bluuebunny/crossref_metadata_2025 huggingface dataset:
Dysregulated miRNAs modulate tumor microenvironment associated signaling networks in pancreatic ductal adenocarcinoma
Authors: Liu Tiantian , Chen Zhong , Chen Wanqiu , Evans Ryan , Xu Jane , Reeves Mark E , de Vera Michael E , Wang Charles
Published: March 2023

The desmoplastic and complex tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) has presented tremendous challenges for developing effective therapeutic strategies. Strategies targeting tumor stroma, albeit with great potential, have met with limited success due to the lack of knowledge on the molecular dynamics within the tumor microenvironment (TME). In pursuit of a better understanding of the influence of miRNAs on TME reprogramming and to explore circulating miRNAs as diagnostic and prognostic biomarkers for PDAC, using RNA-seq, miRNA-seq, and single-cell RNA-seq (scRNA-seq), we investigated the dysregulated signaling pathways in PDAC TME modulated by miRNAs from plasma and tumor tissue. Our bulk RNA-seq in PDAC tumor tissue identified 1445 significantly differentially expressed genes with extracellular matrix and structure organization as the top enriched pathways. Our miRNA-seq identified 322 and 49 abnormally expressed miRNAs in PDAC patient plasma and tumor tissue, respectively. We found many of the TME signaling pathways were targeted by those dysregulated miRNAs in PDAC plasma. Combined with scRNA-seq from patient PDAC tumor, our results revealed that these dysregulated miRNAs were closely associated with extracellular matrix (ECM) remodeling, cell-ECM communication, epithelial-mesenchymal transition, as well as immunosuppression orchestrated by different cellular components of TME. The findings of this study could assist the development of miRNA-based stromal targeting biomarkers or therapy for PDAC patients.
A cryptic natural variant allele of BYPASS2 suppresses the bypass1 mutant phenotype
Authors: Cummins Alexander J , Siler C J , Olson Jacob M , Kaur Amanpreet , Hamdani Adam K , Olson L Kate , Dilkes Brian P , Sieburth Leslie E
Published: March 2023

The Arabidopsis (Arabidopsis thaliana) BYPASS1 (BPS1) gene encodes a protein with no functionally characterized domains, and loss-of-function mutants (e.g. bps1-2 in Col-0) present a severe growth arrest phenotype that is evoked by a root-derived graft-transmissible small molecule that we call dalekin. The root-to-shoot nature of dalekin signaling suggests it could be an endogenous signaling molecule. Here, we report a natural variant screen that allowed us to identify enhancers and suppressors of the bps1-2 mutant phenotype (in Col-0). We identified a strong semi-dominant suppressor in the Apost-1 accession that largely restored shoot development in bps1 and yet continued to overproduce dalekin. Using bulked segregant analysis and allele-specific transgenic complementation, we showed that the suppressor is the Apost-1 allele of a BPS1 paralog, BYPASS2 (BPS2). BPS2 is one of four members of the BPS gene family in Arabidopsis, and phylogenetic analysis demonstrated that the BPS family is conserved in land plants and the four Arabidopsis paralogs are retained duplicates from whole genome duplications. The strong conservation of BPS1 and paralogous proteins throughout land plants, and the similar functions of paralogs in Arabidopsis, suggests that dalekin signaling might be retained across land plants.
AI-tocracy
Authors: Beraja Martin , Kao Andrew , Yang David Y , Yuchtman Noam
Published: March 2023

Recent scholarship has suggested that artificial intelligence (AI) technology and autocratic regimes may be mutually reinforcing. We test for a mutually reinforcing relationship in the context of facial-recognition AI in China. To do so, we gather comprehensive data on AI firms and government procurement contracts, as well as on social unrest across China since the early 2010s. We first show that autocrats benefit from AI: local unrest leads to greater government procurement of facial-recognition AI as a new technology of political control, and increased AI procurement indeed suppresses subsequent unrest. We show that AI innovation benefits from autocrats’ suppression of unrest: the contracted AI firms innovate more both for the government and commercial markets and are more likely to export their products; noncontracted AI firms do not experience detectable negative spillovers. Taken together, these results suggest the possibility of sustained AI innovation under the Chinese regime: AI innovation entrenches the regime, and the regime’s investment in AI for political control stimulates further frontier innovation.
Raising awareness through continuous indoor radon measurements in workplaces
Authors: Săpoi Ruxandra , Cheresteş Margareta , Negreanu Denisa , Cheresteş Codruţ , Filip Valentin
Published: March 2023

When radon is taken out of the scientific context in order to be understood by the public, the way the media approaches radon is prone to sensationalising. Communicating risk in a clear and effective manner was never easy and communication of radon risk poses serious challenges because radon is not widely known and specialists need to be more involved in engagement activities and campaigns to inform about radon exposure. This paper presents the results of the continuous radon measurements performed in workplaces for raising awareness among occupationally exposed workers. Radon measurements were made using Airthings monitors for up to 9 months of monitoring. Measured data correlated to real-time visualisation of the maximum radon levels provided convincing evidence that led to increased interest for radon exposure among exposed workers, raise awareness and empowered their own understanding of radon exposure.
Experience with NORM waste disposal in different European countries
Authors: Gellermann Rainer , Caplin Helen , Chambers Nick , Dongen Oskar van , Grandia Fidel , Hondros Jim , Kunze Christian , Michalik Boguslaw , Pepin Stéphane , Rovenska Katerina N , Trevisi Rosabianca
Published: March 2023

Industrial processes generate various quantities of waste that can be contaminated with radionuclides of natural origin (naturally occurring radioactive material (‘NORM waste’)). The efficient management of this waste is essential for any industries affected by NORM waste generation. To obtain an overview of current practices and approaches in Europe, the IRPA Task Group on NORM conducted a survey among task group members and other experts from European countries. The results revealed significant differences in methods and approaches in the European countries. In many countries, landfills are used to dispose of small- and medium-sized quantities of NORM waste with limited activity concentration. But our survey indicated that despite a uniform reference basis for national legislation in Europe, there are different framework conditions for the disposal of NORM waste in practice. In some countries, the disposal is hampered because the interface between the radiation protection system and the waste regime is not yet clearly regulated. Particular practical problems include the lack of acceptance of waste because of the ‘radioactivity’ stigma and only vague specifications by the legislators on acceptance obligations of the waste management sector.
Fermi problems as a hub for task design in mathematics and stem education
Authors: Ärlebäck Jonas Bergman , Albarracín Lluís
Published: March 2023

In this paper, we draw on recent research on so-called Fermi problems and situate the fundamental principles underlying this type of tasks and their use from a task design perspective. We use the models and modelling perspective on teaching and learning to elaborate on aspects related to the design of single-use, as well as sequences of, Fermi problems. In addition, we discuss a framework (called the Fermi problem activity template [FPAT] framework) for supporting the design and use of Fermi problems to facilitate students' learning within particular mathematics content areas and/or aimed at particular concepts or higher-order thinking skills. We also illustrate how the FPAT framework can be used to (i) facilitate interdisciplinary collaborations with other subjects such as the social sciences, but in particular with the other STEM subjects; and (ii) support teachers in adapting and implementing Fermi problems in their classrooms.
Comprehensive physio-biochemical and transcriptomic characterization to decipher the network of key genes under waterlogging stress and its recuperation inPrunus persica
Authors: Ateeq Muhammad , Khan Aamir Hamid , Zhang Dongmei , Alam Shariq Mahmood , Shen Wanqi , Wei Minghua , Meng Jian , Shen Xingyi , Pan Jiajia , Zhu Kaijie , He Hanzi , Li Guohuai , Liu Junwei
Published: March 2023

Waterlogging is a major abiotic stress that plants encounter as a result of climate change impacts. Peach is very sensitive to hypoxia during waterlogging, which causes poor tree vigor and huge economic losses. The molecular mechanism underlying the peach response to waterlogging and reoxygenation remains unclear. Here, the physiological and molecular responses of 3-week-old peach seedlings under waterlogged and recovery conditions were comprehensively analyzed. As a result, waterlogging significantly reduced plant height and biomass with inhibition of root growth when compared with control and reoxygenation. Similar results were observed for photosynthetic activities and gaseous exchange parameters. Waterlogging increased lipid peroxidation, hydrogen peroxide, proline, glutamic acid and glutathione contents, while superoxide dismutase, peroxidases and catalase activities were decreased. The glucose and fructose contents were accumulated, contrary to sucrose which was reduced remarkably throughout the stress periods. The level of endogenous indole acetic acid (IAA) was increased in waterlogging but decreased after reoxygenation. However, the change trends of jasmonic acid (JA), cytokinins and abscisic acid (ABA) levels were opposite to IAA. In transcriptomic analysis, there were 13,343 differentially expressed genes (DEGs) with higher and 16,112 genes with lower expression. These DEGs were greatly enriched in carbohydrate metabolism, anaerobic fermentation, glutathione metabolism and IAA hormone biosynthesis under waterlogging, while they were significantly enriched in photosynthesis, reactive oxygen species scavenging, ABA and JA hormones biosynthesis in reoxygenation. Moreover, several genes related to stress response, carbohydrate metabolism and hormones biosynthesis were significantly changed in waterlogging and reoxygenation, which indicated unbalanced amino acid, carbon and fatty acid pools in peach roots. Taken together, these results suggest that glutathione, primary sugars and hormone biosynthesis and signaling might play key roles in plant response to waterlogging. Our work provides a comprehensive understanding of gene regulatory networks and metabolites in waterlogging stress and its recuperation, which will facilitate peach waterlogging control.
Model-free adaptive robust control method for high-speed trains
Authors: Li Zhongqi , Zhou Liang , Yang Hui , Yan Yue
Published: March 2023

Aiming at the robustness issue in high-speed trains (HSTs) operation control, this article proposes a model-free adaptive control (MFAC) scheme to suppress disturbance. Firstly, the dynamic linearization data model of train system under the action of measurement disturbance is given, and the Kalman filter (KF) based on this model is derived under the minimum variance estimation criterion. Then, according to the KF, an anti-interference MFAC scheme is designed. This scheme only needs the input and output data of the controlled system to realize the MFAC of the train under strong disturbance. Finally, the simulation experiment of CRH380A HSTs is carried out and compared with the traditional MFAC and the MFAC with attenuation factor. The proposed control algorithm can effectively suppress the measurement disturbance, and obtain smaller tracking error and larger signal to noise ratio with better applicability.
Plastic Surgeons and Equity: Are Merit-based Incentive Payment System (MIPS) Scores Impacted by Minority Patient Caseload?
Authors: Byrd Jacqueline N. , Cichocki Meghan N. , Chung Kevin C.
Published: March 2023

Background

The Centers for Medicare and Medicaid Services introduced the Merit-Based Incentive Payment System (MIPS) in 2017 to extend value-based payment to outpatient physicians. We hypothesized that the MIPS scores for plastic surgeons are impacted by the existing measures of patient disadvantage, minority patient caseload and dual eligibility.

Methods

We conducted a retrospective cohort study of plastic surgeons participating in Medicare and MIPS using the Physicians Compare National Downloadable File and MIPS scores. Minority patient caseload was defined as non-white patient caseload. We evaluated the characteristics of participating plastic surgeons, their patient caseloads and their scores.

Results

Of 4,539 plastic surgeons participating in Medicare, 1,257 participated in MIPS in the first year of scoring. The average patient caseload is 85% White, with racial/ethnicity data available for 73% of participating surgeons. In multivariable regression, higher minority patient caseload is associated with a lower MIPS score.

Conclusions

As minority patient caseload increases, MIPS scores decrease for otherwise similar caseloads. CMS must consider existing and additional measures of patient disadvantage to ensure equitable surgeon scoring.
Emergency department thoracotomy in children: A Pediatric Trauma Society, Western Trauma Association, and Eastern Association for the Surgery of Trauma systematic review and practice management guideline
Authors: Selesner Leigh , Yorkgitis Brian , Martin Matthew , Ng Grace , Mukherjee Kaushik , Ignacio Romeo , Freeman Jennifer , Wong Lye-Yeng , Durbin Samantha , Crandall Marie , Longshore Shannon W. , Gerall Claire , Flynn-O'Brien Katherine T. , Jafri Mubeen
Published: March 2023

BACKGROUND

The role of emergency department resuscitative thoracotomy (EDT) in traumatically injured children has not been elucidated. We aimed to perform a systematic review and create evidence-based guidelines to answer the following PICO (population, intervention, comparator, and outcome) question: should pediatric patients who present to the emergency department pulseless (with or without signs of life [SOL]) after traumatic injuries (penetrating thoracic, penetrating abdominopelvic, or blunt) undergo EDT (vs. no EDT) to improve survival and neurologically intact survival?

METHODS

Using Grading of Recommendations Assessment, Development and Evaluation methodology, a group of 12 pediatric trauma experts from the Pediatric Trauma Society, Western Trauma Association, and Eastern Association for the Surgery of Trauma assembled to perform a systematic review. A consensus conference was conducted, a database was queried, abstracts and manuscripts were reviewed, data extraction was performed, and evidence quality was determined. Evidence tables were generated, and the committee voted on guideline recommendations.

RESULTS

Three hundred three articles were identified. Eleven studies met the inclusion criteria and were used for guideline creation, providing 319 pediatric patients who underwent EDT. No data were available on patients who did not undergo EDT. For each PICO, the quality of evidence was very low based on the serious risk of bias and serious or very serious imprecision.

CONCLUSION

Based on low-quality data, we make the following recommendations. We conditionally recommend EDT when a child presents pulseless with SOL to the emergency department following penetrating thoracic injury, penetrating abdominopelvic injury and after blunt injury if emergency adjuncts point to a thoracic source. We conditionally recommend against EDT when a pediatric patient presents pulseless without SOL after penetrating thoracic and penetrating abdominopelvic injury. We strongly recommend against EDT in the patient without SOL after blunt injury.
Lower incidence of blunt cerebrovascular injury among young, properly restrained children: An ATOMAC multicenter study
Authors: Nickoles Todd A. , Lewit Ruth A. , Notrica David M. , Ryan Mark , Johnson Jeremy , Maxson Robert Todd , Naiditch Jessica A. , Lawson Karla A. , Temkit M'hamed , Padilla Benjamin , Eubanks James W.
Published: March 2023

BACKGROUND

Motor vehicle collision (MVC) remains a leading cause of injury and death among children, but the proper use of child safety seats and restraints has lowered the risks associated with motor vehicle travel. Blunt cerebrovascular injury (BCVI) is rare but significant among children involved in MVC. This study reviewed the incidence of BCVI after MVC causing blunt injury to the head, face, or neck, comparing those that were properly restrained with those that were not.

METHODS

A prospective, multi-institutional observational study of children younger than 15 years who sustained blunt trauma to the head, face, or neck (Abbreviated Injury Scale score >0) and presented at one of six level I pediatric trauma centers from 2017 to 2020 was conducted. Diagnosis of BCVI was made either by imaging or neurological symptoms at 2-week follow-up. Restraint status among those involved in MVC was compared for each age group.

RESULTS

A total of 2,284 patients were enrolled at the 6 trauma centers. Of these, 521 (22.8%) were involved in an MVC. In this cohort, after excluding patients with missing data, 10 of 371 (2.7%) were diagnosed with a BCVI. For children younger than 12 years, none who were properly restrained suffered a BCVI (0 of 75 children), while 7 of 221 (3.2%) improperly restrained children suffered a BCVI. For children between 12 and 15 years of age, the incidence of BCVI was 2 of 36 (5.5%) for children in seat belts compared with 1 of 36 (2.8%) for unrestrained children.

CONCLUSION

In this large multicenter prospectively screened pediatric cohort, the incidence of BCVI among properly restrained children under 12 years after MVC was infrequent, while the incidence was 3.2% among those without proper restraint. This effect was not seen among children older than 12 years. Restraint status in young children may be an important factor in BCVI screening.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level IV.
Plasma thrombin generation kinetics vary by injury pattern and resuscitation characteristics in pediatric and young adult trauma patients
Authors: MacArthur Taleen A. , Goswami Julie , Howick Annelise S. , Ramachandran Dhanya , Polites Stephanie F. , Klinkner Denise B. , Park Myung S.
Published: March 2023

BACKGROUND

Thrombin generation kinetics are not well studied in children. This study aimed to assess how thrombin generation kinetics vary in pediatric and young adult (YA) trauma patients by clinical characteristics and injury pattern.

METHODS

Prospective cohort study where plasma samples were obtained from pediatric (ages 0–17 years) and YA (ages 18–21 years) trauma patients upon emergency department arrival. Thrombin generation (calibrated automated thrombogram [CAT]) was quantified as lag time (LT, minutes), peak height (PH, nM), time to peak (ttPeak, minutes), and endogenous thrombin potential (ETP, nM × minute). Results are expressed as median and quartiles [Q1, Q3] and compared using Wilcoxon rank sum testing with p < 0.05 considered significant.

RESULTS

We enrolled 47 pediatric (median age, 15 [14, 17] years, 78% male, 87% blunt, median Injury Severity Score, 12) and 49 YA (median age 20 [18, 21] years, 67% male, 84% blunt, median Injury Severity Score, 12) patients. Pediatric and YA patients had similar rates of operative intervention (51% vs. 57%), transfusion (25% vs. 20%), and traumatic brain injury (TBI) (53% vs. 49%). Pediatric patients who required an operation had accelerated initiation of thrombin generation, with shorter LT than those who did not (2.58 [2.33, 2.67]; 2.92 [2.54, 3.00], p = 0.034). Shorter LT (2.41 [2.22, 2.67]; 2.67 [2.53, 3.00]) and ttPeak (4.50 [4.23, 4.73]; 5.22 [4.69, 5.75], both p < 0.01) were noted in pediatric patients who required transfusion as compared with those who did not. The YA patients requiring transfusion had shorter LT (2.33 [2.19, 2.74]; 2.83 [2.67, 3.27]) and ttPeak (4.48 [4.33, 5.65]; 5.33 [4.85, 6.28] both p < 0.04) than those who were not transfused. Young adults with TBI had greater ETP than those without (1509 [1356, 1671]; 1284 [1154, 1471], p = 0.032).

CONCLUSION

Thrombin generation kinetics in pediatric trauma patients prior to intervention vary with need for operation and transfusion, while thrombin generation kinetics in young adult patients are influenced by TBI and need for operation or transfusion. This is a promising tool for assessing coagulopathy in young trauma patients.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level III.
Whole-bone toughness is linked to canal and osteocyte lacunae deficits in the ZDSD type 2 diabetic rat model
Authors: Woolley William , Obata Yoshihiro , Martin Kaitlynn , Acevedo Claire
Published: March 2023

Type 2 diabetes mellitus (T2DM) is associated with an increased fracture risk independent of bone mass. The exact origin of this increased fracture risk is still not well understood. Using a polygenic diabetic rat model, synchrotron radiation micro-computed tomography (SRμCT), andin situscanning electron microscope (SEM) fracture toughness, we related the changes at the microscale to toughness and material properties of diabetic rat femurs. The diabetic rat model (ZDSD) displayed overnight fasting hyperglycemia and an increased AGEs content. Additionally, we measured the impairment of post-yield properties and toughness in diabetic rats. The cortical geometry and porosity were also affected in this ZDSD model. We measured a decrease in osteocyte lacunar density associated with a decreased lacunar volume. Moreover, we found decreased canal density while maintaining a similar canal diameter. These results indicate that diabetes impairs bone remodeling, affecting bone microstructure. Because canals and lacunae are also linked with extrinsic toughening mechanisms, we attribute the decreased toughness largely to these microstructural changes. In conclusion, we showed that changes in lacunae and canal density, combined with AGEs accumulation, decreased toughness in T2DM rat bone.
Concussion-related disruptions to hub connectivity in the default mode network are related to symptoms and cognition
Authors: Bouchard Heather C. , Higgins Kate L. , Amadon Grace K. , Laing-Young Julia M. , Maerlender Arthur , Al-Momani Seima , Neta Maital , Savage Cary R. , Schultz Douglas H.
Published: March 2023

Concussions present with a myriad of symptomatic and cognitive concerns; however, the relationship between these functional disruptions and the underlying changes in the brain are not yet well understood. Hubs, or brain regions that are connected to many different functional networks, may be specifically disrupted after concussion. Given the implications in concussion research, we quantified hub disruption within the default mode network (DMN) and between the DMN and other brain networks. We collected resting-state functional magnetic resonance imaging data from collegiate student-athletes (n = 44) at three timepoints: baseline (prior to beginning their athletic season), acute post-injury (approximately 48 hours after a diagnosed concussion), and recovery (after starting return-to-play progression, but prior to returning to contact). We used self-reported symptoms and computerized cognitive assessments collected across similar timepoints to link these functional connectivity changes to clinical outcomes.

Concussion resulted in increased connectivity between regions within the DMN compared to baseline and recovery, and this post-injury connectivity was more positively related to symptoms and more negatively related to visual memory performance compared to baseline and recovery. Further, concussion led to decreased connectivity between DMN hubs and visual network non-hubs relative to baseline and recovery, and this post-injury connectivity was more negatively related to somatic symptoms and more positively related to visual memory performance compared to baseline and recovery. Relationships between functional connectivity, symptoms, and cognition were not significantly different at baseline versus recovery.

These results highlight a unique relationship between self-reported symptoms, visual memory performance and acute functional connectivity changes involving DMN hubs after concussion in athletes. This may provide evidence for a disrupted balance of within- and between-network communication highlighting possible network inefficiencies after concussion. These results aid in our understanding of the pathophysiological disruptions after concussion and inform our understanding of the associations between disruptions in brain connectivity and specific clinical presentations acutely post-injury.
The CRL plastid outer envelope protein supports TOC75-V / OEP80 complex formation inArabidopsis
Authors: Yoshimura Ryo , Minamikawa Syun , Suzuki Takamasa , Latrasse David , Sicar Sanchari , Raynaud Cécile , Benhamed Moussa , Yoshioka Yasushi
Published: March 2023

Embedded β-barrel proteins in the outer envelope membrane mediate most cellular traffic between the cytoplasm and the plastids. Although TOC75-V/OEP80 has been implicated in the insertion and assembly of β-barrel proteins in the outer envelope membrane ofArabidopsis thaliana, relatively little is known about this process.CRUMPLED LEAF(CRL) encodes a protein localizing in the outer envelope membrane, and its loss of function results in pleiotropic defects, including altered plant morphogenesis, growth retardation, suppression of plastid division, and spontaneous light intensity-dependent localized cell death. A suppressor screen conducted on mutagenizedcrlmutants with ethyl methanesulfonate revealed that a missense mutation inOEP80suppressescrl’s pleiotropic defects. Furthermore, we found that the complex formation of OEP80 was compromised incrl. Furthermore, we demonstrated that CRL interacts with OEP80in vivoand that a portion of CRL is present in protein complexes with the same molecular weight as the OEP80-associated complex. Our results suggest that CRL interacts with OEP80 to regulate its complex formation. CRL has been shown to be involved in plastid protein import; therefore, pleiotropic defects incrlare likely due to the combined effects of decreased plastid protein import and altered membrane integration of β-barrel proteins in the outer envelope membrane. This study sheds light on the mechanisms that allow the integration of β-barrel proteins into the outer envelope membrane of plastids and the significance of this finding for plant cellular processes.
An Antibody-Based Molecular Switch for Continuous Biosensing
Authors: Thompson Ian A.P. , Saunders Jason , Zheng Liwei , Hariri Amani A. , Maganzini Nicolò , Cartwright Alyssa P. , Pan Jing , Eisenstein Michael , Soh Hyongsok Tom
Published: March 2023

We present a generalizable approach for designing biosensors that can continuously detect specific biomarkers in real time and without sample preparation. This is achieved by converting existing antibodies into target-responsive “antibody-switches” that enable continuous optical biosensing. To engineer these switches, antibodies are linked to a molecular competitor through a DNA scaffold, such that competitive target binding induces scaffold switching and fluorescent signaling of changing target concentrations. As a demonstration, we designed antibody-switches that achieve rapid, sample-preparation-free sensing of digoxigenin and cortisol in undiluted plasma. We showed that, by substituting the molecular competitor, we can further modulate the sensitivity of our cortisol switch to achieve detection at concentrations spanning 3.3 nM to 3.3 mM. Finally, we integrated this switch with a fiber-optic sensor to achieve hours-long continuous sensing of cortisol in buffer with <5-minute time resolution. We believe this modular sensor design can enable continuous biosensor development for many biomarkers.
Root-derived long-range signals activate ABA synthesis infrd3leaves to enhance drought resistance
Authors: Liu Qian-Qian , Xia Jin-Qiu , Wu Jie , Zhao Ping-Xia , Zhang Gui-Quan , Xiang Cheng-Bin
Published: March 2023

Vascular plants have evolved sophisticated mechanisms of long-distance signaling to cope with environmental stress. Reactive oxygen species (ROS) act as systemic signals in plant stress responses. However, it is not known whether ROS serve as root-to-shoot signals in the drought response. Here, we show thatferric reductase defective3(frd3) mutants exhibit enhanced drought resistance concomitant with increasedNCED3transcript levels and ABA contents in leaves. Thefrd3mutants also have an elevated hydrogen peroxide (H2O2) level in roots and leaves compared with the wild type. Grafting experiments demonstrate that drought resistance can be conferred by thefrd3rootstock, suggesting that long-distance signals derived infrd3roots trigger ABA level increases in leaves and thereby enhance drought resistance and that H2O2is a strong candidate for long-distance signals. Furthermore, comparative transcriptome and proteomics analyses revealed that many genes and proteins involved in the abiotic stress response, ROS homeostasis, and signaling pathways were affected in thefrd3mutant, supporting the drought resistance phenotype. Taken together, our findings suggest thatfrd3root-derived long-range signals activate ABA synthesis in leaves and enhance drought resistance, indicating possible root-to-shoot H2O2signaling in the plant drought response.
Acute alcohol and chronic drinking bidirectionally regulate the excitability of prefrontal cortex vasoactive intestinal peptide interneurons
Authors: Thompson Shannon M. , Ferranti Anthony S. , Joffe Max E.
Published: March 2023

The prefrontal cortex (PFC) regulates drinking behaviors and affective changes following chronic alcohol use. PFC activity is dynamically modulated by local inhibitory interneurons (INs), which can be divided into non-overlapping groups with distinct functional roles. Within deeper layers of neocortex, INs that express either parvalbumin or somatostatin directly inhibit pyramidal cells. By contrast, the plurality of all remaining INs express vasoactive intestinal peptide (VIP), reside within superficial layers, and preferentially target other types of INs. While recent studies have described adaptations to PFC parvalbumin-INs and somatostatin-INs in alcohol use models, whether ethanol or drinking affect the physiology of PFC VIP-INs has not been reported. To address this gap, we used genetically engineered female and male mice to target VIP-INs in layers 1-3 of prelimbic PFC for whole-cell patch-clamp electrophysiology. We found that ethanol (20 mM, ∼0.09 BEC) application to PFC brain slices enhances VIP-IN excitability. We next examined effects following chronic drinking by providing mice with 4 weeks of intermittent access (IA) ethanol two-bottle choice in the home cage. In these studies, VIP-INs from female and male IA ethanol mice displayed reduced excitability relative to cells from water-only controls. Finally, we assessed whether these effects continue into abstinence. After 7-11 days without ethanol, the hypo-excitability of VIP-INs from male IA ethanol mice persisted, whereas cells from female IA ethanol mice were not different from their controls. Together, these findings illustrate that acute ethanol enhances VIP-IN excitability and suggest these cells undergo pronounced homeostatic changes following long-term drinking.
Long-term reliable neural decoding based on flexible implantable microelectronics and machine learning for seizure prediction application
Authors: He Zicong , Zheng Jiajun , Duan Junwei , Jin Zhe , Huang Zixuan , Wu Shuaishuai , He Qian , So Kwok-Fai , Zhang Shuixing , Xiong Zhiyuan
Published: March 2023

Neural decoding is useful for understanding brain functions and developing neural interface applications. However, neural interfaces based on rigid electronics often suffer from recording instability due to the foreign body responses caused by their mechanical mismatch with soft tissues, limiting the longitudinal accuracy of neural decoding methods. Herein, it is reported that flexible electronics can be integrated with machine learning algorithms to achieve long-term reliable neural decoding. Wet-spun conductive polymer microfibers showed mechanical robustness and flexibility, low impedance, and chronic biocompatibility, enabling intracerebral neural recordings in epileptic mice at a high signal-to-noise ratio eight weeks after implantation. When the signals recorded by the flexible electrodes were used in machine learning analyses with diverse complex algorithms, they consistently showed higher prediction accuracy for epileptic seizures than stiff metal electrode signals, particularly in the case of using long-term recordings for testing or small-sample datasets for training. A real-time warning system based on the flexible neural electrodes was built that predicted seizures eight minutes in advance with a low false alarm rate. Our work bridges flexible electronics and artificial intelligence for neural decoding applications such as long-term treatment of chronic neurological disorders.
Phenotypic plasticity in response to drought stress: Comparisons of domesticated tomato and a wild relative
Authors: Lupo Yaniv , Moshelion Menachem
Published: March 2023

Phenotypic plasticity is the ability of an organism to undergo reversible behavioral, morphological or physiological changes in response to environmental conditions. Phenotypic plasticity enables plants to cope with uncertain environmental conditions, such as drought. A primary plastic trait is the rate of stomatal response to changes in ambient conditions, which determines the amount of water lost via transpiration, as well as levels of CO2absorption, growth and productivity. Here, we examined the differences between domesticated and wild tomato species and their responses to drought stress. We found that the domesticated tomato had a higher transpiration rate and higher stomatal conductance (gs). The domesticated tomato also had greater biomass and greater leaf area under drought conditions, as compared to the wild tomato. Despite the domesticated tomato’s higher transpiration rate and higher gs, there was no difference between the photosynthetic rates of the two lines. Moreover, the wild tomato had a higher maximum rate of rubisco activity, which might explain its greater molecular and whole canopy water-use efficiency. The domesticated tomato’s higher transpiration rate and greater leaf area led to its earlier exposure to drought stress, as compared to the wild tomato, which maintained higher levels of soil water, enabling it to maintain steady rates of whole-canopy stomatal conductance (gsc) for extended periods. The wild tomato was also more sensitive to the soil water availability and lowered its maximum transpiration rate at a higher soil-water-content level. Our results suggest that the domestication process of tomatoes favored morphological/anatomical performance traits over physiological efficiency.
Scaling of Protein Function Across the Tree of Life
Authors: Gondhalekar Riddhi , Kempes Christopher P. , McGlynn Shawn Erin
Published: March 2023

Scaling laws are a powerful way to compare genomes because they put all organisms onto a single curve and reveal non-trivial generalities as genomes change in size. The abundance of functional categories in a given genome scales with genome size, suggesting that universal constraints shape category abundance. Here we look across the tree of life to understand how genome evolution may be related to functional scaling. We revisit previous observations of functional genome scaling with an expanded taxonomy by analyzing 3726 bacterial, 220 archaeal, and 79 unicellular eukaryotic genomes. We find that for some functional classes, scaling is best described by multiple exponents, revealing previously unobserved shifts in scaling as genomes grow or contract. Furthermore, scaling varies between phyletic groups and is less universal than previously thought, with scaling shifts varying uniquely between domains and scaling exponents varying uniquely between phyla. We also find that individual phyla frequently span scaling exponents of functional classes, revealing that individual clades can move across scaling exponents. Across the tree of life, variability in functional scaling is not accounted for by genome phylogeny, suggesting that physiological and/or cell plan outweighs phylogeny.
Assigning a social status from face adornments: an fMRI study
Authors: Salagnon M , d’Errico F , Rigaud S , Mellet E
Published: March 2023

The human face has been culturally modified for at least 150,000 years using practices like painting, tattooing and scarification to convey symbolic meanings and individual identity. The present study used functional magnetic resonance imaging to explore the brain networks involved in attributing social status from face decorations. Results showed the fusiform gyrus, orbitofrontal cortex, and salience network were involved in social encoding, categorization, and evaluation. The hippocampus and parahippocampus were activated due to the memory and associative skills required for the task, while the inferior frontal gyrus likely interpreted face ornaments as symbols. Resting-state functional connectivity analysis clarified the interaction between these regions. The study highlights the importance of these neural interactions in the symbolic interpretation of social markers on the human face, which were likely active in early Homo species and intensified with Homo sapiens populations as more complex technologies were developed to culturalize the human face.
Stimulus-evoked and resting-state alpha oscillations show a linked dependence on patterned visual experience for development
Authors: Pant Rashi , Ossandón José , Stange Liesa , Shareef Idris , Kekunnaya Ramesh , Röder Brigitte
Published: March 2023

Persistent visual impairments after congenital blindness due to dense bilateral cataracts have been attributed to altered visual cortex development within a sensitive period. Occipital alpha (8-14 Hz) oscillations were found to be reduced after congenital cataract reversal during visual motion tasks. However, it has been unclear whether reduced alpha oscillations were task-specific, or linked to impaired visual behavior in cataract-reversed individuals. Here, we compared resting-state and stimulus-evoked alpha activity between individuals who had been treated for dense bilateral congenital cataracts (CC, n = 13, mean duration of blindness = 11.0 years) and age-matched, normally sighted individuals (SC, n = 13). We employed the visual impulse response function, adapted from VanRullen and MacDonald (2012), to test for the characteristic alpha response to visual white noise. Participants observed white noise stimuli changing in luminance with equal power at frequencies between 0-30 Hz. Compared to SC individuals, CC individuals demonstrated a reduced likelihood of exhibiting an evoked alpha response. Moreover, stimulus-evoked alpha power was reduced and correlated with a corresponding reduction of resting-state alpha power in the same CC individuals. Finally, CC individuals with an above-threshold evoked alpha peak had better visual acuity than CC individual without an evoked alpha peak. Since alpha oscillations have been linked to feedback communication, we suggest that the concurrent impairment in resting-state and stimulus-evoked alpha oscillations indicates an altered interaction of top-down and bottom-up processing in the visual hierarchy, which likely contributes to incomplete behavioral recovery in individuals who had experienced transient congenital blindness.
Graph theory analysis reveals an assortative pain network vulnerable to attacks
Authors: Chen Chong , Tassou Adrien , Morales Valentina , Scherrer Grégory
Published: March 2023

The neural substrate of pain experience has been described as a dense network of connected brain regions. However, the connectivity pattern of these brain regions remains elusive, precluding a deeper understanding of how pain emerges from the structural connectivity. Here, we use graph theory to systematically characterize the architecture of a comprehensive pain network, including both cortical and subcortical brain areas. This structural brain network consists of 49 nodes denoting pain-related brain areas, linked by edges representing their relative incoming and outgoing axonal projection strengths. Sixty-three percent of brain areas in this structural pain network share reciprocal connections, reflecting a dense network. The clustering coefficient, a measurement of the probability that adjacent nodes are connected, indicates that brain areas in the pain network tend to cluster together. Community detection, the process of discovering cohesive groups in complex networks, successfully reveals two known subnetworks that specifically mediate the sensory and affective components of pain, respectively. Assortativity analysis, which evaluates the tendency of nodes to connect with other nodes with similar features, indicates that the pain network is assortative. Finally, robustness, the resistance of a complex network to failures and perturbations, indicates that the pain network displays a high degree of error tolerance (local failure rarely affects the global information carried by the network) but is vulnerable to attacks (selective removal of hub nodes critically changes network connectivity). Taken together, graph theory analysis unveils an assortative structural pain network in the brain processing nociceptive information, and the vulnerability of this network to attack opens up the possibility of alleviating pain by targeting the most connected brain areas in the network.
The degree of T cell stemness differentially impacts the potency of adoptive cancer immunotherapy in a Lef-1 and Tcf-1 dependent manner
Authors: Rangel Rivera Guillermo O. , Dwyer Connor J. , Knochelmann Hannah M. , Smith Aubrey S. , Aksoy Arman , Cole Anna C. , Wyatt Megan M. , Thaxton Jessica E. , Lesinski Gregory B. , Paulos Chrystal M.
Published: March 2023

Generating stem memory T cells (TSCM) is a key goal for improving cancer immunotherapy. Yet, the optimal way to modulate signaling pathways that enrich TSCMproperties remains elusive. Here, we discovered that the degree to which the PI3Kδ pathway is blocked pharmaceutically can generate T cells with differential levels of stemness properties. This observation was based on the progressive enrichment of transcriptional factors of stemness (Tcf-1 and Lef-1). Additional investigation revealed that T cells with high stemness features had enhanced metabolic plasticity, marked by heightened mitochondrial function and glucose uptake. Conversely, T cells with low or medium features of stemness expressed more inhibitory checkpoint receptors (Tim-3, CD39) and were vulnerable to antigen-induced cell death. Only TCR-antigen specific T cells with high stemness persisted following adoptive transferin vivoand mounted protective immunity to melanoma tumors. Likewise, the strongest level of PI3Kδ blockadein vitrogenerated human tumor infiltrating lymphocytes (TILs) and CAR T cells with heightened stemness properties, in turn bolstering their capacity to regress human mesothelioma tumors. We find that the level of stemness T cells possessin vitrodifferentially impacts their potency upon transfer in three tumor models. Mechanistically, both Lef-1 and Tcf-1 sustain anti-tumor protection by high TSCM, as deletion of either one compromised cellular therapy. Collectively, these findings highlight the therapeutic potential of carefully modulating PI3Kδ signaling in T cells to confer high stemness and mediate protective responses to solid tumors.
Hippocampal sclerosis of aging at post-mortem is evident on MRI more than a decade prior
Authors: Ortega-Cruz Diana , Iglesias Juan Eugenio , Rabano Alberto , Strange Bryan
Published: March 2023

INTRODUCTION

Hippocampal sclerosis of aging (HS) is an important component of combined dementia neuropathology. However, the temporal evolution of its histologically-defined features is unknown. We investigated pre-mortem longitudinal hippocampal atrophy associated with HS, as well as with other dementia-associated pathologies.

METHODS

We analyzed hippocampal volumes from MRI segmentations in 64 dementia patients with longitudinal MRI follow-up and post-mortem neuropathological evaluation, including HS assessment in the hippocampal head and body.

RESULTS

Significant HS-associated hippocampal volume changes were observed thoughout the evaluated timespan, up to 11.75 years before death. These changes were independent of age and Alzheimer’s Disease (AD) burden, and specifically driven by CA1 and subiculum. AD burden, but not HS, significantly associated with the rate of hippocampal atrophy.

DISCUSSION

HS-associated volume changes are detectable on MRI earlier than 10 years before death. These findings could contribute to the derivation of volumetric cut-offs forin vivodifferentiation between HS and AD.
transomics2cytoscape: An automated software for interpretable 2.5-dimensional visualization of trans-omic networks
Authors: Nishida Kozo , Maruyama Junichi , Kaizu Kazunari , Takahashi Koichi , Yugi Katsuyuki
Published: March 2023

Biochemical network visualization is one of the essential technologies for mechanistic interpretation of omics data. In particular, recent advances in multi-omics measurement and analysis require the development of visualization methods that encompass multiple omics data. Visualization in 2.5 dimension (2.5D visualization), which is an isometric view of stacked X-Y planes, is a convenient way to interpret multi-omics/trans-omics data in the context of the conventional layouts of biochemical networks drawn on each of the stacked omics layers. However, 2.5D visualization of trans-omics networks is a state-of-the-art method that primarily relies on time-consuming human efforts involving manual drawing. Here, we present an R Bioconductor package 'transomics2cytoscape' for automated visualization of 2.5D trans-omics networks. We confirmed that transomics2cytoscape could be used for rapid visualization of trans-omics networks presented in published papers within a few minutes. Transomics2cytoscape allows for frequent update/redrawing of trans-omics networks in line with the progress in multi-omics/trans-omics data analysis, thereby enabling network-based interpretation of multi-omics data at each research step. The transomics2cytoscape source code is available at https://github.com/ecell/transomics2cytoscape.