bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Thinning: A Promising Tool to Prevent Fistulina hepatica Heart Rot in Castanea sativa Coppice Stands
Authors: Meijer Andreu , Muñoz-Adalia Emigdio Jordán , Colinas Carlos
Published: September 2024

Castanea sativa is a high-value tree species whose stands have faced significant threats over the past century. The occurrence of one such threat, Chestnut Red Stain—a heartwood discoloration caused by the fungus Fistulina hepatica—has recently increased. This disease devalues the timber by up to 70% due to the rejection of stained wood by the industry. This study aimed to evaluate the effects of three management strategies on the occurrence of F. hepatica in chestnut coppice stands. Additionally, the co-occurrence of F. hepatica and Cryphonectria parasitica, both highly prevalent in the study area, was assessed. In 2013, three different silvicultural treatments were applied to five plots. Seven years later, the stand characteristics were measured, and the incidence of F. hepatica was evaluated using molecular tools. Data modeling revealed that the quadratic mean diameter before the interventions was related to the incidence of F. hepatica. Our results suggest that the thinning at earlier stand stages may be more critical than the type or intensity of the thinning in reducing the incidence of the fungus in the mid-term. This finding provides forest managers with new guidance to improve silvicultural treatments and prevent F. hepatica damage.
Improving Carbon Sequestration in Wetlands Using Native Poplar Genotypes for Reforestation Purposes
Authors: Cantamessa Simone , Chiarabaglio Pier Mario , Rizza Daniele , Debernardi Giacomo , Bergante Sara
Published: September 2024

From the early 2000s, many forestation projects were carried out in the flooding areas of the Po River to preserve abandoned or damaged riverbanks and establish natural populations of Populus nigra L. for species conservation and future seed collection activities. Different clones of P. nigra, belonging to a collection of the Centre for Forestry and Wood (CREA-FL), were planted. The group named ‘POBIA’ comprises 35 selected clones chosen for their survival ability and fast growth. After plantation and a few essential cultural inputs, four establishments were left undisturbed. This study highlights the survival, growth, and performance results of the ‘POBIA’ group compared to other not-selected clones. The ‘POBIA’ clones showed a higher survival than the not-selected clones. Moreover, the ‘POBIA’ groups showed a significantly higher C sink performance in three of four establishments, reaching 278.6 t ha−1 of CO2 obtained in thirteen years in one site. The management of ‘POBIA’ clones in reforestation projects agrees with the EU recommendations for a vital ecosystem service.
The Combined Effect of Taproot and Fibrous Roots of Herbaceous Plants and Shrubs on the Distribution of Soil Water-Stable Aggregates
Authors: Wang Chenguang , Miao Jiahe , Liu Chenguang , Ma Bingzhao , Li Xueyan , Li Gui , Li Zhanbin
Published: September 2024

Soil aggregation, an important indicator of soil restoration in degraded ecosystems, is a fundamental unit of soil structure. However, research on the influence of grass–shrub composites on the distribution of >0.25 mm soil water-stable aggregates (macroaggregates) is scarce. Therefore, this study focuses on the hill and gully region of the Loess Plateau, where vegetation has been well restored since the return of farmland to forests and grasslands. The study investigated the root and macroaggregate distribution characteristics and interrelationships of three widely distributed mixed vegetation types of Caragana korshinskii and Agropyron cristatum (C-AC), C. korshinskii and Bothriochloa ischaemum (C-BI), and C. korshinskii and Artemisia gmelinii (C-AG) in this area. The results indicate that soil macroaggregates decrease with increasing depth. Due to the spatial differences in the distribution of shrub root, the content of macroaggregates at 50 cm from the shrub base was higher than that at the shrub base, with an increase of 25.98%–34.27% in different vegetation associations. In this study, the root length density and root diameter better reflected the influence of roots on the distribution of macroaggregates, and the product of the two had a good power function relationship with the content of macroaggregates (R2 ≥ 0.82, p < 0.01). Grey correlation analysis showed that the influence of root length density on the distribution of large aggregates was greater than that of root diameter. The content of macroaggregates in the vegetation association of taproot herbaceous plants and shrubs was higher than that of fibrous root herbaceous plants. The average soil macroaggregate content in the C-AG was 15.79%–248.6% higher than that in the C-BI and C-AC. In this study, the spatial distribution differences in root caused by shrub growth were the main reason for the spatial heterogeneity of soil macroaggregate content distribution. The improvement ability of soil macroaggregates was higher in the combination of taproot herbaceous plants and shrubs than in the combination of fibrous root herbaceous plants and shrubs. The results of this study can, to some extent, reveal the influence and mechanisms of plant roots on soil aggregates in grass–shrub vegetation association.
Carbon Balance in Soils under Conifers and Broadleaved Species within La Sierra, Dominican Republic
Authors: Bueno-López Santiago W. , Caraballo-Rojas Luis R. , Pérez-Gonzales Esclaudys
Published: September 2024

Our research assesses the effects of four forest species, namely, Swietenia macrophylla King, Swietenia mahagoni (L.) Jack., Pinus occidentalis Swartz, and Pinus caribaea Morelet var. Caribaea, on the soil and litter organic carbon (C) stocks, C dioxide equivalent balance (BCO2 Eq.) diurnal, and periodic dynamics beneath these species. Reforestation projects in the study region cover 1200, 543, 770, and 1152 hectares, respectively, with these four species being the most relevant in reforestation projects within the country. To determine the BCO2 Eq. per unit area, we compared the greenhouse gas (GHG) fluxes of carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O) expressed as CO2 Eq. units with the organic C stocks found in the mineral soil to a depth of 30 cm and in the forest litter. In four measurement periods over 18 months, we conducted field measurements in sixteen stands, four per species. Our results indicate that S. mahagoni emitted the lowest CO2 Eq., while S. macrophylla released the highest amount into the atmosphere. At the end of the 18 months, BCO2 Eq. from S. macrophylla soils was 299.70 metric tons ha−1 year−1, while for P. occidentalis, P. caribaea, and S. mahagoni, the corresponding quantities were 103.64, 146.41, and 72.34, respectively. All species showed a general upward pattern in soil respiration from September 2020 to March 2022. The average CO2 Eq. flux rates to the atmosphere were approximately 65.4, 51.1, and 75.9 percent higher in S. macrophylla soils compared to the respective rates of P. occidentalis, P. caribaea, and S. mahagoni.
Co-Occurrence of Two Plasmids Encoding Transferable blaNDM-1 and tet(Y) Genes in Carbapenem-Resistant Acinetobacter bereziniae
Authors: Opazo-Capurro Andrés , Xanthopoulou Kyriaki , Arazo del Pino Rocío , González-Muñoz Paulina , Matus-Köhler Maximiliano , Amsteins-Romero Luis , Jerez-Olate Christian , Hormazábal Juan Carlos , Vera Rodrigo , Aguilera Felipe , Fuller Sebastián , Higgins Paul G. , González-Rocha Gerardo
Published: September 2024

Acinetobacter bereziniae has emerged as a significant human pathogen, acquiring multiple antibiotic resistance genes, including carbapenemases. This study focuses on characterizing the plasmids harboring the blaNDM-1 and tet(Y) genes in two carbapenem-resistant A. bereziniae isolates (UCO-553 and UCO-554) obtained in Chile during the COVID-19 pandemic. Methods: Antibiotic susceptibility testing was conducted on UCO-553 and UCO-554. Both isolates underwent whole-genome sequencing to ascertain their sequence type (ST), core genome multilocus sequence-typing (cgMLST) profile, antibiotic resistance genes, plasmids, and mobile genetic elements. Conjugation experiments were performed for both isolates. Results: Both isolates exhibited broad resistance, including resistance to carbapenems, third-generation cephalosporins, fluoroquinolones, tetracycline, cotrimoxazole, and aminoglycosides. Both isolates belong to sequence type STPAS1761, with a difference of 17 out of 2984 alleles. Each isolate carried a 47,274 bp plasmid with blaNDM-1 and aph(3′)-VI genes and two highly similar plasmids: a 35,184 bp plasmid with tet(Y), sul2, aph(6)-Id, and aph(3″)-Ib genes, and a 6078 bp plasmid containing the ant(2″)-Ia gene. Quinolone-resistance mutations were identified in the gyrA and parC genes of both isolates. Importantly, blaNDM-1 was located within a Tn125 transposon, and tet(Y) was embedded in a Tn5393 transposon. Conjugation experiments successfully transferred blaNDM-1 and tet(Y) into the A. baumannii ATCC 19606 strain, indicating the potential for horizontal gene transfer. Conclusions: This study highlights the critical role of plasmids in disseminating resistance genes in A. bereziniae and underscores the need for the continued genomic surveillance of this emerging pathogen. The findings emphasize the importance of monitoring A. bereziniae for its potential to cause difficult-to-treat infections and its capacity to spread resistance determinants against clinically significant antibiotics.
Genetic Diversity in Schizophrenia: Developmental Implications of Ultra-Rare, Protein-Truncating Mutations
Authors: Clarin Jacob D. , Bouras Nadia N. , Gao Wen-Jun
Published: September 2024

The genetic basis of schizophrenia (SZ) remains elusive despite its characterization as a highly heritable disorder. This incomplete understanding has led to stagnation in therapeutics and treatment, leaving many suffering with insufficient relief from symptoms. However, recent large-cohort genome- and exome-wide association studies have provided insights into the underlying genetic machinery. The scale of these studies allows for the identification of ultra-rare mutations that confer substantial disease risk, guiding clinicians and researchers toward general classes of genes that are central to SZ etiology. One such large-scale collaboration effort by the Schizophrenia Exome Sequencing Meta-Analysis consortium identified ten, high-risk, ultra-rare, protein-truncating variants, providing the clearest picture to date of the dysfunctional gene products that substantially increase risk for SZ. While genetic studies of SZ provide valuable information regarding “what” genes are linked with the disorder, it is an open question as to “when” during brain development these genetic mutations impose deleterious effects. To shed light on this unresolved aspect of SZ etiology, we queried the BrainSpan developmental mRNA expression database for these ten high-risk genes and discovered three general expression trajectories throughout pre- and postnatal brain development. The elusiveness of SZ etiology, we infer, is not only borne out of the genetic heterogeneity across clinical cases, but also in our incomplete understanding of how genetic mutations perturb neurodevelopment during multiple critical periods. We contextualize this notion within the National Institute of Mental Health’s Research Domain Criteria framework and emphasize the utility of considering both genetic variables and developmental context in future studies.
Substrate-Mediated Regulation of Src Expression Drives Osteoclastogenesis Divergence
Authors: Hu Bo , Chen Yiming , Li Yuman , Deng Chenyu , Niu Yuting , Hu Zhewen , Li Yao , Sun Shiyu , Huang Ying , Deng Xuliang , Wei Yan
Published: September 2024

Background/Objectives: Glass, bone, and dentin are commonly applied substrates for osteoclast cultures; however, the impact of these substrates on osteoclastogenesis remains underexplored. This study aimed to address a significant gap in understanding how different substrates influence the process of osteoclastogenesis. Methods: RAW 264.7 cells were cultured and induced with RANKL on glass, bone, and dentin slides. Histological and molecular techniques were used to identify patterns and differences in osteoclast behavior on each substrate. Results: Osteoclasts cultured on glass slides possessed the greatest number of nuclei and the highest expression levels of ACP5 (TRAP) and CTSK, with osteoclasts on bone and dentin slides displaying progressively lower levels. Src expression was also most pronounced in osteoclasts on glass slides, with decreased levels observed on bone and dentin. This variation in Src expression likely contributed to differences in cytoskeletal remodeling and oxidative phosphorylation (OXPHOS), resulting in substrate-dependent divergences in osteoclastogenesis. Conclusions: Glass slides were the most favorable substrate for inducing osteoclastogenesis, while bone and dentin slides were less effective. The substrate-induced expression of Src played a fundamental role in shaping the phenotypic divergence of osteoclasts. These insights fill important knowledge gaps and have significant implications for the development and selection of in vitro models for bone-related diseases and drug screening platforms.
Evaluating the Efficacy of Target Capture Sequencing for Genotyping in Cattle
Authors: Ren Yan , Khatkar Mehar S. , MacPhillamy Callum , Wang Haofei , McEwin Rudi A. , Chen Tong , Pitchford Wayne S. , Low Wai Yee
Published: September 2024

(1) Background: Target capture sequencing (TCS) is potentially a cost-effective way to detect single-nucleotide polymorphisms (SNPs) and an alternative to SNP array-based genotyping. (2) Methods: We evaluated the effectiveness and reliability of TCS in cattle breeding scenarios using 48 female and 8 male samples. DNA was extracted from blood samples, targeted for 71,746 SNPs with TWIST probes, and sequenced on an MGI platform. GATK and BCFtools were evaluated for the best genotyping calling tool. The genotypes were compared to existing genotypes from the Versa50K SNP array of the same animals by measuring accuracy as concordance (%) and R2. (3) Results: In this study, 71,553 SNPs and 166 indels were identified. The genotype comparison of 37,130 common SNPs between TCS and SNP arrays yielded high agreement, with a mean concordance of 98%, R2 of 0.98 and Cohen’s kappa of 0.97. The concordances of sex prediction, parent verification and validation of five genotype markers of interest important for Wagyu breeding were 100% between TCS and SNP array. The elements of the genomic relationship matrix (GRM) constructed from the SNP array and TCS data demonstrated a correlation coefficient approaching unity (r = 0.9998). (4) Conclusions: Compared to the SNP array, TCS is a comparable, cost-effective and flexible platform for genotyping SNPs, including non-model organisms and underrepresented commercial animal populations.
A Review and Meta-Analysis of Genotype by Environment Interaction in Commercial Shrimp Breeding
Authors: Hasan Md. , Thomson Peter , Raadsma Herman , Khatkar Mehar
Published: September 2024

(1) Background: Genotype-by-environment interaction (G×E) can adversely impact genetic improvement programs. The presence of G×E is mainly measured as the genetic correlation between the same trait measured in different environments where departure from unity can be taken as presence of G×E. (2) Methods: To understand the extent of G×E in shrimp production, a review and meta-analysis was conducted using the results from 32 peer-reviewed studies. (3) Results: Of these, 22 G×E studies were conducted on Pacific white shrimp (Litopenaeus vannamei) with fewer studies reported in other shrimp species. The most frequently studied traits were growth and survival, with relatively few studies on traits of economic importance. The meta-analysis demonstrated a moderately high genetic correlation (rg = 0.72 ± 0.05) for growth, indicating low to moderate levels of G×E with some re-ranking of breeding values across environments. However, substantial G×E was evident for survival where only a moderate genetic correlation (rg = 0.58 ± 0.07) was observed for survival across different environments. A re-ranking of breeding values is likely for this trait and genetic improvement of shrimp for survival in one environment may not be effective in other environments. The results from ANOVA-based studies show that G×E accounted for 6.42 ± 1.05% and 7.13 ± 3.46% of the variation for growth and survival traits, respectively. (4) Conclusion: The significance of G×E necessitates tailored genetic improvement programs in commercial shrimp breeding. We discuss the scope and challenges of G×E for shrimp breeding programs, including opportunities of implementing G×E in genomic selection programs.
The Role of Social Determinants of Health in Self-Reported Psychological Distress among United States Adults Post-COVID-19 Pandemic
Authors: Kalu Kingsley , Shah Gulzar H. , Ayangunna Elizabeth , Shah Bushra , Marshall Nandi
Published: September 2024

Psychological distress, an emotional condition with symptoms of anxiety and depression, leads to impaired function, behavior, and personal traits. The current study examined the association between social determinants of health and the severity of psychological distress among adults in the United States after the COVID-19 pandemic. Using multinomial multivariable logistic regression, we analyzed data from 5106 (n = 5106) participants in the Health Information National Trends Survey (HINTS) 6. Compared to non-Hispanic Whites, African Americans (AOR = 0.62, CI = 0.42–0.93) had lower odds of reporting mild psychological distress rather than no stress. Other variables associated with a higher likelihood of reporting moderate to severe psychological distress, rather than no distress, are being in the 50–64 years age group (AOR = 2.77, CI = 1.45–5.28), divorced (AOR = 2.50, CI = 1.70–3.69), and widowed (AOR = 3.78, CI = 2.15–6.64). Respondents living in an urban area had lower odds of reporting moderate to severe psychological distress (AOR = 0.56, CI = 0.39–0.80) compared to those living in rural areas. Our findings identify several risk factors for psychological distress by sociodemographic characteristics such as age, race, marital status, and urban living, providing empirical evidence for interventions in behavioral health. These findings suggest there is an utmost need for a multi-sectoral approach to address the social determinants of health associated with psychological distress post-COVID-19 pandemic.
The Andrological Landscape in the Twenty-First Century: Making Sense of the Advances in Male Infertility Management for the Busy Clinicians
Authors: Motawi Ahmad , Crafa Andrea , Hamoda Taha , Shah Rupin , Agarwal Ashok
Published: September 2024

Male infertility represents a significant global problem due to its essential health, social, and economic implications. It is unsurprising that scientific research is very active in this area and that advances in the diagnostic and therapeutic fields are notable. This review presents the main diagnostic advances in male infertility, starting from the changes made in the latest WHO Manual of semen analysis and discussing the more molecular aspects inherent to “omics”. Furthermore, the usefulness of artificial intelligence in male infertility diagnostics and the latest advances in varicocele diagnosis will be discussed. In particular, the diagnostic path of male infertility is increasingly moving towards a personalized approach to the search for the specific biomarkers of infertility and the prediction of treatment response. The treatment of male infertility remains empirical in many regards, but despite that, advances have been made to help formulate evidence-based recommendations. Varicocele, the most common correctable cause of male infertility, has been explored for expanded indications for repair. The following expanded indications were discussed: elevated sperm DNA fragmentation, hypogonadism, orchalgia, and the role of varicocele repair in non-obstructive azoospermia. Moving forward with the available data, we discussed the stepwise approach to surgical sperm retrieval techniques and the current measures that have been investigated for optimizing such patients before testicular sperm extraction. Finally, the key points and expert recommendations regarding the best practice for diagnosing and treating men with infertility were summarized to conclude this review.
Oral Problems in Brazilian Individuals with Rare Genetic Diseases That Affect Skeletal Development
Authors: Rabello Flavia , Celestino Mariana Laís Silva , Carneiro Natália Cristina Ruy , Reis-Oliveira Jennifer , Prado Heloísa Vieira , Abreu Mauro Henrique Nogueira Guimarães de , Borges-Oliveira Ana Cristina
Published: September 2024

The present study aimed to compare the prevalence of oral problems between individuals with rare genetic diseases that affect skeletal development and individuals without rare diseases. A cross-sectional study was conducted with 210 individuals between two and fifty-four years of age: 105 with rare genetic diseases (27 with mucopolysaccharidosis [MPS] and 78 with osteogenesis imperfecta [OI]) and 105 without rare diseases. The rare genetic disease group was recruited from hospital units that provide care for patients with MPS and OI in five states of Brazil, and the other group was recruited from the same location. The participants were examined with regards to malocclusion, dental anomalies, dental caries, and gingivitis. A questionnaire was administered addressing individual, sociodemographic, and behavioral characteristics as well as dental history. A descriptive analysis was performed, followed by unadjusted and adjusted binary logistic regression analyses. The mean age was 14.1 ± 12.2 years. Individuals with a rare disease were 12.9-fold more likely to have some type of oral problem (95% CI: 3.7–44.7) compared to the group without rare diseases. The prevalence of oral problems was higher among Brazilians with MPS and OI compared to normotypical individuals.
Problematic Pornography Use, Mental Health, and Suicidality among Young Adults
Authors: Altin Mujde , De Leo Diego , Tribbia Noemi , Ronconi Lucia , Cipolletta Sabrina
Published: September 2024

The relationship between suicidality and problematic pornography use (PPU) is not clear, and the limited research data that exists show contradictory results. The present study aims to explore the associations between these two variables in a sample of young adults, taking into account gender differences and the role of loneliness, emotional states, and well-being. A total of 332 national and international students (60% female) at an Italian University with a mean age of 23 years (SD = 2.84) completed an anonymous online survey during the period from March 2023 to May 2023. The results show that PPU was associated with higher levels of anxiety, depression, stress, loneliness, and suicide ideation, as well as lower life satisfaction. Gender comparison analysis revealed significantly higher scores for PPU and loneliness among men, while women scored higher in stress, anxiety, and life satisfaction. Significant correlations between PPU and suicidal ideation and having a suicide plan were established for female participants despite their lower scores in PPU. Multiple regression analysis revealed that PPU and its interaction with gender were both significant predictors of suicidal ideation. Future attention should be paid to how young women may be influenced by exposure to sexually explicit materials, while always considering the role of loneliness.
Exploring Prehospital Data for Pandemic Preparedness: A Western Brazilian Amazon Case Study on COVID-19
Authors: Fernandes Eduardo , Silva Bernardo Maia da , Goulart Cássia da Luz , Valente Jefferson , Cubas-Vega Nádia , Sato Camila , Rezende Anna Gabriela , Almeida Taynna Vernalha Rocha , de Amorim Robson Luís Oliveira , Salinas Jorge Luis , Monteiro Wuelton Marcelo , Arêas Guilherme Peixoto Tinoco , Almeida-Val Fernando
Published: September 2024

Background: The timely management of rapidly evolving epidemiological scenarios caused by disease outbreaks is crucial to prevent devastating consequences. However, delayed laboratory diagnostics can hamper swift health policy and epidemic response, especially in remote regions such as the western Brazilian Amazon. The aim of the article is to analyze the impact of the COVID-19 pandemic on the volume and characteristics of emergency medical services (EMS) in Manaus, focusing on how the pandemic affected sensitive indicators such as response time and the use of advanced life support ambulances. Additionally, the study seeks to understand how changes in prehospital EMS patterns, triggered by the pandemic, could be utilized as health surveillance tools, enabling a more rapid response in epidemic scenarios. Methods: This retrospective, descriptive study included data from the SAMU (Serviço de Atendimento Móvel de Urgência) medical records between January and June 2020. Results: A total of 45,581 calls resulted in mobile units being dispatched during this period. These patients were predominantly male (28,227, 61.9%), with a median age of 47 years (IQR 30–67). The median response time significantly increased during the pandemic, reaching a median of 45.9 min (IQR 30.6–67.7) (p < 0.001). EMS calls were reduced for trauma patients and increased for other medical emergencies, especially respiratory conditions, concomitantly to an escalation in the number of deaths caused by SARS and COVID-19 (p < 0.001). The employment of advanced life support ambulances was higher during the pandemic phase (p = 0.0007). Conclusion: The COVID-19 pandemic resulted in a temporary disorder in the volume and reason for EMS calls in Manaus. Consequently, sensitive indicators like the response time and the employment of advanced life support ambulances were negatively affected. Sudden prehospital EMS pattern changes could play an important role in health surveillance systems, allowing for earlier establishment of countermeasures in epidemics. The impact of the COVID-19 pandemic on prehospital EMS and its role in health surveillance should be further explored.
A Cross-Sectional Study Investigating Associations between Personality Traits, Glycemic Control, and BMI in Persons with Diabetes: Lolland-Falster Health Study, Denmark
Authors: Pedersen Zandra Overgaard , Ewers Bettina , Wimmelmann Cathrine Lawaetz , Kofoed-Enevoldsen Allan , Køster-Rasmussen Rasmus , Couppé Christian , Simonsen Erik , Dammeyer Jesper
Published: September 2024

There is a growing focus on person-centered care, emphasizing the importance of respecting inter-individual differences and implementing individualized treatment initiatives. Prior research has established an association between personality traits, body mass index, and health-related behaviors. The aim of this study was to explore the potential of personality trait assessments in identifying individuals at risk of glycemic dysregulation and increasing BMI. This cross-sectional study used a dataset comprising 140 participants with diabetes who completed the Big Five personality trait questionnaire from the Lolland-Falster Health Study. Logistic regression was used to investigate associations between personality traits, glycemic control, and BMI ≥ 25. No significant associations between personality traits and glycemic control were found. There was a significant association between agreeableness and lower odds of BMI ≥ 25 in the unadjusted analysis (OR 0.54 (0.34–0.86)), which persisted after adjusting for sex, age, and education (OR 0.54 (0.33–0.89)). No significant association between glycemic control and personality traits was observed in this small sample study. However, higher levels of agreeableness were associated with a lower likelihood of having a BMI of ≥25. This preliminary study suggests that integrating personality assessments could help identify individuals at risk of increasing BMI. These findings highlight the potential of using personality traits to guide targeted interventions, offering a direction for future research.
How Protein Depletion Balances Thrombosis and Bleeding Risk in the Context of Platelet’s Activatory and Negative Signaling
Authors: Montecino-Garrido Hector , Trostchansky Andrés , Espinosa-Parrilla Yolanda , Palomo Iván , Fuentes Eduardo
Published: September 2024

Platelets are small cell fragments that play a crucial role in hemostasis, requiring fast response times and fine signaling pathway regulation. For this regulation, platelets require a balance between two pathway types: the activatory and negative signaling pathways. Activatory signaling mediators are positive responses that enhance stimuli initiated by a receptor in the platelet membrane. Negative signaling regulates and controls the responses downstream of the same receptors to roll back or even avoid spontaneous thrombotic events. Several blood-related pathologies can be observed when these processes are unregulated, such as massive bleeding in activatory signaling inhibition or thrombotic events for negative signaling inhibition. The study of each protein and metabolite in isolation does not help to understand the role of the protein or how it can be contrasted; however, understanding the balance between active and negative signaling could help develop effective therapies to prevent thrombotic events and bleeding disorders.
Exploring Lignin Biosynthesis Genes in Rice: Evolution, Function, and Expression
Authors: Shad Munsif Ali , Li Xukai , Rao Muhammad Junaid , Luo Zixuan , Li Xianlong , Ali Aamir , Wang Lingqiang
Published: September 2024

Lignin is nature’s second most abundant vascular plant biopolymer, playing significant roles in mechanical support, water transport, and stress responses. This study identified 90 lignin biosynthesis genes in rice based on phylogeny and motif constitution, and they belong to PAL, C4H, 4CL, HCT, C3H, CCoAOMT, CCR, F5H, COMT, and CAD families. Duplication events contributed largely to the expansion of these gene families, such as PAL, CCoAOMT, CCR, and CAD families, mainly attributed to tandem and segmental duplication. Microarray data of 33 tissue samples covering the entire life cycle of rice suggested fairly high PAL, HCT, C3H, CCoAOMT, CCR, COMT, and CAD gene expressions and rather variable C4H, 4CL, and F5H expressions. Some members of lignin-related genes (OsCCRL11, OsHCT1/2/5, OsCCoAOMT1/3/5, OsCOMT, OsC3H, OsCAD2, and OsPAL1/6) were expressed in all tissues examined. The expression patterns of lignin-related genes can be divided into two major groups with eight subgroups, each showing a distinct co-expression in tissues representing typically primary and secondary cell wall constitutions. Some lignin-related genes were strongly co-expressed in tissues typical of secondary cell walls. Combined HPLC analysis showed increased lignin monomer (H, G, and S) contents from young to old growth stages in five genotypes. Based on 90 genes’ microarray data, 27 genes were selected for qRT-PCR gene expression analysis. Four genes (OsPAL9, OsCAD8C, OsCCR8, and OsCOMTL4) were significantly negatively correlated with lignin monomers. Furthermore, eleven genes were co-expressed in certain genotypes during secondary growth stages. Among them, six genes (OsC3H, OsCAD2, OsCCR2, OsCOMT, OsPAL2, and OsPAL8) were overlapped with microarray gene expressions, highlighting their importance in lignin biosynthesis.
Wnt/β-Catenin Signaling Regulates Yap/Taz Activity during Embryonic Development in Zebrafish
Authors: Astone Matteo , Tesoriero Chiara , Schiavone Marco , Facchinello Nicola , Tiso Natascia , Argenton Francesco , Vettori Andrea
Published: September 2024

Hippo-YAP/TAZ and Wnt/β-catenin signaling pathways, by controlling proliferation, migration, cell fate, stemness, and apoptosis, are crucial regulators of development and tissue homeostasis. We employed zebrafish embryos as a model system to elucidate in living reporter organisms the crosstalk between the two signaling pathways. Co-expression analysis between the Wnt/β-catenin Tg(7xTCF-Xla.Siam:GFP)ia4 and the Hippo-Yap/Taz Tg(Hsa.CTGF:nlsmCherry)ia49 zebrafish reporter lines revealed shared spatiotemporal expression profiles. These patterns were particularly evident in key developmental regions such as the midbrain–hindbrain boundary (MHB), epidermis, muscles, neural tube, notochord, floorplate, and otic vesicle. To investigate the relationship between the Wnt/β-catenin pathway and Hippo-Yap/Taz signaling in vivo, we conducted a series of experiments employing both pharmacological and genetic strategies. Modulation of the Wnt/β-catenin pathway with IWR-1, XAV939, or BIO resulted in a significant regulation of the Yap/Taz reporter signal, highlighting a clear correlation between β-catenin and Yap/Taz activities. Furthermore, genetic perturbation of the Wnt/β-catenin pathway, by APC inhibition or DKK1 upregulation, elicited evident and robust alteration of Yap/Taz activity. These findings revealed the intricate regulatory mechanisms underlying the crosstalk between the Wnt/β-catenin and Hippo-Yap/Taz signaling, shedding light on their roles in orchestrating developmental processes in vivo.
Omics Studies of Specialized Cells and Stem Cells under Microgravity Conditions
Authors: Abdelfattah Fatima , Schulz Herbert , Wehland Markus , Corydon Thomas J. , Sahana Jayashree , Kraus Armin , Krüger Marcus , González-Torres Luis Fernando , Cortés-Sánchez José Luis , Wise Petra M. , Mushunuri Ashwini , Hemmersbach Ruth , Liemersdorf Christian , Infanger Manfred , Grimm Daniela
Published: September 2024

The primary objective of omics in space with focus on the human organism is to characterize and quantify biological factors that alter structure, morphology, function, and dynamics of human cells exposed to microgravity. This review discusses exciting data regarding genomics, transcriptomics, epigenomics, metabolomics, and proteomics of human cells and individuals in space, as well as cells cultured under simulated microgravity. The NASA Twins Study significantly heightened interest in applying omics technologies and bioinformatics in space and terrestrial environments. Here, we present the available publications in this field with a focus on specialized cells and stem cells exposed to real and simulated microgravity conditions. We summarize current knowledge of the following topics: (i) omics studies on stem cells, (ii) omics studies on benign specialized different cell types of the human organism, (iii) discussing the advantages of this knowledge for space commercialization and exploration, and (iv) summarizing the emerging opportunities for translational regenerative medicine for space travelers and human patients on Earth.
Correction: Jin et al. Comparative Evaluation of STEAP1 Targeting Chimeric Antigen Receptors with Different Costimulatory Domains and Spacers. Int. J. Mol. Sci. 2024, 25, 586
Authors: Jin Yixin , Dunn Claire , Persiconi Irene , Sike Adam , Skorstad Gjertrud , Beck Carole , Kyte Jon Amund
Published: September 2024

In the original publication [...]
Genetic and Functional Studies of Patients with Thyroid Dyshormonogenesis and Defects in the TSH Receptor (TSHR)
Authors: Yeste Diego , Baz-Redón Noelia , Antolín María , Garcia-Arumí Elena , Mogas Eduard , Campos-Martorell Ariadna , González-Llorens Núria , Aguilar-Riera Cristina , Soler-Colomer Laura , Clemente María , Fernández-Cancio Mónica , Camats-Tarruella Núria
Published: September 2024

Genetic defects in the TSH receptor (TSHR) can cause poor thyroid differentiation (thyroid dysgenesis) and/or thyroid malfunction (thyroid dyshormonogenesis). The phenotype spectrum is wide: from severe congenital hypothyroidism to mild hyperthyrotropinemia. Over 250 TSHR variants have been published, many uncharacterized in vitro. We aimed to genetically characterize patients with thyroid dyshormonogenesis with TSHR defects and to study in vitro the effect of the genetic variants to establish the genotype–phenotype relationship. Pediatric patients with thyroid dyshormonogenesis (160 patients, Catalan CH neonatal screening program, confirmation TSH range: 18.4–100 mIU/L), were analyzed by a high-throughput gene panel. In vitro studies measuring the TSH-dependent cAMP–response–element activation were performed. Five patients with mild or severe thyroid dyshormonogenesis presented six TSHR variants, two unpublished. Each variant showed a different in vitro functional profile that was totally or partially deleterious. Depending on the genotype, some of the variants showed partial deficiency in both genotypes, whereas others presented a different effect. In conclusion, the percentage of patients with thyroid dyshormonogenesis and candidate variants in TSHR is 3.13%. Our in vitro studies contributed to the confirmation of the pathogenicity of the variants and highlighted the importance of studying the effect of the patient’s genotype for a correct diagnostic confirmation.
The Neuroprotective Effects of Peripheral Nerve Microcurrent Stimulation Therapy in a Rat Model of Middle Cerebral Artery Occlusion
Authors: Lee Yoon-Jin , Kwon Eun Sang , Moon Yong Suk , Jo Jeong-Rang , Kwon Dong Rak
Published: September 2024

This study investigated the neuroprotective effects of peripheral nerve microcurrent stimulation therapy in a rat model of middle cerebral artery occlusion (MCAO). Twenty 8-week-old male Sprague Dawley rats weighing 300–330 g were categorised into group A, serving as the healthy control; group B, including rats subjected to MCAO; group C, including rats receiving microcurrent therapy immediately after MCAO, which was continued for one week; and group D, including rats receiving microcurrent therapy one week before and one week after MCAO. A gross morphological analysis, behavioural motion analysis, histological examination, immunohistochemistry, and Western blotting were conducted. Microcurrent therapy significantly reduced ischaemic damage and pyramidal cells of the hippocampus CA1 region. Haematoxylin and eosin staining revealed infarction areas/viable pyramidal cell numbers of 0%/94.33, 28.53%/40.05, 17.32%/80.13, and 5.38%/91.34 in groups A, B, C, and D, respectively (p < 0.001). A behavioural analysis revealed that the total distances moved were 1945.24 cm, 767.85 cm, 1781.77 cm, and 2122.22 cm in groups A, B, C, and D, respectively (p < 0.05), and the mean speeds were 6.48 cm/s, 2.50 cm/s, 5.43 cm/s, and 6.82 cm/s, respectively (p < 0.05). Inflammatory markers (cluster of differentiation 68, interleukin-6, and tumour necrosis factor-α) significantly decreased in the treated groups (p < 0.001). Western blotting revealed reduced proinflammatory, oxidative stress, and apoptosis-related protein levels, along with increased angiogenic factors and mitogen-activated protein kinase (MAPK) pathway modulation in the treated groups. Peripheral nerve microcurrent stimulation therapy effectively mitigates ischaemic damage, promotes recovery, reduces inflammation, and modulates protein expression, emphasising its potential as a therapeutic strategy for ischaemic stroke.
L-Glutamate Regulates Npy via the mGluR4-Ca2+-ERK1/2 Signaling Pathway in Mandarin Fish (Siniperca chuatsi)
Authors: Duan Jiahui , Wang Qiuling , He Shan , Liang Xu-Fang , Ding Liyun
Published: September 2024

Metabotropic glutamate receptor 4 (mGluR4) is widely regarded as an umami receptor activated by L-glutamate to exert essential functions. Numerous studies have shown that umami receptors participate in food intake regulation. However, little is known about mGluR4’s role in mediating food ingestion and its possible molecular mechanism. Mandarin fish, a typical carnivorous fish, is sensitive to umami substances and is a promising vertebrate model organism for studying the umami receptor. In this study, we identified the mGluR4 gene and conducted evolutionary analyses from diverse fish species with different feeding habits. mGluR4 of mandarin fish was cloned and functionally expressed to investigate the effects of L-glutamate on mGluR4. We further explored whether the signal pathway mGluR4-Ca2+-ERK1/2 participates in the process in mandarin fish brain cells. The results suggest that L-glutamate could regulate Neuropeptide Y (Npy) via the mGluR4-Ca2+-ERK1/2 signaling pathway in mandarin fish. Our findings unveil the role of mGluR4 in feeding decisions and its possible molecular mechanisms in carnivorous fishes.
The Role of Microbial Metabolites in the Progression of Neurodegenerative Diseases—Therapeutic Approaches: A Comprehensive Review
Authors: Missiego-Beltrán Jorge , Beltrán-Velasco Ana Isabel
Published: September 2024

The objective of this review is to provide a comprehensive examination of the role of microbial metabolites in the progression of neurodegenerative diseases, as well as to investigate potential therapeutic interventions targeting the microbiota. A comprehensive literature search was conducted across the following databases: PubMed, Scopus, Web of Science, ScienceDirect, and Wiley. Key terms related to the gut microbiota, microbial metabolites, neurodegenerative diseases, and specific metabolic products were used. The review included both preclinical and clinical research articles published between 2000 and 2024. Short-chain fatty acids have been demonstrated to play a crucial role in modulating neuroinflammation, preserving the integrity of the blood–brain barrier, and influencing neuronal plasticity and protection. Furthermore, amino acids and their derivatives have been demonstrated to exert a significant influence on CNS function. These microbial metabolites impact CNS health by regulating intestinal permeability, modulating immune responses, and directly influencing neuroinflammation and oxidative stress, which are integral to neurodegenerative diseases. Therapeutic strategies, including prebiotics, probiotics, dietary modifications, and fecal microbiota transplantation have confirmed the potential to restore microbial balance and enhance the production of neuroprotective metabolites. Furthermore, novel drug developments based on microbial metabolites present promising therapeutic avenues. The gut microbiota and its metabolites represent a promising field of research with the potential to advance our understanding of and develop treatments for neurodegenerative diseases.
Emerging Targets in Non-Small Cell Lung Cancer
Authors: Liu Louisa , Soler Joshua , Reckamp Karen L. , Sankar Kamya
Published: September 2024

Lung cancer is responsible for a high burden of disease globally. Over the last two decades, the discovery of targetable oncogenic genomic alterations has revolutionized the treatment landscape for early-stage and advanced non-small cell lung cancer (NSCLC). New molecular drivers continue to emerge as promising therapeutic targets, including KRAS non-G12C, RAF/MEK, HER3, Nectin-4, folate receptor alpha, ITGB6, and PRMT5. In this review, we summarize the emerging molecular targets with a potential clinical impact in advanced NSCLC, elaborating on their clinical characteristics and specific mechanisms and molecular pathways for which targeted treatments are currently available. Additionally, we present an aggregate of ongoing clinical trials investigating the available treatment options targeting such alterations, in addition to their current recruitment status and preliminary efficacy data. These advancements may guide further research endeavors and inform future treatment strategies to improve the management of and transform outcomes for patients with advanced NSCLC.
Sirtuin 1 Inhibits Fatty Acid Synthesis through Forkhead Box Protein O1-Mediated Adipose Triglyceride Lipase Expression in Goat Mammary Epithelial Cells
Authors: He Qiuya , Yao Weiwei , Lv Li , Zhang Xuelin , Wu Jiao , Luo Jun
Published: September 2024

Sirtuin 1 (SIRT1) is a key upstream regulator of lipid metabolism; however, the molecular mechanisms by which SIRT1 regulates milk fat synthesis in dairy goats remain unclear. This study aimed to investigate the regulatory roles of SIRT1 in modulating lipid metabolism in goat mammary epithelial cells (GMECs) and its impact on the adipose triglyceride lipase (ATGL) promoter activity using RNA interference (RNAi) and gene overexpression techniques. The results showed that SIRT1 is significantly upregulated during lactation compared to the dry period. Additionally, SIRT1 knockdown notably increased the expressions of genes related to fatty acid synthesis (SREBP1, SCD1, FASN, ELOVL6), triacylglycerol (TAG) production (DGAT2, AGPAT6), and lipid droplet formation (PLIN2). Consistent with the transcriptional changes, SIRT1 knockdown significantly increased the intracellular contents of TAG and cholesterol and the lipid droplet abundance in the GMECs, while SIRT1 overexpression had the opposite effects. Furthermore, the co-overexpression of SIRT1 and Forkhead box protein O1 (FOXO1) led to a more pronounced increase in ATGL promoter activity, and the ability of SIRT1 to enhance ATGL promoter activity was nearly abolished when the FOXO1 binding sites (FKH1 and FKH2) were mutated, indicating that SIRT1 enhances the transcriptional activity of ATGL via the FKH element in the ATGL promoter. Collectively, our data reveal that SIRT1 enhances the transcriptional activity of ATGL through the FOXO1 binding sites located in the ATGL promoter, thereby regulating lipid metabolism. These findings provide novel insights into the role of SIRT1 in fatty acid metabolism in dairy goats.
Comparative Stem Transcriptome Analysis Reveals Pathways Associated with Drought Tolerance in Maritime Pine Grafts
Authors: Manjarrez Lorenzo Federico , de María Nuria , Vélez María Dolores , Cabezas José Antonio , Mancha José Antonio , Ramos Paula , Pizarro Alberto , Blanco-Urdillo Endika , López-Hinojosa Miriam , Cobo-Simón Irene , Guevara María Ángeles , Díaz-Sala María Carmen , Cervera María Teresa
Published: September 2024

The maritime pine (Pinus pinaster Ait.) is a highly valuable Mediterranean conifer. However, recurrent drought events threaten its propagation and conservation. P. pinaster populations exhibit remarkable differences in drought tolerance. To explore these differences, we analyzed stem transcriptional profiles of grafts combining genotypes with contrasting drought responses under well-watered and water-stress regimes. Our analysis underscored that P. pinaster drought tolerance is mainly associated with constitutively expressed genes, which vary based on genotype provenance. However, we identified key genes encoding proteins involved in water stress response, abscisic acid signaling, and growth control including a PHD chromatin regulator, a histone deubiquitinase, the ABI5-binding protein 3, and transcription factors from Myb-related, DOF NAC and LHY families. Additionally, we identified that drought-tolerant rootstock could enhance the drought tolerance of sensitive scions by regulating the accumulation of transcripts involved in carbon mobilization, osmolyte biosynthesis, flavonoid and terpenoid metabolism, and reactive oxygen species scavenging. These included genes encoding galactinol synthase, CBL-interacting serine/threonine protein kinase 5, BEL1-like homeodomain protein, dihydroflavonol 4-reductase, and 1-deoxy-D-xylulose-5-phosphate. Our results revealed several hub genes that could help us to understand the molecular and physiological response to drought of conifers. Based on all the above, grafting with selected drought-tolerant rootstocks is a promising method for propagating elite recalcitrant conifer species, such as P. pinaster.