bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperthyroidism and clinical depression: a systematic review and meta-analysis
Authors: Bode Henry , Ivens Beatrice , Bschor Tom , Schwarzer Guido , Henssler Jonathan , Baethge Christopher
Published: September 2022

Hyperthyroidism and clinical depression are common, and there is preliminary evidence of substantial comorbidity. The extent of the association in the general population, however, has not yet been estimated meta-analytically. Therefore we conducted this systematic review and meta-analysis (registered in PROSPERO: CRD42020164791). Until May 2020, Medline (via PubMed), PsycINFO, and Embase databases were systematically searched for studies on the association of hyperthyroidism and clinical depression, without language or date restrictions. Two reviewers independently selected epidemiological studies providing laboratory or ICD-based diagnoses of hyperthyroidism and diagnoses of depression according to operationalized criteria (e.g. DSM) or to cut-offs in established rating scales. All data, including study quality based on the Newcastle-Ottawa Scale, were independently extracted by two authors. Odds ratios for the association of clinical depression and hyperthyroidism were calculated in a DerSimonian-Laird random-effects meta-analysis. Out of 3372 papers screened we selected 15 studies on 239 608 subjects, with 61% women and a mean age of 50. Relative to euthyroid individuals, patients with hyperthyroidism had a higher chance of being diagnosed with clinical depression: OR 1.67 ([95% CI: 1.49; 1.87], I2: 6%; prediction interval: 1.40 to 1.99), a result supported in a number of sensitivity and subgroup analyses. The OR was slightly less pronounced for subclinical as opposed to overt hyperthyroidism (1.36 [1.06; 1.74] vs. 1.70 [1.49; 1.93]). This comorbidity calls for clinical awareness and its reasons need investigation and may include neurobiological mechanisms, common genetic vulnerability and a generally heightened risk for clinical depression in patients with chronic somatic disorders.
Layer III pyramidal cells in the prefrontal cortex reveal morphological changes in subjects with depression, schizophrenia, and suicide
Authors: Larsen Nick Y. , Vihrs Ninna , Møller Jesper , Sporring Jon , Tan Xueke , Li Xixia , Ji Gang , Rajkowska Grazyna , Sun Fei , Nyengaard Jens R.
Published: September 2022

Brodmann Area 46 (BA46) has long been regarded as a hotspot of disease pathology in individuals with schizophrenia (SCH) and major depressive disorder (MDD). Pyramidal neurons in layer III of the Brodmann Area 46 (BA46) project to other cortical regions and play a fundamental role in corticocortical and thalamocortical circuits. The AutoCUTS-LM pipeline was used to study the 3-dimensional structural morphology and spatial organization of pyramidal cells. Using quantitative light microscopy, we used stereology to calculate the entire volume of layer III in BA46 and the total number and density of pyramidal cells. Volume tensors estimated by the planar rotator quantified the volume, shape, and nucleus displacement of pyramidal cells. All of these assessments were carried out in four groups of subjects: controls (C, n = 10), SCH (n = 10), MDD (n = 8), and suicide subjects with a history of depression (SU, n = 11). SCH subjects had a significantly lower somal volume, total number, and density of pyramidal neurons when compared to C and tended to show a volume reduction in layer III of BA46. When comparing MDD subjects with C, the measured parameters were inclined to follow SCH, although there was only a significant reduction in pyramidal total cell number. While no morphometric differences were observed between SU and MDD, SU had a significantly higher total number of pyramidal cells and nucleus displacement than SCH. Finally, no differences in the spatial organization of pyramidal cells were found among groups. These results suggest that despite significant morphological alterations in layer III of BA46, which may impair prefrontal connections in people with SCH and MDD, the spatial organization of pyramidal cells remains the same across the four groups and suggests no defects in neuronal migration. The increased understanding of pyramidal cell biology may provide the cellular basis for symptoms and neuroimaging observations in SCH and MDD patients.
The MBNL1/circNTRK2/PAX5 pathway regulates aerobic glycolysis in glioblastoma cells by encoding a novel protein NTRK2-243aa
Authors: Zhao Yubo , Song Jian , Dong Weiwei , Liu Xiaobai , Yang Chunqing , Wang Di , Xue Yixue , Ruan Xuelei , Liu Libo , Wang Ping , Zhang Mengyang , Liu Yunhui
Published: September 2022

Glioblastoma multiforme (GBM) is the most common tumor of the human central nervous system. Aerobic glycolysis has been strongly related to tumor development and malignant behavior. In this study, we found that MBNL1, circNTRK2, and NTRK2-243aa were markedly downregulated and inhibited glycolysis in GBM, whereas PAX5 was upregulated and promoted glycolysis. Functionally, MBNL1 promoted the expression of circNTRK2 by binding to NTRK2 pre-mRNA, as validated using RNA pull-down and nascent RNA immunoprecipitation assays. Mass spectrometry, western blotting, and immunofluorescence staining methods were used to detect the expression of NTRK2-243aa. NTRK2-243aa—encoded by circNTRK2—phosphorylated PAX5 at Y102, leading to the attenuation of the half-life of PAX5, as validated by in vitro kinase and MG132 rescue assays. Besides, PAX5 transcriptionally facilitated the expression of PKM2 and HK2 by binding to their promoter regions, as verified by luciferase reporter and chromatin immunoprecipitation assays. Finally, overexpression of MBNL1 and circNTRK2 combined with PAX5 knockdown effectively inhibited the formation of GBM xenograft tumors and significantly prolonged the survival of orthotopic nude mice. We have delineated that the MBNL1/circNTRK2/PAX5 pathway plays a crucial role in regulating GBM glycolysis and could provide potential targets and alternative strategies for the treatment of GBM.
Structure and activity of particulate methane monooxygenase arrays in methanotrophs
Authors: Zhu Yanan , Koo Christopher W. , Cassidy C. Keith , Spink Matthew C. , Ni Tao , Zanetti-Domingues Laura C. , Bateman Benji , Martin-Fernandez Marisa L. , Shen Juan , Sheng Yuewen , Song Yun , Yang Zhengyi , Rosenzweig Amy C. , Zhang Peijun
Published: September 2022

Methane-oxidizing bacteria play a central role in greenhouse gas mitigation and have potential applications in biomanufacturing. Their primary metabolic enzyme, particulate methane monooxygenase (pMMO), is housed in copper-induced intracytoplasmic membranes (ICMs), of which the function and biogenesis are not known. We show by serial cryo-focused ion beam (cryoFIB) milling/scanning electron microscope (SEM) volume imaging and lamellae-based cellular cryo-electron tomography (cryoET) that these ICMs are derived from the inner cell membrane. The pMMO trimer, resolved by cryoET and subtomogram averaging to 4.8 Å in the ICM, forms higher-order hexagonal arrays in intact cells. Array formation correlates with increased enzymatic activity, highlighting the importance of studying the enzyme in its native environment. These findings also demonstrate the power of cryoET to structurally characterize native membrane enzymes in the cellular context.
Adipocyte-derived lactate is a signalling metabolite that potentiates adipose macrophage inflammation via targeting PHD2
Authors: Feng Tianshi , Zhao Xuemei , Gu Ping , Yang Wah , Wang Cunchuan , Guo Qingyu , Long Qiaoyun , Liu Qing , Cheng Ying , Li Jin , Cheung Cynthia Kwan Yui , Wu Donghai , Kong Xinyu , Xu Yong , Ye Dewei , Hua Shuang , Loomes Kerry , Xu Aimin , Hui Xiaoyan
Published: September 2022

Adipose tissue macrophage (ATM) inflammation is involved with meta-inflammation and pathology of metabolic complications. Here we report that in adipocytes, elevated lactate production, previously regarded as the waste product of glycolysis, serves as a danger signal to promote ATM polarization to an inflammatory state in the context of obesity. Adipocyte-selective deletion of lactate dehydrogenase A (Ldha), the enzyme converting pyruvate to lactate, protects mice from obesity-associated glucose intolerance and insulin resistance, accompanied by a lower percentage of inflammatory ATM and reduced production of pro-inflammatory cytokines such as interleukin 1β (IL-1β). Mechanistically, lactate, at its physiological concentration, fosters the activation of inflammatory macrophages by directly binding to the catalytic domain of prolyl hydroxylase domain-containing 2 (PHD2) in a competitive manner with α-ketoglutarate and stabilizes hypoxia inducible factor (HIF-1α). Lactate-induced IL-1β was abolished in PHD2-deficient macrophages. Human adipose lactate level is positively linked with local inflammatory features and insulin resistance index independent of the body mass index (BMI). Our study shows a critical function of adipocyte-derived lactate in promoting the pro-inflammatory microenvironment in adipose and identifies PHD2 as a direct sensor of lactate, which functions to connect chronic inflammation and energy metabolism.
Structural basis for Gemin5 decamer-mediated mRNA binding
Authors: Guo Qiong , Zhao Shidong , Francisco-Velilla Rosario , Zhang Jiahai , Embarc-Buh Azman , Abellan Salvador , Lv Mengqi , Tang Peiping , Gong Qingguo , Shen Huaizong , Sun Linfeng , Yao Xuebiao , Min Jinrong , Shi Yunyu , Martínez-Salas Encarnacion , Zhang Kaiming , Xu Chao
Published: September 2022

Gemin5 in the Survival Motor Neuron (SMN) complex serves as the RNA-binding protein to deliver small nuclear RNAs (snRNAs) to the small nuclear ribonucleoprotein Sm complex via its N-terminal WD40 domain. Additionally, the C-terminal region plays an important role in regulating RNA translation by directly binding to viral RNAs and cellular mRNAs. Here, we present the three-dimensional structure of the Gemin5 C-terminal region, which adopts a homodecamer architecture comprised of a dimer of pentamers. By structural analysis, mutagenesis, and RNA-binding assays, we find that the intact pentamer/decamer is critical for the Gemin5 C-terminal region to bind cognate RNA ligands and to regulate mRNA translation. The Gemin5 high-order architecture is assembled via pentamerization, allowing binding to RNA ligands in a coordinated manner. We propose a model depicting the regulatory role of Gemin5 in selective RNA binding and translation. Therefore, our work provides insights into the SMN complex-independent function of Gemin5.
NETosis and thrombosis in vaccine-induced immune thrombotic thrombocytopenia
Authors: Leung Halina H. L. , Perdomo Jose , Ahmadi Zohra , Zheng Shiying S. , Rashid Fairooj N. , Enjeti Anoop , Ting Stephen B. , Chong James J. H. , Chong Beng H.
Published: September 2022

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare yet serious adverse effect of the adenoviral vector vaccines ChAdOx1 nCoV-19 (AstraZeneca) and Ad26.COV2.S (Janssen) against COVID-19. The mechanisms involved in clot formation and thrombocytopenia in VITT are yet to be fully determined. Here we show neutrophils undergoing NETosis and confirm expression markers of NETs in VITT patients. VITT antibodies directly stimulate neutrophils to release NETs and induce thrombus formation containing abundant platelets, neutrophils, fibrin, extracellular DNA and citrullinated histone H3 in a flow microfluidics system and in vivo. Inhibition of NETosis prevents VITT-induced thrombosis in mice but not thrombocytopenia. In contrast, in vivo blockage of FcγRIIa abrogates both thrombosis and thrombocytopenia suggesting these are distinct processes. Our findings indicate that anti-PF4 antibodies activate blood cells via FcγRIIa and are responsible for thrombosis and thrombocytopenia in VITT. Future development of NETosis and FcγRIIa inhibitors are needed to treat VITT and similar immune thrombotic thrombocytopenia conditions more effectively, leading to better patient outcomes.
Reversible electrical percolation in a stretchable and self-healable silver-gradient nanocomposite bilayer
Authors: Park Jinhong , Seong Duhwan , Park Yong Jun , Park Sang Hyeok , Jung Hyunjin , Kim Yewon , Baac Hyoung Won , Shin Mikyung , Lee Seunghyun , Lee Minbaek , Son Donghee
Published: September 2022

The reversibly stable formation and rupture processes of electrical percolative pathways in organic and inorganic insulating materials are essential prerequisites for operating non-volatile resistive memory devices. However, such resistive switching has not yet been reported for dynamically cross-linked polymers capable of intrinsic stretchability and self-healing. This is attributable to the uncontrollable interplay between the conducting filler and the polymer. Herein, we present the development of the self-healing, stretchable, and reconfigurable resistive random-access memory. The device was fabricated via the self-assembly of a silver-gradient nanocomposite bilayer which is capable of easily forming the metal-insulator-metal structure. To realize stable resistive switching in dynamic molecular networks, our device features the following properties: i) self-reconstruction of nanoscale conducting fillers in dynamic hydrogen bonding for self-healing and reconfiguration and ii) stronger interaction among the conducting fillers than with polymers for the formation of robust percolation paths. Based on these unique features, we successfully demonstrated stable data storage of cardiac signals, damage-reliable memory triggering system using a triboelectric energy-harvesting device, and touch sensing via pressure-induced resistive switching.
A translational genomics approach identifies IL10RB as the top candidate gene target for COVID-19 susceptibility
Authors: Voloudakis Georgios , Vicari James M. , Venkatesh Sanan , Hoffman Gabriel E. , Dobrindt Kristina , Zhang Wen , Beckmann Noam D. , Higgins Christina A. , Argyriou Stathis , Jiang Shan , Hoagland Daisy , Gao Lina , Corvelo André , Cho Kelly , Lee Kyung Min , Bian Jiantao , Lee Jennifer S. , Iyengar Sudha K. , Luoh Shiuh-Wen , Akbarian Schahram , Striker Robert , Assimes Themistocles L. , Schadt Eric E. , Lynch Julie A. , Merad Miriam , tenOever Benjamin R. , Charney Alexander W. ,   Mount Sinai COVID-19 Biobank,   VA Million Veteran Program COVID-19 Science Initiative, Brennand Kristen J. , Fullard John F. , Roussos Panos
Published: September 2022

Recent efforts have identified genetic loci that are associated with coronavirus disease 2019 (COVID-19) infection rates and disease outcome severity. Translating these genetic findings into druggable genes that reduce COVID-19 host susceptibility is a critical next step. Using a translational genomics approach that integrates COVID-19 genetic susceptibility variants, multi-tissue genetically regulated gene expression (GReX), and perturbagen signatures, we identified IL10RB as the top candidate gene target for COVID-19 host susceptibility. In a series of validation steps, we show that predicted GReX upregulation of IL10RB and higher IL10RB expression in COVID-19 patient blood is associated with worse COVID-19 outcomes and that in vitro IL10RB overexpression is associated with increased viral load and activation of disease-relevant molecular pathways.
Integrating rapid exome sequencing into NICU clinical care after a pilot research study
Authors: D’Gama Alissa M. , Del Rosario Maya C. , Bresnahan Mairead A. , Yu Timothy W. , Wojcik Monica H. , Agrawal Pankaj B.
Published: September 2022

Genomic sequencing is a powerful diagnostic tool in critically ill infants, but performing exome or genome sequencing (ES/GS) in the context of a research study is different from implementing these tests clinically. We investigated the integration of rapid ES into routine clinical care after a pilot research study in a Level IV Neonatal Intensive Care Unit (NICU). We performed a retrospective cohort analysis of infants admitted with suspected genetic disorders to the NICU from December 1, 2018 to March 31, 2021 and compared results to those obtained from a previous research study cohort (March 1, 2017 to November 30, 2018). Clinical rapid ES was performed in 80/230 infants (35%) with a suspected genetic disorder and identified a genetic diagnosis in 22/80 infants (28%). The majority of diagnoses acutely impacted clinical management (14/22 (64%)). Compared to the previous research study, clinically integrated rapid ES had a significantly lower diagnostic yield and increased time from NICU admission and genetics consult to ES report, but identified four genetic diagnoses that may have been missed by the research study selection criteria. Compared to other genetic tests, rapid ES had similar or higher diagnostic yield and similar or decreased time to result. Overall, rapid ES was utilized in the NICU after the pilot research study, often as the first-tier sequencing test, and could identify the majority of disease-causing variants, shorten the diagnostic odyssey, and impact clinical care. Based on our experience, we have identified strategies to optimize the clinical implementation of rapid ES in the NICU.
Integration of body-mounted ultrasoft organic solar cell on cyborg insects with intact mobility
Authors: Kakei Yujiro , Katayama Shumpei , Lee Shinyoung , Takakuwa Masahito , Furusawa Kazuya , Umezu Shinjiro , Sato Hirotaka , Fukuda Kenjiro , Someya Takao
Published: September 2022

Cyborg insects have been proposed for applications such as urban search and rescue. Body-mounted energy-harvesting devices are critical for expanding the range of activity and functionality of cyborg insects. However, their power outputs are limited to less than 1 mW, which is considerably lower than those required for wireless locomotion control. The area and load of the energy harvesting device considerably impair the mobility of tiny robots. Here, we describe the integration of an ultrasoft organic solar cell module on cyborg insects that preserves their motion abilities. Our quantified system design strategy, developed using a combination of ultrathin film electronics and an adhesive–nonadhesive interleaving structure to perform basic insect motion, successfully achieved the fundamental locomotion of traversing and self-righting. The body-mounted ultrathin organic solar cell module achieves a power output of 17.2 mW. We demonstrate its feasibility by displaying the recharging wireless locomotion control of cyborg insects.
Massively parallel genomic perturbations with multi-target CRISPR interrogates Cas9 activity and DNA repair at endogenous sites
Authors: Zou Roger S. , Marin-Gonzalez Alberto , Liu Yang , Liu Hans B. , Shen Leo , Dveirin Rachel K. , Luo Jay X. J. , Kalhor Reza , Ha Taekjip
Published: September 2022

Here we present an approach that combines a clustered regularly interspaced short palindromic repeats (CRISPR) system that simultaneously targets hundreds of epigenetically diverse endogenous genomic sites with high-throughput sequencing to measure Cas9 dynamics and cellular responses at scale. This massive multiplexing of CRISPR is enabled by means of multi-target guide RNAs (mgRNAs), degenerate guide RNAs that direct Cas9 to a pre-determined number of well-mapped sites. mgRNAs uncovered generalizable insights into Cas9 binding and cleavage, revealing rapid post-cleavage Cas9 departure and repair factor loading at protospacer adjacent motif-proximal genomic DNA. Moreover, by bypassing confounding effects from guide RNA sequence, mgRNAs unveiled that Cas9 binding is enhanced at chromatin-accessible regions, and cleavage by bound Cas9 is more efficient near transcribed regions. Combined with light-mediated activation and deactivation of Cas9 activity, mgRNAs further enabled high-throughput study of the cellular response to double-strand breaks with high temporal resolution, revealing the presence, extent (under 2 kb) and kinetics (~1 h) of reversible DNA damage-induced chromatin decompaction. Altogether, this work establishes mgRNAs as a generalizable platform for multiplexing CRISPR and advances our understanding of intracellular Cas9 activity and the DNA damage response at endogenous loci.
Transplantation of human neural progenitor cells secreting GDNF into the spinal cord of patients with ALS: a phase 1/2a trial
Authors: Baloh Robert H. , Johnson J. Patrick , Avalos Pablo , Allred Peggy , Svendsen Soshana , Gowing Genevieve , Roxas Kristina , Wu Amanda , Donahue Becky , Osborne Sheryl , Lawless George , Shelley Brandon , Wheeler Koral , Prina Carolyn , Fine Dana , Kendra-Romito Tami , Stokes Haniah , Manoukian Vicki , Muthukumaran Abirami , Garcia Leslie , Bañuelos Maria G. , Godoy Marlesa , Bresee Catherine , Yu Hong , Drazin Doniel , Ross Lindsey , Naruse Robert , Babu Harish , Macklin Eric A. , Vo Ashley , Elsayegh Ashraf , Tourtellotte Warren , Maya Marcel , Burford Matthew , Diaz Frank , Patil Chirag G. , Lewis Richard A. , Svendsen Clive N.
Published: September 2022

Amyotrophic lateral sclerosis (ALS) involves progressive motor neuron loss, leading to paralysis and death typically within 3–5 years of diagnosis. Dysfunctional astrocytes may contribute to disease and glial cell line-derived neurotrophic factor (GDNF) can be protective. Here we show that human neural progenitor cells transduced with GDNF (CNS10-NPC-GDNF) differentiated to astrocytes protected spinal motor neurons and were safe in animal models. CNS10-NPC-GDNF were transplanted unilaterally into the lumbar spinal cord of 18 ALS participants in a phase 1/2a study (NCT02943850). The primary endpoint of safety at 1 year was met, with no negative effect of the transplant on motor function in the treated leg compared with the untreated leg. Tissue analysis of 13 participants who died of disease progression showed graft survival and GDNF production. Benign neuromas near delivery sites were common incidental findings at post-mortem. This study shows that one administration of engineered neural progenitors can provide new support cells and GDNF delivery to the ALS patient spinal cord for up to 42 months post-transplantation.
Association between Toxoplasma gondii infection and psychiatric disorders: a cross-sectional study in China
Authors: Liu Taixiu , Gao Peng , Bu Deyun , Liu Dong
Published: September 2022

Psychiatric patients have become the focus of public attention, and current research suggests a possible link between Toxoplasma gondii (T. gondii) infection and mental illness. To understand the current situation of T. gondii infection in psychiatric patients in the study area, the relationship between T. gondii infection and mental diseases, and the influence of T. gondii infection on psychiatric patients, this study examined 3101 psychiatric inpatients from 2015 to 2020. All people included in the study were tested for anti-Toxoplasma IgM antibody and anti-Toxoplasma IgG antibody. Additionally, 4040 individuals from the general population were included as controls. The chi-square test and logistic regression analysis were carried out to determine the association between psychiatric disorders and T. gondii infection. The seroprevalence of anti-Toxoplasma IgM antibody was 0.23% (7/3101) in psychiatric inpatients and 0.11% (2/1846) in the general population, and there was no significant difference (p > 0.05). The seroprevalence rate of anti-Toxoplasma IgG antibodies was 3.03% (94/3101) in psychiatric inpatients and 1.05% (23/2194) in the general population, and there was a significant difference (p < 0.01). The seroprevalence of anti-Toxoplasma IgG antibody in psychiatric inpatients was significantly different between different age groups (p < 0.01). The positivity rate of anti-Toxoplasma IgG antibodies was 5.17% (3/58) in patients with mania, 3.24% (8/247) in patients with recurrent depressive disorder, 3.54% (13/367) in patients with depression, 3.22% (39/1213) in patients with schizophrenia, 2.41% (18/748) in patients with bipolar disorder and 2.25% (2/89) in patients with dissociative disorder. Compared to the general population, patients with mania (OR = 5.149 95% CI 1.501–17.659 p = 0.009), schizophrenia (OR = 3.136 95% CI 1.864–5.275 p = 0.000), depression (OR = 3.466 95% CI 1.740–6.906 p = 0.000), recurrent depressive disorder (OR = 3.160 95% CI 1.398–7.142 p = 0.006) and bipolar disorder (OR = 2.327 95% CI 1.249–4.337 p = 0.008) were found to be significantly associated with the seroprevalence of anti-Toxoplasma IgG antibody. This study suggests that the seroprevalence of T. gondii infection in psychiatric patients was higher and that age was an influencing factor of T. gondii infection in psychiatric patients. T. gondii infection was associated with mania, schizophrenia, depression, recurrent depressive disorder and bipolar disorder.
Whole structural reconstruction and quantification of epidermal innervation through the suction blister method and skin-clearing technique
Authors: Kim Dai Hyun , Lee Se Jeong , Kim June Hoan , Park Sung Jin , Seo Soo Hong , Ahn Hyo Hyun , Sun Woong , Kim Byung-Jo , Rhyu Im Joo
Published: September 2022

Three-dimensional (3-D) analysis of intraepidermal nerve fibers (IENFs) is conducted to advance assessment methods for peripheral neuropathies and pruritic skin disorders. The skin-clearing technique was proven to be a reliable method for 3-D imaging of IENFs. Nonetheless, it still requires further improvement in the imaging process. The aim of this study was to standardize the 3-D evaluation method of IENFs and to suggest promising 3-D biomarkers for clinical application. A total of nine healthy individuals were prospectively enrolled. The newly adopted suction blister method was combined with the tissue-clearing technique. The detailed structure of the IENFs was reconstructed and quantified using the neuron tracing software. The suction blister method showed improved linear integrity of IENFs compared with those obtained from the previously used salt-split skin test. The 3-D parameters most significantly related to natural aging were the convex hull two-dimensional perimeter and the total length (both p = 0.020). The meaningful correlations were followed by total volume (p = 0.025), ends (p = 0.026), convex hull 3-D surface, and complexity (both p = 0.030). Thus, the 3-D parameters could be utilized as possible biomarkers to identify ambiguous pathologies of peripheral neuropathies and pruritic skin disorders.
Assessing mammal trapping standards in wild boar drop-net capture
Authors: Conejero Carles , López-Olvera Jorge Ramón , González-Crespo Carlos , Ráez-Bravo Arián , Castillo-Contreras Raquel , Tampach Stefania , Velarde Roser , Mentaberre Gregorio
Published: September 2022

Applying contemporary trapping standards when managing wildlife should no longer be an option, but a duty. Increasing wild boar populations originate a growing number of conflicts and hunting is the only cost-effective management option in most cases. However, new scenarios where hunting is unfeasible emerge and trapping necessities cope with lacking regulatory frameworks and technical guidelines. In this research, we evaluated drop nets, a capture method not considered by the international trapping standards, to capture Eurasian wild boar (Sus scrofa), a wildlife species not included in the list of mammal species under the scope of the Agreement on International Humane Trapping Standards (AIHTS). Less than 20% of the captured wild boars presented moderate or severe injuries attributable to the capture method, hence fulfilling the acceptance thresholds of the outdated AIHTS. Based on the new standards thresholds of acceptance, the humaneness of drop-nets in our study ranged 66–78%, under the 85% required. The capture success and selectivity were 100%, as ensured by operator-driven triggering, which should be considered the main strengths of this method, together with the minimization of animal suffering owing the short duration of the stressful situation. Additionally, in spite of the socially adverse environment, with people contrary to wild boar removal, no disturbances against the capture system or operations occurred. This is the first assessment of a drop-net capture method according to internationally accepted mammal trapping standards, with unconclusive results. However, there is a need for adapted procedures and thresholds of acceptance aimed at not-mechanical traps in general, and specifically at drop-nets. Compared to other live-capture methods, drop-nets minimize the duration of the stressful situation —at the expense of a strong adrenergic acute response—, maximize the probabilities of capturing entire sounders of prosocial species, which may be also considered as more humane, and has the ability to coordinate higher values of capture success, absolute selectivity and adaptability to difficult environments.
Oleanolic acid stimulation of cell migration involves a biphasic signaling mechanism
Authors: Stelling-Férez Javier , Gabaldón José Antonio , Nicolás Francisco José
Published: September 2022

Cell migration is a critical process for wound healing, a physiological phenomenon needed for proper skin restoration after injury. Wound healing can be compromised under pathological conditions. Natural bioactive terpenoids have shown promising therapeutic properties in wound healing. Oleanolic acid (OA), a triterpenoid, enhances in vitro and in vivo cell migration. However, the underlying signaling mechanisms and pathways triggered by OA are poorly understood. We have previously shown that OA activates epidermal growth factor receptor (EGFR) and downstream effectors such as mitogen-activated protein (MAP) kinase cascade and c-Jun N-terminal kinase (JNK), leading to c-Jun transcription factor phosphorylation, all of which are involved in migration. We performed protein expression or migration front protein subcellular localization assays, which showed that OA induces c-Jun activation and its nuclear translocation, which precisely overlaps at wound-edge cells. Furthermore, c-Jun phosphorylation was independent of EGFR activation. Additionally, OA promoted actin cytoskeleton and focal adhesion (FA) dynamization. In fact, OA induced the recruitment of regulator proteins to FAs to dynamize these structures during migration. Moreover, OA changed paxillin distribution and activated focal adhesion kinase (FAK) at focal adhesions (FAs). The molecular implications of these observations are discussed.
Sleep targets highly connected global and local nodes to aid consolidation of learned graph networks
Authors: Feld G. B. , Bernard M. , Rawson A. B. , Spiers H. J.
Published: September 2022

Much of our long-term knowledge is organised in complex networks. Sleep is thought to be critical for abstracting knowledge and enhancing important item memory for long-term retention. Thus, sleep should aid the development of memory for networks and the abstraction of their structure for efficient storage. However, this remains unknown because past sleep studies have focused on discrete items. Here we explored the impact of sleep (night-sleep/day-wake within-subject paradigm with 25 male participants) on memory for graph-networks where some items were important due to dense local connections (degree centrality) or, independently, important due to greater global connections (closeness/betweenness centrality). A network of 27 planets (nodes) sparsely interconnected by 36 teleporters (edges) was learned via discrete associations without explicit indication of any network structure. Despite equivalent exposure to all connections in the network, we found that memory for the links between items with high local connectivity or high global connectivity were better retained after sleep. These results highlight that sleep has the capacity for strengthening both global and local structure from the world and abstracting over multiple experiences to efficiently form internal networks of knowledge.
Reduced variability of bursting activity during working memory
Authors: Lundqvist Mikael , Rose Jonas , Brincat Scott L. , Warden Melissa R. , Buschman Timothy J. , Herman Pawel , Miller Earl K.
Published: September 2022

Working memories have long been thought to be maintained by persistent spiking. However, mounting evidence from multiple-electrode recording (and single-trial analyses) shows that the underlying spiking is better characterized by intermittent bursts of activity. A counterargument suggested this intermittent activity is at odds with observations that spike-time variability reduces during task performance. However, this counterargument rests on assumptions, such as randomness in the timing of the bursts, which may not be correct. Thus, we analyzed spiking and LFPs from monkeys’ prefrontal cortex (PFC) to determine if task-related reductions in variability can co-exist with intermittent spiking. We found that it does because both spiking and associated gamma bursts were task-modulated, not random. In fact, the task-related reduction in spike variability could largely be explained by a related reduction in gamma burst variability. Our results provide further support for the intermittent activity models of working memory as well as novel mechanistic insights into how spike variability is reduced during cognitive tasks.
Roadmap for achieving net-zero emissions in global food systems by 2050
Authors: Costa Ciniro , Wollenberg Eva , Benitez Mauricio , Newman Richard , Gardner Nick , Bellone Federico
Published: September 2022

Food systems (FSs) emit ~ 20 GtCO2e/y (~ 35% of global greenhouse gas emissions). This level tends to raise given the expected increases in food demands, which may threaten global climate targets. Through a rapid assessment, evaluating 60+ scenarios based on existing low-emission and carbon sequestration practices, we estimate that intensifying FSs could reduce its emissions from 21.4 to − 2.0 GtCO2e/y and address increasing food demands without relying on carbon offsets (e.g., related to afforestation and reforestation programs). However, given historical trends and regional contexts, a more diverse portfolio of practices, including diet shifts and new-horizon technologies, will be needed to increase the feasibility of achieving net-zero FSs. One likely pathway consists of implementing practices that shift food production to the 30th-percentile of least emission-intensive FSs (~ 45% emissions reduction), sequester carbon at 50% of its potential (~ 5 GtCO2e/y) and adopt diet shifts and new-horizon technologies (~ 6 GtCO2e/y). For a successful transition to happen, the global FSs would, in the next decade (2020s), need to implement cost-effective mitigation practices and technologies, supported by improvements in countries’ governance and technical assistance, innovative financial mechanisms and research focused on making affordable technologies in the following two decades (2030–2050). This work provides options and a vision to guide global FSs to achieving net-zero by 2050.
The effect of COVID-19 on employees' mental health
Authors: Rodoplu Şahin Didem , Aslan Mustafa , Demirkaya Harun , Ateşoğlu Hülya
Published: September 2022

Long lockdowns, food shortages, and the inability to receive basic primary healthcare have aggravated the effects of pandemics. However, most studies have focused on the health problems of the infected people or the measures employed to keep the disease under control. This cross-sectional study focused primarily on the mental health issues of employees. By employing a convenient sampling method, we reached 237 respondents (135 with coronavirus history) to assess the impact of the pandemic on employees. Multivariate causal relationships were assessed with Structural Equation Modeling (SEM). The predictors included internal entrapment (INT) and difficulty identifying feelings (DIF), which are significant predictors of depression (DEPR). DIF was found to be a significant predictor of INT and EXT feelings, while FEAR was found to be a significant predictor of INT, DIF, and DEPR. Quality of life (QoL) was found to be a significant predictor of DIF and DDF, DEPR, EXT and INT, and FEAR. The results also showed that DIF mainly manifested its effect on depression through INT. The DEPR level of employees working only from home was higher than that of other employees. The depression levels of women, young employees, and those whose QoL was adversely affected by the coronavirus were higher than the rest.
Habitat-use influences severe disease-mediated population declines in two of the most common garden bird species in Great Britain
Authors: Hanmer Hugh J. , Cunningham Andrew A. , John Shinto K. , Magregor Shaheed K. , Robinson Robert A. , Seilern-Moy Katharina , Siriwardena Gavin M. , Lawson Becki
Published: September 2022

The influence of supplementary feeding of wildlife on disease transmission and its consequent impacts on population dynamics are underappreciated. In Great Britain, supplementary feeding is hypothesised to have enabled the spread of the protozoan parasite, Trichomonas gallinae, from columbids to finches, leading to epidemic finch trichomonosis and a rapid population decline of greenfinch (Chloris chloris). More recently, chaffinch (Fringilla coelebs), has also declined markedly from the second to fifth commonest bird in Britain. Using citizen science data, we show that both declines were driven primarily by reduced adult survival, with the greatest reductions occurring in peri-domestic habitats, where supplementary food provision is common. Post-mortem examinations showed a proportional increase in chaffinch trichomonosis cases, near-contemporaneous with its population decline. Like greenfinches, chaffinches often use supplementary food, but are less associated with human habitation. Our results support the hypothesis that supplementary feeding can increase parasite transmission frequency within and between common species. However, the dynamics behind resultant population change can vary markedly, highlighting the need for integrating disease surveillance with demographic monitoring. Other species susceptible to T. gallinae infection may also be at risk. Supplementary feeding guidelines for wildlife should include disease mitigation strategies to ensure that benefits to target species outweigh risks.
A novel scaled-gamma-tanh (SGT) activation function in 3D CNN applied for MRI classification
Authors: Khagi Bijen , Kwon Goo-Rak
Published: September 2022

Activation functions in the neural network are responsible for ‘firing’ the nodes in it. In a deep neural network they ‘activate’ the features to reduce feature redundancy and learn the complex pattern by adding non-linearity in the network to learn task-specific goals. In this paper, we propose a simple and interesting activation function based on the combination of scaled gamma correction and hyperbolic tangent function, which we call Scaled Gamma Tanh (SGT) activation. The proposed activation function is applied in two steps, first is the calculation of gamma version as y = f(x) = axα for x < 0 and y = f(x) = bxβ for x ≥ 0, second is obtaining the squashed value as z = tanh(y). The variables a and b are user-defined constant values whereas $$\alpha$$
α
and $$\beta$$
β
are channel-based learnable parameters. We analyzed the behavior of the proposed SGT activation function against other popular activation functions like ReLU, Leaky-ReLU, and tanh along with their role to confront vanishing/exploding gradient problems. For this, we implemented the SGT activation functions in a 3D Convolutional neural network (CNN) for the classification of magnetic resonance imaging (MRIs). More importantly to support our proposed idea we have presented a thorough analysis via histogram of inputs and outputs in activation layers along with weights/bias plot and t-SNE (t-Distributed Stochastic Neighbor Embedding) projection of fully connected layer for the trained CNN models. Our results in MRI classification show SGT outperforms standard ReLU and tanh activation in all cases i.e., final validation accuracy, final validation loss, test accuracy, Cohen’s kappa score, and Precision.
Tyrosine phosphatase activity is restricted by basic charge substituting mutation of substrates
Authors: Huang Che-Fan , Gottardi Cara J. , Mrksich Milan
Published: September 2022

Phosphorylation controls important cellular signals and its dysregulation leads to disease. While most phospho-regulation studies are focused on kinases, phosphatases are comparatively overlooked. Combining peptide arrays with SAMDI mass spectrometry, we show that tyrosine phosphatase activity is restricted by basic amino acids adjacent to phosphotyrosines. We validate this model using two β-catenin mutants associated with cancer (T653R/K) and a mouse model for intellectual disability (T653K). These mutants introduce a basic residue next to Y654, an established phosphorylation site where modification shifts β-catenin from cell–cell adhesions and towards its essential nuclear role as Wnt-signaling effector. We show that T653-basic mutant β-catenins are less efficiently dephosphorylated by phosphatases, leading to sustained Y654 phosphorylation and elevated Wnt signals, similar to those observed for Y654E phospho-mimic mutant mice. This model rationalizes how basic mutations proximal to phosphotyrosines can restrict counter-regulation by phosphatases, providing new mechanismistic and treatment insights for 6000+ potentially relevant cancer mutations.
Development of Safirinium dyes for new applications: fluorescent staining of bacteria, human kidney cells, and the horny layer of the epidermis
Authors: Fedorowicz Joanna , Bazar Dagmara , Brankiewicz Wioletta , Kapica Hanna , Ciura Krzesimir , Zalewska-Piątek Beata , Piątek Rafał , Cal Krzysztof , Mojsiewicz-Pieńkowska Krystyna , Sączewski Jarosław
Published: September 2022

Low-molecular synthetic fluorophores are convenient tools in bioimaging applications. Several derivatives of Safirinium dyes as well as their reactive N-hydroxysuccinimide (NHS) esters bearing diverse substituents were synthesized and evaluated experimentally in terms of their lipophilicity by means of reverse-phase and immobilized artificial membrane high-performance liquid chromatography. Subsequently, the selected compounds were employed as novel cellular imaging agents for staining Gram-positive and Gram-negative bacteria, human kidney cell line, as well as human skin tissue. The analyzed dyes allowed for visualization of cellular structures such as mitochondria, endoplasmic reticulum, and cellular nuclei. They proved to be useful in fluorescent staining of stratum corneum, especially in the aspect of xenobiotic exposure and its penetration into the skin. The best results were obtained with the use of moderately lipophilic NHS esters of Safirinium Q. The development of Safirinium dyes is a promising alternative for commercially available dyes since the reported molecules have low molecular masses and exhibit efficient staining and remarkable water solubility. Moreover, they are relatively simple and low-cost in synthesis.
Decoding spatiotemporal features of emotional body language in social interactions
Authors: Keck Johannes , Zabicki Adam , Bachmann Julia , Munzert Jörn , Krüger Britta
Published: September 2022

How are emotions perceived through human body language in social interactions? This study used point-light displays of human interactions portraying emotional scenes (1) to examine quantitative intrapersonal kinematic and postural body configurations, (2) to calculate interaction-specific parameters of these interactions, and (3) to analyze how far both contribute to the perception of an emotion category (i.e. anger, sadness, happiness or affection) as well as to the perception of emotional valence. By using ANOVA and classification trees, we investigated emotion-specific differences in the calculated parameters. We further applied representational similarity analyses to determine how perceptual ratings relate to intra- and interpersonal features of the observed scene. Results showed that within an interaction, intrapersonal kinematic cues corresponded to emotion category ratings, whereas postural cues reflected valence ratings. Perception of emotion category was also driven by interpersonal orientation, proxemics, the time spent in the personal space of the counterpart, and the motion–energy balance between interacting people. Furthermore, motion–energy balance and orientation relate to valence ratings. Thus, features of emotional body language are connected with the emotional content of an observed scene and people make use of the observed emotionally expressive body language and interpersonal coordination to infer emotional content of interactions.
Development of the shear displacement of sandy soil due to absorption under constant shear stress for creep failure
Authors: Sasahara Katsuo
Published: September 2022

Measurement of the displacement and pore pressure in physical model slopes and natural slopes revealed that not only an accelerative increase up to failure but also a decelerative increase occurred in surface displacement under a constant groundwater level, which could be recognized as creep deformation under constant stress. The displacement increased significantly at first in both types, which made it difficult to evaluate whether the displacement developed to the point of failure at the start of the increase. It was necessary to find an indicator for evaluation as the first step of the prediction of an onset of slope failure. Measurement of shear and normal displacements of the sandy specimen in an inclined direct shear box with increasing water content was conducted to examine the indicator. The increase in the shear displacement was categorized into three types: the accelerative increase up to failure with increasing volumetric water content (VWC), the accelerative increase up to failure under constant VWC just prior to failure, and the decelerative increase under constant VWC. It was recognized that a constant VWC corresponded to constant suction from the experimental data. Shear displacement increased up to failure with the monotonic decrease in void ratio just prior to failure in the case of increasing VWC. The void ratio monotonically decreased under constant VWC in the case of shear displacement termination under constant VWC, while it significantly varied at first and then converged to a constant value just prior to failure in the case of shear displacement increase with constant VWC. The ultimate void ratio under the same stress conditions might have been unique. These facts revealed that the void ratio can be recognized as an indicator of the failure of specimens under creep deformation according to absorption. When the void ratio converges to a constant value under constant VWC, the shear displacement might increase up to failure, while the void ratio varying under constant VWC indicates that the shear displacement terminates before failure.