bluuebunny/crossref_metadata_2025 huggingface dataset:
The difficulties and path of China’s NGOs participating in marine plastic waste governance
Authors: Cui Ye
Published: March 2024

The problem of marine plastic waste is one of the most urgent issues in global ocean governance and has received much attention from the international community. In the marine plastic waste governance system, non-governmental organizations (NGOs) are indispensable actors with various advantages, playing a crucial role in mobilizing, supplementing, and implementing marine plastic waste governance. In China, NGOs have achieved rapid development over the past two decades and have participated in China’s marine plastic waste governance using political, social, and institutional approaches. However, compared with Western countries and large international NGOs, China’s NGOs still face many difficulties in participation, such as a shortage of funds and personnel, insufficient internal coordination and cooperation, limited participation channels, and a low level of internationalization. Therefore, the Chinese government and China’s NGOs should work together to take various measures to eliminate these difficulties to promote greater development of NGOs and better realize their contributions to marine plastic waste governance.
Utpal Dutt and Political Theatre in Postcolonial India
Authors: Sinha Roy Mallarika
Published: March 2024

Among the most significant playwrights and theatre-makers of postcolonial India, Utpal Dutt (1929–1993), was an early exponent of rethinking colonial history through political theatre. Dutt envisaged political theatre as part of the larger Marxist project, and his incorporation of new developments in Marxist thinking, including the contributions of Antonio Gramsci, makes it possible to conceptualise his protagonists as insurgent subalterns. A decolonial approach to staging history remained a significant element in Dutt's artistic project. This Element examines Dutt's passionate engagement with Marxism and explores how this sense of urgency was actioned through the writing and producing of plays about the peasant revolts and armed anti-colonial movements which took place during the period of British rule. Drawing on contemporary debates in political theatre regarding the autonomy of the spectator and the performance of history, the author locates Dutt's political theatre in a historical frame.
Decolonising African Theatre
Authors: Ravengai Samuel
Published: March 2024

Decolonisation can be pursued in different ways. After many years of developing a critical language to engage coloniality, the most urgent need in African theatre is to develop new theories and methods in our manufactories. This Element uses Afroscenology as a theory to read and comment on African theatre. The Element particularly focuses on the history of laboratories in which it was tested and emerged, the historicization of rombic theatre and the crafting of a theory of the playtext which has been named theatric theory to distinguish it from the Aristotelian dramatic theory. The second dimension of the theory is the performatic technique. This Element also explain Afrosonic mime through examples drawn from the workshops conducted in training performers.
Feminizing the City: Plato on Women, Masculinity, and Thumos
Authors: Ironside Kirsty , Wilburn Josh
Published: March 2024

This paper responds to two trends in debates about Plato's view of women in the Republic. First, many scholars argue or assume that Plato seeks to minimize the influence of femininity in the ideal city, and to make guardian women themselves as “masculine” as possible. Second, scholars who address the relationship between Plato's views of women and his psychological theory tend to focus on the reasoning and appetitive parts of the tripartite soul. In response to the first point, we argue that the idea that Plato seeks to masculinize/de-feminize the city oversimplifies his treatment of Greek gender norms. Although he does want to eliminate some traditionally feminine qualities from the city, he also seeks to eliminate many masculine qualities as well. Moreover, while he tries to make guardian women more like men in some respects, he simultaneously aims to make guardian men more like Greek women in important ways. Regarding the second point, we argue that this project of reimagining gender norms is illuminated by Plato's psychology, but instead of emphasizing reason and appetite, we show how his views are connected to his account of the third, “spirited” part of the soul, thumos, and its dual hard/soft or aggressive/gentle nature.
The Armenian Community and Changing Iranian Perceptions of Minority
Authors: Barry James
Published: March 2024

Until a decade ago, it was unusual for officials in the Islamic Republic to use the word aqaliat (minority) to refer to ethno-linguistic minorities or Muslim sect minorities. Efforts to cast Sunni Muslims as a minority, or Azeri speakers, were treated with hostility, as the state, following a specific proclamation on ethnicity and sectarianism by Ayatollah Khomeini, viewed these concepts as divisive to the ummah and ultimately a threat to national security. Aqaliat was instead reserved for non-Muslims, specifically those recognized as minorities in the constitution: Assyrian, Chaldean and Armenian Christians, and Zoroastrian and Jewish Iranians. It is therefore worthwhile to examine how one such minority community, Iranian Armenians, has reacted to these changes.
Communicate or not: Exploring the different effects of instrumental and expressive networks on thriving at work
Authors: Zhu Mengxiao , Su Ruoxiao , Liu Lin , Contractor Noshir
Published: March 2024

Thriving at work is closely related to the way employees are embedded in their social contexts, such as the structure of their communication relations with coworkers. In previous research, communication relations have been found to negatively relate to thriving at work. However, social network theory suggests that communication relations are beneficial in obtaining resources in the workplace, which might increase thriving at work. To reconcile the seemingly conflicting mechanisms, we draw on social network theory to unpack the mechanisms underlying communication relations by considering the instrumental and expressive roles. Using a structural equation model, we investigate the indirect effects of communication networks on thriving at work via advice-seeking networks (instrumental) and friendship networks (expressive). Our findings indicate communication relations are negatively related to thriving at work via advice-seeking relations, but are positively related to thriving at work via friendship relations.
EXTENSIONS AND LIMITS OF THE SPECKER–BLATTER THEOREM
Authors: FISCHER ELDAR , MAKOWSKY JOHANN A.
Published: March 2024

The original Specker–Blatter theorem (1983) was formulated for classes of structures
$\mathcal {C}$
of one or several binary relations definable in Monadic Second Order Logic MSOL. It states that the number of such structures on the set
$[n]$
is modularly C-finite (MC-finite). In previous work we extended this to structures definable in CMSOL, MSOL extended with modular counting quantifiers. The first author also showed that the Specker–Blatter theorem does not hold for one quaternary relation (2003).

If the vocabulary allows a constant symbol c, there are n possible interpretations on
$[n]$
for c. We say that a constant c is hard-wired if c is always interpreted by the same element
$j \in [n]$
. In this paper we show:

(i)

The Specker–Blatter theorem also holds for CMSOL when hard-wired constants are allowed. The proof method of Specker and Blatter does not work in this case.

(ii)

The Specker–Blatter theorem does not hold already for
$\mathcal {C}$
with one ternary relation definable in First Order Logic FOL. This was left open since 1983.

Using hard-wired constants allows us to show MC-finiteness of counting functions of various restricted partition functions which were not known to be MC-finite till now. Among them we have the restricted Bell numbers
$B_{r,A}$
, restricted Stirling numbers of the second kind
$S_{r,A}$
or restricted Lah-numbers
$L_{r,A}$
. Here r is a non-negative integer and A is an ultimately periodic set of non-negative integers.
Unfreedom and Slavery Under Sail: Intercolonial Trade in the British Atlantic, 1698–1766
Authors: Tucker Hannah Knox
Published: March 2024

Using evidence from 25,250 records of vessels entering and clearing the rivers of the Chesapeake Bay, this article demonstrates that intercolonial trading captains and crews significantly reduced the number of days their vessels spent in port in Virginia between 1698 and 1766. This contraction reflected a quantifying ethos in shipping that emerged during the early age of sail as the result of mutually reinforcing legal requirements and management practices. Responding to these productivity pressures, captains embraced practices that limited sailors’ freedom and turned to enslaved sailors to guarantee their maritime labor force. Embracing unfreedom aided captains to realize the dispatch goals that helped guarantee their investors’ returns.
From Field Walking to Phenomenology: A Review of Recent British Landscape Historiography
Authors: Burchardt Jeremy
Published: March 2024

This review identifies three major traditions in British landscape historiography: material/environmental, cultural, and phenomenological. The continuing vitality, methodological rigour, and popular reach of the material tradition is emphasized, notwithstanding persistent questions about the adequacy of its theoretical foundations. Its close cousin historical ecology has meanwhile developed into a broader environmental history, increasingly sensitive to ideological and institutional influences. The development of the cultural tradition, originating in art historical analysis of the ‘landscape idea’ as a culturally specific ‘way of seeing’, is traced through a rich proliferation of studies connecting landscape with memory, national identity, and governance, and through feminist, postcolonial, and history-from-below perspectives. The pervasive influence of the spatial, mobilities, and material turns is highlighted but phenomenology’s focus on experience perhaps challenges the cultural tradition’s premises more fundamentally. Although historians were slower than anthropologists and archaeologists to adopt phenomenology, medievalists and early modernists have applied it rewardingly to topics such as the settings of elite buildings, peasant landscape perceptions, and collective landscape memories. Few modernists have yet embraced phenomenology but it has great potential here given the abundant life-writing sources available. While scope remains for further convergence between research traditions, British landscape history is therefore in an exciting phase of methodological renewal.
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

Microbial 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

Antarctic 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

The 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

Immune 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

The 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

Picornaviruses 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

Small-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

Dual-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

YEATS 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

Focal 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

Accumulating 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

The 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

Astronauts 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

Thermochemical 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

Mapping 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.
Coexistence of critical phenomena: the concept of manifold multi-spectral criticality
Authors: Chorowski Michał , Kutner Ryszard , Struzik Zbigniew R.
Published: March 2024

Prompted by the ubiquity of empirical observations of critical phenomena, often in non-equilibrium macrostates, we developed a modelling approach in which several critical phenomena coexist. Instead of a single critical point, many coexisting critical points in the system are identified, forming a one-dimensional critical manifold. Identified within our game-of-life-like heterogeneous agent-based simulation model, where agents can be created and annihilated in the presence of a catalyst, each critical point belonging to the critical manifold is associated with a multi-spectrum of critical exponents. We find this situation in non-equilibrium mixed percolation-like macrostates obeying continuous phase transitions. These macrostates are quasi-stationary, where some system characteristics are time-independent while others are not. This novel look at universality signals the existance of complexity of critical phenomena richer than described to date.
Diet replacement with whole insect larvae affects intestinal morphology and microbiota of broiler chickens
Authors: Vasilopoulos Stylianos , Giannenas Ilias , Mellidou Ifigeneia , Stylianaki Ioanna , Antonopoulou Efthimia , Tzora Athina , Skoufos Ioannis , Athanassiou Christos G. , Papadopoulos Elias , Fortomaris Paschalis
Published: March 2024

Insect-based diets are gaining interest as potential ingredients in improving poultry gut health. This study assessed the dietary treatment with whole dried Tenebrio molitor larvae (TM) on broiler chickens’ gut microbiota and morphology. 120 Ross-308 broilers received treated diets with 5% (TM5) and 10% (TM10) replacement ratio in a 35-day trial. Intestinal histomorphometry was assessed, as well as claudin-3 expression pattern and ileal and caecal digesta for microbial community diversity. Null hypothesis was tested with two-way ANOVA considering the intestinal segment and diet as main factors. The TM5 group presented higher villi in the duodenum and ileum compared to the other two (P < 0.001), while treated groups showed shallower crypts in the duodenum (P < 0.001) and deeper in the jejunum and ileum than the control (P < 0.001). Treatments increased the caecal Firmicutes/Bacteroidetes ratio and led to significant changes at the genus level. While Lactobacilli survived in the caecum, a significant reduction was evident in the ileum of both groups, mainly owed to L. aviarius. Staphylococci and Methanobrevibacter significantly increased in the ileum of the TM5 group. Results suggest that dietary supplementation with whole dried TM larvae has no adverse effect on the intestinal epithelium formation and positively affects bacterial population richness and diversity.
BSI-MVS: multi-view stereo network with bidirectional semantic information
Authors: Jia Ruiming , Yu Jun , Hu Zhenghui , Yuan Fei
Published: March 2024

The basic principle of multi-view stereo (MVS) is to perform 3D reconstruction by extracting depth information from multiple views. Most current SOTA MVS networks are based on Vision Transformer, which usually means expensive computational complexity. To reduce computational complexity and improve depth map accuracy, we propose a MVS network with Bidirectional Semantic Information (BSI-MVS). Firstly, we design a Multi-Level Spatial Pyramid module to generate multiple layers of feature map for extracting multi-scale information. Then we propose a 2D Bidirectional-LSTM module to capture bidirectional semantic information at different time steps in the horizontal and vertical directions, which contains abundant depth information. Finally, cost volumes are built based on various levels of feature maps to optimize the final depth map. We experiment on the DTU and BlendedMVS datasets. The result shows that our network, in terms of overall metrics, surpasses TransMVSNet, CasMVSNet, CVP-MVSNet, and AACVP-MVSNet respectively by 17.84%, 36.42%, 14.96%, and 4.86%, which also shows a noticeable performance enhancement in objective metrics and visualizations.
Identification of extracellular vesicles from their Raman spectra via self-supervised learning
Authors: Jensen Mathias N. , Guerreiro Eduarda M. , Enciso-Martinez Agustin , Kruglik Sergei G. , Otto Cees , Snir Omri , Ricaud Benjamin , Hellesø Olav Gaute
Published: March 2024

Extracellular vesicles (EVs) released from cells attract interest for their possible role in health and diseases. The detection and characterization of EVs is challenging due to the lack of specialized methodologies. Raman spectroscopy, however, has been suggested as a novel approach for biochemical analysis of EVs. To extract information from the spectra, a novel deep learning architecture is explored as a versatile variant of autoencoders. The proposed architecture considers the frequency range separately from the intensity of the spectra. This enables the model to adapt to the frequency range, rather than requiring that all spectra be pre-processed to the same frequency range as it was trained on. It is demonstrated that the proposed architecture accepts Raman spectra of EVs and lipoproteins from 13 biological sources and from two laboratories. High reconstruction accuracy is maintained despite large variances in frequency range and noise level. It is also shown that the architecture is able to cluster the biological nanoparticles by their Raman spectra and differentiate them by their origin without pre-processing of the spectra or supervision during learning. The model performs label-free differentiation, including separating EVs from activated vs. non-activated blood platelets and EVs/lipoproteins from prostate cancer patients versus non-cancer controls. The differentiation is evaluated by creating a neural network classifier that observes the features extracted by the model to classify the spectra according to their sample origin. The classification reveals a test sensitivity of $$92.2\%$$

92.2
%

and selectivity of $$92.3\%$$

92.3
%

over 769 measurements from two labs that have different measurement configurations.
Human dental pulp stem cells derived extracellular matrix promotes mineralization via Hippo and Wnt pathways
Authors: Kornsuthisopon Chatvadee , Nowwarote Nunthawan , Chansaenroj Ajjima , Photichailert Suphalak , Rochanavibhata Sunisa , Klincumhom Nuttha , Petit Stephane , Dingli Florent , Loew Damarys , Fournier Benjamin P. J. , Osathanon Thanaphum
Published: March 2024

Extracellular matrix (ECM) is an intricate structure providing the microenvironment niche that influences stem cell differentiation. This study aimed to investigate the efficacy of decellularized ECM derived from human dental pulp stem cells (dECM_DPSCs) and gingival-derived mesenchymal stem cells (dECM_GSCs) as an inductive scaffold for osteogenic differentiation of GSCs. The proteomic analysis demonstrated that common and signature matrisome proteins from dECM_DPSCs and dECM_GSCs were related to osteogenesis/osteogenic differentiation. RNA sequencing data from GSCs reseeded on dECM_DPSCs revealed that dECM_DPSCs upregulated genes related to the Hippo and Wnt signaling pathways in GSCs. In the inhibitor experiments, results revealed that dECM_DPSCs superiorly promoted GSCs osteogenic differentiation, mainly mediated through Hippo and Wnt signaling. The present study emphasizes the promising translational application of dECM_DPSCs as a bio-scaffold rich in favorable regenerative microenvironment for tissue engineering.
Fabrication of date palm kernel biochar-sulfur (DPKB-S) for super adsorption of methylene blue dye from water
Authors: Elkatory Marwa R. , Yılmaz Murat , Hassaan Mohamed A. , El Nemr Ahmed
Published: March 2024

A novel form of biochar was created by dehydration of Date palm kernel with 85% sulfuric acid. It was examined how the newly produced biochar (DPKB-S) affected the aqueous solution's capacity to extract Methylene Blue (MB) dye. The prepared DPKB-S was categorized by BET, BJH, FT-IR, SEM, EDX, DSC, and TGA analyses. The ideal pH for the MB dye adsorption by DPKB-S is 8. With 0.75 g L−1 of DPKB-S and an initial concentration of 50 ppm MB dye, Date Palm Kernel Biochar-Sulfur (DPKB-S) had the highest removal percentage of 100%. The Langmuir and Freundlich isotherm models were used to investigate the collected data. Freundlich model is the model that best covers MB dye adsorption in DPKB-S at low concentrations (0.75–1.25 g L−1) and the Langmuir model at high concentrations (1.5–1.75 g L−1). The Langmuir model maximum adsorption capacity (Qm) of the DPKB-S was 1512.30 mg g−1. Furthermore, a variety of error function models were applied to investigate the isotherm models derived data, including Marquardt’s percent standard deviation (MPSD), the sum of absolute errors (EABS), the sum of the errors squared (ERRSQ), root mean square errors (RMS), Chi-square error (X2), the average relative error (ARE), average percent errors (APE), and hybrid error function (HYBRID). Kinetic data were calculated by intraparticle diffusion (IPD), pseudo-second-order (PSO), pseudo-first-order (PFO), and film diffusion (FD) models. A PSO rate model with a strong correlation (R2 = 1.00) largely regulated the adsorption rate. The removal mechanism of MB dye by DPKB-S is based on the principle that these positively charged dyes are attracted by electrostatic attraction forces due to the growth in the number of negatively charged regions at basic pH value. According to the results, DPKB-S shows promise as an affordable and competent adsorbent for the adsorption of MB dye. It can be used frequently without experiencing a discernible decrease in adsorption efficiency.
A GPS assisted translocation experiment to study the homing behavior of red deer
Authors: Silovský Václav , Landler Lukas , Faltusová Monika , Börger Luca , Burda Hynek , Holton Mark , Lagner Ondřej , Malkemper Erich Pascal , Olejarz Astrid , Spießberger Magdalena , Váchal Adam , Ježek Miloš
Published: March 2024

Many animals return to their home areas (i.e., ‘homing’) after translocation to sites further away. Such translocations have traditionally been used in behavioral ecology to understand the orientation and migration behavior of animals. The movement itself can then be followed by marking and recapturing animals or by tracking, for example, using GPS systems. Most detailed studies investigating this behavior have been conducted in smaller vertebrates (e.g., birds, amphibians, and mice), whereas information on larger mammals, such as red deer, is sparse. We conducted GPS-assisted translocation experiments with red deer at two sites in the Czech Republic. Individuals were translocated over a distance of approximately 11 km and their home journey was tracked. Circular statistics were used to test for significant homeward orientation at distances of 100, 500, 1000, and 5000 m from the release site. In addition, we applied Lavielle trajectory segmentation to identify the different phases of homing behavior. Thirty-one out of 35 translocations resulted in successful homing, with a median time of 4.75 days (range 1.23–100 days). Animals were significantly oriented towards home immediately after release and again when they came closer to home; however, they did not show a significant orientation at the distances in between. We were able to identify three homing phases, an initial ‘exploratory phase’, followed by a ‘homing phase’ which sometimes was again followed by an ‘arrival phase’. The ‘homing phase’ was characterized by the straightest paths and fastest movements. However, the variation between translocation events was considerable. We showed good homing abilities of red deer after translocation. Our results demonstrate the feasibility of conducting experiments with environmental manipulations (e.g., to impede the use of sensory cues) close to the release site. The homing behavior of red deer is comparable to that of other species, and might represent general homing behavior patterns in animals. Follow-up studies should further dissect and investigate the drivers of the individual variations observed and try to identify the sensory cues used during homing.
Prediction uncertainty estimates elucidate the limitation of current NSCLC subtype classification in representing mutational heterogeneity
Authors: Puiu Andrei , Gómez Tapia Carlos , Weiss Maximilian E. R. , Singh Vivek , Kamen Ali , Siebert Matthias
Published: March 2024

The heterogeneous pathogenesis and treatment response of non-small cell lung cancer (NSCLC) has led clinical treatment decisions to be guided by NSCLC subtypes, with lung adenocarcinoma and lung squamous cell carcinoma being the most common subtypes. While histology-based subtyping remains challenging, NSCLC subtypes were found to be distinct at the transcriptomic level. However, unlike genomic alterations, gene expression is generally not assessed in clinical routine. Since subtyping of NSCLC has remained elusive using mutational data, we aimed at developing a neural network model that simultaneously learns from adenocarcinoma and squamous cell carcinoma samples of other tissue types and is regularized using a neural network model trained from gene expression data. While substructures of the expression-based manifold were captured in the mutation-based manifold, NSCLC classification accuracy did not significantly improve. However, performance was increased when rejecting inconclusive samples using an ensemble-based approach capturing prediction uncertainty. Importantly, SHAP analysis of misclassified samples identified co-occurring mutations indicative of both NSCLC subtypes, questioning the current NSCLC subtype classification to adequately represent inherent mutational heterogeneity. Since our model captures mutational patterns linked to clinical heterogeneity, we anticipate it to be suited as foundational model of genomic data for clinically relevant prognostic or predictive downstream tasks.