bluuebunny/crossref_metadata_2025 huggingface dataset:
Intelligent wireless walls for contactless in-home monitoring
Authors: Usman Muhammad , Rains James , Cui Tie Jun , Khan Muhammad Zakir , Kazim Jalil ur Rehman , Imran Muhammad Ali , Abbasi Qammer H.
Published: July 2022

Human activity monitoring is an exciting research area to assist independent living among disabled and elderly population. Various techniques have been proposed to recognise human activities, such as exploiting sensors, cameras, wearables, and contactless microwave sensing. Among these, the microwave sensing has recently gained significant attention due to its merit to solve the privacy concerns of cameras and discomfort caused by wearables. However, the existing microwave sensing techniques have a basic disadvantage of requiring controlled and ideal settings for high-accuracy activity detections, which restricts its wide adoptions in non-line-of-sight (Non-LOS) environments. Here, we propose a concept of intelligent wireless walls (IWW) to ensure high-precision activity monitoring in complex environments wherein the conventional microwave sensing is invalid. The IWW is composed of a reconfigurable intelligent surface (RIS) that can perform beam steering and beamforming, and machine learning algorithms that can automatically detect the human activities with high accuracy. Two complex environments are considered: one is a corridor junction scenario with transmitter and receiver in separate corridor sections and the other is a multi-floor scenario wherein the transmitter and receiver are placed on two different floors of a building. In each of the aforementioned environments, three distinct body movements are considered namely, sitting, standing, and walking. Two subjects, one male and one female perform these activities in both environments. It is demonstrated that IWW provide a maximum detection gain of 28% in multi-floor scenario and 25% in corridor junction scenario as compared to traditional microwave sensing without RIS.
Low-loss microwave photonics links using hollow core fibres
Authors: Zhang Xi , Feng Zitong , Marpaung David , Fokoua Eric Numkam , Sakr Hesham , Hayes John Richard , Poletti Francesco , Richardson David John , Slavík Radan
Published: July 2022

There are a host of applications in communications, sensing, and science, in which analogue signal transmission is preferred over today’s dominant digital transmission. In some of these applications, the advantage is in lower cost, while in others, it lies in superior performance. However, especially for longer analogue photonics links (up to 10 s of km), the performance is strongly limited by the impairments arising from using standard single-mode fibres (SSMF). Firstly, the three key metrics of analogue links (loss, noise figure, and dynamic range) tend to improve with received power, but this is limited by stimulated Brillouin scattering in SSMF. Further degradation is due to the chromatic dispersion of SSMF, which induces radio-frequency (RF) signal fading, increases even-order distortions, and causes phase-to-intensity-noise conversion. Further distortions still, are caused by the Kerr nonlinearity of SSMF. We propose to address all of these shortcomings by replacing SSMFs with hollow-core optical fibres, which have simultaneously six times lower chromatic dispersion and several orders of magnitude lower nonlinearity (Brillouin, Kerr). We demonstrate the advantages in this application using a 7.7 km long hollow-core fibre sample, significantly surpassing the performance of an SSMF link in virtually every metric, including 15 dB higher link gain and 6 dB lower noise figure.
Impaired hippocampal neurogenesis in vitro is modulated by dietary-related endogenous factors and associated with depression in a longitudinal ageing cohort study
Authors: Du Preez Andrea , Lefèvre-Arbogast Sophie , González-Domínguez Raúl , Houghton Vikki , de Lucia Chiara , Low Dorrain Y. , Helmer Catherine , Féart Catherine , Delcourt Cécile , Proust-Lima Cécile , Pallàs Mercè , Sánchez-Pla Alex , Urpi-Sardà Mireia , Ruigrok Silvie R. , Altendorfer Barbara , Aigner Ludwig , Lucassen Paul J. , Korosi Aniko , Manach Claudine , Andres-Lacueva Cristina , Samieri Cécilia , Thuret Sandrine
Published: July 2022

Environmental factors like diet have been linked to depression and/or relapse risk in later life. This could be partially driven by the food metabolome, which communicates with the brain via the circulatory system and interacts with hippocampal neurogenesis (HN), a form of brain plasticity implicated in depression aetiology. Despite the associations between HN, diet and depression, human data further substantiating this hypothesis are largely missing. Here, we used an in vitro model of HN to test the effects of serum samples from a longitudinal ageing cohort of 373 participants, with or without depressive symptomology. 1% participant serum was applied to human fetal hippocampal progenitor cells, and changes in HN markers were related to the occurrence of depressive symptoms across a 12-year period. Key nutritional, metabolomic and lipidomic biomarkers (extracted from participant plasma and serum) were subsequently tested for their ability to modulate HN. In our assay, we found that reduced cell death and increased neuronal differentiation were associated with later life depressive symptomatology. Additionally, we found impairments in neuronal cell morphology in cells treated with serum from participants experiencing recurrent depressive symptoms across the 12-year period. Interestingly, we found that increased neuronal differentiation was modulated by increased serum levels of metabolite butyrylcarnitine and decreased glycerophospholipid, PC35:1(16:0/19:1), levels – both of which are closely linked to diet – all in the context of depressive symptomology. These findings potentially suggest that diet and altered HN could subsequently shape the trajectory of late-life depressive symptomology.
Epigenetic signatures in antidepressant treatment response: a methylome-wide association study in the EMC trial
Authors: Engelmann J. , Zillich L. , Frank J. , Wagner S. , Cetin M. , Herzog D. P. , Müller M. B. , Tadic A. , Foo J. C. , Sirignano L. , Braus D. F. , Dahmen N. , Sordon S. , Riemenschneider M. , Spaniol C. , Gasparoni G. , Rietschel M. , Witt S. H. , Lieb K. , Streit F.
Published: July 2022

Although the currently available antidepressants are well established in the treatment of the major depressive disorder (MDD), there is strong variability in the response of individual patients. Reliable predictors to guide treatment decisions before or in an early stage of treatment are needed. DNA-methylation has been proven a useful biomarker in different clinical conditions, but its importance for mechanisms of antidepressant response has not yet been determined. 80 MDD patients were selected out of >500 participants from the Early Medication Change (EMC) cohort with available genetic material based on their antidepressant response after four weeks and stratified into clear responders and age- and sex-matched non-responders (N = 40, each). Early improvement after two weeks was analyzed as a secondary outcome. DNA-methylation was determined using the Illumina EPIC BeadChip. Epigenome-wide association studies were performed and differentially methylated regions (DMRs) identified using the comb-p algorithm. Enrichment was tested for hallmark gene-sets and in genome-wide association studies of depression and antidepressant response. No epigenome-wide significant differentially methylated positions were found for treatment response or early improvement. Twenty DMRs were associated with response; the strongest in an enhancer region in SORBS2, which has been related to cardiovascular diseases and type II diabetes. Another DMR was located in CYP2C18, a gene previously linked to antidepressant response. Results pointed towards differential methylation in genes associated with cardiac function, neuroticism, and depression. Linking differential methylation to antidepressant treatment response is an emerging topic and represents a step towards personalized medicine, potentially facilitating the prediction of patients’ response before treatment.
G-CSF plus azacitidine versus azacitidine alone for patients with high-risk myelodysplastic syndrome: academic, open label, randomized trial
Authors: Stopka Tomáš , Minařík Lubomír , Dusilková Nina , Pešta Michal , Kulvait Vojtěch , Špaček Martin , Zemanová Zuzana , Kalousová Marta , Jonášová Anna
Published: July 2022

Trial registration

GA trial is registered under EudraCT#: 2013-001639-38.
Topoisomerase I poison-triggered immune gene activation is markedly reduced in human small-cell lung cancers by impairment of the cGAS/STING pathway
Authors: Marinello Jessica , Arleo Andrea , Russo Marco , Delcuratolo Maria , Ciccarelli Francesca , Pommier Yves , Capranico Giovanni
Published: July 2022

Background

Current immunotherapy strategies have contrasting clinical results in human lung cancer patients as small-cell lung cancers (SCLC) often show features of immunological cold tumours. Topoisomerase 1 (TOP1) poisons are effective antitumor drugs with good efficacy against lung cancers.

Methods

We used molecular, genetic and bioinformatic approaches to determine the mechanism of micronuclei formation induced by two TOP1 poisons in different human cancer cells, including SCLC cell lines.

Results

TOP1 poisons stimulate similar levels of micronuclei in all tested cell lines but downstream effects can vary markedly. TOP1 poisons increase micronuclei levels with a mechanism involving R-loops as overexpression of RNaseH1 markedly reduces or abolishes both H2AX phosphorylation and micronuclei formation. TOP1 poison-induced micronuclei activate the cGAS/STING pathway leading to increased expression of immune genes in HeLa cells, but not in human SCLC cell lines, mainly due to lack of STING and/or cGAS expression. Moreover, the expression of STING and antigen-presenting machinery genes is generally downregulated in patient tumours of human lung cancer datasets.

Conclusions

Altogether, our data reveal an immune signalling mechanism activated by TOP1 poisons, which is often impaired in human SCLC tumours.
CHST15 gene germline mutation is associated with the development of familial myeloproliferative neoplasms and higher transformation risk
Authors: Chen Yi , Zhang Yang , Wang Zhihua , Wang Yewei , Luo Yujiao , Sun Nannan , Zheng Shasha , Yan Wenzhe , Xiao Xiang , Liu Sufang , Li Ji , Peng Hongling , Xu Yunxiao , Hu Guoyu , Cheng Zhao , Zhang Guangsen
Published: July 2022

Herein, we describe the clinical and hematological features of three genetically related families predisposed to myeloproliferative neoplasms (MPNs). Using whole-exome sequencing, we identified a c.1367delG mutation(p.Arg456fs) in CHST15 (NM_001270764), a gene encoding a type II transmembraneglycoproteinthat acts as a sulfotransferase and participates in the biosynthesis of chondroitin sulfate E, in germline and somatic cells in familial MPN. CHST15defects caused an increased JAK2V617F allele burden and upregulated p-Stat3 activity,leading to an increase in the proliferative and prodifferentiation potential of transgenic HEL cells. We demonstrated that mutant CHST15 is able to coimmmunoprecipitate the JAK2 protein,suggesting the presence of a CHST15-JAK2-Stat3 signaling axis in familial MPN. Gene expression profiling showed that the FREM1, IFI27 and C4B_2 genes are overexpressed in familial MPN, suggesting the activation of an “inflammatory response-extracellular matrix-immune regulation” signaling network in the CHST15 mutation background.We thus concluded that CHST15 is a novel gene that predisposes to familial MPN and increases the probability of disease development or transformation.
sGRP78 enhances selective autophagy of monomeric TLR4 to regulate myeloid cell death
Authors: Wu Zhenghao , Xu Zhuoshuo , Zhou Xiaoqi , Li Heli , Zhao Liang , Lv Yibing , Guo Yanyan , Shen Guanxin , He Yong , Lei Ping
Published: July 2022

Soluble glucose regulated protein 78 (sGRP78) has long been suggested as a mediator resolution of inflammation. We previously reported that sGRP78 induced the rapid endocytosis of TLR4 with defective TLR4 signaling. To elucidate the underlying mechanisms, in this study, we investigated how sGRP78 influenced the behavior and trafficking of TLR4 in myeloid cells. It was found that sGRP78 promoted LPS endocytosis with monomeric TLR4. This internalized monomeric TLR4 formed complexes with p62–LC3, and was degraded in autolysosomes. Furthermore, the sGRP78-enhanced autophagy-dependent TLR4 degradation caused apoptosis and ferroptosis in myeloid cells, contributing to the sGRP78-mediated resolution of inflammation. These reports establish innovative mechanisms for endotoxin clearance and immune regulation by TLR4 degradation, linking innate immunity with multiple ancient processes, including autophagy, apoptosis, and ferroptosis, together through a shared resolution-associated molecular pattern (RAMP)—sGRP78.
Fluorescence turn on amine detection in a cationic covalent organic framework
Authors: Das Gobinda , Garai Bikash , Prakasam Thirumurugan , Benyettou Farah , Varghese Sabu , Sharma Sudhir Kumar , Gándara Felipe , Pasricha Renu , Baias Maria , Jagannathan Ramesh , Saleh Na’il , Elhabiri Mourad , Olson Mark A. , Trabolsi Ali
Published: July 2022

Ionic covalent organic frameworks (iCOFs) are new examples of porous materials and have shown great potential for various applications. When functionalized with suitable emission sites, guest uptake via the ionic moieties of iCOFs can cause a significant change in luminescence, making them excellent candidates for chemosensors. In here, we present a luminescence sensor in the form of an ionic covalent organic framework (TGH+•PD) composed of guanidinium and phenanthroline moieties for the detection of ammonia and primary aliphatic amines. TGH+•PD exhibits strong emission enhancement in the presence of selective primary amines due to the suppression of intramolecular charge transfer (ICT) with an ultra-low detection limit of 1.2 × 10‒7M for ammonia. The presence of ionic moieties makes TGH+•PD highly dispersible in water, while deprotonation of the guanidinium moiety by amines restricts its ICT process and signals their presence by enhanced fluorescence emission. The presence of ordered pore walls introduces size selectivity among analyte molecules, and the iCOF has been successfully used to monitor meat products that release biogenic amine vapors upon decomposition due to improper storage.
Mutations in DNA polymerase δ subunit 1 co-segregate with CMD2-type resistance to Cassava Mosaic Geminiviruses
Authors: Lim Yi-Wen , Mansfeld Ben N. , Schläpfer Pascal , Gilbert Kerrigan B. , Narayanan Narayanan N. , Qi Weihong , Wang Qi , Zhong Zhenhui , Boyher Adam , Gehan Jackson , Beyene Getu , Lin Zuh-Jyh Daniel , Esuma Williams , Feng Suhua , Chanez Christelle , Eggenberger Nadine , Adiga Gerald , Alicai Titus , Jacobsen Steven E. , Taylor Nigel J. , Gruissem Wilhelm , Bart Rebecca S.
Published: July 2022

Cassava mosaic disease (CMD) suppresses cassava yields across the tropics. The dominantCMD2locus confers resistance to cassava mosaic geminiviruses. It has been reported that CMD2-type landraces lose resistance after regeneration through de novo morphogenesis. As full genome bisulfite sequencing failed to uncover an epigenetic mechanism for this loss of resistance, whole genome sequencing and genetic variant analysis was performed and the CMD2 locus was fine-mapped to a 190 kilobase interval. Collectively, these data indicate that CMD2-type resistance is caused by a nonsynonymous, single nucleotide polymorphism inDNA polymerase δ subunit 1(MePOLD1) located within this region. Virus-induced gene silencing ofMePOLD1in a CMD-susceptible cassava variety produced a recovery phenotype typical of CMD2-type resistance. Analysis of other CMD2-type cassava varieties identified additional candidate resistance alleles withinMePOLD1. Genetic variation ofMePOLD1, therefore, could represent an important genetic resource for resistance breeding and/or genome editing, and elucidating mechanisms of resistance to geminiviruses.
Characterization of core fucosylation via sequential enzymatic treatments of intact glycopeptides and mass spectrometry analysis
Authors: Cao Liwei , Lih T. Mamie , Hu Yingwei , Schnaubelt Michael , Chen Shao-Yung , Zhou Yangying , Guo Chuanyu , Dong Mingming , Yang Weiming , Eguez Rodrigo Vargas , Chen Lijun , Clark David J. , Sodhi Akrit , Li Qing Kay , Zhang Hui
Published: July 2022

Core fucosylation of N-linked glycoproteins has been linked to the functions of glycoproteins in physiological and pathological processes. However, quantitative characterization of core fucosylation remains challenging due to the complexity and heterogeneity of N-linked glycosylation. Here we report a mass spectrometry-based method that employs sequential treatment of intact glycopeptides with enzymes (STAGE) to analyze site-specific core fucosylation of glycoproteins. The STAGE method utilizes Endo F3 followed by PNGase F treatment to generate mass signatures for glycosites that are formerly modified by core fucosylated N-linked glycans. We benchmark the STAGE method and use it to characterize site specific core fucosylation of glycoproteins from human hepatocellular carcinoma and pancreatic ductal adenocarcinoma, resulting in the identification of 1130 and 782 core fucosylated glycosites, respectively. These results indicate that our STAGE method enables quantitative characterization of core fucosylation events from complex protein mixtures, which may benefit our understanding of core fucosylation functions in various diseases.
TGFβ reprograms TNF stimulation of macrophages towards a non-canonical pathway driving inflammatory osteoclastogenesis
Authors: Xia Yuhan , Inoue Kazuki , Du Yong , Baker Stacey J. , Reddy E. Premkumar , Greenblatt Matthew B. , Zhao Baohong
Published: July 2022

It is well-established that receptor activator of NF-κB ligand (RANKL) is the inducer of physiological osteoclast differentiation. However, the specific drivers and mechanisms driving inflammatory osteoclast differentiation under pathological conditions remain obscure. This is especially true given that inflammatory cytokines such as tumor necrosis factor (TNF) demonstrate little to no ability to directly drive osteoclast differentiation. Here, we found that transforming growth factor β (TGFβ) priming enables TNF to effectively induce osteoclastogenesis, independently of the canonical RANKL pathway. Lack of TGFβ signaling in macrophages suppresses inflammatory, but not basal, osteoclastogenesis and bone resorption in vivo. Mechanistically, TGFβ priming reprograms the macrophage response to TNF by remodeling chromatin accessibility and histone modifications, and enables TNF to induce a previously unrecognized non-canonical osteoclastogenic program, which includes suppression of the TNF-induced IRF1-IFNβ-IFN-stimulated-gene axis, IRF8 degradation and B-Myb induction. These mechanisms are active in rheumatoid arthritis, in which TGFβ level is elevated and correlates with osteoclast activity. Our findings identify a TGFβ/TNF-driven inflammatory osteoclastogenic program, and may lead to development of selective treatments for inflammatory osteolysis.
Mode-pairing quantum key distribution
Authors: Zeng Pei , Zhou Hongyi , Wu Weijie , Ma Xiongfeng
Published: July 2022

Quantum key distribution — the establishment of information-theoretically secure keys based on quantum physics — is mainly limited by its practical performance, which is characterised by the dependence of the key rate on the channel transmittance R(η). Recently, schemes based on single-photon interference have been proposed to improve the key rate to $$R=O(\sqrt{\eta })$$
R
=
O

(

η

)

by overcoming the point-to-point secret key capacity bound with interferometers. Unfortunately, all of these schemes require challenging global phase locking to realise a stable long-arm single-photon interferometer with a precision of approximately 100 nm over fibres that are hundreds of kilometres long. Aiming to address this problem, we propose a mode-pairing measurement-device-independent quantum key distribution scheme in which the encoded key bits and bases are determined during data post-processing. Using conventional second-order interference, this scheme can achieve a key rate of $$R=O(\sqrt{\eta })$$
R
=
O

(

η

)

without global phase locking when the local phase fluctuation is mild. We expect this high-performance scheme to be ready-to-implement with off-the-shelf optical devices.
Audiovisual adaptation is expressed in spatial and decisional codes
Authors: Aller Máté , Mihalik Agoston , Noppeney Uta
Published: July 2022

The brain adapts dynamically to the changing sensory statistics of its environment. Recent research has started to delineate the neural circuitries and representations that support this cross-sensory plasticity. Combining psychophysics and model-based representational fMRI and EEG we characterized how the adult human brain adapts to misaligned audiovisual signals. We show that audiovisual adaptation is associated with changes in regional BOLD-responses and fine-scale activity patterns in a widespread network from Heschl’s gyrus to dorsolateral prefrontal cortices. Audiovisual recalibration relies on distinct spatial and decisional codes that are expressed with opposite gradients and time courses across the auditory processing hierarchy. Early activity patterns in auditory cortices encode sounds in a continuous space that flexibly adapts to misaligned visual inputs. Later activity patterns in frontoparietal cortices code decisional uncertainty consistent with these spatial transformations. Our findings suggest that regions within the auditory processing hierarchy multiplex spatial and decisional codes to adapt flexibly to the changing sensory statistics in the environment.
Light sources with bias tunable spectrum based on van der Waals interface transistors
Authors: Henck Hugo , Mauro Diego , Domaretskiy Daniil , Philippi Marc , Memaran Shahriar , Zheng Wenkai , Lu Zhengguang , Shcherbakov Dmitry , Lau Chun Ning , Smirnov Dmitry , Balicas Luis , Watanabe Kenji , Taniguchi Takashi , Fal’ko Vladimir I. , Gutiérrez-Lezama Ignacio , Ubrig Nicolas , Morpurgo Alberto F.
Published: July 2022

Light-emitting electronic devices are ubiquitous in key areas of current technology, such as data communications, solid-state lighting, displays, and optical interconnects. Controlling the spectrum of the emitted light electrically, by simply acting on the device bias conditions, is an important goal with potential technological repercussions. However, identifying a material platform enabling broad electrical tuning of the spectrum of electroluminescent devices remains challenging. Here, we propose light-emitting field-effect transistors based on van der Waals interfaces of atomically thin semiconductors as a promising class of devices to achieve this goal. We demonstrate that large spectral changes in room-temperature electroluminescence can be controlled both at the device assembly stage –by suitably selecting the material forming the interfaces– and on-chip, by changing the bias to modify the device operation point. Even though the precise relation between device bias and kinetics of the radiative transitions remains to be understood, our experiments show that the physical mechanism responsible for light emission is robust, making these devices compatible with simple large areas device production methods.
TET1 dioxygenase is required for FOXA2-associated chromatin remodeling in pancreatic beta-cell differentiation
Authors: Li Jianfang , Wu Xinwei , Ke Jie , Lee Minjung , Lan Qingping , Li Jia , Yu Jianxiu , Huang Yun , Sun De-Qiang , Xie Ruiyu
Published: July 2022

Existing knowledge of the role of epigenetic modifiers in pancreas development has exponentially increased. However, the function of TET dioxygenases in pancreatic endocrine specification remains obscure. We set out to tackle this issue using a human embryonic stem cell (hESC) differentiation system, in which TET1/TET2/TET3 triple knockout cells display severe defects in pancreatic β-cell specification. The integrative whole-genome analysis identifies unique cell-type-specific hypermethylated regions (hyper-DMRs) displaying reduced chromatin activity and remarkable enrichment of FOXA2, a pioneer transcription factor essential for pancreatic endoderm specification. Intriguingly, TET depletion leads to significant changes in FOXA2 binding at the pancreatic progenitor stage, in which gene loci with decreased FOXA2 binding feature low levels of active chromatin modifications and enriches for bHLH motifs. Transduction of full-length TET1 but not the TET1-catalytic-domain in TET-deficient cells effectively rescues β-cell differentiation accompanied by restoring PAX4 hypomethylation. Taking these findings together with the defective generation of functional β-cells upon TET1-inactivation, our study unveils an essential role of TET1-dependent demethylation in establishing β-cell identity. Moreover, we discover a physical interaction between TET1 and FOXA2 in endodermal lineage intermediates, which provides a mechanistic clue regarding the complex crosstalk between TET dioxygenases and pioneer transcription factors in epigenetic regulation during pancreas specification.
Transcriptional programming in a Bacteroides consortium
Authors: Huang Brian D. , Groseclose Thomas M. , Wilson Corey J.
Published: July 2022

Bacteroides species are prominent members of the human gut microbiota. The prevalence and stability of Bacteroides in humans make them ideal candidates to engineer as programmable living therapeutics. Here we report a biotic decision-making technology in a community of Bacteroides (consortium transcriptional programming) with genetic circuit compression. Circuit compression requires systematic pairing of engineered transcription factors with cognate regulatable promoters. In turn, we demonstrate the compression workflow by designing, building, and testing all fundamental two-input logic gates dependent on the inputs isopropyl-β-D-1-thiogalactopyranoside and D-ribose. We then deploy complete sets of logical operations in five human donor Bacteroides, with which we demonstrate sequential gain-of-function control in co-culture. Finally, we couple transcriptional programs with CRISPR interference to achieve loss-of-function regulation of endogenous genes—demonstrating complex control over community composition in co-culture. This work provides a powerful toolkit to program gene expression in Bacteroides for the development of bespoke therapeutic bacteria.
Sex-specific regulation of inhibition and network activity by local aromatase in the mouse hippocampus
Authors: Hernández-Vivanco Alicia , Cano-Adamuz Nuria , Sánchez-Aguilera Alberto , González-Alonso Alba , Rodríguez-Fernández Alberto , Azcoitia Íñigo , de la Prida Liset Menendez , Méndez Pablo
Published: July 2022

Cognitive function relies on a balanced interplay between excitatory and inhibitory neurons (INs), but the impact of estradiol on IN function is not fully understood. Here, we characterize the regulation of hippocampal INs by aromatase, the enzyme responsible for estradiol synthesis, using a combination of molecular, genetic, functional and behavioral tools. The results show that CA1 parvalbumin-expressing INs (PV-INs) contribute to brain estradiol synthesis. Brain aromatase regulates synaptic inhibition through a mechanism that involves modification of perineuronal nets enwrapping PV-INs. In the female brain, aromatase modulates PV-INs activity, the dynamics of network oscillations and hippocampal-dependent memory. Aromatase regulation of PV-INs and inhibitory synapses is determined by the gonads and independent of sex chromosomes. These results suggest PV-INs are mediators of estrogenic regulation of behaviorally-relevant activity.
Highly robust and soft biohybrid mechanoluminescence for optical signaling and illumination
Authors: Li Chenghai , He Qiguang , Wang Yang , Wang Zhijian , Wang Zijun , Annapooranan Raja , Latz Michael I. , Cai Shengqiang
Published: July 2022

Biohybrid is a newly emerging and promising approach to construct soft robotics and soft machines with novel functions, high energy efficiency, great adaptivity and intelligence. Despite many unique advantages of biohybrid systems, it is well known that most biohybrid systems have a relatively short lifetime, require complex fabrication process, and only remain functional with careful maintenance. Herein, we introduce a simple method to create a highly robust and power-free soft biohybrid mechanoluminescence, by encapsulating dinoflagellates, bioluminescent unicellular marine algae, into soft elastomeric chambers. The dinoflagellates retain their intrinsic bioluminescence, which is a near-instantaneous light response to mechanical forces. We demonstrate the robustness of various geometries of biohybrid mechanoluminescent devices, as well as potential applications such as visualizing external mechanical perturbations, deformation-induced illumination, and optical signaling in a dark environment. Our biohybrid mechanoluminescent devices are ultra-sensitive with fast response time and can maintain their light emission capability for weeks without special maintenance.
Assessing the effectiveness of orchestrated climate action from five years of summits
Authors: Chan Sander , Hale Thomas , Deneault Andrew , Shrivastava Manish , Mbeva Kennedy , Chengo Victoria , Atela Joanes
Published: July 2022

Action-oriented summits like the 2018 Global Climate Action Summit and 2019 UN Climate Action Summit, have become a major feature of global climate governance. Their emphasis on cooperative initiatives by a host of non-state and local actors creates high expectations, especially when, according to the IPCC, governments’ policies still set the world on course for a disastrous 2.7 °C warming. While earlier studies have cautioned against undue optimism, empirical evidence on summits and their ability to leverage transnational capacities has been scarce. Here using a dataset of 276 climate initiatives we show important differences in output performance, with no improvement among initiatives associated with more recent summits. A summit’s focus on certain themes and an emphasis on minimal requirements for institutional robustness, however, can positively influence the effectiveness of transnational engagement. These results make an empirical contribution towards understanding the increasingly transnational nature of climate governance.
A randomised controlled trial of interventions for taxane-induced nail toxicity in women with early breast cancer
Authors: Morrison Audrey , Marshall-McKenna Rebecca , McFadyen Angus K. , Hutchison Cathy , Rice Ann-Marie , Stirling Lynne , McIlroy Pauline , Macpherson Iain R.
Published: July 2022

Onycholysis and paronychia has been associated with chemotherapy treatment for women with breast cancer. Our primary aim was to investigate the effectiveness of different topical interventions to ameliorate nail toxicity. Secondary aims were to explore the full range and severity of possible nail changes associated with taxane-based chemotherapy and the specific impact this had on quality of life, using two novel measures. This was an exploratory randomised controlled trial of three topical interventions (standard care, nail polish or specialist nail drops) for the prevention or reduction of nail changes induced by taxane-based chemotherapy. Outcomes included nail toxicity assessed at three time points (baseline, 3 weeks and 3 months post completion of chemotherapy) using two novel clinical tools (NToX-G12, NToX-QoL) and the Common Terminology Criteria for Adverse Events (CTCAE v3) and EQ-5D-5L. A total of 105 women were recruited (35 in each arm) and monitored up to three months post completion of chemotherapy. Almost 20% of patients were over the age of 60 years. There were 26 withdrawals, the majority from the nail polish arm. Residual Maximum Likelihood REML analysis indicated a significant arm, time and interaction effect for each intervention (p < 0.001). Less nail toxicity was observed in patients receiving specialist nail drops or standard care arms in comparison to those using nail polish. This study provides evidence to support clinicians’ suggestions on nail care recommendations based on the patients’ needs and preferences. Future investigations into comparing or combining cryotherapy and topical solutions that can support patient’s decisions are warranted.
Return of large fin whale feeding aggregations to historical whaling grounds in the Southern Ocean
Authors: Herr Helena , Viquerat Sacha , Devas Fredi , Lees Abigail , Wells Lucy , Gregory Bertie , Giffords Ted , Beecham Dan , Meyer Bettina
Published: July 2022

Fin whales (Balaenoptera physalus quoyi) of the Southern Hemisphere were brought to near extinction by twentieth century industrial whaling. For decades, they had all but disappeared from previously highly frequented feeding grounds in Antarctic waters. Our dedicated surveys now confirm their return to ancestral feeding grounds, gathering at the Antarctic Peninsula in large aggregations to feed. We report on the results of an abundance survey and present the first scientific documentation of large fin whale feeding aggregations at Elephant Island, Antarctica, including the first ever video documentation. We interpret high densities, re-establishment of historical behaviours and the return to ancestral feeding grounds as signs for a recovering population. Recovery of a large whale population has the potential to augment primary productivity at their feeding grounds through the effects of nutrient recycling, known as 'the whale pump'. The recovery of fin whales in that area could thus restore ecosystem functions crucial for atmospheric carbon regulation in the world's most important ocean region for the uptake of anthropogenic CO2.
Structural and biochemical analyses of the flagellar expression regulator DegU from Listeria monocytogenes
Authors: Oh Han Byeol , Lee Su-jin , Yoon Sung-il
Published: July 2022

Listeria monocytogenes is a pathogenic bacterium that produces flagella, the locomotory organelles, in a temperature-dependent manner. At 37 °C inside humans, L. monocytogenes employs MogR to repress the expression of flagellar proteins, thereby preventing the production of flagella. However, in the low-temperature environment outside of the host, the antirepressor GmaR inactivates MogR, allowing flagellar formation. Additionally, DegU is necessary for flagellar expression at low temperatures. DegU transcriptionally activates the expression of GmaR and flagellar proteins by binding the operator DNA in the fliN-gmaR promoter as a response regulator of a two-component regulatory system. To determine the DegU-mediated regulation mechanism, we performed structural and biochemical analyses on the recognition of operator DNA by DegU. The DegU-DNA interaction is primarily mediated by a C-terminal DNA-binding domain (DBD) and can be fortified by an N-terminal receiver domain (RD). The DegU DBD adopts a tetrahelical helix-turn-helix structure and assembles into a dimer. The DegU DBD dimer recognizes the operator DNA using a positive patch. Unexpectedly, unlike typical response regulators, DegU interacts with operator DNA in both unphosphorylated and phosphorylated states with similar binding affinities. Therefore, we conclude that DegU is a noncanonical response regulator that is constitutively active irrespective of phosphorylation.
High rates of plasmid cotransformation in E. coli overturn the clonality myth and reveal colony development
Authors: Tomoiaga Delia , Bubnell Jaclyn , Herndon Liam , Feinstein Paul
Published: July 2022

The concept of DNA transfer between bacteria was put forth by Griffith in 1928. During the dawn of molecular cloning of DNA in the 1980s, Hanahan described how the transformation of DNA plasmids into bacteria would allow for cloning of DNA fragments. Through this foundational work, it is widely taught that a typical transformation produces clonal bacterial colonies. Using low concentrations of several plasmids that encode different fluorescent proteins, under the same selective antibiotic, we show that E. coli bacteria readily accept multiple plasmids, resulting in widespread aclonality and reveal a complex pattern of colony development. Cotransformation of plasmids occurs by either CaCl2 or by electroporation methods. A bacterium rod transformed with three plasmids—each expressing a high level of a unique fluorescent protein—and replated on agar, appears to reassign a random number of the three fluorescent plasmids to its daughter cell during cell division. The potential to simultaneously follow multiple lineages of clonally related bacteria in a bacteria colony would allow for mosaic analysis of gene function. We show that clonally related bacterium rods self-organize in a fractal growth pattern and can remain linked during colony development revealing a potential target against microbiota growth.
Nonreproductive effects are more important than reproductive effects in a host feeding parasitoid
Authors: Zhang Yibo , Tian Xiaocao , Wang Hao , Castañé Cristina , Arnó Judit , Wu Suran , Xian Xiaoqing , Liu Wanxue , Desneux Nicolas , Wan Fanghao , Zhang Guifen
Published: July 2022

When female host feeding parasitoids encounter a potential host, they face a complicated trade-off between either laying an egg for investing in current reproduction or feeding on or killing the host for future reproduction. Few studies have measured these behavioral shift patterns in a given host-parasitoid association thus far. We systematically assessed the behavioral shifts and life history traits of a host feeding parasitoid, Necremnus tutae, on different instars of its host Tuta absoluta. N. tutae females, as idiobiont host feeding parasitoids, can act on the 1st–4th instar larvae of T. absoluta by either host feeding, parasitizing or host killing. Moreover, a significant behavioral shift was observed on different instar hosts. N. tutae preferred to feed on the young hosts (1st and 2nd instars), lay eggs on middle-aged hosts (3rd instars) and kill old hosts (4th instars) by ovipositor-mediated stinging. The offspring of N. tutae showed a significant female-biased sex ratio, with the number of instars of T. absoluta larvae that were parasitized increasing. Specifically, nonreproductive host mortality induced by host feeding and host killing accounted for high percentages of the total mortality (ranging from 70% on 3rd instar hosts to 88% on 1st instar and 4th instar hosts). We hypothesize that N. tutae could be not merely a parasitoid but also a predator. Our results shed light on the nonreproductive abilities of a host feeding parasitoid that should be given further attention, especially when evaluating the efficacy of parasitoids.
Phyllanthus amarus shoot cultures as a source of biologically active lignans: the influence of selected plant growth regulators
Authors: Sparzak-Stefanowska Barbara , Krauze-Baranowska Mirosława
Published: July 2022

This is the first comprehensive study of the influence of plant growth regulators (PGRs) on the development of shoots and accumulation of biologically active lignans—phyllanthin and hypophyllanthin, in the shoot culture ofP. amarusSchum. & Thonn. (Euphorbiaceae) obtained by direct organogenesis. The following PGRs were included in the experiments—cytokinins: kinetin (Kin), 6-benzylaminopurine (BAP), 2-isopentenyladenine (2iP), 1-phenyl-3-(1,2,3-thiadiazol-5-yl)urea, thidiazuron (TDZ) and auxin, indole-3-butyric acid (IBA) and used at various concentrations. Depending on PGRs and their concentrations, differences in the culture response and lignan accumulation were observed. The highest content of the investigated compounds was found in the shoot culture grown on Murashige and Skoog’s (MS) medium supplemented with Kin 0.25 mg/L. The sum of phyllanthin and hypophyllanthin was  ~ 10 mg/g of dry weight (DW), which was similar or even higher than that in the plant material obtained from natural conditions. The results of the research provide new data on the selection of the optimal growth medium for the production of plant material with a significant level of phyllanthin and hypophyllanthin biosynthesis. The obtained data may also be valuable in designing systems for large-scale cultivation ofP. amarusshoots with high productivity of hepatoprotective lignans.
Adipocyte differentiation between obese and lean conditions depends on changes in miRNA expression
Authors: Heo Yerim , Kim Hyunjung , Lim Jiwon , Choi Sun Shim
Published: July 2022

Adipogenesis is the process by which precursor cells, preadipocytes (preACs), differentiate into adipocytes (ACs). Here, we investigated differentially expressed miRNAs (DEMs) between the two conditions to understand the regulatory role of miRNAs in altering adipogenesis-related mRNAs. A total of 812 and 748 DEMs were obtained in lean and obese conditions, respectively. The up- and downregulated DEMs were highly concordant with each other in both lean and obese conditions; however, DEMs related to adipogenesis in obese conditions were more strongly downregulated than DEMs related to adipogenesis in lean conditions. There were more obese-specific downregulated DEMs than lean-specific downregulated DEMs; in contrast, there were more lean-specific upregulated DEMs than obese-specific upregulated DEMs. Approximately 45% of DEMs were mapped to the list of miRNA-target mRNA pairs when DEMs were matched to the experimentally validated list of miRNA-target mRNA information of miRTarBase. Many of the target mRNAs were differentially expressed genes (DEGs) with functions in processes such as inflammatory responses and fat metabolism. In particular, a total of 25 miRNAs that target three upregulated adipogenesis-associated inflammatory genes (IL-6, TNF-α, and IL-1β) were commonly altered during adipogenesis. Taken together, our study reveals the types of adipogenesis-related miRNAs that are altered and the degree to which they influence healthy or pathogenic adipogenesis.
Mesenchymal stem cells promote spermatogonial stem/progenitor cell pool and spermatogenesis in neonatal mice in vitro
Authors: Önen Selin , Köse Sevil , Yersal Nilgün , Korkusuz Petek
Published: July 2022

Prepubertal cancer treatment leads to irreversible infertility in half of the male patients. Current in vitro spermatogenesis protocols and cryopreservation techniques are inadequate to expand spermatogonial stem/progenitor cells (SSPC) from testicles. Bone marrow derived mesenchymal stem cells (BM-MSC) bearing a close resemblance to Sertoli cells, improved spermatogenesis in animal models. We asked if a co-culture setup supported by syngeneic BM-MSC that contributes to the air–liquid interphase (ALI) could lead to survival, expansion and differentiation of SSPCs in vitro. We generated an ALI platform able to provide a real-time cellular paracrine contribution consisting of syngeneic BM-MSCs to neonatal C57BL/6 mice testes. We aimed to evaluate the efficacy of this culture system on SSPC pool expansion and spermatogenesis throughout a complete spermatogenic cycle by measuring the number of total germ cells (GC), the undifferentiated and differentiating spermatogonia, the spermatocytes and the spermatids. Furthermore, we evaluated the testicular cell cycle phases, the tubular and luminal areas using histochemical, immunohistochemical and flow cytometric techniques. Cultures in present of BM-MSCs displayed survival of ID4(+) spermatogonial stem cells (SSC), expansion of SALL4(+) and OCT4(+) SSPCs, VASA(+) total GCs and Ki67(+) proliferative cells at 42 days and an increased number of SCP3(+) spermatocytes and Acrosin(+) spermatids at 28 days. BM-MSCs increased the percentage of mitotic cells within the G2-M phase of the total testicular cell cycle increased for 7 days, preserved the cell viability for 42 days and induced testicular maturation by enlargement of the tubular and luminal area for 42 days in comparison to the control. The percentage of PLZF(+) SSPCs increased within the first 28 days of culture, after which the pool started to get smaller while the number of spermatocytes and spermatids increased simultaneously. Our findings established the efficacy of syngeneic BM-MSCs on the survival and expansion of the SSPC pool and differentiation of spermatogonia to round spermatids during in vitro culture of prepubertal mice testes for 42 days. This method may be helpful in providing alternative cures for male fertility by supporting in vitro differentiated spermatids that can be used for round spermatid injection (ROSI) to female oocyte in animal models. These findings can be further exploited for personalized cellular therapy strategies to cure male infertility of prepubertal cancer survivors in clinics.
Detecting lineage-defining mutations in SARS-CoV-2 using colorimetric RT-LAMP without probes or additional primers
Authors: dos Santos Carlos Abelardo , Silva Lívia do Carmo , Souza Júnior Marcio Neres de , Mendes Geovana de Melo , Estrela Paulo Felipe Neves , de Oliveira Kézia Gomes , de Curcio Juliana Santana , Resende Paola Cristina , Siqueira Marilda Mendonça , Pauvolid-Corrêa Alex , Duarte Gabriela Rodrigues Mendes , Silveira-Lacerda Elisângela de Paula
Published: July 2022

Despite the advance of vaccination worldwide, epidemic waves caused by more transmissible and immune evasive genetic variants of SARS-CoV-2 have sustained the ongoing pandemic of COVID-19. Monitoring such variants is expensive, as it usually relies on whole-genome sequencing methods. Therefore, it is necessary to develop alternatives that could help identify samples from specific variants. Reverse transcription loop-mediated isothermal amplification is a method that has been increasingly used for nucleic acid amplification, as it is cheaper and easier to perform when compared to other molecular techniques. As a proof of concept that can help distinguish variants, we present an RT-LAMP assay capable of detecting samples carrying a group of mutations that can be related to specific SARS-CoV-2 lineages, here demonstrated for the Variant of Concern Gamma. We tested 60 SARS-CoV-2 RNA samples extracted from swab samples and the reaction showed a sensitivity of 93.33%, a specificity of 88.89% and a kappa value of 0.822 for samples with a Ct ≤ 22.93. The RT-LAMP assay demonstrated to be useful to distinguish VOC Gamma and may be of particular interest as a screening approach for variants in countries with poor sequencing coverage.