bluuebunny/crossref_metadata_2025 huggingface dataset:
Hukum Perkawinan Campuran dan Hak Atas Tanah di Indonesia
Authors: Oka Setiawan Ketut
Published: September 2023

Mixed marriage in Law No. 1 of 1974 (UUP) is a marriage between two people who in Indonesia are subject to different laws, because of differences in nationality and one of the parties is a foreign citizen and one of the parties is an Indonesian citizen (Article 57 UUP). Based on this statement, according to the UUP, mixed marriage regulations prohibit brides and grooms from different religions. The prohibition is mentioned indirectly in Article 2 paragraph (1) of the UUP, "marriage is valid if it is carried out according to the laws of each religion". If a husband and wife buy a piece of land after their marriage, it will automatically become the property of both of them (husband and wife), based on the provisions of Article 35 paragraph (1) of the UUP. However, if at the time or before the marriage takes place, they make a marriage agreement with separate assets, their ownership becomes each of the husband/wife (Article 29 yo 35 UUP). In mixed marriages referred to in Article 57 UUP, namely a marriage between two people who in Indonesia are subject to different laws, because of differences in nationality and one party is a foreign citizen and one party is an Indonesian citizen, it does not change their citizenship status, still for Indonesian citizens in this case their rights are limited and they are not even given the opportunity to become subjects of HM, HGU and HGB, if at the time or before their marriage they do not make a marriage agreement with separate assets. According to the law, a marriage agreement can only be made at or before the marriage, in other words a marriage agreement cannot be made after the marriage.
Quo Vadis Amandemen Konstitusi: Kebijakan Hukum Partisipatif-Populis Versus Representatif-Elitis
Authors: Rondonuwu Partice
Published: September 2023

Constitutional and governmental issues and problems occur by looking at the interests of the elite and the will of the people who want fundamental changes related to state life and government life which affect the overall life of a nation state. Indonesia is a very large nation state with a state government that is managed from Sabang to Merauke with various tribes, religions, races and groups that are full of diversity. State and government life is not free from various problems at the elitist and populist levels which are resolved by just and civilized constitutional and governmental mechanisms. One of the various ways to make changes to constitutional legal policy is by making constitutional amendments to the 1945 NRI Constitution. Constitutional amendments to the 1945 NRI Constitution can be seen in the elitist representative legal policy model and the participatory-populist legal policy model. The battle of issues and problems as well as solutions based on representative-elitist legal policy versus populist participatory legal policy will create positive things (constructive nation-building in all fields) and negative things (destructive constitutional movements that destroy the foundations of the unitary state). Anticipating the occurrence of negative things will make the constitutional amendment run smoothly and all parties can accept it openly.
Impaired ability to feel: indication for haptotherapy
Authors: Klabbers Gert A.
Published: September 2023

In this article, I attempt to provide insight into my vision of haptotherapy. Illustrated with an event from my own life and based on experiences in my haptotherapy practice, I come to the conclusion that ‘impaired ability to feel’ can be an indication for haptotherapy.
The Use and Evaluation of Haptotherapy by Cancer Patients
Authors: Visser Adriaan
Published: September 2023

Objective To describe the use and evaluation of haptotherapy in a Dutch psycho-oncological center. Research questions (a).How many cancer patients are referred to haptotherapy? (b). Which social and medical background characteristics influence the choice for haptotherapy? (c). How do patients evaluate the haptotherapy they received? and (d). Do patient background characteristics influence the evaluation of the haptotherapy? Method An historical cohort study, re-analyzing patient-reported outcomes in the annual evaluation reports between 2007 and 2015 from the psychosocial oncology center, De Vruchtenburg, in Rotterdam, the Netherlands. The use of haptotherapy was measured by direct questions to the clients. and checked with the client registration files. Satisfaction was measured on a scale from 0 to 10. Measured background characteristics were gender, age, education level, number of years suffering from cancer, and the medical condition of the patients. Results Of the 1202 clients seen during the years 2007 to 2015, 12% was referred to haptotherapy. Satisfaction varies during these years from 7.3 to 8.5 (with a mean of 8.1). Compared to other forms of therapy the haptotherapy satisfaction scores are quite high. Most of the background characteristics do not influence the choice nor the satisfaction of the clients. However, it are primarily clients who are not very ill who use the haptotherapy. Conclusion Haptotherapy is used less because of the limited capacity of therapists and the increased likelihood that haptotherapy may not be eligible for healthcare coverage. The generalization is small due to the missing numbers, as well as the fact that the data are only available from one psycho-social cancer institute
La Protección de los Derechos de Autor en La Era Digital.
Authors: López Medina Pedro Alejandro
Published: September 2023

El presente artículo de revisión se enfoca en la protección de los derechos de autor en la era digital y tiene como objetivo identificar los principales desafíos y soluciones en este ámbito. Se realizaron búsquedas en las bases de datos Scopus, Scielo y Latindex para seleccionar artículos de revisión y artículos originales de autores internacionales y latinoamericanos que han publicado en los últimos 5 años. Se analizaron los métodos utilizados, los resultados obtenidos y las conclusiones alcanzadas en cada uno de los artículos seleccionados. Los resultados de la revisión bibliográfica destacan la importancia de considerar un enfoque integral y equilibrado para la protección efectiva de los derechos de autor en la era digital. Se identificó la necesidad de equilibrar los derechos de autor con el derecho de acceso a la cultura, la gestión colectiva de derechos de autor, la perspectiva regional, las nuevas formas de explotación de contenidos y los desafíos tecnológicos y culturales que se presentan. En conclusión, los hallazgos de esta revisión bibliográfica resaltan la necesidad de soluciones innovadoras y efectivas para la gestión y protección de los derechos de autor en la era digital. Asimismo, se destacó la importancia de considerar los aspectos tecnológicos, legales y culturales para encontrar soluciones efectivas y sostenibles a los desafíos que se presentan en este ámbito.
Exploratory Model of Security Perception in the COVID-19 Era
Authors:   Departamento de Ciencias Administrativas, Universidad Católica Luis Amigó, Montoya Elías Alexander Vallejo , Lirios Cruz García ,   Departamento de Trabajo Social, Universidad Autónoma del Estado de México, López Diego León Restrepo ,   Departamento de Ciencias Administrativas, Universidad Católica Luis Amigó, Urzola Berrío Héctor Enrique ,   Departamento de Ciencias Administrativas, UAJS, Brito Carrillo Clara Judith ,   Departamento de Trabajo Social, Universidad de La Guajira
Published: September 2023

The perception of the police action in the face of Covid-19 was the objective of this work. A cross-sectional, psychometric and correlational study was carried out with a sample of 100 students, considering their participation in the public health system as social servants or professional practitioners through a platform. A four-factor structure was found that explained 63% of the total variance, although the findings are only applicable to the sample, and its extension to other scenarios is recommended.
Political Gender Violence Against Women in Brazil
Authors:   Specialist in Adult Intensive Care Nursing and Neonatal Nursing by UERJ and Occupational Nursing (UFRJ), Santa Ursula University in Rio de Janeiro-RJ, Brazil, Bogossian Tricia
Published: September 2023

Political gender violence against women is a specific form of violence that occurs in the political context, characterized by the use of gender stereotypes and prejudices to limit women’s access to spaces of political power. This form of violence has serious consequences for democracy, security, and economic and social development. To tackle political gender-based violence against women, it is necessary to adopt effective measures to prevent and punish it, as well as to promote gender equality and the full participation of women in politics and public life. Promoting education and awareness about gender equality and creating support networks for women involved in politics are some of the actions that can be adopted to combat this form of violence and build a more just and egalitarian society. This article aims to discuss political gender violence against women in Brazil. The type of research to be carried out in this work was a Literature Review, in which books, dissertations and scientific articles were consulted.
The art of storytelling: against the instrumentalisation of stories as information sources in climate communication
Authors: Graminius Carin , Dodds Philip
Published: September 2023

Storytelling is an important tool of public engagement for researchers, not least for climate scholars. However, a problem arises when stories are treated instrumentally as means of delivering specific messages and as information sources. In particular, controlled experiments measuring the impact of stories on readers may misrepresent how stories work in practice. In this article, we shift perspective and re-emphasise the complexity of storytelling by analyzing the role of stories in three “climate fiction” novels: Sands of Sarasvati by Risto Isomäki, Green Earth by Kim Stanley Robinson and Tentacle by Rita Indiana. We highlight four underrepresented perspectives on storytelling: (1) stories may be used as time-resistant sources of scientific evidence; (2) stories may provide moral guidance; (3) stories have the ability to make connections, organizing events and agencies; and (4) stories afford storytellers agency to act on climate change. We thus conclude that efforts to evaluate the impact of stories require an understanding of how stories function in specific works of art.
The Impact of the Price Factor on Farmers' Incomes in Turbulent Conditions
Authors: Belinska Stefanii , Bielik Peter , Belinska Yanina
Published: September 2023

Farmers face various types of risks that affect their behavioural strategies and well-being. In 2022, the main problem was the rapid and uncontrolled acceleration of inflation in the markets of raw materials, energy and food products. Farmers have faced price volatility in food, raw materials and energy. The purpose of the article was to analyse the impact of the price factor on farmers' incomes, including the total impact of prices on manufactured products and energy carriers. The regression-based analysis showed the negative nature of such an impact, which requires increased state support for farm income during the crisis period. As a result of the study, we proposed to reorient government support from simple subsidies to incentives for farmers to produce bioenergy from waste. This measure will increase farmers' energy independence, reduce income dependence on rising energy prices, and increase the efficiency of public spending.
Correlation between the Greatest Agricultural Products Exporters to the EU: is Ukraine included?
Authors: Kiforenko Oksana
Published: September 2023

Due to the challenges we are experiencing nowadays, the importance of food security is gaining in its attention, making the subjects supplying agricultural production and ready-made food products more important and influential either economically or politically. The data under research are the agricultural products exports of Brazil, Canada, China, Ukraine, the United Kingdom and the United States to the European Union. The agricultural products are the goods from SITC (0+1) groups. The timeframe under analysis is eleven years – from 2012 to 2022 included. The purpose of the research is to assess whether the Ukrainian agricultural exports to the EU are correlated with the said exports of Brazil, Canada, China, the UK and the USA, and, if they are, how strong the correlation is. The comparative analysis of the dynamics, simple statistics, differences with the previous periods for the agricultural products exports of the analysed subjects to the EU was conducted. The trend lines for the analysed data during the given timeframe and two following years, were built using the appropriate function. The Pearson and Spearman correlation coefficients and their corresponding p-values were calculated and analysed.
EU Sanctions Against the Russian Federation and Their Implications for the Foreign Trade of the Czech Republic
Authors: Malý Michal , Cvik Eva Daniela , MacGregor Pelikánová Radka
Published: September 2023

Modern European integration entails the common foreign and security policy. In February 2022, the Russian aggression against Ukraine moved the deplorable situation from 2014 to another level calling for an EU reaction via legal instruments. Based on them, ten sanctions packages have emerged with significant consequences. The aim of this paper is to analyze it, in particular the connection of these ten sanctions packages and foreign trade between the Czech Republic and the Russian Federation. This aim is achieved by addressing three sets of goals: (i) the legal analysis of EU trade policy instruments, (ii) an advanced statistical and critical analysis of the trade between Czech Republic and Russian Federation and (iii) a creation of a timeline of the application and its ramifications. This reveals interesting propositions about the impact of these sanctions packages on the Czech foreign trade and about the effectiveness of the EU´s trade policy.
Surgical treatment of low grade lumbar spondylolisthesis
Authors: DOĞU Hüseyin
Published: September 2023

Background Data: Lumbar spondylolisthesis is a prevalent cause of lower back pain and is a focal interest of spinal surgery. A diverse set of decompression and fusion techniques are used in surgery.

Purpose: To investigate the surgical and clinical outcomes patients with spondylolisthesis who received surgical intervention.

Materials and Methods: Data of 25 patients (15 women; 10 men; mean age, 48.8 ± 12.4 years; range, 27–66 years) with low-grade spondylolisthesis who received surgical intervention were retrospectively analyzed. Posterolateral and posterior interbody fusion was used in 17 and 8 patients, respectively, and 19 received posterior pedicle screws and 6 received only fusion and decompression.

Results: According to the Kirkaldy–Willis criteria, the clinical outcomes of 11 (44%), 9 (36%), 3 (12%), and 2 (8%) patients were rated excellent, good, fair, and poor, respectively, with a success rate of 80%. Furthermore, fusion was observed in 21 patients (84%). Favorable outcomes were achieved in 17 (90%) patients with pedicle screws and in 3 (50%) with only decompression and fusion (p=0.048; p0.05). Two out of three patients with revision surgery had poor clinical outcomes (p=0.091; p
DETERMINATION OF CHANGES IN VITAMIN D, FOLIC ACID AND VITAMIN B12 LEVELS IN PATIENTS PRESENTING TO THE EMERGENCY DEPARTMENT AFTER SUICIDAL INTERVENTIONS
Authors: GENÇER Tansu , TEKİN Yusuf Kenan , GENÇER Samet Barış
Published: September 2023

ABSTRACT

Introduction: Depression is a psychological and physiological destruction process. In recent years, it has been one of the leading causes of public health problems in our country and in the world. Patients with depressive mood are at a higher risk compared to the normal population in terms of realizing suicidal ideation. Since the first place of application after a suicide attempt is usually the emergency services, the studies carried out in the ED are extremely important in this sense.

Methods: Data in the study were analyzed using SPSS Data:23.0 (SPSS Inc., Chicago, Illinois, USA). Continuous variables were expressed as mean ± standard deviation (SD). In the evaluation of the data, the significance test of the difference between the two means (Independent t test) was used when the parametric test assumptions were fulfilled, and the Man Whitney U test was used when the parametric test assumptions were not fulfilled.

Results: In our study, we compared the levels of vitamin D, folic acid and vitamin B12 in patients who applied to the emergency department after a suicide attempt with the normal population. Vitamin D and vitamin B12 levels were found to be significantly lower in the patient group compared to the control group.

Conclusions: Our current clinical study supports many studies in the literature, with the detection of low levels of vitamin D and vitamin B12 after the examinations of the patient group who came to the emergency room with a depressive episode and the control group.
The Impact of Vitamin D and Acute Phase Proteins in the Diagnosis of Hyperemesis Gravidarum
Authors: KARADEMİR Dilay , YURTÇU Nazan
Published: September 2023

Objective: Hyperemesis gravidarum (HG) has severe and dramatic consequences, and the cause of this severe disease has not yet been determined clearly. It is known that hormonal, metabolic, immunological, and inflammatory agents may be effective in their etiology. Our study aimed to investigate the possible role of vitamin D, Lactate Dehydrogenase (LDH), Procalcitonin (PCT), and C- reactive Protein (CRP) in the etiology of HG.

Method: In this retrospective study, between June 1, 2021, and January 1, 2022, 110 pregnant women between the ages of 18 and 35 were admitted to the Obstetrics and Gynecology Polyclinic of the Sivas Cumhuriyet University Faculty of Medicine. Fifty-five patients diagnosed with HG were taken as a study group, and fifty-five healthy pregnant women not diagnosed with HG were taken as a control group. Obstetric data and serum vitamin D, LDH, PCT, and CRP values of pregnant women were detected retrospectively.

Results: When the groups with and without HG were compared, although the CRP and LDH levels were high in the HG group, they were not statistically significant (p = 0.084, p = 0.546). Vitamin D and PCT were significantly higher in the HG group than in the control group (p = 0.001, p = 0.047).

Conclusion: Our study found that vitamin D and PCT levels were high in pregnant women with HG. Further studies with more participants are needed before these inflammatory markers can be used to diagnose HG.
Coevolution of the CDCA7-HELLS ICF-related nucleosome remodeling complex and DNA methyltransferases
Authors: Funabiki Hironori , Wassing Isabel E , Jia Qingyuan , Luo Ji-Dung , Carroll Thomas
Published: September 2023

5-Methylcytosine (5mC) and DNA methyltransferases (DNMTs) are broadly conserved in eukaryotes but are also frequently lost during evolution. The mammalian SNF2 family ATPase HELLS and its plant ortholog DDM1 are critical for maintaining 5mC. Mutations in HELLS, its activator CDCA7, and the de novo DNA methyltransferase DNMT3B, cause immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome, a genetic disorder associated with the loss of DNA methylation. We here examine the coevolution of CDCA7, HELLS and DNMTs. While DNMT3, the maintenance DNA methyltransferase DNMT1, HELLS, and CDCA7 are all highly conserved in vertebrates and green plants, they are frequently co-lost in other evolutionary clades. The presence-absence patterns of these genes are not random; almost all CDCA7 harboring eukaryote species also have HELLS and DNMT1 (or another maintenance methyltransferase, DNMT5). Coevolution of presence-absence patterns (CoPAP) analysis in Ecdysozoa further indicates coevolutionary linkages among CDCA7, HELLS, DNMT1 and its activator UHRF1. We hypothesize that CDCA7 becomes dispensable in species that lost HELLS or DNA methylation, and/or the loss of CDCA7 triggers the replacement of DNA methylation by other chromatin regulation mechanisms. Our study suggests that a unique specialized role of CDCA7 in HELLS-dependent DNA methylation maintenance is broadly inherited from the last eukaryotic common ancestor.
The CD4 transmembrane GGXXG and juxtamembrane (C/F)CV+C motifs mediate pMHCII-specific signaling independently of CD4-LCK interactions
Authors: Lee Mark S , Tuohy Peter J , Kim Caleb Y , Yost Philip P , Lichauco Katrina , Parrish Heather L , Van Doorslaer Koenraad , Kuhns Michael S
Published: September 2023

CD4+ T cell activation is driven by five-module receptor complexes. The T cell receptor (TCR) is the receptor module that binds composite surfaces of peptide antigens embedded within MHCII molecules (pMHCII). It associates with three signaling modules (CD3γε, CD3δε, and CD3ζζ) to form TCR-CD3 complexes. CD4 is the coreceptor module. It reciprocally associates with TCR-CD3-pMHCII assemblies on the outside of a CD4+ T cells and with the Src kinase, LCK, on the inside. Previously, we reported that the CD4 transmembrane GGXXG and cytoplasmic juxtamembrane (C/F)CV+C motifs found in eutherian (placental mammal) CD4 have constituent residues that evolved under purifying selection (Lee et al., 2022). Expressing mutants of these motifs together in T cell hybridomas increased CD4-LCK association but reduced CD3ζ, ZAP70, and PLCγ1 phosphorylation levels, as well as IL-2 production, in response to agonist pMHCII. Because these mutants preferentially localized CD4-LCK pairs to non-raft membrane fractions, one explanation for our results was that they impaired proximal signaling by sequestering LCK away from TCR-CD3. An alternative hypothesis is that the mutations directly impacted signaling because the motifs normally play an LCK-independent role in signaling. The goal of this study was to discriminate between these possibilities. Using T cell hybridomas, our results indicate that: intracellular CD4-LCK interactions are not necessary for pMHCII-specific signal initiation; the GGXXG and (C/F)CV+C motifs are key determinants of CD4-mediated pMHCII-specific signal amplification; the GGXXG and (C/F)CV+C motifs exert their functions independently of direct CD4-LCK association. These data provide a mechanistic explanation for why residues within these motifs are under purifying selection in jawed vertebrates. The results are also important to consider for biomimetic engineering of synthetic receptors.
Hierarchical morphogenesis of swallowtail butterfly wing scale nanostructures
Authors: Seah Kwi Shan , Saranathan Vinodkumar
Published: September 2023

The study of color patterns in the animal integument is a fundamental question in biology, with many lepidopteran species being exemplary models in this endeavor due to their relative simplicity and elegance. While significant advances have been made in unraveling the cellular and molecular basis of lepidopteran pigmentary coloration, the morphogenesis of wing scale nanostructures involved in structural color production is not well understood. Contemporary research on this topic largely focuses on a few nymphalid model taxa (e.g., Bicyclus, Heliconius), despite an overwhelming diversity in the hierarchical nanostructural organization of lepidopteran wing scales. Here, we present a time-resolved, comparative developmental study of hierarchical scale nanostructures in Parides eurimedes and five other papilionid species. Our results uphold the putative conserved role of F-actin bundles in acting as spacers between developing ridges, as previously documented in several nymphalid species. Interestingly, while ridges are developing in P. eurimedes, plasma membrane manifests irregular mesh-like crossribs characteristic of Papilionidae, which delineate the accretion of cuticle into rows of planar disks in between ridges. Once the ridges have grown, disintegrating F-actin bundles appear to reorganize into a network that supports the invagination of plasma membrane underlying the disks, subsequently forming an extruded honeycomb lattice. Our results uncover a previously undocumented role for F-actin in the morphogenesis of complex wing scale nanostructures, likely specific to Papilionidae.
Diffusive lensing as a mechanism of intracellular transport and compartmentalization
Authors: Raja Venkatesh Achuthan , Le Kathy H , Weld David M , Brandman Onn
Published: September 2023

While inhomogeneous diffusivity has been identified as a ubiquitous feature of the cellular interior, its implications for particle mobility and concentration at different length scales remain largely unexplored. In this work, we use agent-based simulations of diffusion to investigate how heterogeneous diffusivity affects the movement and concentration of diffusing particles. We propose that a nonequilibrium mode of membrane-less compartmentalization arising from the convergence of diffusive trajectories into low-diffusive sinks, which we call ‘diffusive lensing,’ is relevant for living systems. Our work highlights the phenomenon of diffusive lensing as a potentially key driver of mesoscale dynamics in the cytoplasm, with possible far-reaching implications for biochemical processes.
Goal-directed vocal planning in a songbird
Authors: Zai Anja T , Stepien Anna E , Giret Nicolas , Hahnloser Richard HR
Published: September 2023

Songbirds’ vocal mastery is impressive, but to what extent is it a result of practice? Can they, based on experienced mismatch with a known target, plan the necessary changes to recover the target in a practice-free manner without intermittently singing? In adult zebra finches, we drive the pitch of a song syllable away from its stable (baseline) variant acquired from a tutor, then we withdraw reinforcement and subsequently deprive them of singing experience by muting or deafening. In this deprived state, birds do not recover their baseline song. However, they revert their songs toward the target by about 1 standard deviation of their recent practice, provided the sensory feedback during the latter signaled a pitch mismatch with the target. Thus, targeted vocal plasticity does not require immediate sensory experience, showing that zebra finches are capable of goal-directed vocal planning.
Inhibition of CERS1 in skeletal muscle exacerbates age-related muscle dysfunction
Authors: Wohlwend Martin , Laurila Pirkka-Pekka , Goeminne Ludger J.E. , Lima Tanes , Lalou Amelia , Li Xiaoxu , von Alvensleben Giacomo , Crisol Barbara , Mangione Renata , Gallart-Ayala Hector , Burri Olivier , Butler Stephen , Morris Jonathan , Turner Nigel , Ivanisevic Julijana , Auwerx Johan
Published: September 2023

Age-related muscle wasting and dysfunction render the elderly population vulnerable and incapacitated, while underlying mechanisms are poorly understood. Here, we implicate the
CERS1
enzyme of the de novo sphingolipid synthesis pathway in the pathogenesis of age-related skeletal muscle impairment. In humans,
CERS1
abundance declines with aging in skeletal muscle cells and, correlates with biological pathways involved in muscle function and myogenesis. Furthermore,
CERS1
is upregulated during myogenic differentiation. Pharmacological or genetic inhibition of
CERS1
in aged mice blunts myogenesis and deteriorates aged skeletal muscle mass and function, which is associated with the occurrence of morphological features typical of inflammation and fibrosis. Ablation of the
CERS1
orthologue
lagr-1
in
C. elegans
similarly exacerbates the age-associated decline in muscle function and integrity. We discover genetic variants reducing
CERS1
expression in human skeletal muscle and Mendelian randomization analysis in the UK biobank cohort shows that these variants reduce muscle grip strength and overall health. In summary, our findings link age-related impairments in muscle function to a reduction in
CERS1
, thereby underlining the importance of the sphingolipid biosynthesis pathway in age-related muscle homeostasis.
Immunoglobulin M regulates airway hyperresponsiveness independent of T helper 2 allergic inflammation
Authors: Hadebe Sabelo , Savulescu Anca Flavia , Khumalo Jermaine , Jones Katelyn , Mangali Sandisiwe , Mthembu Nontobeko , Musaigwa Fungai , Maepa Welcome , Ndlovu Hlumani , Ngomti Amkele , Scibiorek Martyna , Okendo Javan , Brombacher Frank
Published: September 2023

Allergic asthma is a disease driven by T helper 2 (Th2) cells, eosinophilia, airway hyperresponsiveness (AHR) and IgE-secreting B cells. Asthma is largely controlled by corticosteroids and β
2
adregenic receptor agonists that target and relax airway smooth muscle (ASM). Immunoglobulin M (IgM) isotype secreted by naïve B cells is important for class switching but may have other undefined functions.We investigated the role of IgM in a house dust mite (HDM)-induced Th2 allergic asthma model.We sensitised wild-type (WT) and IgM-deficient (IgM
-/-
) mice with HDM and measured AHR, and Th2 responses. We performed RNA sequencing on the whole lung of WT and IgM
-/-
mice sensitised to saline or HDM. We validated our AHR data on human ASM by deleting genes using CRISPR and measuring contraction by single-cell force cytometry.We found IgM to be essential in AHR but not Th2 airway inflammation or eosinophilia. RNA sequencing of lung tissue suggested that IgM regulated AHR through modulating brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (
Baiap2l1
) and other genes. Deletion of
BAIAP2L1
led to a differential reduction in human ASM contraction when stimulated with TNF-α and Acetylcholine, but not IL-13.These findings have implications for future treatment of asthma beyond current therapies.
Structure and dynamics of cholesterol-mediated aquaporin-0 arrays and implications for lipid rafts
Authors: Chiu Po-Lin , Orjuela Juan D , de Groot Bert L , Aponte Santamaría Camilo , Walz Thomas
Published: September 2023

Aquaporin-0 (AQP0) tetramers form square arrays in lens membranes through a yet unknown mechanism, but lens membranes are enriched in sphingomyelin and cholesterol. Here, we determined electron crystallographic structures of AQP0 in sphingomyelin/cholesterol membranes and performed molecular dynamics (MD) simulations to establish that the observed cholesterol positions represent those seen around an isolated AQP0 tetramer and that the AQP0 tetramer largely defines the location and orientation of most of its associated cholesterol molecules. At a high concentration, cholesterol increases the hydrophobic thickness of the annular lipid shell around AQP0 tetramers, which may thus cluster to mitigate the resulting hydrophobic mismatch. Moreover, neighboring AQP0 tetramers sandwich a cholesterol deep in the center of the membrane. MD simulations show that the association of two AQP0 tetramers is necessary to maintain the deep cholesterol in its position and that the deep cholesterol increases the force required to laterally detach two AQP0 tetramers, not only due to protein–protein contacts but also due to increased lipid–protein complementarity. Since each tetramer interacts with four such ‘glue’ cholesterols, avidity effects may stabilize larger arrays. The principles proposed to drive AQP0 array formation could also underlie protein clustering in lipid rafts.
Enhanced Aversive Signals During Classical Conditioning in Dopamine Axons in Medial Prefrontal Cortex
Authors: Abe Kenta , Kambe Yuki , Majima Kei , Hu Zijing , Ohtake Makoto , Momennezhad Ali , Izumi Hideki , Tanaka Takuma , Matunis Ashley , Stacy Emma , Itokazu Takahide , Sato Takashi R. , Sato Tatsuo K.
Published: September 2023

Midbrain dopamine neurons impact neural processing in the prefrontal cortex (PFC) through mesocortical projections. However, the signals conveyed by dopamine projections to the PFC remain unclear, particularly at the single-axon level. Here, we investigated dopaminergic axonal activity in the medial PFC (mPFC) during reward and aversive processing. By optimizing microprism-mediated two-photon calcium imaging of dopamine axon terminals, we found diverse responses in dopamine axons, with some preferring reward and others preferring aversive stimuli, with a strong bias for the latter at the population level. Long-term longitudinal imaging revealed that the preference was maintained in reward- and aversive-preferring axons throughout classical conditioning in which rewarding and aversive stimuli were paired with preceding auditory cues. However, as mice learned to discriminate reward or aversive cues, a cue activity preference gradually developed only in aversive-preferring axons, becoming more selective for aversive processing. We inferred the trial-by-trial cue discrimination based on machine learning using anticipatory licking or facial expressions, and found that successful discrimination was accompanied by sharper selectivity for the aversive cue in aversive-preferring axons. Our findings implicate mesocortical dopamine axon activity in the encoding of aversive processing that is modulated by both classical conditioning across days and trial-by-trial discrimination within a day.Two-photon calcium imaging revealed that many mesocortical dopamine axons show enhanced selectivity for aversive cue processing during classical conditioning.
Metabolomics identifies and validates serum androstenedione as novel biomarker for diagnosing primary angle closure glaucoma and predicting the visual field progression
Authors: Li Shengjie , Ren Jun , Jiang Zhendong , Qiu Yichao , Shao Mingxi , Li Yingzhu , Wu Jianing , Song Yunxiao , Sun Xinghuai , Gao Shunxiang , Cao Wenjun
Published: September 2023

Background:

Primary angle closure glaucoma (PACG) is the leading cause of irreversible blindness in Asia, and no reliable, effective diagnostic, and predictive biomarkers are used in clinical routines. A growing body of evidence shows metabolic alterations in patients with glaucoma. We aimed to develop and validate potential metabolite biomarkers to diagnose and predict the visual field progression of PACG.

Methods:

Here, we used a five-phase (discovery phase, validation phase 1, validation phase 2, supplementary phase, and cohort phase) multicenter (EENT hospital, Shanghai Xuhui Central Hospital), cross-sectional, prospective cohort study designed to perform widely targeted metabolomics and chemiluminescence immunoassay to determine candidate biomarkers. Five machine learning (random forest, support vector machine, lasso, K-nearest neighbor, and GaussianNaive Bayes [NB]) approaches were used to identify an optimal algorithm. The discrimination ability was evaluated using the area under the receiver operating characteristic curve (AUC). Calibration was assessed by Hosmer-Lemeshow tests and calibration plots.

Results:

Studied serum samples were collected from 616 participants, and 1464 metabolites were identified. Machine learning algorithm determines that androstenedione exhibited excellent discrimination and acceptable calibration in discriminating PACG across the discovery phase (discovery set 1, AUCs=1.0 [95% CI, 1.00–1.00]; discovery set 2, AUCs = 0.85 [95% CI, 0.80–0.90]) and validation phases (internal validation, AUCs = 0.86 [95% CI, 0.81–0.91]; external validation, AUCs = 0.87 [95% CI, 0.80–0.95]). Androstenedione also exhibited a higher AUC (0.92–0.98) to discriminate the severity of PACG. In the supplemental phase, serum androstenedione levels were consistent with those in aqueous humor (r=0.82, p=0.038) and significantly (p=0.021) decreased after treatment. Further, cohort phase demonstrates that higher baseline androstenedione levels (hazard ratio = 2.71 [95% CI: 1.199–6.104], p=0.017) were associated with faster visual field progression.

Conclusions:

Our study identifies serum androstenedione as a potential biomarker for diagnosing PACG and indicating visual field progression.

Funding:

This work was supported by Youth Medical Talents – Clinical Laboratory Practitioner Program (2022-65), the National Natural Science Foundation of China (82302582), Shanghai Municipal Health Commission Project (20224Y0317), and Higher Education Industry-Academic-Research Innovation Fund of China (2023JQ006).
Conformation selection by ATP-competitive inhibitors and allosteric communication in ERK2
Authors: Anderson Jake W , Vaisar David , Jones David N , Pegram Laurel M , Vigers Guy P , Chen Huifen , Moffat John G , Ahn Natalie G
Published: September 2023

Activation of the extracellular signal-regulated kinase-2 (ERK2) by phosphorylation has been shown to involve changes in protein dynamics, as determined by hydrogen-deuterium exchange mass spectrometry (HDX-MS) and NMR relaxation dispersion measurements. These can be described by a global exchange between two conformational states of the active kinase, named ‘L’ and ‘R,’ where R is associated with a catalytically productive ATP-binding mode. An ATP-competitive ERK1/2 inhibitor, Vertex-11e, has properties of conformation selection for the R-state, revealing movements of the activation loop that are allosterically coupled to the kinase active site. However, the features of inhibitors important for R-state selection are unknown. Here, we survey a panel of ATP-competitive ERK inhibitors using HDX-MS and NMR and identify 14 new molecules with properties of R-state selection. They reveal effects propagated to distal regions in the P+1 and helix αF segments surrounding the activation loop, as well as helix αL16. Crystal structures of inhibitor complexes with ERK2 reveal systematic shifts in the Gly loop and helix αC, mediated by a Tyr-Tyr ring stacking interaction and the conserved Lys-Glu salt bridge. The findings suggest a model for the R-state involving small movements in the N-lobe that promote compactness within the kinase active site and alter mobility surrounding the activation loop. Such properties of conformation selection might be exploited to modulate the protein docking interface used by ERK substrates and effectors.
Comparative Assessment of SSR and RAPD markers for genetic diversity in some Mango cultivars
Authors: A. A. Hussein Mohammed , Eid Manal , Rahimi Mehdi , Filimban Faten Zubair , Abd El-Moneim Diaa
Published: September 2023

Genetic improvement mainly depends on the level of genetic variability present in the population, and the degree of genetic diversity in a population largely determines the rate of genetic advancement. For analyzing genetic diversity and determining cultivar identities, a molecular marker is a useful tool. Using 30 SSR (simple sequence repeat) and 30 RAPD (randomly amplified polymorphic DNA) markers, this study evaluated the genetic divergence of 17 mango cultivars. The effectiveness of the two marker systems was evaluated using their genetic diversity characteristics. Additionally, the effects of SM (simple matching) and Dice similarity coefficients and their effects on mango clustering were evaluated. The findings showed that SSR markers generated 192 alleles, all of which were polymorphic (100%). With RAPD markers, 434 bands were obtained, 361 of which were polymorphic (83%). The average polymorphic information content (PIC) for RAPD and SSR was 0.378 and 0.735, respectively. Using SSR markers resulted in much higher values for other genetic diversity parameters compared to RAPD markers. Furthermore, grouping the genotypes according to the two similarity coefficients without detailed consideration of these coefficients could not influence the study results. The RAPD markers OPA_01, OPM_12 followed by OPO_12 and SSR markers MIAC_4, MIAC_5 followed by mMiCIR_21 were the most informative in terms of describing genetic variability among the cultivars under study; they can be used in further investigations such as genetic mapping or marker-assisted selection. Overall, ‘Zebda’ cultivar was the most diverse of the studied cultivars.
A metagenomic comparison of clearwater, probiotic, and Rapid BFTTM on Pacific whiteleg shrimp, Litopenaeus vannamei cultures
Authors: Waiho Khor , Abd Razak Muhammad Syafiq , Abdul Rahman Mohd Zaidy , Zaid Zainah , Ikhwanuddin Mhd , Fazhan Hanafiah , Shu-Chien Alexander Chong , Lau Nyok-Sean , Azmie Ghazali , Ishak Ahmad Najmi , Syahnon Mohammad , Kasan Nor Azman
Published: September 2023

Biofloc technology improves water quality and promote the growth of beneficial bacteria community in shrimp culture. However, little is known about the bacteria community structure in both water and gut of cultured organisms. To address this, the current study characterised the metagenomes derived from water and shrimp intestine samples of novel Rapid BFTTM with probiotic and clearwater treatments using 16S V4 region and full length 16S sequencing. Bacteria diversity of water and intestine samples of Rapid BFTTM and probiotic treatments were similar. Based on the 16S V4 region, water samples of >20 μm biofloc had the highest abundance of amplicon sequence variant (ASV). However, based on full length 16S, no clear distinction in microbial diversity was observed between water samples and intestine samples. Proteobacteria was the most abundant taxon in all samples based on both 16S V4 and full length 16S sequences. Vibrio was among the highest genus based on 16S V4 region but only full length 16S was able to discern up to species level, with three Vibrios identified—V. harveyi, V. parahaemolyticus and V. vulnificus. Vibrio harveyi being the most abundant species in all treatments. Among water samples, biofloc water samples had the lowest abundance of all three Vibrios, with V. vulnificus was present only in bioflocs of <20 μm. Predicted functional profiles of treatments support the beneficial impacts of probiotic and biofloc inclusion into shrimp culture system. This study highlights the potential displacement of opportunistic pathogens by the usage of biofloc technology (Rapid BFTTM) in shrimp culture.
DisVar: an R library for identifying variants associated with diseases using large-scale personal genetic information
Authors: Chanasongkhram Khunanon , Damkliang Kasikrit , Sangket Unitsa
Published: September 2023

Background

Genetic variants may potentially play a contributing factor in the development of diseases. Several genetic disease databases are used in medical research and diagnosis but the web applications used to search these databases for disease-associated variants have limitations. The application may not be able to search for large-scale genetic variants, the results of searches may be difficult to interpret and variants mapped from the latest reference genome (GRCH38/hg38) may not be supported.

Methods

In this study, we developed a novel R library called “DisVar” to identify disease-associated genetic variants in large-scale individual genomic data. This R library is compatible with variants from the latest reference genome version. DisVar uses five databases of disease-associated variants. Over 100 million variants can be simultaneously searched for specific associated diseases.

Results

The package was evaluated using 24 Variant Call Format (VCF) files (215,054 to 11,346,899 sites) from the 1000 Genomes Project. Disease-associated variants were detected in 298,227 hits across all the VCF files, taking a total of 63.58 m to complete. The package was also tested on ClinVar’s VCF file (2,120,558 variants), where 20,657 hits associated with diseases were identified with an estimated elapsed time of 45.98 s.

Conclusions

DisVar can overcome the limitations of existing tools and is a fast and effective diagnostic and preventive tool that identifies disease-associated variations from large-scale genetic variants against the latest reference genome.
Carbon monoxide poisoning: beyond survival - mortality, morbidities, and risk factors, a Turkey sample
Authors: Öz Erdoğan , Küçükkelepçe Osman , Kurt Osman , Vural Aşkı
Published: September 2023

Background

We aimed to investigate the effect of poisoning on mortality leading to new morbidities in people who survived the poisoning.

Methods

The descriptive-retrospective study evaluated all carbon monoxide poisoning cases between 2012 and 2022 in the Adiyaman. For the fatality, all cases were followed up through Turkey’s death notification system until the end of 2022. One-year health records of cases treated as inpatients in Adiyaman hospitals were analyzed for nine diagnoses. A total of 4,395 carbon monoxide cases, recorded over 11 years, were all noted to be accidental cases.

Results

The rate of carbon monoxide poisoning in Adıyaman was calculated as 63.2 per hundred thousand. A total of 87 (2%) of the cases died. The population’s hospitalization rate was 1.71, while the mortality rate was 1.25 in a hundred thousand. Among the cases, the hospitalization rate was 2.7, and the admission to intensive care rate was 1.7. The fatality rate was 6.5% for those hospitalized and 12.2% for those admitted to the intensive care unit. The highest fatality rate was 65.5% in patients aged 65 and above. One out of five morbidities was developed in 8.4% of cases within one year. The fatality rate of those who developed morbidities (40%) was higher than those who did not (5.5%). Being male posed a 1,886-fold risk for mortality, and each increase in age posed a 1,086-fold risk for mortality.

Conclusion

Individuals who had carbon monoxide poisoning should be followed up closely for one year after poisoning due to the possibility of the emergence of new morbidities that increase the risk of mortality.
Differences in and associations between belief in just deserts and human rights restrictions over a 3-year period in five countries during the COVID-19 pandemic
Authors: Murakami Michio , Hiraishi Kai , Yamagata Mei , Nakanishi Daisuke , Ortolani Andrea , Mifune Nobuhiro , Li Yang , Miura Asako
Published: September 2023

Discrimination, which arose during the coronavirus disease 2019 outbreak, is a global public health issue. This study aimed to provide fundamental knowledge in proposing control measures to mitigate discrimination. We focused on two psychological variables: belief in just deserts (BJD, i.e., the belief that the infected individual deserves to be infected), a psychological factor that potentially promotes discrimination and prejudice, and human rights restrictions (HRR; i.e., the degree of individuals’ agreement with government restrictions on citizens’ behavior during emergencies). Differences in these items, as well as their annual trends from 2020 to 2022, were examined in Japan, the United States (US), the United Kingdom (UK), Italy, and China. In addition, the associations between BJD and HRR by country and year and the direction of the associations between them in Japan and Italy were analyzed. Online surveys were conducted annually, with 392–518 participants per country and year. The BJD was higher in Japan and lower in the UK. BJD increased significantly from 2020 to 2021 in all countries, except in China. Meanwhile, HRR was higher in China and lower in Japan. The HRR decreased from 2020 to 2021 in Japan and decreased from 2020 to 2022 in the US, the UK, and Italy. There were significant positive associations between BJD and HRR in Japan and Italy. Cross-lagged panel models revealed positive bidirectional associations between BJD and HRR in Japan and Italy, respectively, indicating that the HRR declined among those with weak BJD and that the BJD increased among those with high HRR. In Japan and Italy, the dissemination of public messages targeting those with a high HRR in the early stages of an infectious disease outbreak could potentially mitigate the adverse impact of the BJD, eventually reducing discrimination, especially when the infection is not attributed to the fault of the infected individuals.