. Increased calcium carbonate flux during MIS‐3 warming events likely reflects coccolithophore production in response to sea surface temperatures, which, would increase carbonate counter pump strength and reduce CO2 sequestration. Concomitant decreases in bottom water oxygen, inferred from redox‐sensitive U and Mn sediment concentrations, and increases in the 14C age of deep waters, suggest that old, nutrient‐rich waters influenced southwest Pacific middepth waters during warming events. This signature may reflect an expansion of Pacific Deep Water into the SO during warming. Taken together, our multi‐proxy data set reveals that the southwest subantarctic Pacific acted as a source of CO2 during millennial‐scale warming events of MIS‐3.
β-Receptor blocker enhances the anabolic effect of PTH after osteoporotic fracture
Authors: Huang Jie , Wu Tong , Jiang Yi-Rong , Zheng Xuan-Qi , Wang Huan , Liu Hao , Wang Hong , Leng Hui-Jie , Fan Dong-Wei , Yuan Wan-Qiong , Song Chun-Li 
Published: March 2024

AbstractThe autonomic nervous system plays a crucial role in regulating bone metabolism, with sympathetic activation stimulating bone resorption and inhibiting bone formation. We found that fractures lead to increased sympathetic tone, enhanced osteoclast resorption, decreased osteoblast formation, and thus hastened systemic bone loss in ovariectomized (OVX) mice. However, the combined administration of parathyroid hormone (PTH) and the β-receptor blocker propranolol dramatically promoted systemic bone formation and osteoporotic fracture healing in OVX mice. The effect of this treatment is superior to that of treatment with PTH or propranolol alone. In vitro, the sympathetic neurotransmitter norepinephrine (NE) suppressed PTH-induced osteoblast differentiation and mineralization, which was rescued by propranolol. Moreover, NE decreased the PTH-induced expression of Runx2 but enhanced the expression of Rankl and the effect of PTH-stimulated osteoblasts on osteoclastic differentiation, whereas these effects were reversed by propranolol. Furthermore, PTH increased the expression of the circadian clock gene Bmal1, which was inhibited by NE-βAR signaling. Bmal1 knockdown blocked the rescue effect of propranolol on the NE-induced decrease in PTH-stimulated osteoblast differentiation. Taken together, these results suggest that propranolol enhances the anabolic effect of PTH in preventing systemic bone loss following osteoporotic fracture by blocking the negative effects of sympathetic signaling on PTH anabolism.
Spatial relationships in the urothelial and head and neck tumor microenvironment predict response to combination immune checkpoint inhibitors
Authors: Gil-Jimenez Alberto , van Dijk Nick , Vos Joris L. , Lubeck Yoni , van Montfoort Maurits L. , Peters Dennis , Hooijberg Erik , Broeks Annegien , Zuur Charlotte L. , van Rhijn Bas W. G. , Vis Daniel J. , van der Heijden Michiel S. , Wessels Lodewyk F. A. 
Published: March 2024

AbstractImmune checkpoint inhibitors (ICI) can achieve remarkable responses in urothelial cancer (UC), which may depend on tumor microenvironment (TME) characteristics. However, the relationship between the TME, usually characterized by immune cell density, and response to ICI is unclear. Here, we quantify the TME immune cell densities and spatial relationships (SRs) of 24 baseline UC samples, obtained before pre-operative combination ICI treatment, using multiplex immunofluorescence. We describe SRs by approximating the first nearest-neighbor distance distribution with a Weibull distribution and evaluate the association between TME metrics and ipilimumab+nivolumab response. Immune cell density does not discriminate between response groups. However, the Weibull SR metrics of CD8+ T cells or macrophages to their closest cancer cell positively associate with response. CD8+ T cells close to B cells are characteristic of non-response. We validate our SR response associations in a combination ICI cohort of head and neck tumors. Our data confirm that SRs, in contrast to density metrics, are strong biomarkers of response to pre-operative combination ICIs.
Effective light cone and digital quantum simulation of interacting bosons
Authors: Kuwahara Tomotaka , Vu Tan Van , Saito Keiji 
Published: March 2024

AbstractThe speed limit of information propagation is one of the most fundamental features in non-equilibrium physics. The region of information propagation by finite-time dynamics is approximately restricted inside the effective light cone that is formulated by the Lieb-Robinson bound. To date, extensive studies have been conducted to identify the shape of effective light cones in most experimentally relevant many-body systems. However, the Lieb-Robinson bound in the interacting boson systems, one of the most ubiquitous quantum systems in nature, has remained a critical open problem for a long time. This study reveals a tight effective light cone to limit the information propagation in interacting bosons, where the shape of the effective light cone depends on the spatial dimension. To achieve it, we prove that the speed for bosons to clump together is finite, which in turn leads to the error guarantee of the boson number truncation at each site. Furthermore, we applied the method to provide a provably efficient algorithm for simulating the interacting boson systems. The results of this study settle the notoriously challenging problem and provide the foundation for elucidating the complexity of many-body boson systems.
Parechovirus infection in human brain organoids: host innate inflammatory response and not neuro-infectivity correlates to neurologic disease
Authors: Capendale Pamela E. , García-Rodríguez Inés , Ambikan Anoop T. , Mulder Lance A. , Depla Josse A. , Freeze Eline , Koen Gerrit , Calitz Carlemi , Sood Vikas , Vieira de Sá Renata , Neogi Ujjwal , Pajkrt Dasja , Sridhar Adithya , Wolthers Katja C. 
Published: March 2024

AbstractPicornaviruses are a leading cause of central nervous system (CNS) infections. While genotypes such as parechovirus A3 (PeV-A3) and echovirus 11 (E11) can elicit severe neurological disease, the highly prevalent PeV-A1 is not associated with CNS disease. Here, we expand our current understanding of these differences in PeV-A CNS disease using human brain organoids and clinical isolates of the two PeV-A genotypes. Our data indicate that PeV-A1 and A3 specific differences in neurological disease are not due to infectivity of CNS cells as both viruses productively infect brain organoids with a similar cell tropism. Proteomic analysis shows that PeV-A infection significantly alters the host cell metabolism. The inflammatory response following PeV-A3 (and E11 infection) is significantly more potent than that upon PeV-A1 infection. Collectively, our findings align with clinical observations and suggest a role for neuroinflammation, rather than viral replication, in PeV-A3 (and E11) infection.
The binding and mechanism of a positive allosteric modulator of Kv3 channels
Authors: Liang Qiansheng , Chi Gamma , Cirqueira Leonardo , Zhi Lianteng , Marasco Agostino , Pilati Nadia , Gunthorpe Martin J. , Alvaro Giuseppe , Large Charles H. , Sauer David B. , Treptow Werner , Covarrubias Manuel 
Published: March 2024

AbstractSmall-molecule modulators of diverse voltage-gated K+ (Kv) channels may help treat a wide range of neurological disorders. However, developing effective modulators requires understanding of their mechanism of action. We apply an orthogonal approach to elucidate the mechanism of action of an imidazolidinedione derivative (AUT5), a highly selective positive allosteric modulator of Kv3.1 and Kv3.2 channels. AUT5 modulation involves positive cooperativity and preferential stabilization of the open state. The cryo-EM structure of the Kv3.1/AUT5 complex at a resolution of 2.5 Å reveals four equivalent AUT5 binding sites at the extracellular inter-subunit interface between the voltage-sensing and pore domains of the channel’s tetrameric assembly. Furthermore, we show that the unique extracellular turret regions of Kv3.1 and Kv3.2 essentially govern the selective positive modulation by AUT5. High-resolution apo and bound structures of Kv3.1 demonstrate how AUT5 binding promotes turret rearrangements and interactions with the voltage-sensing domain to favor the open conformation.
Flexible temperature-pressure dual sensor based on 3D spiral thermoelectric Bi2Te3 films
Authors: Yu Hailong , Hu Zhenqing , He Juan , Ran Yijun , Zhao Yang , Yu Zhi , Tai Kaiping 
Published: March 2024

AbstractDual-parameter pressure-temperature sensors are widely employed in personal health monitoring and robots to detect external signals. Herein, we develop a flexible composite dual-parameter pressure-temperature sensor based on three-dimensional (3D) spiral thermoelectric Bi2Te3 films. The film has a (000l) texture and good flexibility, exhibiting a maximum Seebeck coefficient of −181 μV K–1 and piezoresistance gauge factor of approximately −9.2. The device demonstrates a record-high temperature-sensing performance with a high sensing sensitivity (−426.4 μV K−1) and rapid response time (~0.95 s), which are better than those observed in most previous studies. In addition, owing to the piezoresistive effect in the Bi2Te3 film, the 3D-spiral deviceexhibits significant pressure-response properties with a pressure-sensing sensitivity of 120 Pa–1. This innovative approach achieves high-performance dual-parameter sensing using one kind of material with high flexibility, providing insight into the design and fabrication of many applications, such as e-skin.
GAS41 modulates ferroptosis by anchoring NRF2 on chromatin
Authors: Wang Zhe , Yang Xin , Chen Delin , Liu Yanqing , Li Zhiming , Duan Shoufu , Zhang Zhiguo , Jiang Xuejun , Stockwell Brent R. , Gu Wei 
Published: March 2024

AbstractYEATS domain-containing protein GAS41 is a histone reader and oncogene. Here, through genome-wide CRISPR-Cas9 screenings, we identify GAS41 as a repressor of ferroptosis. GAS41 interacts with NRF2 and is critical for NRF2 to activate its targets such as SLC7A11 for modulating ferroptosis. By recognizing the H3K27-acetylation (H3K27-ac) marker, GAS41 is recruited to the SLC7A11 promoter, independent of NRF2 binding. By bridging the interaction between NRF2 and the H3K27-ac marker, GAS41 acts as an anchor for NRF2 on chromatin in a promoter-specific manner for transcriptional activation. Moreover, the GAS41-mediated effect on ferroptosis contributes to its oncogenic role in vivo. These data demonstrate that GAS41 is a target for modulating tumor growth through ferroptosis. Our study reveals a mechanism for GAS41-mediated regulation in transcription by anchoring NRF2 on chromatin, and provides a model in which the DNA binding activity on chromatin by transcriptional factors (NRF2) can be directly regulated by histone markers (H3K27-ac).
Focal adhesions contain three specialized actin nanoscale layers
Authors: Kumari Reena , Ven Katharina , Chastney Megan , Kokate Shrikant B. , Peränen Johan , Aaron Jesse , Kogan Konstantin , Almeida-Souza Leonardo , Kremneva Elena , Poincloux Renaud , Chew Teng-Leong , Gunning Peter W. , Ivaska Johanna , Lappalainen Pekka 
Published: March 2024

AbstractFocal adhesions (FAs) connect inner workings of cell to the extracellular matrix to control cell adhesion, migration and mechanosensing. Previous studies demonstrated that FAs contain three vertical layers, which connect extracellular matrix to the cytoskeleton. By using super-resolution iPALM microscopy, we identify two additional nanoscale layers within FAs, specified by actin filaments bound to tropomyosin isoforms Tpm1.6 and Tpm3.2. The Tpm1.6-actin filaments, beneath the previously identified α-actinin cross-linked actin filaments, appear critical for adhesion maturation and controlled cell motility, whereas the adjacent Tpm3.2-actin filament layer beneath seems to facilitate adhesion disassembly. Mechanistically, Tpm3.2 stabilizes ACF-7/MACF1 and KANK-family proteins at adhesions, and hence targets microtubule plus-ends to FAs to catalyse their disassembly. Tpm3.2 depletion leads to disorganized microtubule network, abnormally stable FAs, and defects in tail retraction during migration. Thus, FAs are composed of distinct actin filament layers, and each may have specific roles in coupling adhesions to the cytoskeleton, or in controlling adhesion dynamics.
Nucleus accumbens D1- and D2-expressing neurons control the balance between feeding and activity-mediated energy expenditure
Authors: Walle Roman , Petitbon Anna , Fois Giulia R. , Varin Christophe , Montalban Enrica , Hardt Lola , Contini Andrea , Angelo Maria Florencia , Potier Mylène , Ortole Rodrigue , Oummadi Asma , De Smedt-Peyrusse Véronique , Adan Roger A. , Giros Bruno , Chaouloff Francis , Ferreira Guillaume , de Kerchove d’Exaerde Alban , Ducrocq Fabien , Georges François , Trifilieff Pierre 
Published: March 2024

AbstractAccumulating evidence points to dysregulations of the Nucleus Accumbens (NAc) in eating disorders (ED), however its precise contribution to ED symptomatic dimensions remains unclear. Using chemogenetic manipulations in male mice, we found that activity of dopamine D1 receptor-expressing neurons of the NAc core subregion facilitated effort for a food reward as well as voluntary exercise, but decreased food intake, while D2-expressing neurons have opposite effects. These effects are congruent with D2-neurons being more active than D1-neurons during feeding while it is the opposite during running. Chronic manipulations of each subpopulations had limited effects on energy balance. However, repeated activation of D1-neurons combined with inhibition of D2-neurons biased behavior toward activity-related energy expenditure, whilst the opposite manipulations favored energy intake. Strikingly, concomitant activation of D1-neurons and inhibition of D2-neurons precipitated weight loss in anorexia models. These results suggest that dysregulations of NAc dopaminoceptive neurons might be at the core of EDs.
Asymmetric synthesis of P-stereogenic phosphindane oxides via kinetic resolution and their biological activity
Authors: Yin Long , Li Jiajia , Wu Changhui , Zhang Haoran , Zhao Wenchao , Fan Zhiyuan , Liu Mengxuan , Zhang Siqi , Guo Mengzhe , Dou Xiaowei , Guo Dong 
Published: March 2024

AbstractThe importance of P-stereogenic heterocycles has been widely recognized with their extensive use as privileged chiral ligands and bioactive compounds. The catalytic asymmetric synthesis of P-stereogenic phosphindane derivatives, however, remains a challenging task. Herein, we report a catalytic kinetic resolution of phosphindole oxides via rhodium-catalyzed diastereo- and enantioselective conjugate addition to access enantiopure P-stereogenic phosphindane and phosphindole derivatives. This kinetic resolution method features high efficiency (s factor up to >1057), excellent stereoselectivities (all >20:1 dr, up to >99% ee), and a broad substrate scope. The obtained chiral phosphindane oxides exhibit promising therapeutic efficacy in autosomal dominant polycystic kidney disease (ADPKD), and compound 3az is found to significantly inhibit renal cyst growth both in vitro and in vivo, thus ushering in a promising scaffold for ADPKD drug discovery. This study will not only advance efforts towards the asymmetric synthesis of challenging P-stereogenic heterocycles, but also surely inspire further development of P-stereogenic entities for bioactive small-molecule discovery.
Cellular mechanotransduction of human osteoblasts in microgravity
Authors: Wubshet Nadab H. , Cai Grace , Chen Samuel J. , Sullivan Molly , Reeves Mark , Mays David , Harrison Morgan , Varnado Paul , Yang Benjamin , Arreguin-Martinez Esmeralda , Qu Yunjia , Lin Shan-Shan , Duran Pamela , Aguilar Carlos , Giza Shelby , Clements Twyman , Liu Allen P. 
Published: March 2024

AbstractAstronauts experience significant and rapid bone loss as a result of an extended stay in space, making the International Space Station (ISS) the perfect laboratory for studying osteoporosis due to the accelerated nature of bone loss on the ISS. This prompts the question, how does the lack of load due to zero-gravity propagate to bone-forming cells, human fetal osteoblasts (hFOBs), altering their maturation to mineralization? Here, we aim to study the mechanotransduction mechanisms by which bone loss occurs in microgravity. Two automated experiments, microfluidic chips capable of measuring single-cell mechanics via aspiration and cell spheroids incubated in pressure-controlled chambers, were each integrated into a CubeLab deployed to the ISS National Laboratory. For the first experiment, we report protrusion measurements of aspirated cells after exposure to microgravity at the ISS and compare these results to ground control conducted inside the CubeLab. We found slightly elongated protrusions for space samples compared to ground samples indicating softening of hFOB cells in microgravity. In the second experiment, we encapsulated osteoblast spheroids in collagen gel and incubated the samples in pressure-controlled chambers. We found that microgravity significantly reduced filamentous actin levels in the hFOB spheroids. When subjected to pressure, the spheroids exhibited increased pSMAD1/5/9 expression, regardless of the microgravity condition. Moreover, microgravity reduced YAP expression, while pressure increased YAP levels, thus restoring YAP expression for spheroids in microgravity. Our study provides insights into the influence of microgravity on the mechanical properties of bone cells and the impact of compressive pressure on cell signaling in space.
Life cycle and techno-economic assessment of bioresource production from wastewater
Authors: Clack Kevin , Rajagopal Deepak , Hoek Eric M.V. 
Published: March 2024

AbstractThermochemical conversion technologies present an opportunity to flip the paradigm of wastewater biosolids management operations from energy-intense and expensive waste management processes into energy-positive and economical resource extraction centers. Herein, we present a uniform “grading framework” to consistently evaluate the environmental and commercial benefits of established and emerging wastewater biosolids management processes from a life cycle and techno-economic perspective. Application of this approach reveals that established wastewater biosolids management practices such as landfilling, land application, incineration, and anaerobic digestion, while commercially viable, offer little environmental benefit. On the other hand, emerging thermochemical bioresource recovery technologies such as hydrothermal liquefaction, gasification, pyrolysis, and torrefaction show potential to provide substantial economic and environmental benefit through the recovery of carbon and nutrients from wastewater biosolids in the form of biofuels, fertilizers, and other high-value products. Some emerging thermochemical technologies have developed beyond pilot scale although their commercial viability remains to be seen.
RoboEM: automated 3D flight tracing for synaptic-resolution connectomics
Authors: Schmidt Martin , Motta Alessandro , Sievers Meike , Helmstaedter Moritz 
Published: March 2024

AbstractMapping neuronal networks from three-dimensional electron microscopy (3D-EM) data still poses substantial reconstruction challenges, in particular for thin axons. Currently available automated image segmentation methods require manual proofreading for many types of connectomic analysis. Here we introduce RoboEM, an artificial intelligence-based self-steering 3D ‘flight’ system trained to navigate along neurites using only 3D-EM data as input. Applied to 3D-EM data from mouse and human cortex, RoboEM substantially improves automated state-of-the-art segmentations and can replace manual proofreading for more complex connectomic analysis problems, yielding computational annotation cost for cortical connectomes about 400-fold lower than the cost of manual error correction.