bluuebunny/crossref_metadata_2025 huggingface dataset:
LINC01089 blocks malignant progression of thyroid cancer by binding miR-27b-3p to enhance the FBLN5 protein level
Authors: Pan Yong-qin , Huang Kun-song , Chong Tsz-Hong , Li Jin-yi
Published: October 2022

LINC01089 suppresses the malignant progression of breast, colorectal, and non-small cell lung cancers. However, the function of LINC01089 in thyroid cancer has not yet been elucidated. Here, The Cancer Genome Atlas (TCGA) database showed that LINC01089 expression is remarkably reduced in thyroid cancer tissues. Lower LINC01089 expression was correlated with higher tumor stage and regional lymph node metastasis. Furthermore, LINC01089 overexpression effectively blocked thyroid cancer cell proliferation, migration, and invasion. LINC01089 acted as a competing endogenous RNA for miR-27b-3p, thus inhibiting miR-27b-3p expression. miR-27b-3p overexpression promoted the proliferation, migration, and invasion of thyroid cancer, reversing the effect of LINC01089 overexpression on thyroid cancer. Fibulin-5 (FBLN5) was discovered as a target of miR-27b-3p in thyroid cancer. FBLN5 expression was found to be underexpressed in thyroid cancer and was enhanced and reduced by LINC00987 overexpression and miR-27b-3p overexpression, respectively. Furthermore, FBLN5 knockdown promoted the malignant progression of thyroid cancer cells by counteracting the effect of LINC00987. In conclusion, LINC01089 plays a tumor-suppressive role by binding miR-27b-3p to increase FBLN5 expression, confirming that LINC01089 has tremendous potential to become a therapeutic target for thyroid cancer treatment.
Starch-grafted-poly(acrylic acid)/Pterocladia capillacea–derived activated carbon composite for removal of methylene blue dye from water
Authors: Shoaib Amany G. M. , Sikaily Amany El , Ragab Safaa , Masoud Mamdouh S. , Ramadan Mohamed S. , El Nemr Ahmed
Published: October 2022

Starch-g-poly(acrylic acid)/Pterocladia capillacea–derived activated carbon (St-g-P(AA)/P-AC) composites were prepared via aqueous solution graft copolymerization using starch, acrylic acid, and activated carbon of red alga Pterocladia capillacea (0–10%) with N,N′-methylenebisacrylamide crosslinker and ammonium persulfate (NH4)2S2O8 initiator. Fourier-transform infrared (FTIR) spectroscopy, Brunauer–Emmett–Teller (BET), X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDX) were used to characterize St-g-P(AA)/P-AC composites. Additionally, St-g-P(AA)/P-AC composites were investigated for methylene blue (MB) dye removal from water. The impact of the beginning concentration of MB dye, temperature, pH, and adsorption time on MB dye removal was examined. The maximum adsorption capacity obtained at pH 8 was 496.29 mg/g at 0.02 mg/L composites dose and 100 mg/L MB dye. The properties of adsorption were studied by the adsorption isotherm, kinetic, and thermodynamic models. The pseudo-first-order and Freundlich isotherm models demonstrated the kinetics and equilibrium adsorptions data, respectively. The maximum monolayer capacity (qm) was 1428.57 mg/g from Langmuir isotherm. Thermodynamic parameters indicated that the MB dye adsorption is exothermic physisorption and spontaneous. The results show that St-g-P(AA)/P-AC composites were effective for MB dye adsorption from water solution and could be recycled.
Nonexistence and umbilicity of spacelike submanifolds with second fundamental form locally timelike
Authors: de Lima Henrique F. , Rocha Lucas S. , Velásquez Marco Antonio L.
Published: October 2022

Under the assumption that the second fundamental form is locally timelike, we establish new nonexistence and umbilicity results concerning n-dimensional spacelike submanifolds immersed with parallel mean curvature vector in the $$(n+p)$$

(
n
+
p
)

-dimensional de Sitter space $$\mathbb {S}^{n+p}_q$$

S

q

n
+
p

of index q, such that $$1\le q\le p$$

1
≤
q
≤
p

. Our approach is based on a Simon’s type inequality involving the norm of the total umbilicity tensor, obtained by Mariano in [17], jointly with suitable maximum principles due to Alías, Caminha and do Nascimento [6, 7] for complete noncompact Riemannian manifolds and a weak version of Omori–Yau’s maximum principle for stochastically complete Riemanian manifolds proved by Pigola, Rigoli and Setti [20, 21].
Measuring Personal Damage in a Large-Scale Disaster: A Review of the Reports Published by the Japanese Fire and Disaster Management Agency on the Great East Japan Earthquake and Tsunami
Authors: Kinoshita Mari , Shikida Mikifumi
Published: October 2022

Objective:

The study’s aim is to identify the challenges in estimating personal damages in the early stages of a disaster.

Methods:

The study reviewed personal damage data in the reports on the Great East Japan earthquake and tsunami published by Japanese public agencies from 2011 to 2020, including 159 situation reports by the Fire and Disaster Management Agency and 17 disaster-related indirect death reports by the Reconstruction Agency. The study compared the reported number of deaths, missing persons, and injuries with the latest statistics to evaluate how soon the disaster’s real damages were estimated.

Results:

The reported number of deaths significantly increased in the first 1.5 years, whereas the number of missing persons spiked in the first 30 days. It required approximately 1 year until the numbers approximated the current reference rate. The total casualties included 3739 indirect deaths.

Conclusion:

The results indicated an overestimation of missing persons, a possible underestimation of injuries, and the excess deaths due to indirect causes that complicated the estimation. The limitations of the current data collection approaches are the delay in reporting from the field and incomplete and unreliable information. A novel system is proposed, which directly collects data from all affected individuals anonymously.
Authority matters: propaganda and the coevolution of behaviour and attitudes
Authors: Gavrilets Sergey , Richerson Peter J.
Published: October 2022

Human decision-making is controlled by various factors including material cost–benefit considerations, values and beliefs, social influences, cognitive factors and errors. Among social influences, those by external authorities (e.g. educational, cultural, religious, political, administrative, etc.) are particularly important owing to their potential reach and power. To better understand the effects of ‘soft’ power of authorities we develop a unifying theoretical framework integrating material, cognitive and social forces controlling the joint dynamics of individual actions and beliefs. We apply our approach to three different phenomena: evolution of food sharing in small-scale societies, participation in political protests and effects of priming social identity in behavioural experiments. For each of these applications, we show that our approach leads to different (or simpler) explanations of human behaviour than alternatives. We highlight the type of measurements which can be helpful in developing practical applications of our approach. We identify and explicitly characterise the degree of mismatch between individual actions and attitudes. We assert that the effects of external authorities, of changing beliefs and of differences between people must be studied empirically, included in mathematical models, and accounted for when developing different policies aiming to modify or sustain human behaviour.
And the Master Answered?: Deferrals of Authority in Contemporary Sufism in Iran
Authors: Golestaneh Seema
Published: October 2022

Authority in Islam is often understood to operate as a site of negotiation. Based on textual analysis and ethnographic research, this article examines three case studies of disparate Shi'i Sufi Orders where a willing deferral of certain types of authority exists. In the first case study, the Soltanalishahi Order refer their members to an outsidemujtahidfor all matters relating to theshariat, therein limiting the powers of theirshaykhs andqotb. The second case study looks at debates concerning the nature of theqotb's authority within a single order, particularly as it pertains to the power of touch and transmissibility of blessing (barakat) fromqotbto object to person, with the order's leadership refuting the idea of charismatic embodied authority despite some of their lay members’ beliefs. Finally, the third case study addresses a group who refute the need for any centralized leadership at all and instead recognize and read the works of multipleqotbs from disparate Iranian orders. By focusing on the deferral of authority, as a type of editing, as a type of shaping, I hope to show that the refuting of certain duties is just as formative as the amassing of powers.
The more the better? How and when can high-performance work systems fuel the proactive fire
Authors: Lin Chiou-Shiu , Xiao Ran , Huang Pei-Chi , Huang Liang-Chih , Jin Ming
Published: October 2022

Drawing on the job demands-resources model and conservation of resources theory, this study investigates how and when the high-performance work systems (HPWS) influence proactive workforce. Using the data obtained from 204 supervisor-employee dyads in China, we developed and tested a moderated mediation model in which leader-member exchange (LMX) moderates the positive relationship between HPWS and proactive behavior via work engagement. Our results demonstrated that the association between HPWS and proactivity was fully mediated by work engagement. We also found that the indirect effect of HPWS on proactivity was significantly weaker among employees with high-quality LMX. Theoretical and practical implications, as well as directions for future research, are then discussed.
Relaxing Assumptions, Improving Inference: Integrating Machine Learning and the Linear Regression
Authors: RATKOVIC MARC
Published: October 2022

Valid inference in an observational study requires a correct control specification, but a correct specification is never known. I introduce a method that constructs a control vector from the observed data that, when included in a linear regression, adjusts for several forms of bias. These include nonlinearities and interactions in the background covariates, biases induced by heterogeneous treatment effects, and specific forms of interference. The first is new to political science; the latter two are original contributions. I incorporate random effects, a set of diagnostics, and robust standard errors. With additional assumptions, the estimates allow for causal inference on both binary and continuous treatment variables. In total, the model provides a flexible means to adjust for biases commonly encountered in our data, makes minimal assumptions, returns efficient estimates, and can be implemented through publicly available software.
Irremediability in psychiatric euthanasia: examining the objective standard
Authors: Nicolini Marie E. , Jardas EJ , Zarate Carlos A. , Gastmans Chris , Kim Scott Y. H.
Published: October 2022

Background

Irremediability is a key requirement for euthanasia and assisted suicide for psychiatric disorders (psychiatric EAS). Countries like the Netherlands and Belgium ask clinicians to assess irremediability in light of the patient's diagnosis and prognosis and ‘according to current medical understanding’. Clarifying the relevance of a default objective standard for irremediability when applied to psychiatric EAS is crucial for solid policymaking. Yet so far, a thorough examination of this standard is lacking.

Methods

Using treatment-resistant depression (TRD) as a test case, through a scoping review in PubMed, we analyzed the state-of-the-art evidence for whether clinicians can accurately predict individual long-term outcome and single out irremediable cases, by examining the following questions: (1) What is the definition of TRD; (2) What are group-level long-term outcomes of TRD; and (3) Can clinicians make accurate individual outcome predictions in TRD?

Results

A uniform definition of TRD is lacking, with over 150 existing definitions, mostly focused on psychopharmacological research. Available yet limited studies about long-term outcomes indicate that a majority of patients with long-term TRD show significant improvement over time. Finally, evidence about individual predictions in TRD using precision medicine is growing, but methodological shortcomings and varying predictive accuracies pose important challenges for its implementation in clinical practice.

Conclusion

Our findings support the claim that, as per available evidence, clinicians cannot accurately predict long-term chances of recovery in a particular patient with TRD. This means that the objective standard for irremediability cannot be met, with implications for policy and practice of psychiatric EAS.
Cooperative collision avoidance in multirobot systems using fuzzy rules and velocity obstacles
Authors: Tang Wenbing , Zhou Yuan , Zhang Tianwei , Liu Yang , Liu Jing , Ding Zuohua
Published: October 2022

Collision avoidance is critical in multirobot systems. Most of the current methods for collision avoidance either require high computation costs (e.g., velocity obstacles and mathematical optimization) or cannot always provide safety guarantees (e.g., learning-based methods). Moreover, they cannot deal with uncertain sensing data and linguistic requirements (e.g., the speed of a robot should not be large when it is near to other robots). Hence, to guarantee real-time collision avoidance and deal with linguistic requirements, a distributed and hybrid motion planning method, named Fuzzy-VO, is proposed for multirobot systems. It contains two basic components: fuzzy rules, which can deal with linguistic requirements and compute motion efficiently, and velocity obstacles (VOs), which can generate collision-free motion effectively. The Fuzzy-VO applies an intruder selection method to mitigate the exponential increase of the number of fuzzy rules. In detail, at any time instant, a robot checks the robots that it may collide with and retrieves the most dangerous robot in each sector based on the predicted collision time; then, the robot generates its velocity in real-time via fuzzy inference and VO-based fine-tuning. At each time instant, a robot only needs to retrieve its neighbors’ current positions and velocities, so the method is fully distributed. Extensive simulations with a different number of robots are carried out to compare the performance of Fuzzy-VO with the conventional fuzzy rule method and the VO-based method from different aspects. The results show that: Compared with the conventional fuzzy rule method, the average success rate of the proposed method can be increased by 306.5%; compared with the VO-based method, the average one-step decision time is reduced by 740.9%.
On stochastic ordering among extreme shock models
Authors: Manesh Sirous Fathi , Izadi Muhyiddin , Khaledi Baha-Eldin
Published: October 2022

In the usual shock models, the shocks arrive from a single source. Bozbulut and Eryilmaz [(2020). Generalized extreme shock models and their applications. Communications in Statistics – Simulation and Computation49(1): 110–120] introduced two types of extreme shock models when the shocks arrive from one of $m\geq 1$ possible sources. In Model 1, the shocks arrive from different sources over time. In Model 2, initially, the shocks randomly come from one of $m$ sources, and shocks continue to arrive from the same source. In this paper, we prove that the lifetime of Model 1 is less than Model 2 in the usual stochastic ordering. We further show that if the inter-arrival times of shocks have increasing failure rate distributions, then the usual stochastic ordering can be generalized to the hazard rate ordering. We study the stochastic behavior of the lifetime of Model 2 with respect to the severity of shocks using the notion of majorization. We apply the new stochastic ordering results to show that the age replacement policy under Model 1 is more costly than Model 2.
An outbreak of Cryptosporidium parvum linked to pasteurised milk from a vending machine in England: a descriptive study, March 2021
Authors: Gopfert Anya , Chalmers Rachel M. , Whittingham Sarah , Wilson Laura , van Hove Maria , Ferraro Claire F. , Robinson Guy , Young Nick , Nozad Bayad
Published: October 2022

We describe the investigations and management of a Cryptosporidium parvum outbreak of linked to consumption of pasteurised milk from a vending machine. Multiple locus variable number of tandem repeats analysis was newly used, confirming that C. parvum detected in human cases was indistinguishable from that in a calf on the farm. This strengthened the evidence for milk from an on-farm vending machine as the source of the outbreak because of post-pasteurisation contamination. Bacteriological indicators of post-pasteurisation contamination persisted after the initial hygiene improvement notice. We propose that on-farm milk vending machines may represent an emerging public health risk.
Frühsommer-Meningoenzephalitis
Authors: Zens Kyra D.
Published: October 2022

Zusammenfassung. Das Frühsommer-Meningoenzephalitis-Virus (FSMEV bzw. «Tick-borne Encephalitis Virus», TBEV) ist ein Flavivirus, das hauptsächlich durch den Biss infizierter Ixodes-Zecken auf den Menschen übertragen wird. Eine Infektion mit FSMEV führt zu Frühsommer-Meningoenzephalitis (FSME), einer akuten Erkrankung des Zentralnervensystems (ZNS), die zu erheblichen Langzeitfolgen führen kann. In den letzten Jahrzehnten haben das geografische Verbreitungsgebiet von FSMEV und die Inzidenz von FSME erheblich zugenommen. Das FSMEV ist heute in weiten Teilen Mitteleuropas, einschliesslich Teilen Deutschlands, Österreichs und der Schweiz, endemisch und wird zunehmend als Problem für die öffentliche Gesundheit erkannt. Zwar gibt es keine spezifischen Therapien für FSME, doch sind in Europa zwei Impfstoffe zugelassen und erhältlich: Encepur® und FSME-Immun®. Beide gelten als sicher und wirksam. Nach der Impfung wird die Bildung von virusneutralisierenden Antikörpern oft als Indikator für den Schutz vor der Krankheit angesehen. Obwohl neuere Erkenntnisse darauf hindeuten, dass zellvermittelte Immunreaktionen wahrscheinlich ebenfalls eine wichtige Rolle beim Schutz spielen, ist die zellvermittelte Immunität nach einer Infektion und Impfung nach wie vor nur unzureichend beschrieben. Wie bei vielen Impfstoffen wird die anfängliche Reaktion auf die FSME-Impfung von mehreren Faktoren beeinflusst. Im Folgenden wird untersucht, wie sich Alter, Immunsuppression, die Einhaltung der empfohlenen Impfpläne und die Verwendung eines einzigen Impfstofftyps während der Impfung auf die Immunität nach einer FSME-Impfung auswirken können. Darüber hinaus erörtern wir die Durchimpfungsrate und die Krankheitsprävention sowie die Faktoren, die sich auf die individuelle Impfstoffaufnahme auswirken.
Incorporating Network Scale River Bathymetry to Improve Characterization of Fluvial Processes in Flood Modeling
Authors: Dey Sayan , Saksena Siddharth , Winter Danielle , Merwade Venkatesh , McMillan Sara
Published: October 2022

Several studies have focused on the importance of river bathymetry (channel geometry) in hydrodynamic routing along individual reaches. However, its effect on other watershed processes such as infiltration and surface water (SW)‐groundwater (GW) interactions has not been explored across large river networks. Surface and sbsurface processes are interdependent, therefore, errors due to inaccurate representation of one watershed process can cascade across other hydraulic or hydrologic processes. This study hypothesizes that accurate bathymetric representation is not only essential for simulating channel hydrodynamics but also affects subsurface processes by impacting SW‐GW interactions. Moreover, quantifying the effect of bathymetry on surface and subsurface hydrological processes across a river network can facilitate an improved understanding of how bathymetric characteristics affect these processes across large spatial domains. The study tests this hypothesis by developing physically based distributed models capable of bidirectional coupling (SW‐GW) with four configurations with progressively reduced levels of bathymetric representation. A comparison of hydrologic and hydrodynamic outputs shows that changes in channel geometry across the four configurations has a considerable effect on infiltration, lateral seepage, and location of water table across the entire river network. For example, when using bathymetry with inaccurate channel conveyance capacity but accurate channel depth, peak lateral seepage rate exhibited 58% error. The results from this study provide insights into the level of bathymetric detail required for accurately simulating flooding‐related physical processes while also highlighting potential issues with ignoring bathymetry across lower order streams such as spurious backwater flow, inaccurate water table elevations, and incorrect inundation extents.
An Inclusive Approach to Oceangoing Research
Authors: Duncombe Jenessa
Published: October 2022

The bread and butter of oceanography, sea voyages rarely include minoritized communities and nonscientists. The Inclusion Mission wants to change that.
The universal stem cell
Authors: Quesenberry Peter J. , Wen Sicheng , Goldberg Laura R. , Dooner Mark S.
Published: October 2022

Current dogma is that there exists a hematopoietic pluripotent stem cell, resident in the marrow, which is quiescent, but with tremendous proliferative and differentiative potential. Furthermore, the hematopoietic system is essentially hierarchical with progressive differentiation from the pluripotent stem cells to different classes of hematopoietic cells. However, results summarized here indicate that the marrow pluripotent hematopoietic stem cell is actively cycling and thus continually changing phenotype. As it progresses through cell cycle differentiation potential changes as illustrated by sequential changes in surface expression of B220 and GR-1 epitopes. Further data indicated that the potential of purified hematopoietic stem cells extends to multiple other non-hematopoietic cells. It appears that marrow stem cells will give rise to epithelial pulmonary cells at certain points in cell cycle. Thus, it appears that the marrow “hematopoietic” stem cell is also a stem cell for other non-hematopoietic tissues. These observations give rise to the concept of a universal stem cell. The marrow stem cell is not limited to hematopoiesis and its differentiation potential continually changes as it transits cell cycle. Thus, there is a universal stem cell in the marrow which alters its differentiation potential as it progresses through cell cycle. This potential is expressed when it resides in tissues compatible with its differentiation potential, at a particular point in cell cycle transit, or when it interacts with vesicles from that tissue.
Alterations in the p53 isoform ratio govern breast cancer cell fate in response to DNA damage
Authors: Steffens Reinhardt Luiza , Zhang Xiajie , Groen Kira , Morten Brianna C. , De Iuliis Geoffry N. , Braithwaite Antony W. , Bourdon Jean-Christophe , Avery-Kiejda Kelly A.
Published: October 2022

Our previous studies have shown that p53 isoform expression is altered in breast cancer and related to prognosis. In particular, a high ∆40p53:p53α ratio is associated with worse disease-free survival. In this manuscript, the influence of altered Δ40p53 and p53α levels on the response to standard of care DNA-damaging agents used in breast cancer treatment was investigated in vitro. Our results revealed that a high Δ40p53:p53α ratio causes cells to respond differently to doxorubicin and cisplatin treatments. Δ40p53 overexpression significantly impairs the cells’ sensitivity to doxorubicin through reducing apoptosis and DNA damage, whereas Δ40p53 knockdown has the opposite effect. Further, a high Δ40p53:p53α ratio inhibited the differential expression of several genes following doxorubicin and promoted DNA repair, impairing the cells’ canonical response. Overall, our results suggest that the response of breast cancer cells to standard of care DNA-damaging therapies is dependent on the expression of p53 isoforms, which may contribute to outcomes in breast cancer.
Integrated proteogenomic characterization across major histological types of pituitary neuroendocrine tumors
Authors: Zhang Fan , Zhang Qilin , Zhu Jiajun , Yao Boyuan , Ma Chi , Qiao Nidan , He Shiman , Ye Zhao , Wang Yunzhi , Han Rui , Feng Jinwen , Wang Yongfei , Qin Zhaoyu , Ma Zengyi , Li Kai , Zhang Yichao , Tian Sha , Chen Zhengyuan , Tan Subei , Wu Yue , Ran Peng , Wang Ye , Ding Chen , Zhao Yao
Published: October 2022

Pituitary neuroendocrine tumor (PitNET) is one of the most common intracranial tumors. Due to its extensive tumor heterogeneity and the lack of high-quality tissues for biomarker discovery, the causative molecular mechanisms are far from being fully defined. Therefore, more studies are needed to improve the current clinicopathological classification system, and advanced treatment strategies such as targeted therapy and immunotherapy are yet to be explored. Here, we performed the largest integrative genomics, transcriptomics, proteomics, and phosphoproteomics analysis reported to date for a cohort of 200 PitNET patients. Genomics data indicate that GNAS copy number gain can serve as a reliable diagnostic marker for hyperproliferation of the PIT1 lineage. Proteomics-based classification of PitNETs identified 7 clusters, among which, tumors overexpressing epithelial-mesenchymal transition (EMT) markers clustered into a more invasive subgroup. Further analysis identified potential therapeutic targets, including CDK6, TWIST1, EGFR, and VEGFR2, for different clusters. Immune subtyping to explore the potential for application of immunotherapy in PitNET identified an association between alterations in the JAK1-STAT1-PDL1 axis and immune exhaustion, and between changes in the JAK3-STAT6-FOS/JUN axis and immune infiltration. These identified molecular markers and alternations in various clusters/subtypes were further confirmed in an independent cohort of 750 PitNET patients. This proteogenomic analysis across traditional histological boundaries improves our current understanding of PitNET pathophysiology and suggests novel therapeutic targets and strategies.
Towards the engineering of a photon-only two-stroke rotary molecular motor
Authors: Filatov Michael , Paolino Marco , Pierron Robin , Cappelli Andrea , Giorgi Gianluca , Léonard Jérémie , Huix-Rotllant Miquel , Ferré Nicolas , Yang Xuchun , Kaliakin Danil , Blanco-González Alejandro , Olivucci Massimo
Published: October 2022

The rational engineering of photoresponsive materials, e.g., light-driven molecular motors, is a challenging task. Here, we use structure-related design rules to prepare a prototype molecular rotary motor capable of completing an entire revolution using, exclusively, the sequential absorption of two photons; i.e., a photon-only two-stroke motor. The mechanism of rotation is then characterised using a combination of non-adiabatic dynamics simulations and transient absorption spectroscopy measurements. The results show that the rotor moiety rotates axially relative to the stator and produces, within a few picoseconds at ambient T, an intermediate with the same helicity as the starting structure. We discuss how such properties, that include a 0.25 quantum efficiency, can help overcome the operational limitations of the classical overcrowded alkene designs.
On the fluorescence enhancement of arch neuronal optogenetic reporters
Authors: Barneschi Leonardo , Marsili Emanuele , Pedraza-González Laura , Padula Daniele , De Vico Luca , Kaliakin Danil , Blanco-González Alejandro , Ferré Nicolas , Huix-Rotllant Miquel , Filatov Michael , Olivucci Massimo
Published: October 2022

The lack of a theory capable of connecting the amino acid sequence of a light-absorbing protein with its fluorescence brightness is hampering the development of tools for understanding neuronal communications. Here we demonstrate that a theory can be established by constructing quantum chemical models of a set of Archaerhodopsin reporters in their electronically excited state. We found that the experimentally observed increase in fluorescence quantum yield is proportional to the computed decrease in energy difference between the fluorescent state and a nearby photoisomerization channel leading to an exotic diradical of the protein chromophore. This finding will ultimately support the development of technologies for searching novel fluorescent rhodopsin variants and unveil electrostatic changes that make light emission brighter and brighter.
Library adaptors with integrated reference controls improve the accuracy and reliability of nanopore sequencing
Authors: Gunter Helen M. , Youlten Scott E. , Madala Bindu Swapna , Reis Andre L. M. , Stevanovski Igor , Wong Ted , Kummerfield Sarah K. , Deveson Ira W. , Santini Nadia S. , Marcellin Esteban , Mercer Tim R.
Published: October 2022

Library adaptors are short oligonucleotides that are attached to RNA and DNA samples in preparation for next-generation sequencing (NGS). Adaptors can also include additional functional elements, such as sample indexes and unique molecular identifiers, to improve library analysis. Here, we describe Control Library Adaptors, termed CAPTORs, that measure the accuracy and reliability of NGS. CAPTORs can be integrated within the library preparation of RNA and DNA samples, and their encoded information is retrieved during sequencing. We show how CAPTORs can measure the accuracy of nanopore sequencing, evaluate the quantitative performance of metagenomic and RNA sequencing, and improve normalisation between samples. CAPTORs can also be customised for clinical diagnoses, correcting systematic sequencing errors and improving the diagnosis of pathogenic BRCA1/2 variants in breast cancer. CAPTORs are a simple and effective method to increase the accuracy and reliability of NGS, enabling comparisons between samples, reagents and laboratories, and supporting the use of nanopore sequencing for clinical diagnosis.
Oxygen mediated oxidative couplings of flavones in alkaline water
Authors: Yang Xin , Lim Sophie Hui Min , Lin Jiachen , Wu Jie , Tang Haidi , Zhao Fengyue , Liu Fang , Sun Chenghua , Shi Xiangcheng , Kuang Yulong , Toy Joanne Yi Hui , Du Ke , Zhang Yuannian , Wang Xiang , Sun Mingtai , Song Zhixuan , Wang Tian , Wu Ji’en , Houk K. N. , Huang Dejian
Published: October 2022

Catalyzedoxidative C-C bond coupling reactions play an important role in the chemical synthesis of complex natural products of medicinal importance. However, the poor functional group tolerance renders them unfit for the synthesis of naturally occurring polyphenolic flavones. We find that molecular oxygen in alkaline water acts as a hydrogen atom acceptor and oxidant incatalyst-free(without added catalyst) oxidative coupling of luteolin and other flavones. By this facile method, we achieve the synthesis of a small collection of flavone dimers and trimers including naturally occurring dicranolomin, philonotisflavone, dehydrohegoflavone, distichumtriluteolin, and cyclodistichumtriluteolin. Mechanistic studies using both experimental and computational chemistry uncover the underlying reasons for optimal pH, oxygen availability, and counter-cations that define the success of the reaction. We expect our reaction opens up a green and sustainable way to synthesize flavonoid dimers and oligomers using the readily available monomeric flavonoids isolated from biomass and exploiting their use for health care products and treatment of diseases.
Light activation of Orange Carotenoid Protein reveals bicycle-pedal single-bond isomerization
Authors: Chukhutsina Volha U. , Baxter James M. , Fadini Alisia , Morgan Rhodri M. , Pope Matthew A. , Maghlaoui Karim , Orr Christian M. , Wagner Armin , van Thor Jasper J.
Published: October 2022

Orange Carotenoid protein (OCP) is the only known photoreceptor which uses carotenoid for its activation. It is found exclusively in cyanobacteria, where it functions to control light-harvesting of the photosynthetic machinery. However, the photochemical reactions and structural dynamics of this unique photosensing process are not yet resolved. We present time-resolved crystal structures at second-to-minute delays under bright illumination, capturing the early photoproduct and structures of the subsequent reaction intermediates. The first stable photoproduct shows concerted isomerization of C9’-C8’ and C7’-C6’ single bonds in the bicycle-pedal (s-BP) manner and structural changes in the N-terminal domain with minute timescale kinetics. These are followed by a thermally-driven recovery of the s-BP isomer to the dark state carotenoid configuration. Structural changes propagate to the C-terminal domain, resulting, at later time, in the H-bond rupture of the carotenoid keto group with protein residues. Solution FTIR and UV/Vis spectroscopy support the single bond isomerization of the carotenoid in the s-BP manner and subsequent thermal structural reactions as the basis of OCP photoreception.
Multiciliated cells use filopodia to probe tissue mechanics during epithelial integration in vivo
Authors: Ventura Guilherme , Amiri Aboutaleb , Thiagarajan Raghavan , Tolonen Mari , Doostmohammadi Amin , Sedzinski Jakub
Published: October 2022

During embryonic development, regeneration, and homeostasis, cells have to migrate and physically integrate into the target tissues where they ultimately execute their function. While much is known about the biochemical pathways driving cell migration in vivo, we are only beginning to understand the mechanical interplay between migrating cells and their surrounding tissue. Here, we reveal that multiciliated cell precursors in the Xenopus embryo use filopodia to pull at the vertices of the overlying epithelial sheet. This pulling is effectively used to sense vertex stiffness and identify the preferred positions for cell integration into the tissue. Notably, we find that pulling forces equip multiciliated cells with the ability to remodel the epithelial junctions of the neighboring cells, enabling them to generate a permissive environment that facilitates integration. Our findings reveal the intricate physical crosstalk at the cell-tissue interface and uncover previously unknown functions for mechanical forces in orchestrating cell integration.
Van der Waals lattice-induced colossal magnetoresistance in Cr2Ge2Te6 thin flakes
Authors: Zhu Wenxuan , Song Cheng , Han Lei , Guo Tingwen , Bai Hua , Pan Feng
Published: October 2022

Recent discovery of two-dimensional (2D) magnets with van der Waals (vdW) gapped layered structure prospers the fundamental research of magnetism and advances the miniaturization of spintronics. Due to their unique lattice anisotropy, their band structure has the potential to be dramatically modulated by the spin configuration even in thin flakes, which is still unexplored. Here, we demonstrate the vdW lattice-induced spin modulation of band structure in thin flakes of vdW semiconductor Cr2Ge2Te6 (CGT) through the measurement of magnetoresistance (MR). The significant anisotropic lattice constructed by the interlayer vdW force and intralayer covalent bond induces anisotropic spin-orbit field, resulting in the spin orientation-dependent band splitting. Consequently, giant variation of resistance is induced between the magnetization aligned along in-plane and out-of-plane directions. Based on this, a colossal MR beyond 1000% was realized in lateral nonlocal devices with CGT acting as a magneto switch. Our finding provides a unique feature for the vdW magnets and would advance its applications in spintronics.
Immune correlates of protection following Rift Valley fever virus vaccination
Authors: Doyle Joshua D. , Barbeau Dominique J. , Cartwright Haley N. , McElroy Anita K.
Published: October 2022

Rift Valley fever virus (RVFV) is a hemorrhagic fever virus with the potential for significant economic and public health impact. Vaccination with an attenuated strain, DelNSsRVFV, provides protection from an otherwise lethal RVFV challenge, but mechanistic determinants of protection are undefined. In this study, a murine model was used to assess the contributions of humoral and cellular immunity to DelNSsRVFV-mediated protection. Vaccinated mice depleted of T cells were protected against subsequent challenge, and passive transfer of immune serum from vaccinated animals to naïve animals was also protective, demonstrating that T cells were dispensable in the presence of humoral immunity and that humoral immunity alone was sufficient. Animals depleted of B cells and then vaccinated were protected against challenge. Total splenocytes, but not T cells alone, B cells alone, or B + T cells harvested from vaccinated animals and then transferred to naïve animals were sufficient to confer protection, suggesting that multiple cellular interactions were required for effective cellular immunity. Together, these data indicate that humoral immunity is sufficient to confer vaccine-mediated protection and suggests that cellular immunity plays a role in protection that requires the interaction of various cellular components.
Smoking modulates different secretory subpopulations expressing SARS-CoV-2 entry genes in the nasal and bronchial airways
Authors: Xu Ke , Shi Xingyi , Husted Christopher , Hong Rui , Wang Yichen , Ning Boting , Sullivan Travis B. , Rieger-Christ Kimberly M. , Duan Fenghai , Marques Helga , Gower Adam C. , Xiao Xiaohui , Liu Hanqiao , Liu Gang , Duclos Grant , Platt Michael , Spira Avrum E. , Mazzilli Sarah A. , Billatos Ehab , Lenburg Marc E. , Campbell Joshua D. , Beane Jennifer E.
Published: October 2022

SARS-CoV-2 infection and disease severity are influenced by viral entry (VE) gene expression patterns in the airway epithelium. The similarities and differences of VE gene expression (ACE2, TMPRSS2, and CTSL) across nasal and bronchial compartments have not been fully characterized using matched samples from large cohorts. Gene expression data from 793 nasal and 1673 bronchial brushes obtained from individuals participating in lung cancer screening or diagnostic workup revealed that smoking status (current versus former) was the only clinical factor significantly and reproducibly associated with VE gene expression. The expression of ACE2 and TMPRSS2 was higher in smokers in the bronchus but not in the nose. scRNA-seq of nasal brushings indicated that ACE2 co-expressed genes were highly expressed in club and C15orf48+ secretory cells while TMPRSS2 co-expressed genes were highly expressed in keratinizing epithelial cells. In contrast, these ACE2 and TMPRSS2 modules were highly expressed in goblet cells in scRNA-seq from bronchial brushings. Cell-type deconvolution of the gene expression data confirmed that smoking increased the abundance of several secretory cell populations in the bronchus, but only goblet cells in the nose. The association of ACE2 and TMPRSS2 with smoking in the bronchus is due to their high expression in goblet cells which increase in abundance in current smoker airways. In contrast, in the nose, these genes are not predominantly expressed in cell populations modulated by smoking. In individuals with elevated lung cancer risk, smoking-induced VE gene expression changes in the nose likely have minimal impact on SARS-CoV-2 infection, but in the bronchus, smoking may lead to higher viral loads and more severe disease.
How dynamic adsorption controls surfactant-enhanced boiling
Authors: Mata Mario R. , Ortiz Brandon , Luhar Dhruv , Evereux Vesper , Cho H. Jeremy
Published: October 2022

Improving boiling is challenging due to the unpredictable nature of bubbles. One way to enhance boiling is with surfactants, which alter the solid–liquid and liquid–vapor interfaces. The conventional wisdom established by previous studies suggests that heat transfer enhancement is optimized near the critical micelle concentration (CMC), which is an equilibrium property that depends on surfactant type. However, these studies only tested a limited number of surfactants over small concentration ranges. Here, we test a larger variety of nonionic and anionic surfactants over the widest concentration range and find that a universal, optimal concentration range exists, irrespective of CMC. To explain this, we show that surfactant-enhanced boiling is controlled by two competing phenomena: (1) the dynamic adsorption of surfactants to the interfaces and (2) the increase in liquid dynamic viscosity at very high surfactant concentrations. This dynamic adsorption is time-limited by the millisecond-lifetime of bubbles on the boiling surface—much shorter than the timescales required to see equilibrium behaviors such as CMC. At very high concentrations, increased viscosity inhibits rapid bubble growth, reducing heat transfer. We combine the effects of adsorption and viscosity through a simple proportionality, providing a succinct and useful understanding of this enhancement behavior for boiling applications.
Theoretical and numerical analysis of COVID-19 pandemic model with non-local and non-singular kernels
Authors: Cui Ting , Liu Peijiang , Din Anwarud , Ali Fawad
Published: October 2022

The global consequences of Coronavirus (COVID-19) have been evident by several hundreds of demises of human beings; hence such plagues are significantly imperative to predict. For this purpose, the mathematical formulation has been proved to be one of the best tools for the assessment of present circumstances and future predictions. In this article, we propose a fractional epidemic model of coronavirus (COVID-19) with vaccination effects. An arbitrary order model of COVID-19 is analyzed through three different fractional operators namely, Caputo, Atangana-Baleanu-Caputo (ABC), and Caputo-Fabrizio (CF), respectively. The fractional dynamics are composed of the interaction among the human population and the external environmental factors of infected peoples. It gives an extra description of the situation of the epidemic. Both the classical and modern approaches have been tested for the proposed model. The qualitative analysis has been checked through the Banach fixed point theory in the sense of a fractional operator. The stability concept of Hyers-Ulam idea is derived. The Newton interpolation scheme is applied for numerical solutions and by assigning values to different parameters. The numerical works in this research verified the analytical results. Finally, some important conclusions are drawn that might provide further basis for in-depth studies of such epidemics.
Biosynthetic regulatory network of flavonoid metabolites in stems and leaves of Salvia miltiorrhiza
Authors: Yang Hanting , Li Hongyan , Li Qian
Published: October 2022

Flavonoid secondary metabolites can treat and prevent many diseases, but systematic studies on regulation of the biosynthesis of such metabolites in aboveground parts of Salvia miltiorrhiza are lacking. In this study, metabonomic and transcriptomic analyses of different S. miltiorrhiza phenotypes were conducted to explore pathways of synthesis, catalysis, accumulation, and transport of the main flavonoid secondary metabolites regulating pigment accumulation. Tissue localization and quantitative analysis of flavonoid secondary metabolites were conducted by laser scanning confocal microscopy (LSCM). A total 3090 differentially expressed genes were obtained from 114,431 full-length unigenes in purple and green phenotypes, and 108 functional genes were involved in flavonoid biosynthesis. Five key phenylpropane structural genes (PAL, 4CL, ANS, 3AT, HCT) were highly differentially expressed, and four transcription factor genes (MYB, WRKY, bHLH, bZiP) were identified. In addition, six GST genes, nine ABC transporters, 22 MATE genes, and three SNARE genes were detected with key roles in flavonoid transport. According to LSCM, flavonoids were mainly distributed in epidermis, cortex, and collenchyma. Thus, comprehensive and systematic analyses were used to determine biosynthesis, accumulation, and transport of flavonoids in stems and leaves of different S. miltiorrhiza phenotypes. The findings will provide a reference for flavonoid production and cultivar selection.
Performance evaluation of a preclinical SPECT/CT system for multi-animal and multi-isotope quantitative experiments
Authors: Prieto Elena , Irazola Leticia , Collantes María , Ecay Margarita , Cuenca Teresa , Martí-Climent Josep Mª , Peñuelas Iván
Published: October 2022

The aim was to study the performance of the U-SPECT6/CT E-class system for preclinical imaging, to later demonstrate the viability of simultaneous multi-animal and multi-isotope imaging with reliable quantitative accuracy. The performance of the SPECT was evaluated for two collimators dedicated for mouse (UHS-M) and rat imaging (UHR-RM) in terms of sensitivity, energy resolution, uniformity and spatial resolution. Point sources, hot‑rod and uniform phantoms were scanned, and additional tests were carried out to evaluate singular settings such as simultaneous multi-isotope acquisition and imaging with a multi-bed system. For in-vivo evaluation, simultaneous triple-isotope and multi-animal studies were performed on mice. Sensitivity for 99mTc was 2370 cps/MBq for the UHS-M collimator and 493 cps/MBq for the UHR-RM. Rods of 0.6 mm and 0.9 mm were discernible with the UHS-M and UHR-RM collimators respectively, with optimized reconstruction. Uniformity in low counting conditions has proven to be poor (> 75%). Multi-isotope and multi-bed phantom acquisitions demonstrated accurate quantification. In mice, simultaneous multi-isotope imaging provided the separate distribution of 3 tracers and image quality of the multi-mouse bone scan was adequate. The U-SPECT6/CT E-class has shown good sensitivity and spatial resolution. This system provides quantitative images with suitable image quality for multi-mouse and multi-isotope acquisitions.
Prevalence and clinical association of sarcopenia among Thai patients with systemic sclerosis
Authors: Sangaroon Arthitaya , Foocharoen Chingching , Theerakulpisut Daris , Srichompoo Kannikar , Mahakkanukrauh Ajanee , Suwannaroj Siraphop , Seerasaporn Patpiya , Pongchaiyakul Chatlert
Published: October 2022

Patients with systemic sclerosis (SSc) have some potential factors associated with an increased risk of sarcopenia. There has been currently no study to examine such associations in SSc patients. We aimed to determine the prevalence of sarcopenia among SSc patients and examine its association with clinical manifestations and laboratory tests. A cross-sectional study was conducted in 180 adult SSc patients at the Scleroderma Clinic, Khon Kaen University, Thailand, between July 2019 and April 2020. Clinical data, laboratory tests for inflammatory markers, serology, hormone, body composition by dual-energy X-ray absorptiometry, handgrip strength, functional lower extremity strength, and usual gait speed were collected and measured. Sarcopenia was defined according to the criteria of the Asian Working Group for Sarcopenia. One hundred and eighty patients were recruited. Ninety-four cases (52.2%) were the diffuse cutaneous SSc subset. The respective mean age and duration of disease was 58.8 ± 9.4 and 6.2 ± 5.3 years. Sarcopenia was revealed in 41 SSc patients for a prevalence of 22.8% (95% CI 12.1–34.8), while the prevalence was higher in patients with the diffuse cutaneous SSc (dcSSc) compared to the limited cutaneous SSc. BMI at the onset of SSc and C-reactive protein > 5 mg/dL were significantly associated with sarcopenia with a respective OR of 0.60 (95% CI 0.48–0.75) and 3.18 (1.06–9.54). Sarcopenia is common in patients with SSc, but the prevalence is more pronounced in the dcSSc. Inflammatory markers, particularly the CRP level, are strongly associated. BMI at the onset had a negative association with sarcopenia among SSc patients.