bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Onset Colorectal Cancer: An Emerging Cancer Risk in Patients with Diamond Blackfan Anemia
Authors: Lipton Jeffrey M. , Molmenti Christine L. S. , Desai Pooja , Lipton Alexander , Ellis Steven R. , Vlachos Adrianna
Published: December 2021

Diamond Blackfan anemia (DBA) is a rare inherited bone marrow failure syndrome, the founding member of a class of disorders known as ribosomopathies. Most cases result from loss of function mutations or deletions in 1 of 23 genes encoding either a small or large subunit-associated ribosomal protein (RP), resulting in RP haploinsufficiency. DBA is characterized by red cell hypoplasia or aplasia, poor linear growth and congenital anomalies. Small case series and case reports demonstrate DBA to be a cancer predisposition syndrome. Recent analyses from the Diamond Blackfan Anemia Registry of North America (DBAR) have quantified the cancer risk in DBA. These studies reveal the most prevalent solid tumor, presenting in young adults and in children and adolescents, to be colorectal cancer (CRC) and osteogenic sarcoma, respectively. Of concern is that these cancers are typically detected at an advanced stage in patients who, because of their constitutional bone marrow failure, may not tolerate full-dose chemotherapy. Thus, the inability to provide optimal therapy contributes to poor outcomes. CRC screening in individuals over the age of 50 years, and now 45 years, has led to early detection and significant improvements in outcomes for non-DBA patients with CRC. These screening and surveillance strategies have been adapted to detect familial early onset CRC. With the recognition of DBA as a moderately penetrant cancer risk syndrome a rational screening and surveillance strategy will be implemented. The downstream molecular events, resulting from RP haploinsufficiency and leading to cancer, are the subject of significant scientific inquiry.
Rapid Cis–Trans Coevolution Driven by a Novel Gene Retroposed from a Eukaryotic Conserved CCR4–NOT Component in Drosophila
Authors: Krinsky Benjamin H. , Arthur Robert K. , Xia Shengqian , Sosa Dylan , Arsala Deanna , White Kevin P. , Long Manyuan
Published: December 2021

Young, or newly evolved, genes arise ubiquitously across the tree of life, and they can rapidly acquire novel functions that influence a diverse array of biological processes. Previous work identified a young regulatory duplicate gene in Drosophila, Zeus that unexpectedly diverged rapidly from its parent, Caf40, an extremely conserved component in the CCR4–NOT machinery in post-transcriptional and post-translational regulation of eukaryotic cells, and took on roles in the male reproductive system. This neofunctionalization was accompanied by differential binding of the Zeus protein to loci throughout the Drosophila melanogaster genome. However, the way in which new DNA-binding proteins acquire and coevolve with their targets in the genome is not understood. Here, by comparing Zeus ChIP-Seq data from D. melanogaster and D. simulans to the ancestral Caf40 binding events from D. yakuba, a species that diverged before the duplication event, we found a dynamic pattern in which Zeus binding rapidly coevolved with a previously unknown DNA motif, which we term Caf40 and Zeus-Associated Motif (CAZAM), under the influence of positive selection. Interestingly, while both copies of Zeus acquired targets at male-biased and testis-specific genes, D. melanogaster and D. simulans proteins have specialized binding on different chromosomes, a pattern echoed in the evolution of the associated motif. Using CRISPR-Cas9-mediated gene knockout of Zeus and RNA-Seq, we found that Zeus regulated the expression of 661 differentially expressed genes (DEGs). Our results suggest that the evolution of young regulatory genes can be coupled to substantial rewiring of the transcriptional networks into which they integrate, even over short evolutionary timescales. Our results thus uncover dynamic genome-wide evolutionary processes associated with new genes.
Tidally Driven Dispersion of a Deep-Sea Sediment Plume Originating from Seafloor Disturbance in the DISCOL Area (SE-Pacific Ocean)
Authors: Baeye Matthias , Purkiani Kaveh , de Stigter Henko , Gillard Benjamin , Fettweis Michael , Greinert Jens
Published: December 2021

The purpose of the study was to measure in situ the background suspended particulate matter concentration (SPMC) in the DISCOL area (SE Pacific) and its increase due to mechanical mobilization of the seabed. The disturbance experiment imitated future manganese nodule exploitations and was designed to measure the sediment plume generated by such activities. In the direct vicinity of the disturbance, landers equipped with acoustic and optical sensors measured the current velocities and the SPMC. The SPMC at the disturbance was easily up to 10 mg/L and thus about 200 times higher than the background concentration. The downstream sediment plume, measured by the lander, had a SPMC of about 1 mg/L. After tide reversal, the sediment plume was recorded a second time. A sediment transport model reproduced the plume dispersion. After rapid settling of the coarser fraction, a plume of hardly settling fine particles remained in suspension (and no deposition–resuspension cycles). The transport was controlled by the tides and by the vertical velocity component that resulted from bathymetrical differences. The plume may continue to disperse up to 100+ days (up to hundreds of km) depending on the particle size and until background concentration is reached.
How Academics and the Public Experienced Immersive Virtual Reality for Geo-Education
Authors: Bonali Fabio , Russo Elena , Vitello Fabio , Antoniou Varvara , Marchese Fabio , Fallati Luca , Bracchi Valentina , Corti Noemi , Savini Alessandra , Whitworth Malcolm , Drymoni Kyriaki , Mariotto Federico , Nomikou Paraskevi , Sciacca Eva , Bressan Sofia , Falsaperla Susanna , Reitano Danilo , van Wyk de Vries Benjamin , Krokos Mel , Panieri Giuliana , Stiller-Reeve Mathew , Vizzari Giuseppe , Becciani Ugo , Tibaldi Alessandro
Published: December 2021

Immersive virtual reality can potentially open up interesting geological sites to students, academics and others who may not have had the opportunity to visit such sites previously. We study how users perceive the usefulness of an immersive virtual reality approach applied to Earth Sciences teaching and communication. During nine immersive virtual reality-based events held in 2018 and 2019 in various locations (Vienna in Austria, Milan and Catania in Italy, Santorini in Greece), a large number of visitors had the opportunity to navigate, in immersive mode, across geological landscapes reconstructed by cutting-edge, unmanned aerial system-based photogrammetry techniques. The reconstructed virtual geological environments are specifically chosen virtual geosites, from Santorini (Greece), the North Volcanic Zone (Iceland), and Mt. Etna (Italy). Following the user experiences, we collected 459 questionnaires, with a large spread in participant age and cultural background. We find that the majority of respondents would be willing to repeat the immersive virtual reality experience, and importantly, most of the students and Earth Science academics who took part in the navigation confirmed the usefulness of this approach for geo-education purposes.
3D Numerical Prediction of Thermal Weakening of Granite under Tension
Authors: Saksala Timo
Published: December 2021

This paper deals with numerical prediction of temperature (weakening) effects on the tensile strength of granitic rock. A 3D numerical approach based on the embedded discontinuity finite elements is developed for this purpose. The governing thermo-mechanical initial/boundary value problem is solved with an explicit (in time) staggered method while using extreme mass scaling to increase the critical time step. Rock fracture is represented by the embedded discontinuity concept implemented here with the linear (4-node) tetrahedral elements. The rock is modelled as a linear elastic (up to fracture by the Rankine criterion) heterogeneous material consisting of Quartz, Feldspar and Biotite minerals. Due to its strong and anomalous temperature dependence upon approaching the α-β transition at the Curie point (~573 °C), only Quartz in the numerical rock depends on temperature in the present approach. In the numerical testing, the sample is first volumetrically heated to a target temperature. Then, the uniaxial tension test is performed on the cooled down sample. The simulations demonstrate the validity of the proposed approach as the experimental deterioration, by thermally induced cracking, of the rock tensile strength is predicted with a good accuracy.
Nonlinear Associations between Medical Expenditure, Perceived Medical Attitude, and Sociodemographics, and Older Adults’ Self-Rated Health in China: Applying the Extreme Gradient Boosting Model
Authors: Liang Yuqing , Zheng Wanwan , Lee Woon-Seek
Published: December 2021

Background: although China’s total health expenditure has been dramatically increased so that the country can cope with its aging population, inequalities among individuals in terms of their medical expenditures (relative to their income level) have exacerbated health problems among older adults. This study aims to examine the nonlinear associations between each of medical expenditure, perceived medical attitude, and sociodemographics, and older adults’ self-rated health (SRH); it does so by using data from the 2018 China Family Panel Studies survey. Method: we used the extreme gradient boosting model to explore the nonlinear association between various factors and older adults’ SRH outcomes. We then conducted partial dependence plots to examine the threshold effects of each factor on older adults’ SRH. Results: older adults’ medical expenditure exceeded their overall income. Body mass index (BMI) and personal health expenditure play an essential role in predicting older adults’ SRH outcomes. We found older adult age, physical exercise status, and residential location to be robust predictors of SRH outcomes in older adults. Partial dependence plots of the results visualized the nonlinear association between variables and the threshold effects of factors on older adults’ SRH outcomes. Conclusions: findings from this study underscore the importance of medical expenditure, perceived medical attitudes, and BMI as important predictors of health benefits in older adults. The potential threshold effects of medical expenditure on older adults’ SRH outcomes provide a better understanding of the formation of appropriate medical policy interventions by balancing the government and personal medical expenditure to promote health benefits among older adults.
A Case Study in Attention-Deficit/Hyperactivity Disorder: An Innovative Neurofeedback-Based Approach
Authors: Cabaleiro Paloma , Cueli Marisol , Cañamero Laura M. , González-Castro Paloma
Published: December 2021

In research about attention-deficit/hyperactivity disorder (ADHD) there is growing interest in evaluating cortical activation and using neurofeedback in interventions. This paper presents a case study using monopolar electroencephalogram recording (brain mapping known as MiniQ) for subsequent use in an intervention with neurofeedback for a 10-year-old girl presenting predominantly inattentive ADHD. A total of 75 training sessions were performed, and brain wave activity was assessed before and after the intervention. The results indicated post-treatment benefits in the beta wave (related to a higher level of concentration) and in the theta/beta ratio, but not in the theta wave (related to higher levels of drowsiness and distraction). These instruments may be beneficial in the evaluation and treatment of ADHD.
Relationships between Strength and Step Frequency with Fatigue Index in Repeated Sprint Ability
Authors: González-Frutos Pablo , Aguilar-Navarro Millán , Morencos Esther , Mallo Javier , Veiga Santiago
Published: December 2021

Force−velocity profile (FVP) and repeated-sprint ability (RSA) tests are indicators of physical capacities in most team sport players. The purpose of this study was to examine the stride kinematics during a repeated-sprint ability (RSA) test and to analyze the relationship between Bosco’s force−velocity profile (FVP) and RSA performance in elite female field hockey players. Thirteen elite-female players performed both RSA (six 30 m maximal sprints) and jumping (CMJ weighted and body weight) tests. Sprinting time fatigue indexes during a 30 m RSA test were correlated with step frequency fatigue indexes (r > 0.7; p < 0.01). CMJ50 showed a large relationship with sprint time fatigue indexes. FV50 showed a very large relationship with sprint time fatigue indexes (r > 0.7; p < 0.01), and a large relationship with the step frequency fatigue indexes (r > 0.5; p < 0.05). This study highlighted two possible ways to improve fatigue indexes in RSA, with the aim of maximizing the distances covered at high-intensities during the matches: (a) strength training and (b) focusing on step frequency during speed training.
Through the Lens: Youth Experiences with Cancer in Rural Appalachian Kentucky Using Photovoice
Authors: Gaines Katie , Martin Courtney , Prichard Chris , Vanderford Nathan L.
Published: December 2021

Rural Appalachian Kentucky experiences disproportionately high cancer incidence and mortality rates. This cancer burden is due to social determinants of health and cultural factors prominent in the region. The firsthand experiences of community members—especially young people—can highlight these factors and identify areas for improvement. The purpose of this study was to encourage Appalachian Kentucky youth to consider determinants of cancer and visualize the effects that cancer has on their families or communities by asking them to take photographs of cancer-related objects around them. Content analysis was performed on 238 photographs submitted by 25 students, and photographs were organized into themes, subthemes, and subtopics. The six themes that emerged were risk factors and exposures, marketing, awareness and support, health care, experiences, and metaphorical representations. Many of the submitted photographs aligned with cultural, environmental and/or situational factors prevalent in Appalachian Kentucky. Of the submitted photographs, 54 were displayed as an installment in two Kentucky art galleries. Viewer comments at the exhibitions demonstrated that young community members can educate and motivate change in those around them. Ultimately, this project demonstrates that young community members can recognize cancer-related issues around them and connect personal experiences back to the larger Appalachian Kentucky cancer disparity while also having an impact on other community members.
Comprehensive Knowledge and Preparedness among Dental Community to Confront COVID-19—A Multicentric Cross-Sectional Study
Authors: Almutairi Nada Faleh , Almaymuni Amani Abdullah , Thomas Julie Toby , Thomas Toby , Almalki Abdullah , Uthappa Roshan
Published: December 2021

The healthcare policy changes need to be updated for better management of the COVID-19 outbreak; hence, there is an urgent need to understand the knowledge and preparedness of healthcare workers regarding the infection control COVID-19. Therefore, the present study aims to assess the knowledge and preparedness towards COVID-19 among dentists, undergraduate, and postgraduates in dental universities one year after the COVID-19 outbreak. The multi-centric cross-sectional study was conducted by evaluating 395 structured, pre-coded, and validated questionnaires obtained from sample units comprising full-time dental students (undergraduates, interns, and postgraduates) and dentists who were currently in practice and who were able to comprehend the languages English or Arabic. The first part of the questionnaire included questions related to demographic characteristics. The second part of the survey consisted of questions that address knowledge concerning COVID-19. The third part of the survey addressed questions based on the preparedness to fight against COVID-19 including sharp injuries during this period. Comparing the knowledge scores of dentists, dental undergraduates, and postgraduates using the ANOVA test, dentists have higher knowledge and preparedness scores than postgraduates and undergraduates (p-value < 0.05). Univariate logistic regression analysis demonstrated that undergraduates and postgraduates were 2.567 and 1.352 times less aware of the personal protective measures against COVID-19 than dentists, respectively. Dentists had the comparatively better perception in knowledge and awareness of COVID-19 than undergraduates and postgraduates.
Impact of Gender and Age on Claim Rates of Dread Disease and Cancer Insurance Policies in Taiwan
Authors: Li Chu-Shiu , Hung Chih-Jen , Peng Sheng-Chang , Ho Ya-Lee
Published: December 2021

In this paper, the impact of both gender and age on the claim rates of dread disease and cancer insurance policies were examined using unique data taken from Taiwan’s private health insurance policies issued by non-life insurers during the 2012 to 2015 policy years. Those aged 30–39 served as the reference group. For the total number of dread disease policies, male insureds had a higher non-cancer claim probability than female insureds, while an age under 20 was associated with much lower claim rates for dread disease policies than for ages over 50. The claim rate for dread disease policies increased rapidly beginning at age 40 for both cancerous and non-cancerous diseases amongst male insureds. Amongst female insureds, those under 20 had much lower claim rates for dread disease policies. Only those aged 50–59 had a higher claim rate for non-cancerous diseases. For the total number of cancer insurance policies, male insureds had lower claim rates than female insureds, with an upward trend being associated with age. For male (female) insureds aged over 40 (20), the claim rates of cancer increased with age.
COVID-19 Daily Realities for Families: A South African Sample
Authors: October Kezia Ruth , Petersen Lisa Rene’ , Adebiyi Babatope , Rich Edna , Roman Nicolette Vanessa
Published: December 2021

The COVID-19 pandemic affected families globally. Empirical research has been explored to understand the impact of COVID-19 on families across countries, however, there are limited findings of how COVID-19 has affected the daily realities of families in South Africa. This study used an exploratory qualitative research approach to explore the experiences of COVID-19 for South African families. Findings suggest that the negative outcomes of COVID-19 experienced by South African families included a shift in the daily routines, restrictions on family events, lack of socialization and loss of connections, family conflicts, financial constraints as well as psychological impacts. On the contrary, the positive outcomes included increased family time and communication, cleanliness, and good health status, and improved financial management. Implications for future research should include research focused on the health impacts of COVID-19 on diverse family structures, family compositions, and family dynamics. In-depth research and findings can assist in developing policies and interventions for families.
An Investigation into Art Therapy Aided Health and Well-Being Research: A 75-Year Bibliometric Analysis
Authors: Liu Zhen , Yang Zulan , Xiao Chang , Zhang Ke , Osmani Mohamed
Published: December 2021

Considering the physical, and psychological impacts and challenges brought about the coronavirus disease 2019 (COVID-19), art therapy (AT) provides opportunities to promote human health and well-being. There are few systematic analysis studies in the fields of AT, which can provide content and direction for the potential value and impact of AT. Therefore, this paper aims to critically analyze the published work in the field of AT from the perspective of promoting health and well-being, and provides insights into current research status, hotspots, limitations, and future development trends of AT. This paper adopts a mixed method of quantitative and qualitative analysis including bibliometric analysis and keyword co-occurrence analysis. The results indicate that: (1) the current studies on AT are mostly related to research and therapeutic methods, types of AT, research populations and diseases, and evaluation of therapeutic effect of AT. The research method of AT mainly adopts qualitative research, among which creative arts therapy and group AT are common types of AT, and its main research populations are children, veterans, and adolescents. AT-aided diseases are trauma, depression, psychosis, dementia, and cancer. In addition, the therapeutic methods are mainly related to psychotherapy, drama, music, and dance/movement. Further, computer systems are an important evaluation tool in the research of AT; (2) the future development trend of AT-aided health and well-being based on research hotspots, could be focused on children, schizophrenia, well-being, mental health, palliative care, veterans, and the elderly within the context of addressing COVID-19 challenges; and (3) future AT-aided health and well-being could pay more attention to innovate and integrate the therapeutic methods of behavior, movement, and technology, such as virtual reality and remote supervision.
Health Risk Assessment in Southern Carpathians Small Rural Communities Using Karst Springs as a Drinking Water Source
Authors: Moldovan Ana , Török Anamaria Iulia , Mirea Ionuț Cornel , Micle Valer , Moldovan Oana Teodora , Levei Erika Andrea
Published: December 2021

The chemical quality of waters from eight karst springs from the Southern Carpathians and the health risk of small rural communities using these springs as a drinking water source were assessed. The results indicated that the spring waters in the studied area are chemically suitable to be used as drinking water and pose no health risks for adults and children. The spring water can be generally described as having circumneutral pH, Ca-Mg-HCO3− facies, excellent to good palatability, and low trace metal and nitrate content. The variation of chemical parameters between spring and autumn was low. These springs could become appropriate drinking water sources for the neighboring rural communities after the assessment of their microbiological status and, if it is the case, proper water treatment. Moreover, periodic monitoring of the water’s chemical parameters, mostly nitrates, as well as the establishment of a protected area near the springs to prevent the negative impact of anthropogenic sources on water quality is recommended.
Genome-Wide Identification of OSC Gene Family and Potential Function in the Synthesis of Ursane- and Oleanane-Type Triterpene in Momordica charantia
Authors: Han Yutong , Yang Ya , Li Yan , Yin Xin , Chen Zhiyu , Yang Danni , Yang Yongping , Yang Yunqiang , Yang Xuefei
Published: December 2021

The triterpenes in bitter gourd (Momordica charantia) show a variety of medicinal activities. Oxidosqualene cyclase (OSC) plays an indispensable role in the formation of triterpene skeletons during triterpene biosynthesis. In this study, we identified nine genes encoding OSCs from bitter gourd (McOSC1–9). Analyses of their expression patterns in different tissues suggested that characteristic triterpenoids may be biosynthesized in different tissues and then transported. We constructed a hairy root system in which McOSC7 overexpression led to an increased accumulation of camaldulenic acid, enoxolone, and quinovic acid. Thus, the overexpression of McOSC7 increased the active components content in bitter gourd. Our data provide an important foundation for understanding the roles of McOSCs in triterpenoid synthesis.
Perisomatic Inhibition and Its Relation to Epilepsy and to Synchrony Generation in the Human Neocortex
Authors: Tóth Estilla Zsófia , Szabó Felicia Gyöngyvér , Kandrács Ágnes , Molnár Noémi Orsolya , Nagy Gábor , Bagó Attila G. , Erőss Loránd , Fabó Dániel , Hajnal Boglárka , Rácz Bence , Wittner Lucia , Ulbert István , Tóth Kinga
Published: December 2021

Inhibitory neurons innervating the perisomatic region of cortical excitatory principal cells are known to control the emergence of several physiological and pathological synchronous events, including epileptic interictal spikes. In humans, little is known about their role in synchrony generation, although their changes in epilepsy have been thoroughly investigated. This paper demonstraits how parvalbumin (PV)- and type 1 cannabinoid receptor (CB1R)-positive perisomatic interneurons innervate pyramidal cell bodies, and their role in synchronous population events spontaneously emerging in the human epileptic and non-epileptic neocortex, in vitro. Quantitative electron microscopy showed that the overall, PV+ and CB1R+ somatic inhibitory inputs remained unchanged in focal cortical epilepsy. On the contrary, the size of PV-stained synapses increased, and their number decreased in epileptic samples, in synchrony generating regions. Pharmacology demonstrated—in conjunction with the electron microscopy—that although both perisomatic cell types participate, PV+ cells have stronger influence on the generation of population activity in epileptic samples. The somatic inhibitory input of neocortical pyramidal cells remained almost intact in epilepsy, but the larger and consequently more efficient somatic synapses might account for a higher synchrony in this neuron population. This, together with epileptic hyperexcitability, might make a cortical region predisposed to generate or participate in hypersynchronous events.
Fructose-Rich Diet Is a Risk Factor for Metabolic Syndrome, Proximal Tubule Injury and Urolithiasis in Rats
Authors: Flisiński Mariusz , Brymora Andrzej , Skoczylas-Makowska Natalia , Stefańska Anna , Manitius Jacek
Published: December 2021

Excessive consumption of fructose (FR) leads to obesity, metabolic syndrome (MS) and insulin resistance, which are known risk factors for kidney stones. The epidemiological study has suggested the association between fructose consumption and urolithiasis, but the precise mechanism is still not well understood. Male Wistar rats were assigned for 8 weeks to three groups with different FR content in diet: RD (n = 5)—regular diet with a FR < 3%; F10 (n = 6)—regular diet with an addition of 10% Fr in drinking water; F60 (n = 5)—60% FR as a solid food. Serum concentration of FR, creatinine (Cr), insulin (Ins), triglycerides (Tg), homocysteine (HCS), uric acid (UA), calcium (Ca), phosphate (Pi), magnesium (Mg) and sodium (Na) were measured. Based on 24 h urine collection the following tests were performed: urine pH, proteinuria (PCR), excretion of N-Acetyl-(D)-Glucosaminidase (NAG), monocyte chemoattractant protein (MCP-1), uric acid (uUAEx), phosphate (uPiEx), calcium (uCaEx), magnesium (uMgEx) and sodium (uNaEx). The creatinine clearance (CrCl) was calculated. Calcium deposits in kidney sections were examined using hematoxylin and eosin (HE) and von Kossa stains. The rats on F10 and F60, as compared to the RD diet, showed a tendency for lower CrCl, higher HCS level and some features of MS as higher Ins and TG levels. Interestingly, F10 (fluid) versus F60 (solid) diet led to higher serum Ins levels. F10 and F60 versus RD demonstrated higher urinary excretion of MCP-1 and NAG which were suggestive for inflammatory injury of the proximal tubule. F10 and F60 as compared to RD showed significantly lower uUAEx, although there were no differences in clearance and fractional excretion of UA. F60 versus RD induced severe phosphaturia (>30×) and natriuria (4×) and mild calciuria. F10 versus RD induced calciuria (3×), phosphaturia (2×) and mild natriuria. Calcium phosphate stones within the tubules and interstitium were found only in rats on FR diet, respectively, in two rats from the F10 group and another two in the F60 group. The rats which developed stones were characterized by significantly higher serum insulin concentration and urinary excretion of calcium and magnesium. A fructose-rich diet may promote development of calcium stones due to proximal tubule injury and metabolic syndrome.
Hippocampal Sclerosis in Pilocarpine Epilepsy: Survival of Peptide-Containing Neurons and Learning and Memory Disturbances in the Adult NMRI Strain Mouse
Authors: Mátyás Adrienne , Borbély Emőke , Mihály András
Published: December 2021

The present experiments reveal the alterations of the hippocampal neuronal populations in chronic epilepsy. The mice were injected with a single dose of pilocarpine. They had status epilepticus and spontaneously recurrent motor seizures. Three months after pilocarpine treatment, the animals were investigated with the Barnes maze to determine their learning and memory capabilities. Their hippocampi were analyzed 2 weeks later (at 3.5 months) with standard immunohistochemical methods and cell counting. Every animal displayed hippocampal sclerosis. The neuronal loss was evaluated with neuronal-N immunostaining, and the activation of the microglia was measured with Iba1 immunohistochemistry. The neuropeptide Y, parvalbumin, and calretinin immunoreactive structures were qualitatively and quantitatively analyzed in the hippocampal formation. The results were compared statistically to the results of the control mice. We detected neuronal loss and strongly activated microglia populations. Neuropeptide Y was significantly upregulated in the sprouting axons. The number of parvalbumin- and calretinin-containing interneurons decreased significantly in the Ammon’s horn and dentate gyrus. The epileptic animals displayed significantly worse learning and memory functions. We concluded that degeneration of the principal neurons, a numerical decrease of PV-containing GABAergic neurons, and strong peptidergic axonal sprouting were responsible for the loss of the hippocampal learning and memory functions.
TARBP2 Suppresses Ubiquitin-Proteasomal Degradation of HIF-1α in Breast Cancer
Authors: Li Jie-Ning , Chen Pai-Sheng , Chiu Ching-Feng , Lyu Yu-Jhen , Lo Chiao , Tsai Li-Wei , Wang Ming-Yang
Published: December 2021

TAR (HIV-1) RNA binding protein 2 (TARBP2) is an RNA-binding protein participating in cytoplasmic microRNA processing. Emerging evidence has shown the oncogenic role of TARBP2 in promoting cancer progression, making it an unfavorable prognosis marker for breast cancer. Hypoxia is a hallmark of the tumor microenvironment which induces hypoxia-inducible factor-1α (HIF-1α) for transcriptional regulation. HIF-1α is prone to be rapidly destabilized by the ubiquitination–proteasomal degradation system. In this study, we found that TARBP2 expression is significantly correlated with induced hypoxia signatures in human breast cancer tissues. At a cellular level, HIF-1α protein level was maintained by TARBP2 under either normoxia or hypoxia. Mechanistically, TARBP2 enhanced HIF-1α protein stability through preventing its proteasomal degradation. In addition, downregulation of multiple E3 ligases targeting HIF-1α (VHL, FBXW7, TRAF6) and reduced ubiquitination of HIF-1α were also induced by TARBP2. In support of our clinical findings that TARBP2 is correlated with tumor hypoxia, our IHC staining showed the positive correlation between HIF-1α and TARBP2 in human breast cancer tissues. Taken together, this study indicates the regulatory role of TARBP2 in the ubiquitination–proteasomal degradation of HIF-1α protein in breast cancer.
Site-Search Process for Synaptic Protein-DNA Complexes
Authors: Vemulapalli Sridhar , Hashemi Mohtadin , Lyubchenko Yuri L.
Published: December 2021

The assembly of synaptic protein-DNA complexes by specialized proteins is critical for bringing together two distant sites within a DNA molecule or bridging two DNA molecules. The assembly of such synaptosomes is needed in numerous genetic processes requiring the interactions of two or more sites. The molecular mechanisms by which the protein brings the sites together, enabling the assembly of synaptosomes, remain unknown. Such proteins can utilize sliding, jumping, and segmental transfer pathways proposed for the single-site search process, but none of these pathways explains how the synaptosome assembles. Here we used restriction enzyme SfiI, that requires the assembly of synaptosome for DNA cleavage, as our experimental system and applied time-lapse, high-speed AFM to directly visualize the site search process accomplished by the SfiI enzyme. For the single-site SfiI-DNA complexes, we were able to directly visualize such pathways as sliding, jumping, and segmental site transfer. However, within the synaptic looped complexes, we visualized the threading and site-bound segment transfer as the synaptosome-specific search pathways for SfiI. In addition, we visualized sliding and jumping pathways for the loop dissociated complexes. Based on our data, we propose the site-search model for synaptic protein-DNA systems.
Rigosertib and Cholangiocarcinoma: A Cell Cycle Affair
Authors: Malacrida Alessio , Cavaletti Guido , Miloso Mariarosaria
Published: December 2021

Rigosertib is multi-kinase inhibitor that could represent an interesting therapeutic option for non-resectable patients with cholangiocarcinoma, a very aggressive hepatic cancer with limited effective treatments. The Western blotting technique was used to evaluate alterations in the expression of proteins involved in the regulation of the cell cycle of cholangiocarcinoma EGI-1 cells. Our results show an increase in EMI1 and Cyclin B protein levels after Rigosertib treatment. Moreover, the phosphorylation of CDK1 is significantly reduced by Rigosertib, while PLK1 expression increased after 24 h of treatment and decreased after 48 h. Finally, we evaluated the role of p53. Its levels increase after Rig treatment, and, as shown in the cell viability experiment with the p53 inhibitor Pifithrin, its activity is necessary for the effects of Rigosertib against the cell viability of EGI-1 cells. In conclusion, we hypothesized the mechanism of the action of Rigosertib against cholangiocarcinoma EGI-1 cells, highlighting the importance of proteins involved in the regulation of cell cycles. The CDK1-Cyclin B complex and p53 play an important role, explaining the Block in the G2/M phase of the cell cycle and the effect on cell viability
Mechanisms of Melatonin in Obesity: A Review
Authors: Guan Qingyun , Wang Zixu , Cao Jing , Dong Yulan , Chen Yaoxing
Published: December 2021

Obesity and its complications have become a prominent global public health problem that severely threatens human health. Melatonin, originally known as an effective antioxidant, is an endogenous hormone found throughout the body that serves various physiological functions. In recent decades, increasing attention has been paid to its unique function in regulating energy metabolism, especially in glucose and lipid metabolism. Accumulating evidence has established the relationship between melatonin and obesity; nevertheless, not all preclinical and clinical evidence indicates the anti-obesity effect of melatonin, which makes it remain to conclude the clinical effect of melatonin in the fight against obesity. In this review, we have summarized the current knowledge of melatonin in regulating obesity-related symptoms, with emphasis on its underlying mechanisms. The role of melatonin in regulating the lipid profile, adipose tissue, oxidative stress, and inflammation, as well as the interactions of melatonin with the circadian rhythm, gut microbiota, sleep disorder, as well as the α7nAChR, the opioidergic system, and exosomes, make melatonin a promising agent to open new avenues in the intervention of obesity.
Lipofuscin Granule Bisretinoid Oxidation in the Human Retinal Pigment Epithelium forms Cytotoxic Carbonyls
Authors: Yakovleva Marina , Dontsov Alexander , Trofimova Natalia , Sakina Natalia , Kononikhin Alexey , Aybush Arseny , Gulin Alexander , Feldman Tatiana , Ostrovsky Mikhail
Published: December 2021

Age-related macular degeneration (AMD) is the primary cause of central blindness among the elderly. AMD is associated with progressive accumulation of lipofuscin granules in retinal pigment epithelium (RPE) cells. Lipofuscin contains bisretinoid fluorophores, which are photosensitizers and are phototoxic to RPE and neuroretinal cells. In the presence of oxygen, bisretinoids are also oxidized, forming various products, consisting primarily of aldehydes and ketones, which are also potentially cytotoxic. In a prior study, we identified that in AMD, bisretinoid oxidation products are increased in RPE lipofuscin granules. The purpose of the present study was to determine if these products were toxic to cellular structures. The physicochemical characteristics of bisretinoid oxidation products in lipofuscin, which were obtained from healthy donor eyes, were studied. Raman spectroscopy and time-of-flight secondary ion mass spectrometry (ToF–SIMS) analysis identified the presence of free-state aldehydes and ketones within the lipofuscin granules. Together, fluorescence spectroscopy, high-performance liquid chromatography, and mass spectrometry revealed that bisretinoid oxidation products have both hydrophilic and amphiphilic properties, allowing their diffusion through lipofuscin granule membrane into the RPE cell cytoplasm. These products contain cytotoxic carbonyls, which can modify cellular proteins and lipids. Therefore, bisretinoid oxidation products are a likely aggravating factor in the pathogenesis of AMD.
Insight into microRNAs-Mediated Communication between Liver and Brain: A Possible Approach for Understanding Acute Liver Failure?
Authors: Orzeł-Gajowik Karolina , Milewski Krzysztof , Zielińska Magdalena
Published: December 2021

Acute liver failure (ALF) is a life-threatening consequence of hepatic function rapid loss without preexisting liver disease. ALF may result in a spectrum of neuropsychiatric symptoms that encompasses cognitive impairment, coma, and often death, collectively defined as acute hepatic encephalopathy. Micro RNAs are small non-coding RNAs that modulate gene expression and are extensively verified as biomarker candidates in various diseases. Our systematic literature review based on the last decade’s reports involving a total of 852 ALF patients, determined 205 altered circulating miRNAs, of which 25 miRNAs were altered in the blood, regardless of study design and methodology. Selected 25 miRNAs, emerging predominantly from the analyses of samples obtained from acetaminophen overdosed patients, represent the most promising biomarker candidates for a diagnostic panel for symptomatic ALF. We discussed the role of selected miRNAs in the context of tissue-specific origin and its possible regulatory role for molecular pathways involved in blood–brain barrier function. The defined several common pathways for 15 differently altered miRNAs were relevant to cellular community processes, indicating loss of intercellular, structural, and functional components, which may result in blood-brain barrier impairment and brain dysfunction. However, a causational relationship between circulating miRNAs differential expression, and particular clinical features of ALF, has to be demonstrated in a further study.
SOX2 Regulates Neuronal Differentiation of the Suprachiasmatic Nucleus
Authors: Cheng Arthur H. , Fung Samuel W. , Hegazi Sara , Abdalla Osama Hasan Mustafa Hasan , Cheng Hai-Ying Mary
Published: December 2021

In mammals, the hypothalamic suprachiasmatic nucleus (SCN) functions as the central circadian pacemaker, orchestrating behavioral and physiological rhythms in alignment to the environmental light/dark cycle. The neurons that comprise the SCN are anatomically and functionally heterogeneous, but despite their physiological importance, little is known about the pathways that guide their specification and differentiation. Here, we report that the stem/progenitor cell transcription factor, Sex determining region Y-box 2 (Sox2), is required in the embryonic SCN to control the expression of SCN-enriched neuropeptides and transcription factors. Ablation of Sox2 in the developing SCN leads to downregulation of circadian neuropeptides as early as embryonic day (E) 15.5, followed by a decrease in the expression of two transcription factors involved in SCN development, Lhx1 and Six6, in neonates. Thymidine analog-retention assays revealed that Sox2 deficiency contributed to reduced survival of SCN neurons during the postnatal period of cell clearance, but did not affect progenitor cell proliferation or SCN specification. Our results identify SOX2 as an essential transcription factor for the proper differentiation and survival of neurons within the developing SCN.
Inherent P2X7 Receptors Regulate Macrophage Functions during Inflammatory Diseases
Authors: Ren Wenjing , Rubini Patrizia , Tang Yong , Engel Tobias , Illes Peter
Published: December 2021

Macrophages are mononuclear phagocytes which derive either from blood-borne monocytes or reside as resident macrophages in peripheral (Kupffer cells of the liver, marginal zone macrophages of the spleen, alveolar macrophages of the lung) and central tissue (microglia). They occur as M1 (pro-inflammatory; classic) or M2 (anti-inflammatory; alternatively activated) phenotypes. Macrophages possess P2X7 receptors (Rs) which respond to high concentrations of extracellular ATP under pathological conditions by allowing the non-selective fluxes of cations (Na+, Ca2+, K+). Activation of P2X7Rs by still higher concentrations of ATP, especially after repetitive agonist application, leads to the opening of membrane pores permeable to ~900 Da molecules. For this effect an interaction of the P2X7R with a range of other membrane channels (e.g., P2X4R, transient receptor potential A1 [TRPA1], pannexin-1 hemichannel, ANO6 chloride channel) is required. Macrophage-localized P2X7Rs have to be co-activated with the lipopolysaccharide-sensitive toll-like receptor 4 (TLR4) in order to induce the formation of the inflammasome 3 (NLRP3), which then activates the pro-interleukin-1β (pro-IL-1β)-degrading caspase-1 to lead to IL-1β release. Moreover, inflammatory diseases (e.g., rheumatoid arthritis, Crohn’s disease, sepsis, etc.) are generated downstream of the P2X7R-induced upregulation of intracellular second messengers (e.g., phospholipase A2, p38 mitogen-activated kinase, and rho G proteins). In conclusion, P2X7Rs at macrophages appear to be important targets to preserve immune homeostasis with possible therapeutic consequences.
Resonance-Assisted Hydrogen Bond—Revisiting the Original Concept in the Context of Its Criticism in the Literature
Authors: Domagała Małgorzata , Simon Sílvia , Palusiak Marcin
Published: December 2021

In the presented research, we address the original concept of resonance-assisted hydrogen bonding (RAHB) by means of the many-body interaction approach and electron density delocalization analysis. The investigated molecular patterns of RAHBs are open chains consisting of two to six molecules in which the intermolecular hydrogen bond stabilizes the complex. Non-RAHB counterparts are considered to be reference systems. The results show the influence of the neighbour monomers on the unsaturated chains in terms of the many-body interaction energy contribution. Exploring the relation between the energy parameters and the growing number of molecules in the chain, we give an explicit extrapolation of the interaction energy and its components in the infinite chain. Electron delocalization within chain motifs has been analysed from three different points of view: three-body delocalization between C=C-C, two-body hydrogen bond delocalization indices and also between fragments (monomers). A many-body contribution to the interaction energy as well as electron density helps to establish the assistance of resonance in the strength of hydrogen bonds upon the formation of the present molecular chains. The direct relation between interaction energy and delocalization supports the original concept, and refutes some of the criticisms of the RAHB idea.
The Insulin-like Growth Factor Signalling Pathway in Cardiac Development and Regeneration
Authors: Díaz del Moral Sandra , Benaouicha Maha , Muñoz-Chápuli Ramón , Carmona Rita
Published: December 2021

Insulin and Insulin-like growth factors (IGFs) perform key roles during embryonic development, regulating processes of cell proliferation and survival. The IGF signalling pathway comprises two IGFs (IGF1, IGF2), two IGF receptors (IGFR1, IGFR2), and six IGF binding proteins (IGFBPs) that regulate IGF transport and availability. The IGF signalling pathway is essential for cardiac development. IGF2 is the primary mitogen inducing ventricular cardiomyocyte proliferation and morphogenesis of the compact myocardial wall. Conditional deletion of the Igf1r and the insulin receptor (Insr) genes in the myocardium results in decreased cardiomyocyte proliferation and ventricular wall hypoplasia. The significance of the IGF signalling pathway during embryonic development has led to consider it as a candidate for adult cardiac repair and regeneration. In fact, paracrine IGF2 plays a key role in the transient regenerative ability of the newborn mouse heart. We aimed to review the current knowledge about the role played by the IGF signalling pathway during cardiac development and also the clinical potential of recapitulating this developmental axis in regeneration of the adult heart.
Object Detection of Road Assets Using Transformer-Based YOLOX with Feature Pyramid Decoder on Thai Highway Panorama
Authors: Panboonyuen Teerapong , Thongbai Sittinun , Wongweeranimit Weerachai , Santitamnont Phisan , Suphan Kittiwan , Charoenphon Chaiyut
Published: December 2021

Due to the various sizes of each object, such as kilometer stones, detection is still a challenge, and it directly impacts the accuracy of these object counts. Transformers have demonstrated impressive results in various natural language processing (NLP) and image processing tasks due to long-range modeling dependencies. This paper aims to propose an exceeding you only look once (YOLO) series with two contributions: (i) We propose to employ a pre-training objective to gain the original visual tokens based on the image patches on road asset images. By utilizing pre-training Vision Transformer (ViT) as a backbone, we immediately fine-tune the model weights on downstream tasks by joining task layers upon the pre-trained encoder. (ii) We apply Feature Pyramid Network (FPN) decoder designs to our deep learning network to learn the importance of different input features instead of simply summing up or concatenating, which may cause feature mismatch and performance degradation. Conclusively, our proposed method (Transformer-Based YOLOX with FPN) learns very general representations of objects. It significantly outperforms other state-of-the-art (SOTA) detectors, including YOLOv5S, YOLOv5M, and YOLOv5L. We boosted it to 61.5% AP on the Thailand highway corpus, surpassing the current best practice (YOLOv5L) by 2.56% AP for the test-dev data set.
Prey Status Affects Paralysis Investment in the Ponerine Ant Harpegnathos venator
Authors: Nie Lei , Zhao Fei , Chen Yiming , Xiao Qian , Pan Zhiping , Ran Hao , Xu Yijuan
Published: December 2021

The paralysis behavior of some ponerine ants when foraging may be important for food storage and colony development. However, how workers invest in paralysis under different prey circumstances is often overlooked. Here, we report the prey-foraging behavior and paralysis behavior of Harpegnathos venator under different food supply conditions. Solitary hunting was the main foraging mode of H. venator, with occasional simple collective hunting. Nymphal cockroaches with high activity were the most attractive to H. venator. In the experiment, we found that the stings of H. venator completely paralyzed the cockroaches. The stinging time was significantly longer at a higher prey activity level and for larger cockroaches. In addition, there was no significant difference in the stinging time of H. venator for different prey densities. The results showed that the longer similar cockroaches were stung, the longer it took for them to revive and move. These results are helpful for further understanding the behavioral mechanism underlying the food storage of live prey by predatory insects.