bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomics of autism and Alzheimer’s mouse models reveal common alterations in mTOR signaling pathway
Authors: Mencer Shira , Kartawy Maryam , Lendenfeld Felix , Soluh Huda , Tripathi Manish Kumar , Khaliulin Igor , Amal Haitham
Published: September 2021

Autism spectrum disorder (ASD) and Alzheimer’s disease (AD) are two different neurological disorders that share common clinical features, such as language impairment, executive functions, and motor problems. A genetic convergence has been proposed as well. However, the molecular mechanisms of these pathologies are still not well understood. Protein S-nitrosylation (SNO), the nitric oxide (NO)-mediated posttranslational modification, targets key proteins implicated in synaptic and neuronal functions. Previously, we have shown that NO and SNO are involved in the InsG3680(+/+) ASD and P301S AD mouse models. Here, we performed large-scale computational biology analysis of the SNO-proteome followed by biochemical validation to decipher the shared mechanisms between the pathologies. This analysis pointed to the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway as one of the shared molecular mechanisms. Activation of mTOR in the cortex of both mouse models was confirmed by western blots that showed increased phosphorylation of RPS6, a major substrate of mTORC1. Other molecular alterations affected by SNO and shared between the two mouse models, such as synaptic-associated processes, PKA signaling, and cytoskeleton-related processes were also detected. This is the first study to decipher the SNO-related shared mechanisms betweenSHANK3andMAPTmutations. Understanding the involvement of SNO in neurological disorders and its intersection between ASD and AD might help developing an effective novel therapy for both neuropathologies.
Lead-substituted barium hexaferrite for tunable terahertz optoelectronics
Authors: Alyabyeva L. N. , Prokhorov A. S. , Vinnik D. A. , Anzin V. B. , Ahmed A. G. , Mikheykin A. , Bednyakov P. , Kadlec C. , Kadlec F. , de Prado E. , Prokleška J. , Proschek P. , Kamba S. , Pronin A. V. , Dressel M. , Abalmasov V. A. , Dremov V. V. , Schmid S. , Savinov M. , Lunkenheimer P. , Gorshunov B. P.
Published: September 2021

Due to their outstanding dielectric and magnetic properties, hexaferrites are attracting ever-increasing attention for developing electronic components of next-generation communication systems. The complex crystal structure of hexaferrites and the critical dependences of their electric and magnetic properties on external factors, such as magnetic/electric fields, pressure, and doping, open ample opportunities for targeted tuning of these properties when designing specific devices. Here we explored the electromagnetic properties of lead-substituted barium hexaferrite, Ba1−xPbxFe12O19, a compound featuring an extremely rich set of physical phenomena that are inherent in the dielectric and magnetic subsystems and can have a significant effect on its electromagnetic response at terahertz frequencies. We performed the first detailed measurements of the temperature-dependent (5–300 K) dielectric response of single-crystalline Ba1−xPbxFe12O19 in an extremely broad spectral range of 1 Hz–240 THz. We fully analyzed numerous phenomena with a corresponding wide distribution of specific energies that can affect the terahertz properties of the material. The most important fundamental finding is the observation of a ferroelectric-like terahertz excitation with an unusual temperature behavior of its frequency and strength. We suggest microscopic models that explain the origin of the excitation and its nonstandard temperature evolution. Several narrower terahertz excitations are associated with electronic transitions between the fine-structure components of the Fe2+ ground state. The discovered radio-frequency relaxations are attributed to the response of magnetic domains. Gigahertz resonances are presumably of magnetoelectric origin. The obtained data on diverse electromagnetic properties of Ba1−xPbxFe12O19 compounds provide information that makes the entire class of hexaferrites attractive for manufacturing electronic devices for the terahertz range.
Narrow-band high-lying excitons with negative-mass electrons in monolayer WSe2
Authors: Lin Kai-Qiang , Ong Chin Shen , Bange Sebastian , Faria Junior Paulo E. , Peng Bo , Ziegler Jonas D. , Zipfel Jonas , Bäuml Christian , Paradiso Nicola , Watanabe Kenji , Taniguchi Takashi , Strunk Christoph , Monserrat Bartomeu , Fabian Jaroslav , Chernikov Alexey , Qiu Diana Y. , Louie Steven G. , Lupton John M.
Published: September 2021

Monolayer transition-metal dichalcogenides (TMDCs) show a wealth of exciton physics. Here, we report the existence of a new excitonic species, the high-lying exciton (HX), in single-layer WSe2 with an energy of ~3.4 eV, almost twice the band-edge A-exciton energy, with a linewidth as narrow as 5.8 meV. The HX is populated through momentum-selective optical excitation in the K-valleys and is identified in upconverted photoluminescence (UPL) in the UV spectral region. Strong electron-phonon coupling results in a cascaded phonon progression with equidistant peaks in the luminescence spectrum, resolvable to ninth order. Ab initio GW-BSE calculations with full electron-hole correlations explain HX formation and unmask the admixture of upper conduction-band states to this complex many-body excitation. These calculations suggest that the HX is comprised of electrons of negative mass. The coincidence of such high-lying excitonic species at around twice the energy of band-edge excitons rationalizes the excitonic quantum-interference phenomenon recently discovered in optical second-harmonic generation (SHG) and explains the efficient Auger-like annihilation of band-edge excitons.
Cross-species behavior analysis with attention-based domain-adversarial deep neural networks
Authors: Maekawa Takuya , Higashide Daiki , Hara Takahiro , Matsumura Kentarou , Ide Kaoru , Miyatake Takahisa , Kimura Koutarou D. , Takahashi Susumu
Published: September 2021

Since the variables inherent to various diseases cannot be controlled directly in humans, behavioral dysfunctions have been examined in model organisms, leading to better understanding their underlying mechanisms. However, because the spatial and temporal scales of animal locomotion vary widely among species, conventional statistical analyses cannot be used to discover knowledge from the locomotion data. We propose a procedure to automatically discover locomotion features shared among animal species by means of domain-adversarial deep neural networks. Our neural network is equipped with a function which explains the meaning of segments of locomotion where the cross-species features are hidden by incorporating an attention mechanism into the neural network, regarded as a black box. It enables us to formulate a human-interpretable rule about the cross-species locomotion feature and validate it using statistical tests. We demonstrate the versatility of this procedure by identifying locomotion features shared across different species with dopamine deficiency, namely humans, mice, and worms, despite their evolutionary differences.
Promoter-proximal elongation regulates transcription in archaea
Authors: Blombach Fabian , Fouqueau Thomas , Matelska Dorota , Smollett Katherine , Werner Finn
Published: September 2021

Recruitment of RNA polymerase and initiation factors to the promoter is the only known target for transcription activation and repression in archaea. Whether any of the subsequent steps towards productive transcription elongation are involved in regulation is not known. We characterised how the basal transcription machinery is distributed along genes in the archaeon Saccharolobus solfataricus. We discovered a distinct early elongation phase where RNA polymerases sequentially recruit the elongation factors Spt4/5 and Elf1 to form the transcription elongation complex (TEC) before the TEC escapes into productive transcription. TEC escape is rate-limiting for transcription output during exponential growth. Oxidative stress causes changes in TEC escape that correlate with changes in the transcriptome. Our results thus establish that TEC escape contributes to the basal promoter strength and facilitates transcription regulation. Impaired TEC escape coincides with the accumulation of initiation factors at the promoter and recruitment of termination factor aCPSF1 to the early TEC. This suggests two possible mechanisms for how TEC escape limits transcription, physically blocking upstream RNA polymerases during transcription initiation and premature termination of early TECs.
Incipient diploidization of the medicinal plant Perilla within 10,000 years
Authors: Zhang Yujun , Shen Qi , Leng Liang , Zhang Dong , Chen Sha , Shi Yuhua , Ning Zemin , Chen Shilin
Published: September 2021

Perilla is a young allotetraploid Lamiaceae species widely used in East Asia as herb and oil plant. Here, we report the high-quality, chromosome-scale genomes of the tetraploid (Perilla frutescens) and the AA diploid progenitor (Perilla citriodora). Comparative analyses suggest post Neolithic allotetraploidization within 10,000 years, and nucleotide mutation in tetraploid is 10% more than in diploid, both of which are dominated by G:C → A:T transitions. Incipient diploidization is characterized by balanced swaps of homeologous segments, and subsequent homeologous exchanges are enriched towards telomeres, with excess of replacements of AA genes by fractionated BB homeologs. Population analyses suggest that the crispa lines are close to the nascent tetraploid, and involvement of acyl-CoA: lysophosphatidylcholine acyltransferase gene for high α-linolenic acid content of seed oil is revealed by GWAS. These resources and findings provide insights into incipient diploidization and basis for breeding improvement of this medicinal plant.
A phase 2, proof of concept, randomised controlled trial of berberine ursodeoxycholate in patients with presumed non-alcoholic steatohepatitis and type 2 diabetes
Authors: Harrison Stephen A. , Gunn Nadege , Neff Guy W. , Kohli Anita , Liu Liping , Flyer Abbey , Goldkind Lawrence , Di Bisceglie Adrian M.
Published: September 2021

Non-alcoholic steatohepatitis is frequently associated with diabetes and may cause progressive liver disease. Current treatment options are limited. Here we report on a prospective, randomised, double-blind, placebo-controlled trial of two doses of HTD1801 (berberine ursodeoxycholate, an ionic salt of berberine and ursodeoxycholic acid), versus placebo that was conducted in 100 subjects with fatty liver disease and diabetes (NCT03656744). Treatment was for 18 weeks with a primary endpoint of reduction in liver fat content measured by magnetic resonance imaging proton density fat fraction. Key secondary endpoints included improvement in glycemic control, liver-associated enzymes and safety. The pre-specified primary endpoint was met. Thus, subjects receiving 1000 mg twice a day of berberine ursodeoxycholate had significantly greater reduction in liver fat content than in placebo recipients (mean absolute decrease −4.8% vs. −2.0% (p = 0.011). Compared to placebo, subjects receiving this dose also experienced significant improvement in glycemic control as well as reductions in liver-associated enzymes and significant weight loss. Diarrhea and abdominal discomfort were the most frequently reported adverse events. We conclude that berberine ursodeoxycholate has a broad spectrum of metabolic activity in patients with presumed NASH and diabetes. It is relatively well tolerated and merits further development as a treatment for NASH with diabetes.
Lethal microbial blooms delayed freshwater ecosystem recovery following the end-Permian extinction
Authors: Mays Chris , McLoughlin Stephen , Frank Tracy D. , Fielding Christopher R. , Slater Sam M. , Vajda Vivi
Published: September 2021

Harmful algal and bacterial blooms linked to deforestation, soil loss and global warming are increasingly frequent in lakes and rivers. We demonstrate that climate changes and deforestation can drive recurrent microbial blooms, inhibiting the recovery of freshwater ecosystems for hundreds of millennia. From the stratigraphic successions of the Sydney Basin, Australia, our fossil, sedimentary and geochemical data reveal bloom events following forest ecosystem collapse during the most severe mass extinction in Earth’s history, the end-Permian event (EPE; c. 252.2 Ma). Microbial communities proliferated in lowland fresh and brackish waterbodies, with algal concentrations typical of modern blooms. These initiated before any trace of post-extinction recovery vegetation but recurred episodically for >100 kyrs. During the following 3 Myrs, algae and bacteria thrived within short-lived, poorly-oxygenated, and likely toxic lakes and rivers. Comparisons to global deep-time records indicate that microbial blooms are persistent freshwater ecological stressors during warming-driven extinction events.
MAPK-pathway inhibition mediates inflammatory reprogramming and sensitizes tumors to targeted activation of innate immunity sensor RIG-I
Authors: Brägelmann Johannes , Lorenz Carina , Borchmann Sven , Nishii Kazuya , Wegner Julia , Meder Lydia , Ostendorp Jenny , Ast David F. , Heimsoeth Alena , Nakasuka Takamasa , Hirabae Atsuko , Okawa Sachi , Dammert Marcel A. , Plenker Dennis , Klein Sebastian , Lohneis Philipp , Gu Jianing , Godfrey Laura K. , Forster Jan , Trajkovic-Arsic Marija , Zillinger Thomas , Haarmann Mareike , Quaas Alexander , Lennartz Stefanie , Schmiel Marcel , D’Rozario Joshua , Thomas Emily S. , Li Henry , Schmitt Clemens A. , George Julie , Thomas Roman K. , von Karstedt Silvia , Hartmann Gunther , Büttner Reinhard , Ullrich Roland T. , Siveke Jens T. , Ohashi Kadoaki , Schlee Martin , Sos Martin L.
Published: September 2021

Kinase inhibitors suppress the growth of oncogene driven cancer but also enforce the selection of treatment resistant cells that are thought to promote tumor relapse in patients. Here, we report transcriptomic and functional genomics analyses of cells and tumors within their microenvironment across different genotypes that persist during kinase inhibitor treatment. We uncover a conserved, MAPK/IRF1-mediated inflammatory response in tumors that undergo stemness- and senescence-associated reprogramming. In these tumor cells, activation of the innate immunity sensor RIG-I via its agonist IVT4, triggers an interferon and a pro-apoptotic response that synergize with concomitant kinase inhibition. In humanized lung cancer xenografts and a syngeneic Egfr-driven lung cancer model these effects translate into reduction of exhausted CD8+ T cells and robust tumor shrinkage. Overall, the mechanistic understanding of MAPK/IRF1-mediated intratumoral reprogramming may ultimately prolong the efficacy of targeted drugs in genetically defined cancer patients.
A cell-free nanobody engineering platform rapidly generates SARS-CoV-2 neutralizing nanobodies
Authors: Chen Xun , Gentili Matteo , Hacohen Nir , Regev Aviv
Published: September 2021

Antibody engineering technologies face increasing demands for speed, reliability and scale. We develop CeVICA, a cell-free nanobody engineering platform that uses ribosome display for in vitro selection of nanobodies from a library of 1011 randomized sequences. We apply CeVICA to engineer nanobodies against the Receptor Binding Domain (RBD) of SARS-CoV-2 spike protein and identify >800 binder families using a computational pipeline based on CDR-directed clustering. Among 38 experimentally-tested families, 30 are true RBD binders and 11 inhibit SARS-CoV-2 pseudotyped virus infection. Affinity maturation and multivalency engineering increase nanobody binding affinity and yield a virus neutralizer with picomolar IC50. Furthermore, the capability of CeVICA for comprehensive binder prediction allows us to validate the fitness of our nanobody library. CeVICA offers an integrated solution for rapid generation of divergent synthetic nanobodies with tunable affinities in vitro and may serve as the basis for automated and highly parallel nanobody engineering.
Mixing between chemically variable primitive basalts creates and modifies crystal cargoes
Authors: Neave David A. , Beckmann Philipp , Behrens Harald , Holtz François
Published: September 2021

Basaltic crystal cargoes often preserve records of mantle-derived chemical variability that have been erased from their carrier liquids by magma mixing. However, the consequences of mixing between similarly primitive but otherwise chemically variable magmas remain poorly understood despite ubiquitous evidence of chemical variability in primary melt compositions and mixing-induced disequilibrium within erupted crystal cargoes. Here we report observations from magma–magma reaction experiments performed on analogues of primitive Icelandic lavas derived from distinct mantle sources to determine how their crystal cargoes respond to mixing-induced chemical disequilibrium. Chemical variability in our experimental products is controlled dominantly by major element diffusion in the melt that alters phase equilibria and triggers plagioclase resorption within regions that were initially plagioclase saturated. Isothermal mixing between chemically variable basaltic magmas may therefore play important but previously underappreciated roles in creating and modifying crystal cargoes by unlocking plagioclase-rich mushes and driving resorption, (re-)crystallisation and solid-state diffusion.
Synthetic essentiality between PTEN and core dependency factor PAX7 dictates rhabdomyosarcoma identity
Authors: Langdon Casey G. , Gadek Katherine E. , Garcia Matthew R. , Evans Myron K. , Reed Kristin B. , Bush Madeline , Hanna Jason A. , Drummond Catherine J. , Maguire Matthew C. , Leavey Patrick J. , Finkelstein David , Jin Hongjian , Schreiner Patrick A. , Rehg Jerold E. , Hatley Mark E.
Published: September 2021

PTENpromoter hypermethylation is nearly universal andPTENcopy number loss occurs in ~25% of fusion-negative rhabdomyosarcoma (FN-RMS). Here we showPtendeletion in a mouse model of FN-RMS results in less differentiated tumors more closely resembling human embryonal RMS. PTEN loss activated the PI3K pathway but did not increase mTOR activity. In wild-type tumors, PTEN was expressed in the nucleus suggesting loss of nuclear PTEN functions could account for these phenotypes.Ptendeleted tumors had increased expression of transcription factors important in neural and skeletal muscle development includingDbx1andPax7.Pax7deletion completely rescued the effects ofPtenloss. Strikingly, thesePten;Pax7deleted tumors were no longer FN-RMS but displayed smooth muscle differentiation similar to leiomyosarcoma. These data highlight howPtenloss in FN-RMS is connected to a PAX7 lineage-specific transcriptional output that creates a dependency or synthetic essentiality on the transcription factor PAX7 to maintain tumor identity.
Trigger point injection for post-mastectomy pain: a simple intervention with high rate of long-term relief
Authors: Khoury Amal L. , Keane Holly , Varghese Flora , Hosseini Ava , Mukhtar Rita , Eder Suzanne E. , Weinstein Philip R. , Esserman Laura J.
Published: September 2021

Post-mastectomy pain syndrome (PMPS) is a common and often debilitating condition. The syndrome is defined by chest wall pain unresponsive to standard pain medications and the presence of exquisite point tenderness along the inframammary fold at the site of the T4 and T5 cutaneous intercostal nerve branches as they exit from the chest wall. Pressure at the site triggers and reproduces the patient’s spontaneous or motion-evoked pain. The likely pathogenesis is neuroma formation after injury to the T4 and T5 intercostal nerves during breast surgery. We assessed the rate of long-term resolution of post-mastectomy pain after trigger point injections (2 mL of 1:1 mixture of 0.5% bupivacaine and 4 mg/mL dexamethasone) to relieve neuropathic pain in a prospective single-arm cohort study. Fifty-two women (aged 31–92) who underwent partial mastectomy with reduction mammoplasty or mastectomy with or without reconstruction, and who presented with PMPS were enrolled at the University of California San Francisco Breast Care Center from August 2010 through April 2018. The primary outcome was a long-term resolution of pain, defined as significant or complete relief of pain for greater than 3 months. A total of 91 trigger points were treated with mean follow-up 43.9 months with a 91.2% (83/91) success rate. Among those with a long-term resolution of pain, 60 trigger points (72.3%) required a single injection to achieve long-lasting relief. Perineural infiltration with bupivacaine and dexamethasone is a safe, simple, and effective treatment for PMPS presenting as trigger point pain along the inframammary fold.
Iminodibenzyl induced redirected COX-2 activity inhibits breast cancer progression
Authors: Shah Harshit , Pang Lizhi , Qian Steven , Sathish Venkatachalem
Published: September 2021

Knocking down delta-5-desaturase (D5D) by siRNA or shRNA is a promising strategy to achieve 8-hydroxyoctanoic acid (8-HOA) production for cancer inhibition. However, the RNAi-based strategy to stimulate 8-HOA is restricted due to endonucleases mediated physiological degradation and off-target effects. Thus, to get persistent 8-HOA in the cancer cell, we recognized a D5D inhibitor Iminodibenzyl. Here, we have postulated that Iminodibenzyl, by inhibiting D5D activity, could shift the di-homo-gamma-linolenic acid (DGLA) peroxidation from arachidonic acid to 8-HOA in high COX-2 microenvironment of 4T1 and MDA-MB-231 breast cancer cells. We observed that Iminodibenzyl stimulated 8-HOA caused HDAC activity reduction resulting in intrinsic apoptosis pathway activation. Additionally, reduced filopodia and lamellipodia, and epithelial-mesenchymal transition markers give rise to decreased cancer cell migration. In the orthotopic breast cancer model, the combination of Iminodibenzyl and DGLA reduced tumor size. From in vitro and in vivo studies, we concluded that Iminodibenzyl could reprogram COX-2 induced DGLA peroxidation to produce anti-cancer activity.
Effects of microgravity exposure and fructo-oligosaccharide ingestion on the proteome of soleus and extensor digitorum longus muscles in developing mice
Authors: Ohira Takashi , Ino Yoko , Kimura Yayoi , Nakai Yusuke , Kimura Ayuko , Kurata Yoichi , Kagawa Hiroyuki , Kimura Mitsuo , Egashira Kenji , Matsuda Chie , Ohira Yoshinobu , Furukawa Satoshi , Hirano Hisashi
Published: September 2021

Short-chain fatty acids produced by the gut bacterial fermentation of non-digestible carbohydrates, e.g., fructo-oligosaccharide (FOS), contribute to the maintenance of skeletal muscle mass and oxidative metabolic capacity. We evaluated the effect of FOS ingestion on protein expression of soleus (Sol) and extensor digitorum longus muscles in mice exposed to microgravity (μ-g). Twelve 9-week-old male C57BL/6J mice were raised individually on the International Space Station under μ-g or artificial 1-g and fed a diet with or without FOS (n = 3/group). Regardless of FOS ingestion, the absolute wet weights of both muscles tended to decrease, and the fiber phenotype in Sol muscles shifted toward fast-twitch type following μ-g exposure. However, FOS ingestion tended to mitigate the μ-g-exposure-related decrease in oxidative metabolism and enhance glutathione redox detoxification in Sol muscles. These results indicate that FOS ingestion mildly suppresses metabolic changes and oxidative stress in antigravity Sol muscles during spaceflight.
Technology-based therapy-response and prognostic biomarkers in a prospective study of a de novo Parkinson’s disease cohort
Authors: Di Lazzaro Giulia , Ricci Mariachiara , Saggio Giovanni , Costantini Giovanni , Schirinzi Tommaso , Alwardat Mohammad , Pietrosanti Luca , Patera Martina , Scalise Simona , Giannini Franco , Pisani Antonio
Published: September 2021

Early noninvasive reliable biomarkers are among the major unmet needs in Parkinson’s disease (PD) to monitor therapy response and disease progression. Objective measures of motor performances could allow phenotyping of subtle, undetectable, early stage motor impairments of PD patients. This work aims at identifying prognostic biomarkers in newly diagnosed PD patients and quantifying therapy-response. Forty de novo PD patients underwent clinical and technology-based kinematic assessments performing motor tasks (MDS-UPDRS part III) to assess tremor, bradykinesia, gait, and postural stability (T0). A visit after 6 months (T1) and a clinical and kinematic assessment after 12 months (T2) where scheduled. A clinical follow-up was provided between 30 and 36 months after the diagnosis (T3). We performed an ANOVA for repeated measures to compare patients’ kinematic features at baseline and at T2 to assess therapy response. Pearson correlation test was run between baseline kinematic features and UPDRS III score variation between T0 and T3, to select candidate kinematic prognostic biomarkers. A multiple linear regression model was created to predict the long-term motor outcome using T0 kinematic measures. All motor tasks significantly improved after the dopamine replacement therapy. A significant correlation was found between UPDRS scores variation and some baseline bradykinesia (toe tapping amplitude decrement, p = 0.009) and gait features (velocity of arms and legs, sit-to-stand time, p = 0.007; p = 0.009; p = 0.01, respectively). A linear regression model including four baseline kinematic features could significantly predict the motor outcome (p = 0.000214). Technology-based objective measures represent possible early and reproducible therapy-response and prognostic biomarkers.
Stroke impairs the control of isometric forces and muscle activations in the ipsilesional arm
Authors: Pellegrino Laura , Coscia Martina , Giannoni Psiche , Marinelli Lucio , Casadio Maura
Published: September 2021

Stroke often impairs the control of the contralesional arm, thus most survivors rely on the ipsilesional arm to perform daily living activities that require an efficient control of movements and forces. Whereas the ipsilesional arm is often called ‘unaffected’ or ‘unimpaired’, several studies suggested that during dynamic tasks its kinematics and joint torques are altered. Is stroke also affecting the ability of the ipsilesional arm to produce isometric force, as when pushing or pulling a handle? Here, we address this question by analyzing behavioral performance and muscles’ activity when subjects applied an isometric force of 10 N in eight coplanar directions. We found that stroke affected the ability to apply well-controlled isometric forces with the ipsilesional arm, although to a minor extent compared to the contralesional arm. The spinal maps, the analysis of single muscle activities and the organization of muscle synergies highlighted that this effect was mainly associated with abnormal activity of proximal muscles with respect to matched controls, especially when pushing or pulling in lateral directions.
Neurogenesis in the adult brain functionally contributes to the maintenance of chronic neuropathic pain
Authors: Tan Linette Liqi , Alfonso Julieta , Monyer Hannah , Kuner Rohini
Published: September 2021

Maladaptive adult neurogenesis in the mammalian brain has been associated with diverse behaviors including disrupted learning, negative mood disorders and psychiatric conditions. However, its functional role in the generation and maintenance of chronic pathological pain has not yet been elucidated. Using an inducible genetic deletion in vivo mouse model, different behavioural paradigms and home cage monitoring systems, we show that an absence of adult neurogenesis does not impact the development of neuropathic injury-induced peripheral nociceptive hypersensitivity, but rather promotes the recovery of pathological pain as well as improves parameters associated with the state of well-being of the injured mice. These results provide a mechanistic insight into the mechanisms of chronic pain and implicate neurogenic processes as a potential therapeutic target for reducing pain and improving the quality of life for patients.
Shugoshin 2 is a biomarker for pathological grading and survival prediction in patients with gliomas
Authors: Kao Ying , Tsai Wen-Chiuan , Chen Ssu-Han , Hsu Shao-Yuan , Huang Li-Chun , Chang Chih-Ju , Huang Shih-Ming , Hueng Dueng-Yuan
Published: September 2021

Glioblastomas are the most common type of adult primary brain neoplasms. Clinically, it is helpful to identify biomarkers to predict the survival of patients with gliomas due to its poor outcome. Shugoshin 2 (SGO2) is critical in cell division and cell cycle progression in eukaryotes. However, the association of SGO2 with pathological grading and survival in patients with gliomas remains unclear. We analyzed the association between SGO2 expression and clinical outcomes from Gene Expression Omnibus (GEO) dataset profiles, The Cancer Genome Atlas (TCGA), and Chinese Glioma Genome Atlas (CGGA). SGO2 mRNA and protein expression in normal brain tissue and glioma cell lines were investigated via quantitative RT-PCR, Western blot, and IHC staining. The roles of SGO2 in proliferation, migration, and apoptosis of GBM cells were studied with wound-healing assay, BrdU assay, cell cycle analysis, and JC-1 assay. The protein–protein interaction (PPI) was analyzed via Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). SGO2 mRNA expression predicted higher grade gliomas than non-tumor brain tissues. Kaplan–Meier survival analysis showed that patients with high-grade gliomas with a higher SGO2 expression had worse survival outcomes. SGO2 mRNA and protein expression were upper regulated in gliomas than in normal brain tissue. Inhibition of SGO2 suppressed cell proliferation and migration. Also, PPI result showed SGO2 to be a potential hub protein, which was related to the expression of AURKB and FOXM1. SGO2 expression positively correlates with WHO pathological grading and patient survival, suggesting that SGO2 is a biomarker that is predictive of disease progression in patients with gliomas.
Impact of cognitive reserve on dance intervention-induced changes in brain plasticity
Authors: Mitterová Kristína , Klobušiaková Patrícia , Šejnoha Minsterová Alžběta , Kropáčová Sylvie , Balážová Zuzana , Točík Jaroslav , Vaculíková Pavlína , Skotáková Alena , Grmela Roman , Rektorová Irena
Published: September 2021

Dance is a complex sensorimotor activity with positive effects on physical fitness, cognition, and brain plasticity in the aging population. We explored whether individual levels of cognitive reserve (CR) proxied by education moderate dance intervention (DI)-induced plasticity assessed by resting-state functional connectivity (rs-FC) changes of the sensorimotor network (SMN), and between the dorsal attention network (DAN) and anterior default mode network (aDMN). Our cohort consisted of 99 subjects, randomly assigned to either a DI group who underwent a 6-month intervention (n = 49, Mage = 69.02 ± 5.40) or a control group (n = 50, Mage = 69.37 ± 6.10). Moderation analyses revealed that CR moderated DI-induced increase of the SMN rs-FC with significant changes observed in participants with ≥ 15 years of education (b = 0.05, t(62) = 3.17, p = 0.002). Only DI alone was a significant predictor of the DAN–aDMN crosstalk change (b = 0.06, t(64) = 2.16, p = 0.035). The rs-FC increase in the SMN was correlated with an improved physical fitness measure, and changes in the DAN–aDMN connectivity were linked to better performance on figural fluency. Consistent with the passive CR hypothesis, we observed that CR correlated only with baseline behavioral scores, not their change.
Sensitive detection of Plasmodium vivax malaria by the rotating-crystal magneto-optical method in Thailand
Authors: Orbán Ágnes , Longley Rhea J. , Sripoorote Piyarat , Maneechai Nongnuj , Nguitragool Wang , Butykai Ádám , Mueller Ivo , Sattabongkot Jetsumon , Karl Stephan , Kézsmárki István
Published: September 2021

The rotating-crystal magneto-optical detection (RMOD) method has been developed for the rapid and quantitative diagnosis of malaria and tested systematically on various malaria infection models. Very recently, an extended field trial in a high-transmission region of Papua New Guinea demonstrated its great potential for detecting malaria infections, in particular Plasmodium vivax. In the present small-scale field test, carried out in a low-transmission area of Thailand, RMOD confirmed malaria in all samples found to be infected with Plasmodium vivax by microscopy, our reference method. Moreover, the magneto-optical signal for this sample set was typically 1–3 orders of magnitude higher than the cut-off value of RMOD determined on uninfected samples. Based on the serial dilution of the original patient samples, we expect that the method can detect Plasmodium vivax malaria in blood samples with parasite densities as low as $$\sim$$
∼
5–10 parasites per microliter, a limit around the pyrogenic threshold of the infection. In addition, by investigating the correlation between the magnitude of the magneto-optical signal, the parasite density and the erythrocytic stage distribution, we estimate the relative hemozoin production rates of the ring and the trophozoite stages of in vivo Plasmodium vivax infections.
Extracellular vesicles cargo from head and neck cancer cell lines disrupt dendritic cells function and match plasma microRNAs
Authors: de Paula Silva Elisangela , Marti Luciana Cavalheiro , Andreghetto Flávia Maziero , de Sales Romário Oliveira , Hoberman Martin , dos Santos Dias Bárbara , Diniz Larissa Figueiredo Alves , dos Santos Alessandro Marins , Moyses Raquel Ajub , Curioni Otávio Alberto , Lopez Rossana Veronica Mendoza , Nunes Fabio Daumas , Tajara Eloiza Helena , Severino Patricia
Published: September 2021

Extracellular vesicles (EVs) are mediators of the immune system response. Encapsulated in EVs, microRNAs can be transferred between cancer and immune cells. To define the potential effects of EVs originated from squamous cell carcinoma cells on immune system response, we performed microRNA profiling of EVs released from two distinct cell lines and treated dendritic cells derived from circulating monocytes (mono-DCs) with these EVs. We confirmed the internalization of EVs by mono-DCs and the down-regulation of microRNA mRNA targets in treated mono-DCs. Differences in surface markers of dendritic cells cultivated in the presence of EVs indicated that their content disrupts the maturation process. Additionally, microRNAs known to interfere with dendritic cell function, and detected in EVs, matched microRNAs from squamous cell carcinoma patients’ plasma: miR-17-5p in oropharyngeal squamous cell carcinoma, miR-21 in oral squamous cell carcinoma, miR-16, miR-24, and miR-181a circulating in both oral and oropharyngeal squamous cell carcinoma, and miR-23b, which has not been previously described in plasma of head and neck squamous cell carcinoma, was found in plasma from patients with these cancer subtypes. This study contributes with insights on EVs in signaling between cancer and immune cells in squamous cell carcinoma of the head and neck.
Stabilizing nanolasers via polarization lifetime tuning
Authors: Roos Aycke , Meinecke Stefan , Lüdge Kathy
Published: September 2021

We investigate the emission dynamics of mutually coupled nanolasers and predict ways to optimize their stability, i.e., maximize their locking range. We find that tuning the cavity lifetime to the same order of magnitude as the dephasing time of the microscopic polarization yields optimal operation conditions, which allow for wider tuning ranges than usually observed in conventional semiconductor lasers. The lasers are modeled by Maxwell–Bloch type class-C equations. For our analysis, we analytically determine the steady state solutions, analyze the symmetries of the system and numerically characterize the emission dynamics via the underlying bifurcation structure. The polarization lifetime is found to be a crucial parameter, which impacts the observed dynamics in the parameter space spanned by frequency detuning, coupling strength and coupling phase.
The effect of chemical and structural modifiers on the haemostatic process and cytotoxicity of the beta-chitin patch
Authors: Sabab Ahad , Liu Sha , Javadiyan Shari , McAdam C. John , Hanton Lyall R. , Jukes Alistair , Vreugde Sarah , Wormald Peter-John
Published: September 2021

Beta-chitin patch has previously been proven to be an effective haemostat, but whether modifying the patch affects its efficacy and safety, remains unanswered. In this study, the patch was modified using polyethylene oxide, Pluronic-F127, calcium, increased thickness or polyphosphate, and their effect on the process of haemostasis and cytotoxicity was tested and compared with standard-of-care, Surgicel and FloSeal. Whole blood collected from volunteers was applied to the patches to test their whole blood clotting and thrombin generation capacities, whilst platelet isolates were used to test their platelet aggregation ability. The fluid absorption capacity of the patches was tested using simulated body fluid. Cytotoxicity of the patches was tested using AlamarBlue assays and PC12 cells and the results were compared with the standard-of-care. In this study, beta-chitin patch modifications failed to improve its whole blood clotting, platelet aggregation and thrombin generation capacity. Compared to non-modified patch, modifications with polyethylene oxide or calcium reduced platelet aggregation and thrombin generation capacity, while increasing the thickness or adding polyphosphate decreased platelet aggregation capacity. The cytotoxicity assays demonstrated that the beta-chitin patches were non-toxic to cells. In vivo research is required to evaluate the safety and efficacy of the beta-chitin patches in a clinical setting.
Blunted emotion judgments of body movements in Parkinson’s disease
Authors: Bellot Emmanuelle , Garnier-Crussard Antoine , Pongan Elodie , Delphin-Combe Floriane , Coste Marie-Hélène , Gentil Claire , Rouch Isabelle , Hénaff Marie-Anne , Schmitz Christina , Tillmann Barbara , Krolak-Salmon Pierre
Published: September 2021

Some of the behavioral disorders observed in Parkinson’s disease (PD) may be related to an altered processing of social messages, including emotional expressions. Emotions conveyed by whole body movements may be difficult to generate and be detected by PD patients. The aim of the present study was to compare valence judgments of emotional whole body expressions in individuals with PD and in healthy controls matched for age, gender and education. Twenty-eight participants (13 PD patients and 15 healthy matched control participants) were asked to rate the emotional valence of short movies depicting emotional interactions between two human characters presented with the “Point Light Displays” technique. To ensure understanding of the perceived scene, participants were asked to briefly describe each of the evaluated movies. Patients’ emotional valence evaluations were less intense than those of controls for both positive (p < 0.001) and negative (p < 0.001) emotional expressions, even though patients were able to correctly describe the depicted scene. Our results extend the previously observed impaired processing of emotional facial expressions to impaired processing of emotions expressed by body language. This study may support the hypothesis that PD affects the embodied simulation of emotional expression and the potentially involved mirror neuron system.
Multi GPU parallelization of maximum likelihood expectation maximization method for digital rock tomography data
Authors: Prakash Jaya , Agarwal Umang , Yalavarthy Phaneendra K.
Published: September 2021

Digital rock is an emerging area of rock physics, which involves scanning reservoir rocks using X-ray micro computed tomography (XCT) scanners and using it for various petrophysical computations and evaluations. The acquired micro CT projections are used to reconstruct the X-ray attenuation maps of the rock. The image reconstruction problem can be solved by utilization of analytical (such as Feldkamp–Davis–Kress (FDK) algorithm) or iterative methods. Analytical schemes are typically computationally more efficient and hence preferred for large datasets such as digital rocks. Iterative schemes like maximum likelihood expectation maximization (MLEM) are known to generate accurate image representation over analytical scheme in limited data (and/or noisy) situations, however iterative schemes are computationally expensive. In this work, we have parallelized the forward and inverse operators used in the MLEM algorithm on multiple graphics processing units (multi-GPU) platforms. The multi-GPU implementation involves dividing the rock volumes and detector geometry into smaller modules (along with overlap regions). Each of the module was passed onto different GPU to enable computation of forward and inverse operations. We observed an acceleration of $$\sim 30$$

∼
30

times using our multi-GPU approach compared to the multi-core CPU implementation. Further multi-GPU based MLEM obtained superior reconstruction compared to traditional FDK algorithm.
Searching for metastable particles using graph computing
Authors: Kotwal Ashutosh V.
Published: September 2021

The reconstruction of charged particle trajectories at the Large Hadron Collider and future colliders relies on energy depositions in sensors placed at distances ranging from a centimeter to a meter from the colliding beams. We propose a method of detecting charged particles that decay invisibly after traversing a short distance of about 25 cm inside the experimental apparatus. One of the decay products may constitute the dark matter known to be 84% of all matter at galactic and cosmological distance scales. Our method uses graph computing to cluster spacepoints recorded by two-dimensional silicon pixel sensors into mathematically-defined patterns. The algorithm may be implemented on silicon-based integrated circuits using field-programmable gate array technology to augment or replace traditional computing platforms.
Oxidation-enhanced thermoelectric efficiency in a two-dimensional phosphorene oxide
Authors: Lee Seungjun , Song Jeong-Pil , Kang Seoung-Hun , Kwon Young-Kyun
Published: September 2021

We performed density functional theory calculations to investigate the thermoelectric properties of phosphorene oxide (PO) expected to form by spontaneous oxidation of phosphorene. Since thermoelectric features by nature arise from the consequences of the electron-phonon interaction, we computed the phonon-mediated electron relaxation time, which was fed into the semiclassical Boltzmann transport equation to be solved for various thermoelectric-related quantities. It was found that PO exhibits superior thermoelectric performance compared with its pristine counterpart, which has been proposed to be a candidate for the use of future thermoelectric applications. We revealed that spontaneous oxidation of phosphorene leads to a significant enhancement in the thermoelectric properties of n-doped phosphorene oxide, which is attributed to the considerable reduction of lattice thermal conductivity albeit a small decrease in electrical conductivity. Our results suggest that controlling oxidation may be utilized to improve thermoelectric performance in nanostructures, and PO can be a promising candidate for low-dimensional thermoelectric devices.
Multiscale computational modeling of cancer growth using features derived from microCT images
Authors: Zangooei M. Hossein , Margolis Ryan , Hoyt Kenneth
Published: September 2021

Advances in medical imaging technologies now allow noninvasive image acquisition from individual patients at high spatiotemporal resolutions. A relatively new effort of predictive oncology is to develop a paradigm for forecasting the future status of an individual tumor given initial conditions and an appropriate mathematical model. The objective of this study was to introduce a comprehensive multiscale computational method to predict cancer and microvascular network growth patterns. A rectangular lattice-based model was designed so different evolutionary scenarios could be simulated and for predicting the impact of diffusible factors on tumor morphology and size. Further, the model allows prediction-based simulation of cell and microvascular behavior. Like a single cell, each agent is fully realized within the model and interactions are governed in part by machine learning methods. This multiscale computational model was developed and incorporated input information from in vivo microscale computed tomography (microCT) images acquired from breast cancer-bearing mice. It was found that as the difference between expansion of the cancer cell population and microvascular network increases, cells undergo proliferation and migration with a greater probability compared to other phenotypes. Overall, multiscale computational model agreed with both theoretical expectations and experimental findings (microCT images) not used during model training.
Cognitive control affects motor learning through local variations in GABA within the primary motor cortex
Authors: Maruyama Shuki , Fukunaga Masaki , Sugawara Sho K. , Hamano Yuki H. , Yamamoto Tetsuya , Sadato Norihiro
Published: September 2021

The primary motor cortex (M1) is crucial for motor learning; however, its interaction with other brain areas during motor learning remains unclear. We hypothesized that the fronto-parietal execution network (FPN) provides learning-related information critical for the flexible cognitive control that is required for practice. We assessed network-level changes during sequential finger tapping learning under speed pressure by combining magnetic resonance spectroscopy and task and resting-state functional magnetic resonance imaging. There was a motor learning-related increase in preparatory activity in the fronto-parietal regions, including the right M1, overlapping the FPN and sensorimotor network (SMN). Learning-related increases in M1-seeded functional connectivity with the FPN, but not the SMN, were associated with decreased GABA/glutamate ratio in the M1, which were more prominent in the parietal than the frontal region. A decrease in the GABA/glutamate ratio in the right M1 was positively correlated with improvements in task performance (p = 0.042). Our findings indicate that motor learning driven by cognitive control is associated with local variations in the GABA/glutamate ratio in the M1 that reflects remote connectivity with the FPN, representing network-level motor sequence learning formations.
Emergence of topological superconductivity in doped topological Dirac semimetals under symmetry-lowering lattice distortions
Authors: Cheon Sangmo , Lee Ki Hoon , Chung Suk Bum , Yang Bohm-Jung
Published: September 2021

Recently, unconventional superconductivity having a zero-bias conductance peak is reported in doped topological Dirac semimetal (DSM) with lattice distortion. Motivated by the experiments, we theoretically study the possible symmetry-lowering lattice distortions and their effects on the emergence of unconventional superconductivity in doped topological DSM. We find four types of symmetry-lowering lattice distortions that reproduce the crystal symmetries relevant to experiments from the group-theoretical analysis. Considering inter-orbital and intra-orbital electron density-density interactions, we calculate superconducting phase diagrams. We find that the lattice distortions can induce unconventional superconductivity hosting gapless surface Andreev bound states (SABS). Depending on the lattice distortions and superconducting pairing interactions, the unconventional inversion-odd-parity superconductivity can be either topological nodal superconductivity hosting a flat SABS or topological crystalline superconductivity hosting a gapless SABS. Remarkably, the lattice distortions increase the superconducting critical temperature, which is consistent with the experiments. Our work opens a pathway to explore and control pressure-induced topological superconductivity in doped topological semimetals.