Crucial Event Research Articles

Long-term monitoring of the columnar cactus Cipocereus minensis reveals unforeseeable reproductive phenology

Phenological studies with species of cactus have grown in recent decades but the number of species studied remains very low, considering the high species richness of this group. In addition, temporal patterns of flowering and fruiting are important to understanding the processes that govern these crucial events of plant demography and ecology. Based on a five-year study of the reproductive phenology of C. minensis we asked if there is seasonality of flowering and fruiting. Secondly, we tested which climatic variables trigger C. minensis reproductive events in the Espinhaço region. We found that not all individuals produced flowers and fruits each year and a few individuals contributed with most flowers. Flower and immature fruit production is higher during the dry months, with fruits maturing during the rainy season or just before. In general, phenological events were seasonal, except for mature fruit production in 2010 and flower production in 2011. Some phenological traits such as flower timing, frequency, duration, and timing of immature fruit production had not been reported for the genus Cipocereus and were detected only because of the long-term phenological observations. Phenological heterogeneity in cactus might be a response to annual climatic fluctuations, mainly rainfall.

Resilient coral reef ecosystems: The case study of turbid-mesophotic coral buildups during the Late Oligocene Warming Event (Tertiary Piedmont Basin, NW Italy)

Nowadays, but also in the geological record, coral communities living in marginal conditions (i.e. low light, high turbidity, extreme temperatures, high nutrients and sediment input) are quite common and there is evidence that some of these reefs, often associated with mesophotic environments, may be more resilient to the current global warming trend, thus serving as possible ecological refugia.As an attempt to understand the response and resilience to past warming events of marine calcifying organisms, such as zooxanthellate corals of marginal reefs, herein we reconstruct the palaeoenvironment of an Oligocene mixed siliciclastic‑carbonate system in the Tertiary Piedmont Basin (NW Italy), where a suite of coral assemblages formed small buildups at the edge of a coarse-grained delta system. Geochronological dating by strontium isotope stratigraphy places the coral buildups in the middle Chattian, thus within the Late Oligocene Warming Event (LOWE): a crucial climatic event for coral reefs as characterised by substantial warming coincident with declining atmospheric CO2.The depositional model that we propose is ascribed to a fan-delta system, deposited within a narrow valley cutting through the metamorphic basement, where small and laterally discontinuous coral buildups grow-up in the prodelta setting, thus suggesting a mesophotic environment. In this context, the coral buildups appear to have been intermittently deactivated or smothered by fine-grained terrigenous input during flood phases or shifts in distributary channels until their final suffocation by fluvial sediments input.Within the coral buildups, the four distinguished coral facies (branching Stylophora floatstone, Acropora-Stylophora floatstone/rudstone, Goniopora/Caulastraea pillarstone, and mixed-coral domestone) are characterised in general by sediment-resistant corals and by specific taphonomic features.These coral facies shifted in time and space during the LOWE, highlighting the noteworthy adaptability and resilience of Oligocene corals to a complex interplay of environmental stressors such as turbidity, hydrodynamic energy, sediment and nutrient supply within a mesophotic setting.

Utilidad en la prevención, tratamiento y pronóstico de la medicina de precisión en oncología

Introduction: advances in genetics in recent decades has ushered a new era. Precision medicine has used these advances to play an increasingly important role in cancer prevention, diagnosis and treatment. Objetive: was to evaluate the usefulness of precisión medicine in improving prevention, treatment and prognosis in oncology. Discussion: studies on carcinogenesis have propelled the discovery of crucial events in the development of malignant neoplasms, identifying specific molecular subtypes of several common tumors. This has resulted in a better charaterization of tumors, which previously depended only on anatomapathological findings, and has enabled the development of new drugs, which have shifted the oncologic care paradigm. The identification of mutations that may determine predisposition to cancer, such as, BRCA mutations in breast cáncer, has facilitated screening to identify patients and help improve decision making and modify risk. Conclusions: the efficacy of various antitumor therapies suggests the beginning of an era in which preventive actions and clinical decisions will be based on the profile of genetic abnormalities of the tumor, improving patient prognosis and quality of life. This will allow an increase in the use of this type of precision treatments based on the profile of genetic changes.

Identification of Early Events in Serrated Pathway Colorectal Tumorigenesis by Using Digital Spatial Profiling.

The colorectal serrated pathway involves precursor lesions known as sessile serrated lesions (SSL) and traditional serrated adenomas (TSA). Mutations in BRAF or KRAS are crucial early events in this pathway. Additional genetic and epigenetic changes contribute to the progression of these lesions into high-grade lesions and, eventually, invasive carcinoma. We employed digital spatial profiling to investigate the transcriptional changes associated with SSL and TSA. The genes identified are confirmed by immunohistochemical (IHC) staining. Colorectal cancer (CRC) cell lines with CEACAM6 overexpression and knockdown were established to study the roles of CEACAM6 on tumorigenesis of CRC. Ten genes were upregulated in SSL and TSA, and seven were upregulated in both types of lesions. IHC staining confirmed overexpression of CEACAM6, LCN2, KRT19, and lysozyme in SSL and TSA. CEACAM6 expression is an early event in the serrated pathway but a late event in the conventional pathway. Using cell line models, we confirmed that CEACAM6 promotes CRC cells' proliferation, migration, and invasion abilities. These results highlight that the transcriptional changes in the early stages of tumorigenesis exhibit relative uniformity. Identifying these early events may hold significant promise in elucidating the mechanisms behind tumor initiation.

Hydrophobic C-Terminal Peptide Analog Aβ31-41 Protects the Neurons from Aβ-Induced Toxicity.

Spontaneous aggregation of amyloid beta (Aβ) leads to the formation of neurotoxic senile plaque considered as the most crucial event in Alzheimer's disease (AD) progression. Inhibition or disruption of this deadly aggregate formation is one of the most efficient strategies for the development of potential therapeutics, and extensive research is in progress by various research groups. In this direction, the development of a peptide analogous to that of the native Aβ peptide is an attractive strategy. Based on this rationale, β-sheet breakers were developed from the Aβ central hydrophobic core. These peptide derivatives will bind to the full length of the parent Aβ and interfere in self-recognition, thereby preventing the folding of the Aβ peptide into cross β-sheet neurotoxic aggregates. However, this approach is effective in the inhibition of fibrillar aggregation, but this strategy is ineffective in the Aβ neurotoxic oligomer formation. Therefore, an alternative and efficient approach is to use the Aβ peptide analogous to the C-terminal region, which arbitrates fibrillation and oligomerization. Herein, we developed the Aβ C-terminal fragment (ACT-1 to ACT-7) for inhibition of oligomerization as well as fibrillar aggregation. Screening of these seven peptides resulted in an efficient anti-Aβ peptide aggregative agent (ACT-7), which was evaluated by the ThT assay peptide. The ThT assay reveals complete inhibition and showed significant neuroprotection of PC-12-derived neurons from Aβ-induced toxicity and reduced cell apoptosis. Further, analysis using CD and FTIR spectroscopy reveals that the ACT-7 peptide efficiently inhibits the formation of the β-sheet secondary structure content. HR-TEM microscopic analysis confirmed the inhibition of formation. Therefore, the inhibition of β-sheet Aβ fibrillary aggregation by the protease-stable ACT-7 peptide may provide a beneficial effect on AD treatment to control the Aβ aggregates. Finally, we anticipate that our newly designed ACT peptides may also assist as a template molecular scaffold for designing potential anti-AD therapeutics.

Combating Misinformation: Leveraging Deep Learning for Hoax Detection in Indonesian Political Social Media

The rampant spread of hoax news in social media, especially in the political domain, poses a significant challenge that requires immediate attention. To address this issue, automatic hoax news detection using machine learning-based artificial intelligence has emerged as a promising approach. With the approaching presidential election in Indonesia in 2024, the need for effective detection methods becomes even more pressing.This research focuses on proposing an efficient deep learning model for detecting political hoax news on Indonesian social media. Word2vec feature representation and three deep learning models – LSTM, CNN, and Hybrid CNN-LSTM – are evaluated to determine the most effective approach. Experimental results reveal that the CNN-LSTM hybrid model outperforms the others, achieving an accuracy of 96% in detecting hoax news on Indonesian social media in the political domain. By leveraging state-of-the-art deep learning techniques, particularly the CNN-LSTM hybrid model, this study contributes to the advancement of hoax news detection in Indonesia's political landscape. The findings underscore the importance of utilizing sophisticated machine learning methods to combat the spread of misinformation, particularly during crucial political events such as elections.

Early histological transformation of follicular lymphoma to diffuse large B-cell lymphoma indicating adverse survival: A population-based analysis and validation.

The histological transformation (HT) of follicular lymphoma (FL) is a crucial biological event. The study aimed to evaluate the incidence, clinicial characteristics, prognosis and impact of HT time on survival of FL transforming to diffuse large B-cell lymphoma in population-based large-scale cohorts. A retrospective cohort study of FL with HT was performed in the Surveillance, Epidemiology, and End Results database. The Hematological Malignancy Research Network FL cohort and Aristotle study FL cohort were used to assess the external validity. Among 44,127 FL cases from the Surveillance, Epidemiology, and End Results database, 1311 cases were pathology-proven recorded to transform to diffuse large B-cell lymphoma. The cumulative rates of HT at 5, 10, and 15 years after FL diagnosis were estimated to be 1.19%, 2.93%, and 5.01%, respectively. Significantly worse overall survival and cancer-specific survival were exhibited in patients with HT than those without HT. Early HT (transformation of FL within 48 months after FL diagnosis [TOD48]) was an independent predictor for adverse overall survival of HT patients, regardless of treatment modalities before transformation. The adverse prognostic effect of TOD48 was validated in the Hematological Malignancy Research Network cohort and Aristotle study cohort. Older age (>75 years) and B symptoms within FL at diagnosis were the independent risk factors of TOD48. Furthermore, a novel prognostic model combining TOD48 with Follicular Lymphoma International Prognostic Index (TOD48-FLIPI) was constructed and validated for risk stratification. TOD48 was a risk indicator of HT, and the novel prognostic model "TOD48-FLIPI" for HT patients was proposed.

Effect of Anchoring Dynamics on Proton-Coupled Electron Transfer in the Ru(bda) Coordination Oligomer on a Graphitic Surface.

The oligomeric ruthenium-based water oxidation catalyst, Ru(bda), is known to be experimentally anchored on graphitic surfaces through CH-π stacking interactions between the auxiliary bda ([2,2'-bipyridine]-6,6'-dicarboxylate) ligand bonded to ruthenium and the hexagonal rings of the surface. This anchoring provides control over their molecular coverage and enables efficient catalysis of water oxidation to dioxygen. The oligomeric nature of the molecule offers multiple anchoring sites at the surface, greatly enhancing the overall stability of the hybrid catalyst-graphitic surface anode through dynamic bonding. However, the impact of this dynamic anchoring on the overall catalytic mechanism is still a topic of debate. In this study, a crucial proton-coupled electron transfer event in the catalytic cycle is investigated using DFT-based molecular dynamics simulations plus metadynamics. The CH-π stacking anchoring plays a critical role not only in stabilizing this hybrid system but also in facilitating the proton-coupled electron transfer event with possible vibronic couplings between the anchoring bonds motion and charge fluctuations at the catalyst - graphitic surface interface. Furthermore, this computational investigation displays the presence of a quartet spin state intermediate that can lead to the experimentally observed and thermodynamically more stable doublet spin state.

Neurotoxicity and Developmental Neurotoxicity of Copper Sulfide Nanoparticles on a Human Neuronal In-Vitro Test System.

Nanoparticles (NPs) are becoming increasingly important novel materials for many purposes, including basic research, medicine, agriculture, and engineering. Increasing human and environmental exposure to these promising compounds requires assessment of their potential health risks. While the general direct cytotoxicity of NPs is often routinely measured, more indirect possible long-term effects, such as reproductive or developmental neurotoxicity (DNT), have been studied only occasionally and, if so, mostly on non-human animal models, such as zebrafish embryos. In this present study, we employed a well-characterized human neuronal precursor cell line to test the concentration-dependent DNT of green-manufactured copper sulfide (CuS) nanoparticles on crucial early events in human brain development. CuS NPs turned out to be generally cytotoxic in the low ppm range. Using an established prediction model, we found a clear DNT potential of CuS NPs on neuronal precursor cell migration and neurite outgrowth, with IC50 values 10 times and 5 times, respectively, lower for the specific DNT endpoint than for general cytotoxicity. We conclude that, in addition to the opportunities of NPs, their risks to human health should be carefully considered.

Revealing an adverse outcome pathway network for reproductive toxicity induced by atrazine, via oxidative stress

Adverse outcome pathway AOPs are conceptual frameworks that organize scientific knowledge about how stressors disrupt specific biological targets, pathways. AOP network consists of two or more AOPs that share common key events (KEs), including crucial events like molecular initiating events (MIEs) and adverse outcomes (AOs), which offer the opportunity to link toxicological pathways. Thus, to better understand the sequential series of KEs involved in the AOP 492 (https://aopwiki.org/aops/492), which is triggered by atrazine (ATZ), we first generated a Reproductive Toxicity via Oxidative Stress (RTOS) AOP network from individual AOPs published in the AOP-Wiki database, using this AOP as a seed. The KEs “Increased, Reactive oxygen species” and “Apoptosis” were considered the most common/highly connected KE within this network and an important point of divergence. Furthermore, “Increased, DNA damage and mutations” is a critical KE within the network, as it is highly connected and central, and represents a point of divergence. This suggests that these three KEs have a high predictive value and could, for example, serve as a basis for the development/selection of in vitro assays to assess reproductive toxicity. The in silico analyses revealed that the pivotal target proteins for ATZ-induced infertility via oxidative stress in humans are Tp53, Bcl2, Esr1, and Nos3, which interact indirectly with ATZ via intermediary factors such as Mapk3, Mapk1, and Cyp19a1. Further, the gene enrichment analyses indicate that these entities are involved in several biological processes and pathways directly associated with oxidative stress, DNA damage and apoptosis, further reinforcing the developed network.

A Comprehensive Exploration of Caspase Detection Methods: From Classical Approaches to Cutting-Edge Innovations.

The activation of caspases is a crucial event and an indicator of programmed cell death, also known as apoptosis. These enzymes play a central role in cancer biology and are considered one promising target for current and future advancements in therapeutic interventions. Traditional methods of measuring caspase activity such as antibody-based methods provide fundamental insights into their biological functions, and are considered essential tools in the fields of cell and cancer biology, pharmacology and toxicology, and drug discovery. However, traditional methods, though extensively used, are now recognized as having various shortcomings. In addition, these methods fall short of providing solutions to and matching the needs of the rapid and expansive progress achieved in studying caspases. For these reasons, there has been a continuous improvement in detection methods for caspases and the network of pathways involved in their activation and downstream signaling. Over the past decade, newer methods based on cutting-edge state-of-the-art technologies have been introduced to the biomedical community. These methods enable both the temporal and spatial monitoring of the activity of caspases and their downstream substrates, and with enhanced accuracy and precision. These include fluorescent-labeled inhibitors (FLIs) for live imaging, single-cell live imaging, fluorescence resonance energy transfer (FRET) sensors, and activatable multifunctional probes for in vivo imaging. Recently, the recruitment of mass spectrometry (MS) techniques in the investigation of these enzymes expanded the repertoire of tools available for the identification and quantification of caspase substrates, cleavage products, and post-translational modifications in addition to unveiling the complex regulatory networks implicated. Collectively, these methods are enabling researchers to unravel much of the complex cellular processes involved in apoptosis, and are helping generate a clearer and comprehensive understanding of caspase-mediated proteolysis during apoptosis. Herein, we provide a comprehensive review of various assays and detection methods as they have evolved over the years, so to encourage further exploration of these enzymes, which should have direct implications for the advancement of therapeutics for cancer and other diseases.

Does the Belt and Road Initiative reduce the green logistics efficiency of partner countries?

As a crucial event in the process of China’s trade cooperation and openness, the Belt and Road Initiative (BRI) relies on the logistics as the foundational industry for its sustainable development. This study measures the green logistics efficiency (GLE) of BRI partner countries using panel data from 2013 to 2019 and evaluates the BRI’s impact on their GLE. We find that: (1) The GLE of BRI partner countries is generally low, with only 15.9% achieving effectiveness. High-income countries have notably higher GLE than middle-income ones. (2) The GLE of BRI partner countries shows an upward trend annually, especially in middle-income countries, which are closing the gap with high-income countries. (3) The BRI has a significant positive impact on the GLE growth of partner countries. Heterogeneity analysis reveals that this growth effect is more pronounced in middle-income countries. These results indicate and enhance the understanding of GLE among BRI partner countries and addresses some skepticism regarding BRI’s sustainable development.

Impact of Inducible Nitric Oxide Synthase Activation on Endothelial Behavior under Magnesium Deficiency.

Endothelial dysfunction is a crucial event in the early pathogenesis of cardiovascular diseases and is linked to magnesium (Mg) deficiency. Indeed, in endothelial cells, low Mg levels promote the acquisition of a pro-inflammatory and pro-atherogenic phenotype. This paper investigates the mechanisms by which Mg deficiency promotes oxidative stress and affects endothelial behavior in human umbilical vascular endothelial cells (HUVECs). Our data show that low Mg levels trigger oxidative stress initially by increasing NAPDH oxidase activity and then by upregulating the pro-oxidant thioredoxin-interacting protein TXNIP. The overproduction of reactive oxygen species (ROS) activates NF-κB, leading to its increased binding to the inducible nitric oxide synthase (iNOS) promoter, with the consequent increase in iNOS expression. The increased levels of nitric oxide (NO) generated by upregulated iNOS contribute to disrupting endothelial cell function by inhibiting growth and increasing permeability. In conclusion, we provide evidence that multiple mechanisms contribute to generate a pro-oxidant state under low-Mg conditions, ultimately affecting endothelial physiology. These data add support to the notion that adequate Mg levels play a significant role in preserving cardiovascular health and may suggest new approaches to prevent or manage cardiovascular diseases.

Celastrol nano-emulsions selectively regulate apoptosis of synovial macrophage for alleviating rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune inflammation. Excessive proliferation and inadequate apoptosis of synovial macrophages are the crucial events of RA. Therefore, delivering therapeutic molecules to synovial macrophages specifically to tackle apoptotic insufficiency probably can be an efficient way to reduce joint inflammation and bone erosion. Based on the characteristics of dextran sulphate (DS) specifically binding scavenger receptor A (SR-A) on macrophage and celastrol (CLT) inducing apoptosis, we designed synovial macrophage-targeted nano-emulsions encapsulated with CLT (SR-CLTNEs) and explored their anti-RA effect. After intravenous injection, fluorescence-labelled SR-CLTNEs successfully targeted inflammatory joints and synovial macrophages in a mouse model of RA, with the macrophage targeting efficiency of SR-CLTNEs, CLTNEs and free DID was 20.53%, 13.93% and 9.8%, respectively. In vivo and in vitro studies showed that SR-CLTNEs effectively promoted the apoptosis of macrophages, reshaped the balance between apoptosis and proliferation, and ultimately treated RA in a high efficiency and low toxicity manner. Overall, our work demonstrates the efficacy of using SR-CLTNEs as a novel nanotherapeutic approach for RA therapy and the great translational potential of SR-CLTNEs.

Sodium arsenite induces hepatic stellate cells activation by m6A modification of TGF-β1 during liver fibrosis

The compound known as Sodium arsenite (NaAsO2), which is a prevalent type of inorganic arsenic found in the environment, has been strongly associated with liver fibrosis (LF), a key characteristic of nonalcoholic fatty liver disease (NAFLD), which has been demonstrated in our previous study. Our previous research has shown that exposure to NaAsO2 triggers the activation of hepatic stellate cells (HSCs), a crucial event in the development of LF. However, the molecular mechanism is still unknown. N6-methyladenosine (m6A) modification is the most crucial post-transcriptional modification in liver disease. Nevertheless, the precise function of m6A alteration in triggering HSCs and initiating LF caused by NaAsO2 remains unknown. Here, we found that NaAsO2 induced LF and HSCs activation through TGF-β/Smad signaling, which could be reversed by TGF-β1 knockdown. Furthermore, NaAsO2 treatment enhanced the m6A modification level both in vivo and in vitro. Significantly, NaAsO2 promoted the specific interaction of METTL14 and IGF2BP2 with TGF-β1 and enhanced the TGF-β1 mRNA stability. Notably, NaAsO2-induced TGF-β/Smad pathway and HSC-t6 cells activation might be avoided by limiting METTL14/IGF2BP2-mediated m6A modification. Our findings showed that the NaAsO2-induced activation of HSCs and LF is made possible by the METTL14/IGF2BP2-mediated m6A methylation of TGF-β1, which may open up new therapeutic options for LF brought on by environmental hazards.

Abstract 2005: Interrogating The Cross-talk: Endothelial-Macrophage Interactions In Diabetic Vascular Dysfunction

Cardiovascular disease (CVD) occurs 15 years earlier in diabetics compared to those without, but the underlying mechanisms driving diabetes-accelerated CVDs (DACVDs) pathogenesis remains incompletely understood. Endothelial cells (ECs) and macrophages (MΦ) are key players in vascular wall and their crosstalk is crucial in DACVD. In diabetes, ECs activation enables monocytes recruitment, which transmigrate across the intima and differentiate into macrophages (MΦ). Beyond this established diapedesis model, EC-MΦ interplay is highly intricate and heterogenous. Here, we leveraged human mesenteric arteries of varied diabetic state and used single cell (sc)- and spatial transcriptome mapping to interrogate the functional crosstalk between MΦ subtypes and ECs in diabetes. We identified diabetes-induced EC-MΦ interactions and explored their consequences in vitro and in vivo, in peripheral artery disease (PAD), a prominent DACVD. Integrative scRNA-seq and spatial transcriptome (Visium) profiling identified a remarkable increase of MΦ subtype expressing triggering receptor expressed on myeloid cells (TREM2) with concomitant increased EC-derived TREM2 ligands in human diabetic vs non-diabetic vessels. Such induction of TREM2 MΦ was consistently observed in arteries from type I and II diabetes mouse models. Compared to the condition medium from MΦ cultured under normal glucose, that from MΦ cultured under high glucose conditions reduced EC migration and increased inflammatory markers, which were reversed by the medium from MΦ with TREM2-knockdown. We further evaluated the functional importance of EC-TREM2 interaction in vivo in a mouse hindlimb ischemia (HLI) model. In diabetic mice under HLI, a TREM2 neutralizing antibody promoted tissue recovery and perfusion. Finally, we showed that TREM2 was increased, especially in proximity to ECs, in ischemic sites, as compared to non-ischemic regions in limb muscles from human PAD patients.Taken together, our study presents a diabetic artery atlas and identifies EC-TREM2 interaction as a crucial event in DACVDs, such as PAD. Our findings provide novel insights into the EC-MΦ interplay in diabetes and vascular inflammation and how these cellular interactions may be targeted to ameliorate DACVD.

Unveiling the mystery of nuclear RNA homeostasis

How nuclear RNA homeostasis impacts cellular functions remains elusive. In this issue of Cell Stem Cell, Han etal.1 utilized a controllable protein degradation system targeting EXOSC2 to perturb RNA homeostasis in mouse pluripotent embryonic stem cells, revealing its vital role in orchestrating crucial nuclear events for cellular fitness.

Proteomic Analysis of Prehypertensive and Hypertensive Patients: A Novel Role of Actin Cytoskeleton in Disease Progression

Background: Hypertension is a pervasive and widespread health condition that poses a significant risk factor for cardiovascular disease, which includes conditions such as heart attack, stroke, and heart failure. Despite its widespread occurrence, the exact cause of hypertension remains unknown, and the mechanisms underlying the progression from prehypertension to hypertension require further investigation. Methods: To uncover potential biomarkers related to disease development, proteomic profiling using SOMAscan proteomic platform was conducted on Qatari individuals with prehypertension and hypertension. In this study, proteomic data collected from the Qatar Biobank were analyzed to compare participants with prehypertension, hypertension, and normal blood pressure. Statistical analysis was performed to identify altered protein expression between the study groups and to elucidate the biological pathways contributing to this disease. Results: The results revealed a cluster of proteins, including the SRC family, CAMK2B and CAMK2D, TEC, GSK3, VAV, and RAC, that were markedly upregulated in patients with hypertension compared to those with prehypertension (fold change ≥ 1.6 or ≤ -1.6, area under the curve ≥ 0.8, and q-value < 0.05). Pathway analysis showed that the majority of these proteins play a role in actin cytoskeleton remodeling, a crucial pathological event involved in hypertension progression. Conclusion: Actin cytoskeleton reorganization affects various biological processes that contribute to the maintenance of blood pressure, including vascular tone, endothelial function, cellular signaling, inflammation, fibrosis, and mechanosensing. Therefore, the findings of this study suggest a potential novel role of actin cytoskeleton-related proteins in the progression from prehypertension to hypertension. The present study sheds light on the underlying pathological mechanisms involved in hypertension and could pave the way for new diagnostic and therapeutic approaches for the treatment of this disease. This study was made possible through the support of Qatar University. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Humanized Childbirth: An Experience Report of the Assistance Offered by the Unified Health System in a City in the SouthEast of Brazil

Background: Childbirth is a crucial event in a woman’s life and her baby’s, with significant implications for the health and well-being of both. In Brazil, the predominant approach has been medicalized childbirth, with frequent medical interventions during the birthing process. However, growing evidence highlights the benefits of humanized childbirth for the physical and emotional health of the mother and baby. In this context, this study analyzes the transition towards more humanized childbirth practices in Brazil, its impacts, and associated challenges. Objectives: This study aims to analyze the implementation of humanized childbirth practices in Brazil, focusing on the stages of pregnant women reception, preparing the environment for the child’s arrival, and the symbolism of childbirth through Placenta Printing. Specific objectives include evaluating pregnant women’s satisfaction with the childbirth experience, analyzing the reduction of unnecessary medical interventions, and assessing neonatal outcomes associated with these practices. Methods: The study is an experience report that occurred in a municipal hospital in Minas Gerais, Brazil, during the year 2024. Humanized childbirths were followed through the Brazilian public healthcare system, which offers free and universal assistance to pregnant women during childbirth. The stages of pregnant women reception, preparing the environment for the child’s arrival, and the symbolism of childbirth through Placenta Printing were detailed and implemented according to established protocols. Pregnant women’s satisfaction was assessed through postpartum interviews, while data related to the rate of medical interventions and neonatal outcomes were collected and analyzed. Results: The results demonstrated high satisfaction among pregnant women with the humanized childbirth experience, highlighting empathetic reception, clear and respectful communication, and consideration of their preferences in preparing the environment and practicing Placenta Printing. Additionally, there was a significant reduction in unnecessary medical interventions, reflected in a decrease in the cesarean section rate, episiotomies, and other medical procedures during childbirth. Neonatal outcomes were also positive, with favorable neonatal adaptation indicators. Conclusion: The experience of humanized childbirth in Brazil represents a significant advancement in promoting maternal and neonatal health. Despite the challenges faced, the benefits associated with this comprehensive approach to childbirth are undeniable. It is crucial for health authorities, healthcare professionals, and society to continue supporting and promoting humanized childbirth practices as part of a broader effort to improve maternal and neonatal health outcomes in Brazil

Deep learning insights into the architecture of the mammalian egg-sperm fusion synapse

A crucial event in sexual reproduction is when haploid sperm and egg fuse to form a new diploid organism at fertilization. In mammals, direct interaction between egg JUNO and sperm IZUMO1 mediates gamete membrane adhesion, yet their role in fusion remains enigmatic. We used AlphaFold to predict the structure of other extracellular proteins essential for fertilization to determine if they could form a complex that may mediate fusion. We first identified TMEM81, whose gene is expressed by mouse and human spermatids, as a protein having structural homologies with both IZUMO1 and another sperm molecule essential for gamete fusion, SPACA6. Using a set of proteins known to be important for fertilization and TMEM81, we then systematically searched for predicted binary interactions using an unguided approach and identified a pentameric complex involving sperm IZUMO1, SPACA6, TMEM81 and egg JUNO, CD9. This complex is structurally consistent with both the expected topology on opposing gamete membranes and the location of predicted N-glycans not modeled by AlphaFold-Multimer, suggesting that its components could organize into a synapse-like assembly at the point of fusion. Finally, the structural modeling approach described here could be more generally useful to gain insights into transient protein complexes difficult to detect experimentally.