Biological Processes Research Articles

Unravelling the role of key genes involved coffee leaf rust resistance

The biotrophic fungus Hemileia vastatrix is the pathogen responsible for coffee leaf rust, a devastating disease in several coffee-producing countries. Despite the importance of studying the interaction between Coffea and H. vastatrix, a more comprehensive understanding of the mechanisms involved in this pathosystem is necessary. The role of eight candidate genes was analyzed aiming at identifying and validating new important coffee resistance genes and understanding their interaction with H. vastatrix. These genes were identified in the most important sources of coffee resistance, the Híbrido de Timor CIFC 832/2 and CIFC 832/1. Previous works found six resistance genes and, in our research, other two new genes were identified in BAC clones and validated by RT-qPCR during compatible and incompatible interactions between Coffea and H. vastatrix. An interactome approach was performed using Coffea-H. vastatrix and Coffea-Coffea proteins to better understand the biological process and the interaction of the host-pathogen. Two networks of interactions from the compiled data were built focused on candidate genes associated with pre-haustorial resistance (12 and 24h.a.i) in coffee plants against the pathogen. The results showed, for the first time, differentially expressed proteins (DEPs) positively regulated in the incompatible interaction Coffea-H. vastatrix. These coffee proteins interact with each other and with secreted and/or transmembrane pathogen proteins. The obtained results also show that DEPs found are involved in important plant defense pathways such as pathways associated with the response to wounds, signaling, regulation of the innate immune response and the transmembrane receptor protein serine/threonine kinase pathway. The present work shows the involvement of genes in both pathogen recognition and signaling cascades, which act in pre-haustorial defense mechanisms of HdT coffee. Therefore, the candidate genes analyzed, together with the biological processes elucidated, have the potential to contribute to the development of new control strategies against the fungus H. vastatrix within coffee breeding programs aiming to develop cultivars with durable resistance.

New promising routes in peptic ulcers: Toll-like receptors and semaphorins.

Peptic ulcers (PU) are one of the commonest yet problematic diseases found to be existing in the majority of the population. Today, drugs from a wide range of therapeutic classes are available for the management of the disease. Still, the complications of the condition are difficult to tackle and the side effect profile is quite a concern. The literature indicates that Toll-like receptors (TLRs) and Semaphorins (SEMAs) have been under study for their various pharmacological actions over the past few decades. Both these signalling pathways are found to regulate immunological and inflammatory responses. Moreover, receptors and signalling molecules from the family of TLRs and SEMAs are found to have bacterial recognition and antibacterial properties which are essential in eradicating Helicobacter pylori (H. pylori), one of the major causative agents of PU. Our understanding of SEMAs, a class of proteins involved in cell signalling, is relatively less developed compared to TLRs, another class of proteins involved in the immune response. SEMAs and TLRs play different roles in biological processes, with SEMAs primarily involved in guiding cell migration and axon guidance during development, while TLRs are responsible for recognizing pathogens and initiating an immune response. Here, in this review, we will discuss in detail the signalling cascade of TLRs and SEMAs and thereby understand its association with PU for future therapeutic targeting. The review also aims at providing an overview of the study that has been into exploring the role of these signalling pathways in the management of PU.

Role of TBK1 Inhibition in Targeted Therapy of Cancer.

TANK-binding kinase 1 (TBK1) is a serine/threonine protein that plays a crucial role in various biological processes like immunity, autophagy, cell survival, and proliferation. The level and kinase activity of the TBK1 protein is regulated through post-translational modifications (PTMs). TBK1 mainly mediates the activation of IRF3/7 and NF-κB signaling pathways while also participating in the regulation of cellular activities such as autophagy, mitochondrial metabolism, and cell proliferation. TBK1 regulates immune, metabolic, inflammatory, and tumor occurrence and development within the body through these cellular activities. TBK1 kinase has emerged as a promising therapeutic target for tumor immunity. However, its molecular mechanism of action remains largely unknown. The identification of selective TBK1 small molecule inhibitors can serve as valuable tools for investigating the biological function of TBK1 protein and also as potential drug candidates for tumor immunotherapy. The current research progress indicates that some TBK1 inhibitors (compounds 15,16 and 21) exhibit certain antitumor effects in vitro culture systems. Here, we summarize the mechanism of action of TBK1 in tumors in recent years and the progress of small molecule inhibitors of TBK1.

Insights into the mechanism of phosphorus enrichment and stripping in side-stream enhanced biological phosphorus removal and enrichment process

In-depth research on the side-stream enhanced biological phosphorus removal (S2EBPR) process holds promise for addressing the challenge of low phosphorus (P) enrichment concentration. This study developed a side-stream enhanced biological phosphorus enrichment/removal (S2EBPE/R) reactor by improving a S2EBPR process. The P removal, enrichment, and mass balance were used to evaluate polyphosphate-accumulating organisms (PAOs) activity. Microbial community structures were investigated to reveal the mechanism of P enrichment and stripping. The results showed that the P removal efficiency reached up to 93% in the S2EBPE/R process. Approximately 13% of P-rich liquid could be stably obtained from the side-stream system, with a concentration of 108.85 ± 4.53mgP/L. Apart from responses to EBPR activity (P/HAc) of up to 0.41 P-mol/C-mol, enrichment of typical PAOs of up to 12.0% enhanced the P enrichment and removal performance. The abundance of functional microorganisms (PAOs and glycogen accumulating organisms (GAOs)) related to P was as high as 13.4%. These findings highlighted the outstanding advantages of the S2EBPE/R process in P enrichment and removal, thereby making significant contributions to P recovery from wastewater.

Mesenchymal Stem Cells-Conditioned Medium; An Effective Cell-Free Therapeutic Option for in vitro Maturation of Oocytes.

Infertility is a major reproductive health issue worldwide. One of the main problems in infertile women is the failure to generate or release a mature egg. Therefore, the development of new technologies for in vitro generation or induction of mature oocytes can improve various ART procedures. Recently, stem cell-based therapy has opened a new window for several pathological complications. Mesenchymal stem cells (MSCs) are multipotent stem cells with the capacity to self-renew and differentiate into the mesodermal lineage. MSCs contain various bioactive molecules which are involved in the regulation of key biological processes. They can secret multiple paracrine factors, such as VEGF, IGF, HGF, EGF, and FGF to stimulate egg maturation. Although MSCs represent a promising source for cell therapy, the potential risk of tumor development reduces their clinical applications. Recent studies have suggested that the supernatant or conditioned medium of MSCs also contains similar components and regulates the oocyte behavior. The MSC-conditioned medium can eliminate the safety concerns associated with MSC transplantation and avoid rejection problems. Although MSC and MSC-CM could improve oocyte quality, ovarian function, and fertility, these improvements have not yet been demonstrated in clinical trials in humans. Hereby, we summarized recent research findings of MSCs-derived conditioned medium in in vitro development of immature oocytes.

Impact of Humic Substances on Alleviation of Soil Salinity and the Enhancement of Plant Productivity: a review

Humic substances (HS) are a major component of organic matter in soil, and they have long been recognized for their ability to promote plant growth in a sustainable manner. Recently, there has been a lot of effort put into using multiple approaches to study the connection between the chemical structure of HS compounds and their effect on plant biological processes. Positive physiological responses at the local and systemic levels have been linked to the presence of specific functional groups in HS. Hormone-like signaling pathways are responsible for eliciting these reactions. This review was written with one goal in mind: to help readers gain a firm grasp on the research surrounding the application of HSs. The spatial arrangement of hydrophilic and hydrophobic regions, as well as the dosage, source, molecular size, degree of hydrophobicity, and aromaticity, all contribute significantly to HS's biological efficacy. Therefore, our hypothesis explains the beneficial effect of HS in salt-affected rhizospheres, likely attributed to both direct and indirect influences on plant metabolism, soil microorganism metabolism, soil nutrient uptake dynamics, and soil physical conditions. Keywords: Humic substance, germination, salinity, plant growth

Laboratory sprayer for dsRNA application: design and bioassay validation

The shortage of commercially available and reliable laboratory spraying equipment for testing different preparations can be a major obstacle to achieve field-comparable results in the laboratory conditions.RNA interference is natural biological process which, when used for plant protection, can be designed method combining sustainability and minimal environmental side effects. Spraying of dsRNA is a field-relevant method that should ensure consistency and repeatability if conducted in laboratory.We built a portable spray device for laboratory use and tested its suitability for dsRNA application. For that, we carried out bioassay on three plant species with different leaf surface textures. DsRNA were detected in all samples 3 days post-treatment indicating its suitability for dsRNA delivery.We built a portable spray device for laboratory use and tested its suitability for dsRNA application. For that, we carried out:• bioassay on three plant species with different leaf surface textures.DsRNA were detected in all samples 3 days post-treatment indicating its suitability for dsRNA delivery.

Computational protein design - where it goes?

Proteins have been playing a critical role in the regulation of diverse biological processes related to human life. With the increasing demand, functional proteins are sparse in this immense sequence space. Therefore, protein design has become an important task in various fields, including medicine, food, energy, materials, etc. Directed evolution has recently led to significant achievements. Molecular modification of proteins through directed evolution technology has significantly advanced the fields of enzyme engineering, metabolic engineering, medicine, and beyond. However, it is impossible to identify desirable sequences from a large number of synthetic sequences alone. As a result, computational methods, including data-driven machine learning and physics-based molecular modeling, have been introduced to protein engineering to produce more functional proteins. This review focuses on recent advances in computational protein design, highlighting the applicability of different approaches as well as their limitations.

Assessment of molecularly imprinted polymers for selective removal of diclofenac from wastewater by laboratory and pilot-scale adsorption tests

This study investigated the potential of Molecularly Imprinted Polymers (MIPs) to integrate schemes for wastewater reuse and to serve as effective adsorbent for the removal of a target emerging contaminant (i.e., diclofenac – DCF), after or within pilot scale anaerobic biological treatments. Batch tests were performed to evaluate the effect on DCF removal during anaerobic biological processes by enriching activated sludge of an Upflow Anaerobic Sludge Blanket (UASB) reactor (TSS =19.6 g/L), and an Anaerobic Membrane Bioreactor (AnMBR) (TSS = 120 mg/L) reactors with MIPs (3 mg/L). Therefore, tertiary treatments were investigated by columns adsorption tests that were performed first at lab scale using DCF (15 mg/L) solution in deionized water, and then in-site by treating the anaerobic permeate effluent from the AnMBR at pilot scale level (DCF 500 μg/L). Clogging or blockage of the column bed was not observed during these field tests, where the saturation process of MIPs was slower compared to laboratory tests that used deionized water. In addition, the empirical Thomas Model, Yoon-Nelson Model, Dose-Response Model and Adam Bohart Model showed very good fittings with the experimental data obtained during experiments performed with both synthetic water and anaerobic effluents showing their suitability for the description of breakthrough curves. Finally, it was observed that after regeneration the MIPs can be efficiently reused since adsorption capacity is sufficiently preserved.

Mutual annotation-based prediction of protein domain functions with Domain2GO.

Identifying unknown functional properties of proteins is essential for understanding their roles in both health and disease states. The domain composition of a protein can reveal critical information in this context, as domains are structural and functional units that dictate how the protein should act at the molecular level. The expensive and time-consuming nature of wet-lab experimental approaches prompted researchers to develop computational strategies for predicting the functions of proteins. In this study, we proposed a new method called Domain2GO that infers associations between protein domains and function-defining gene ontology (GO) terms, thus redefining the problem as domain function prediction. Domain2GO uses documented protein-level GO annotations together with proteins' domain annotations. Co-annotation patterns of domains and GO terms in the same proteins are examined using statistical resampling to obtain reliable associations. As a use-case study, we evaluated the biological relevance of examples selected from the Domain2GO-generated domain-GO term mappings via literature review. Then, we applied Domain2GO to predict unknown protein functions by propagating domain-associated GO terms to proteins annotated with these domains. For function prediction performance evaluation and comparison against other methods, we employed Critical Assessment of Function Annotation 3 (CAFA3) challenge datasets. The results demonstrated the high potential of Domain2GO, particularly for predicting molecular function and biological process terms, along with advantages such as producing interpretable results and having an exceptionally low computational cost. The approach presented here can be extended to other ontologies and biological entities to investigate unknown relationships in complex and large-scale biological data. The source code, datasets, results, and user instructions for Domain2GO are available at https://github.com/HUBioDataLab/Domain2GO. Additionally, we offer a user-friendly online tool at https://huggingface.co/spaces/HUBioDataLab/Domain2GO, which simplifies the prediction of functions of previously unannotated proteins solely using amino acid sequences.

Phytol and α-Bisabolol Synergy Induces Autophagy and Apoptosis in A549 Cells and Additional Molecular Insights through Comprehensive Proteome Analysis via Nano LC-MS/MS.

Non-Small Cell Lung Cancer (NSCLC) is a malignancy with a significant prevalence and aggressive nature, posing a considerable challenge in terms of therapeutic interventions. Autophagy and apoptosis, two intricate cellular processes, are integral to NSCLC pathophysiology, each affecting the other through shared signaling pathways. Phytol (Phy) and α -bisabolol (Bis) have shown promise as potential anticancer agents individually, but their combined effects in NSCLC have not been extensively investigated. The present study was to examine the synergistic impact of Phy and Bis on NSCLC cells, particularly in the context of autophagy modulation, and to elucidate the resulting differential protein expression using LCMS/ MS analysis. The A549 cell lines were subjected to the patented effective concentration of Phy and Bis, and subsequently, the viability of the cells was evaluated utilizing the MTT assay. The present study utilized real-time PCR analysis to assess the expression levels of crucial apoptotic genes, specifically Bcl-2, Bax, and Caspase-9, as well as autophagy-related genes, including Beclin-1, SQSTM1, Ulk1, and LC3B. The confirmation of autophagy marker expression (Beclin-1, LC3B) and the autophagy-regulating protein SQSTM1 was achieved through the utilization of Western blot analysis. Differentially expressed proteins were found using LC-MS/MS analysis. The combination of Phy and Bis demonstrated significant inhibition of NSCLC cell growth, indicating their synergistic effect. Real-time PCR analysis revealed a shift towards apoptosis, with downregulation of Bcl-2 and upregulation of Bax and Caspase-9, suggesting a shift towards apoptosis. Genes associated with autophagy regulation, including Beclin-1, SQSTM1 (p62), Ulk1, and LC3B, showed significant upregulation, indicating potential induction of autophagy. Western blot analysis confirmed increased expression of autophagy markers, such as Beclin-1 and LC3B, while the autophagy-regulating protein SQSTM1 exhibited a significant decrease. LC-MS/MS analysis revealed differential expression of 861 proteins, reflecting the modulation of cellular processes. Protein-protein interaction network analysis highlighted key proteins involved in apoptotic and autophagic pathways, including STOML2, YWHAB, POX2, B2M, CDA, CAPN2, TXN, ECHS1, PEBP1, PFN1, CDC42, TUBB1, HSPB1, PXN, FGF2, and BAG3, emphasizing their crucial roles. Additionally, PANTHER pathway analysis uncovered enriched pathways associated with the differentially expressed proteins, revealing their involvement in a diverse range of biological processes, encompassing cell signaling, metabolism, and cellular stress responses. The combined treatment of Phy and Bis exerts a synergistic inhibitory effect on NSCLC cell growth, mediated through the interplay of apoptosis and autophagy. The differential protein expression observed, along with the identified proteins and enriched pathways, provides valuable insights into the underlying molecular mechanisms. These findings offer a foundation for further exploration of the therapeutic potential of Phy and Bis in the management of NSCLC.

Synthesis and In Silico Studies of Quinazolinones as PARP-1 Inhibitors.

Cancer is a leading threat to humankind, accounting for nearly one million deaths in 2018, and the expected number of cancer-related deaths in 2040 is more than 16 million. The most common causes of cancer deaths are lung, colorectal, stomach, liver and breast cancer, while the highest number of new cancer cases belong to lung, breast, colorectal, prostate, stomach and liver cancer. PARP-1 is an enzyme that plays an important role in DNA repair, cell propagation/survival and death due to its influence on numerous biological processes. Quinazolinones represent an important scaffold in medicinal chemistry and have a broad spectrum of biological activities. In this study, we have synthesized quinazolinones by reaction of 2-aminobenzamide and substituted aldehydes. Molecular docking studies of synthesized compounds were performed for their PARP-1 binding affinities using Schrodinger 2016 software. In silico ADME studies were also performed for the synthesized compounds using the QikProp tool of Schrodinger software. Results of molecular docking studies indicated that synthesized quinazolinones had a good affinity towards active site of PARP-1 and compound 4 had the best docking score (-10.343). Results of ADME studies indicated the drug-like properties of synthesized compounds, which make them suitable drug candidates. All the synthesized compounds have a better docking score than niraparib (-9.05). Further, the synthesized compounds have a favorable ADME profile. Therefore, they may serve as important leads in discovering PARP-1 inhibitors.

Investigation of the Molecular Mechanism Underlying the Therapeutic Effect of Perilla frutescens L. Essential Oil on Acute Lung Injury Using Gas Chromatography Mass Spectrometry and Network Pharmacology.

The present study aimed to investigate the molecular mechanism through which Perilla essential oil treats acute lung injury (ALI) through network pharmacology, molecular docking, and in vitro assays. Relevant ALI targets of the active ingredients of Perilla essential oil were predicted using the SwissTargetPrediction database and meta TarFisher database. These ALI targets were then screened using GeneCards and DisGeNET, and differentially expressed ALI target genes were identified using the Gene Expression Omnibus (GEO) database. Next, key targets were enriched using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Protein-protein interaction network analysis was performed to obtain targets with the highest degree values for molecular docking with Perilla essential oil active ingredients. For in vitro experiments, lipopolysaccharide (LPS) was used to induce an ALI inflammation model using RAW264.7 cells. The model cells were then treated with Perilla essential oil to detect the protein expression levels of vascular endothelial factor (NO), tumor necrosis factor (TNF-α), and p65 nuclear transcription factor in them. Sixty-eight key targets of Perilla oil were identified for the treatment of ALI. These targets were found to be involved in biological processes related to peptides, response to lipopolysaccharides, the positive regulation of cytokine production, etc., using GO. The signaling pathways found to be associated with the targets included the AGE-RAGE signaling pathway in diabetic complications, the NF-kappa B signaling pathway, and small cell lung cancer and other inflammatory signaling pathways. The five key targets that showed good binding activity with Perilla oil active ingredients included TNF, RELA, PARP1, PTGS2, and IRAK4. In vitro assays showed that Perilla essential oil could significantly reduce NO and TNF-α levels and inhibit the phosphorylation of nuclear transcription factor P65, thus inhibiting the activation of NF-κB signaling pathway. Conclusion Perilla essential oil can play a role in the treatment of ALI by inhibiting the activation of the NF-κB signaling pathway and preventing an excessive inflammatory response. This study thus provides a reference for the in-depth study of the mechanisms through which Perilla essential oil treats ALI.

Evaluation of the mechanism of Sinomenii Caulis in treating ulcerative colitis based on network pharmacology and molecular docking.

Studies have indicated that Sinomenii Caulis (SC) has several physiological activities, such as anti-inflammatory, anti-cancer, immunosuppression, and so on. SC is currently widely used in the treatment of rheumatoid arthritis, skin disease, and other diseases. However, the mechanism of SC in the treatment of ulcerative colitis (UC) remains unclear. To predict the active components of SC and determine the mechanism of SC on UC. Active components and targets of SC were screened and obtained by TCMSP, PharmMapper, and CTD databases. The target genes of UC were searched from GEO (GSE9452), and DisGeNET databases. Based on the String database, Cytoscape 3.7.2 software, and David 6.7 database, we analyzed the relationship between SC active components and UC potential targets or pathways. Finally, identification of SC targets in anti-UC by molecular docking. GROMACS software was used to perform molecular dynamics simulations of protein and compound complexes and to perform free energy calculations. Six main active components, 61 potential anti-UC gene targets, and the top 5 targets with degree value are IL6, TNF, IL1β, CASP3, and SRC. According to GO enrichment analysis, the vascular endothelial growth factor receptor and vascular endothelial growth factor stimulus may be relevant biological processes implicated in the treatment of UC by SC. The KEGG pathway analysis result was mainly associated with the IL-17, AGE-RAGE, and TNF signaling pathways. Based on molecular docking results, beta-sitosterol, 16-epi-Isositsirikine, Sinomenine, and Stepholidine are strongly bound to the main targets. Molecular dynamics simulation results showed that IL1B/beta-sitosterol and TNF/16-epi-Isositsirikine binding was more stable. SC can play a therapeutic role in UC through multiple components, targets, and pathways. The specific mechanism of action needs to be further explored.

Adding mechanobiological cell features to finite element analysis of an immediately loaded dental implant.

Finite element analysis (FEA) has been used to analyze the behavior of dental materials, mainly in implantology. However, FEA is a mechanical analysis and few studies have tried to simulate the biological characteristics of the healing process of loaded implants. This study used the rule of mixtures to simulate the biological healing process of immediate implants in an alveolus socket and bone-implant junction interface through FEA. Three-dimensional geometric models of the structures were obtained, and material properties were derived from the literature. The rule of mixtures was used to simulate the healing periods-immediate and early loading, in which the concentration of each cell type, based on in vivo studies, influenced the final elastic moduli. A 100 N occlusal load was simulated in axial and oblique directions. The models were evaluated for maximum and minimum principal strains, and the bone overload was assessed through Frost's mechanostat. There was a higher strain concentration in the healing regions and cortical bone tissue near the cervical portion. The bone overload was higher in the immediate load condition. The method used in this study may help to simulate the biological healing process and could be useful to relate FEA results to clinical practice.

Terahertz fingerprint reveals the effect of alcohols on sodium ions hydration shell.

Ion hydration plays a crucial role in numerous fundamental processes. Various spectroscopic methods are employed to investigate the slowing down of hydration bond dynamics in the proximity of both anions and cations. To date, most of these studies have primarily focused on the properties of binary systems. However, in comparison to ion-water binary systems, ternary systems that involve ions, water, and organic matter are more prevalent in nature and provide more realistic insights into biological processes. This study focuses on ion hydration in water and alcohol mixture using terahertz spectroscopy and x-ray diffraction (XRD). The results reveal a distinct behavior depending on the type of alcohol used. Specifically, the presence of both methanol and ethanol results in the disappearance of absorption peaks associated with NaCl hydrate at low temperatures. In contrast, tert-butanol does not exhibit such an effect, and isopropanol demonstrates a more complex response. By combining these terahertz spectroscopic findings with low-temperature XRD data, we gain insights into the formation, or lack thereof, of NaCl · 2H2O hydrate crystals. Crucially, our observations suggest a dominant correlation between the polarity of the alcohol molecules and its impact on the Na+ hydration. Strongly polar alcohols preferentially solvating the Na+ ion lead to the failure of hydrate formation, while weakly polar alcohols do not have this effect.

A Negative Regulatory Feedback Loop within the JAK-STAT Pathway Mediated by the Protein Tyrosine Phosphatase DUSP14 in Shrimp.

The JAK-STAT pathway is a central communication node for various biological processes. Its activation is characterized by phosphorylation and nuclear translocation of the transcription factor STAT. The regulatory balance of JAK-STAT signaling is important for maintenance of immune homeostasis. Protein tyrosine phosphatases (PTPs) induce dephosphorylation of tyrosine residues in intracellular proteins and generally function as negative regulators in cell signaling. However, the roles of PTPs in JAK-STAT signaling, especially in invertebrates, remain largely unknown. Pacific white shrimp Penaeus vannamei is currently an important model for studying invertebrate immunity. This study identified a novel member of the dual-specificity phosphatase (DUSP) subclass of the PTP superfamily in P. vannamei, named PvDUSP14. By interacting with and dephosphorylating STAT, PvDUSP14 inhibits the excessive activation of the JAK-STAT pathway, and silencing of PvDUSP14 significantly enhances humoral and cellular immunity in shrimp. The promoter of PvDUSP14 contains a STAT-binding motif and can be directly activated by STAT, suggesting that PvDUSP14 is a regulatory target gene of the JAK-STAT pathway and mediates a negative feedback regulatory loop. This feedback loop plays a role in maintaining homeostasis of JAK-STAT signaling and is involved in antibacterial and antiviral immune responses in shrimp. Therefore, the current study revealed a novel inhibitory mechanism of JAK-STAT signaling, which is of significance for studying the regulatory mechanisms of immune homeostasis in invertebrates.

Sensitivity of root production to long‐term aridity under environmental perturbations in Chihuahuan Desert ecosystems

Abstract Root production influences carbon and nutrient cycles and subsidizes soil biodiversity. However, the long‐term dynamics and drivers of belowground production are poorly understood for most ecosystems. In drylands, fire, eutrophication, and precipitation regimes could affect not only root production but also how roots track interannual variability in climate. We manipulated the intra‐annual precipitation regime, soil nitrogen, and fire in four common Chihuahuan Desert ecosystem types (three grasslands and one shrubland) in New Mexico, USA, where the 100‐year record indicates both long‐term drying and increasing interannual variability in aridity. First, we evaluated how root production tracked aridity over 10–17 years using climate sensitivity functions, which quantify long‐term, nonlinear relationships between biological processes and climate. Next, we determined the degree to which perturbations by fire, nitrogen addition or intra‐annual rainfall altered the sensitivity of root production to both mean and interannual variability in aridity. All ecosystems had nonlinear climate sensitivities that predicted declines in production with increases in the interannual variance of aridity. However, root production was the most sensitive to aridity in Chihuahuan Desert shrubland, with reduced production under drier and more variable aridity. Among the perturbations, only fire altered the sensitivity of root production to aridity. Root production was more than twice as sensitive to declines with aridity following prescribed fire than in unburned conditions. Neither the intra‐annual seasonal rainfall regime nor chronic nitrogen fertilization altered the sensitivity of roots to aridity. Synthesis. Our results yield new insight into how dryland plant roots respond to climate change. Our comparison of dryland ecosystems of the northern Chihuahuan Desert predicted that root production in shrublands would be more sensitive to future climates that are drier and more variable than root production in dry grasslands. Field manipulations revealed that fire could amplify the climate sensitivity of dry grassland root production, but in contrast, the climate sensitivity of root production was largely resistant to changes in the seasonal rainfall regime or increased soil fertilization.

Macrocephaly and Finger Changes: A Narrative Review

Macrocephaly, characterized by an abnormally large head circumference, often co-occurs with distinctive finger changes, presenting a diagnostic challenge for clinicians. This review aims to provide a current synthetic overview of the main acquired and genetic etiologies associated with macrocephaly and finger changes. The genetic cause encompasses several categories of diseases, including bone marrow expansion disorders, skeletal dysplasias, ciliopathies, inherited metabolic diseases, RASopathies, and overgrowth syndromes. Furthermore, autoimmune and autoinflammatory diseases are also explored for their potential involvement in macrocephaly and finger changes. The intricate genetic mechanisms involved in the formation of cranial bones and extremities are multifaceted. An excess in growth may stem from disruptions in the intricate interplays among the genetic, epigenetic, and hormonal factors that regulate human growth. Understanding the underlying cellular and molecular mechanisms is important for elucidating the developmental pathways and biological processes that contribute to the observed clinical phenotypes. The review provides a practical approach to delineate causes of macrocephaly and finger changes, facilitate differential diagnosis and guide for the appropriate etiological framework. Early recognition contributes to timely intervention and improved outcomes for affected individuals.

Bta-miR-181d and Bta-miR-196a mediated proliferation, differentiation, and apoptosis in Bovine Myogenic Cells.

Skeletal muscle is an important component of livestock and poultry organisms. The proliferation and differentiation of myoblasts are highly coordinated processes, which rely on the regulation of miRNA. MiRNAs are widely present in organisms and play roles in various biological processes, including cell proliferation, differentiation, and apoptosis. MiR-181d and miR-196a, identified as tumor suppressors, have been found to be involved in cell proliferation, apoptosis, directed differentiation, and cancer cell invasion. However, their role in beef cattle skeletal muscle metabolism remains unclear. In this study, we discovered that overexpression of bta-miR-181d and bta-miR-196a in Qinchuan cattle myoblasts inhibited proliferation and apoptosis while promoting myogenic differentiation through EDU staining, flow cytometry analysis, immunofluorescence staining, and Western blotting. RNA-seq analysis of differential gene expression revealed that after overexpression of bta-miR-181d and bta-miR-196a, the differentially expressed genes were mainly enriched in the PI3K-Akt and MAPK signaling pathways. Furthermore，the phosphorylation levels of key proteins p-AKT in the PI3K signaling pathway and p-MAPK in the MAPK signaling pathway were significantly decreased after overexpression of bta-miR-181d and bta-miR-196a. Overall，this study provides preliminary evidence that bta-miR-181d and bta-miR-196a may regulate proliferation，apoptosis，and differentiation processes in Qinchuan cattle myoblasts by affecting the phosphorylation status of key proteins in PI3K-Akt and MAPK-ERK signaling pathways.