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Hypertrophic Cardiomyopathy-Associated CRYABR123W Activates Calcineurin, Reduces Calcium Sequestration, Alters the CRYAB Interactome and the Proteomic Response to Pathological Hypertrophy
Andres Thorkelsson,
Chun Chou,
Audrey Tripp,
Samia A. Ali,
Jonas Galper,
Michael T. Chin
Posted: 19 February 2025
Genetic Results and Clinical Pregnancy Outcomes Following Preimplantation Genetic Testing: A Retrospective Analysis of 2577 Embryo Biopsies
Gorka Barrrenetxea,
Ricardo Celis,
Sheila Samojluk,
Julen Barrenetxea,
Edurne Martínez,
María De Las Heras,
Oihane Gómez,
Olaia Aguirre
Background and Objectives: This study investigates the impact of maternal age and blastocyst development stage on aneuploidy rates. It evaluates the effectiveness of preimplantation genetic testing for aneuploidy (PGT-A) in improving clinical outcomes in in vitro fertilization (IVF). While PGT-A is often recommended for older patients, this study highlights its value across all maternal age groups in optimizing embryo selection. Methods: A retrospective observational study was conducted, analyzing 691 IVF cycles with PGT-A and 2,577 biopsied blastocysts between January 2019 and December 2023 at a single reproductive center. Patients were stratified into five age groups (<30, 31–33, 34–35, 36–40, >40 years), and blastocyst biopsies were performed on days 5 or 6 for genetic testing. Primary outcomes included euploidy and aneuploidy rates, while secondary outcomes assessed embryo availability and pregnancy complications. Results: The overall euploidy rate was 34.5%, declining with age from 43.6% (<30 years) to 15.9% (>40 years), while aneuploidy rates peaked at 75.43% (>40 years). Blastocysts biopsied on day 5 showed higher euploidy rates than on day 6 (40.16% vs. 27.92%, p<0.001). PGT-A cycles demonstrated superior ongoing pregnancy rates compared to cycles without genetic testing, with the most significant benefit observed in patients aged 36–40 (OR: 2.16, 95% CI: 1.07–4.35). However, all age groups benefited from PGT-A in reducing failed transfers due to non-viable embryos. Conclusions: This study underscores the universal utility of PGT-A in IVF, demonstrating its effectiveness in enhancing clinical outcomes and embryo selection, not only among older patients but across all maternal age groups. These findings highlight PGT-A as a valuable tool for optimizing IVF success regardless of patient age.
Background and Objectives: This study investigates the impact of maternal age and blastocyst development stage on aneuploidy rates. It evaluates the effectiveness of preimplantation genetic testing for aneuploidy (PGT-A) in improving clinical outcomes in in vitro fertilization (IVF). While PGT-A is often recommended for older patients, this study highlights its value across all maternal age groups in optimizing embryo selection. Methods: A retrospective observational study was conducted, analyzing 691 IVF cycles with PGT-A and 2,577 biopsied blastocysts between January 2019 and December 2023 at a single reproductive center. Patients were stratified into five age groups (<30, 31–33, 34–35, 36–40, >40 years), and blastocyst biopsies were performed on days 5 or 6 for genetic testing. Primary outcomes included euploidy and aneuploidy rates, while secondary outcomes assessed embryo availability and pregnancy complications. Results: The overall euploidy rate was 34.5%, declining with age from 43.6% (<30 years) to 15.9% (>40 years), while aneuploidy rates peaked at 75.43% (>40 years). Blastocysts biopsied on day 5 showed higher euploidy rates than on day 6 (40.16% vs. 27.92%, p<0.001). PGT-A cycles demonstrated superior ongoing pregnancy rates compared to cycles without genetic testing, with the most significant benefit observed in patients aged 36–40 (OR: 2.16, 95% CI: 1.07–4.35). However, all age groups benefited from PGT-A in reducing failed transfers due to non-viable embryos. Conclusions: This study underscores the universal utility of PGT-A in IVF, demonstrating its effectiveness in enhancing clinical outcomes and embryo selection, not only among older patients but across all maternal age groups. These findings highlight PGT-A as a valuable tool for optimizing IVF success regardless of patient age.
Posted: 19 February 2025
The Meninges as CNS Interfaces and the Roles of Meningeal Macrophages
Chihiro Hiraki,
Fuminori Tsuruta
Posted: 19 February 2025
The Balance of MFN2 and OPA1 in Mitochondrial Dynamics, Cellular Homeostasis, and Disease
Paola Zanfardino,
Alessandro Amati,
Mirko Perrone,
Vittoria Petruzzella
Posted: 19 February 2025
Changes in Microstructure and Starch Granule Content in the Endosperm of Germinated Seeds of Pouteria campechiana
Karen Maybel Granados-Vega,
Silvia Evangelista-Lozano,
Tomás Rodríguez-García,
José Fernando Pérez-Barcena,
Ma. del Carmen Ángeles González-Chávez,
Daniel Tapia-Maruri,
Mario Rodríguez-Monroy
Starch is a polysaccharide produced by plants, which varies in size, shape and appearance and can be observed at different levels. Pouteria campechiana is a fruit tree of the Sapotaceae family. The fruits contain one to five large seeds with a high starch content. Given the increasing demand for food, it is crucial to explore alternative sources of non-conventional energy for human consumption. This study aims to characterize the starch granules of P. campechiana seeds at various stages of germination. Fruits were collected in the state of Morelos, Mexico and seeds were germinated. Samples were taken at 3, 33, 50, 50, 74, 98 and 130 days after sowing (das). They were fixed in FAA (formaldehyde, acetic acid and alcohol) and cut for embedding in paraffin. Sections were obtained with a microtome, stained with toluidine blue and mounted with resin. They were observed under the microscope. The microphotographs were subjected to digital analysis. The following were measured: area, circularity, solidity, roundness, diameter. At 3 das, the highest amount of starch was found, while at 50 and 130 das, the lowest amount was recorded. The majority of the granules are simple, round, large and small. As germination progresses, they become deformed, taking on a polygonal shape.
Starch is a polysaccharide produced by plants, which varies in size, shape and appearance and can be observed at different levels. Pouteria campechiana is a fruit tree of the Sapotaceae family. The fruits contain one to five large seeds with a high starch content. Given the increasing demand for food, it is crucial to explore alternative sources of non-conventional energy for human consumption. This study aims to characterize the starch granules of P. campechiana seeds at various stages of germination. Fruits were collected in the state of Morelos, Mexico and seeds were germinated. Samples were taken at 3, 33, 50, 50, 74, 98 and 130 days after sowing (das). They were fixed in FAA (formaldehyde, acetic acid and alcohol) and cut for embedding in paraffin. Sections were obtained with a microtome, stained with toluidine blue and mounted with resin. They were observed under the microscope. The microphotographs were subjected to digital analysis. The following were measured: area, circularity, solidity, roundness, diameter. At 3 das, the highest amount of starch was found, while at 50 and 130 das, the lowest amount was recorded. The majority of the granules are simple, round, large and small. As germination progresses, they become deformed, taking on a polygonal shape.
Posted: 19 February 2025
Digestion of PET Plastic by Genetically Modified E. Coli in Simple Batch Style Bioreactors
Malcolm Bogroff,
Clemente Brogca
In light of the discovery of the bacteria Ideonella Sakaiensis in 2016, enzyme based recycling has become a very promising field of study. The bacteria was found in the sludge of a Japanese recycling plant and produced the enzyme PET hydrolase. This was one of the first enzymes discovered capable of breaking down type 1 plastic. As time went on, researchers began developing more efficient versions of PET hydrolase. Though it has amazing potential, its ability in a low fidelity setting is still unknown. In our study, we produced a series of low fidelity bioreactors to test the enzyme’s capabilities under stress. For our procedures, we used E. Coli modified with the pET21b(+)-Is-PETase plasmid [3] to produce the enzyme for our study. We conducted our experiment over the course of 4 weeks with 5 unique batch style bioreactors. In our research we were able to determine that E.Coli was able to decrease the weight of 0.6 grams (± 200 milligrams) PET plastic strips by 0.2 milligrams (± 0.1 milligram).
[M1]Refs. Citation are not allowed in abstract, please move them to maintext.
In light of the discovery of the bacteria Ideonella Sakaiensis in 2016, enzyme based recycling has become a very promising field of study. The bacteria was found in the sludge of a Japanese recycling plant and produced the enzyme PET hydrolase. This was one of the first enzymes discovered capable of breaking down type 1 plastic. As time went on, researchers began developing more efficient versions of PET hydrolase. Though it has amazing potential, its ability in a low fidelity setting is still unknown. In our study, we produced a series of low fidelity bioreactors to test the enzyme’s capabilities under stress. For our procedures, we used E. Coli modified with the pET21b(+)-Is-PETase plasmid [3] to produce the enzyme for our study. We conducted our experiment over the course of 4 weeks with 5 unique batch style bioreactors. In our research we were able to determine that E.Coli was able to decrease the weight of 0.6 grams (± 200 milligrams) PET plastic strips by 0.2 milligrams (± 0.1 milligram).
[M1]Refs. Citation are not allowed in abstract, please move them to maintext.
Posted: 19 February 2025
The Toxicity of RNA Polymerase Inhibitors Opens the Door to New Drug Generation Modulating Longevity
Ahmed Mohamed Helaly,
Doaa Ghorab
There are many RNA polymerase inhibitors, such as rifampicin, which acts as an antituberculosis agent, and relatively new antiviral drugs, such as sofosbuvir. These drugs have a safe profile and strong efficacy in treating tuberculosis and hepatitis C infections. Studies have shown that high doses of these compounds promote cell longevity (prolonging life span) in humans. It is hypothesized that these drugs also affect human RNA polymerases at high doses. We predicted that such inhibition inhibits the RNA transcription machinery, which is considered a pacemaker of the biological clock. It is important to shift research to human RNA polymerase modulators to develop new versions of drugs treating diseases such as neurodegenerative disorders. Although there is no data about the crystal structure of the human RNA polymerase, the mammalian and even the bacterial structures look conserved. It is important to raise concerns about cancer risk from potential new drugs targeting RNA polymerase. However, adding adjuvant therapy, such as vascular endothelial growth factor inhibitors, to RNA polymerase inhibitors can be a wise strategy at the end of the tunnel. The speed of RNA polymerase elongation modulates longevity. Aging affects the transcription machinery, and transcription activity affects longevity, creating a loop.
There are many RNA polymerase inhibitors, such as rifampicin, which acts as an antituberculosis agent, and relatively new antiviral drugs, such as sofosbuvir. These drugs have a safe profile and strong efficacy in treating tuberculosis and hepatitis C infections. Studies have shown that high doses of these compounds promote cell longevity (prolonging life span) in humans. It is hypothesized that these drugs also affect human RNA polymerases at high doses. We predicted that such inhibition inhibits the RNA transcription machinery, which is considered a pacemaker of the biological clock. It is important to shift research to human RNA polymerase modulators to develop new versions of drugs treating diseases such as neurodegenerative disorders. Although there is no data about the crystal structure of the human RNA polymerase, the mammalian and even the bacterial structures look conserved. It is important to raise concerns about cancer risk from potential new drugs targeting RNA polymerase. However, adding adjuvant therapy, such as vascular endothelial growth factor inhibitors, to RNA polymerase inhibitors can be a wise strategy at the end of the tunnel. The speed of RNA polymerase elongation modulates longevity. Aging affects the transcription machinery, and transcription activity affects longevity, creating a loop.
Posted: 19 February 2025
Influence of Summer Drought on Resprouting and Leaf Senescence in a Common Garden of Prunus spinosa L.
Kristine Vander Mijnsbrugge,
Stefaan Moreels,
Sharon Moreels,
Damien Buisset,
Karen Van Campenhout,
Eduardo Notivol Paino
Posted: 19 February 2025
Biological Barrier Models-on-Chip: An Innovative Tool for Studying Diseases and Discovering New Drug Therapies
Giusi Caragnano,
Anna Grazia Monteduro,
Silvia Rizzato,
Gianluigi Giannelli,
Giuseppe Maruccio
The exploration of alternatives to the use of animal models and cell cultures has culminated in the creation of organ-on-a-chip systems in which organs in physio-pathological conditions and their reactions to the presence of external stimuli are simulated. In addition, they support the recreation of tissue interfaces such as tissue-air, tissue-liquid and tissue-tissue, which are very similar to those present in vivo, even through the presence of biomechanical stimuli. In this way they are best suited to mimic biological barriers, such as the skin, placenta, blood-brain barrier and others, which are characterized by tissue interface and their functioning is important to ensure the homeostasis of the organism. This review shows the different biological membranes that we can simulate within an organ-on-chip, also using induced pluripotent stem cells to act in the direction of personalized medicine. Different methods that can be used to detect barrier formation, including the integration of electrodes for real-time monitoring, are also explained, highlighting advantages and challenges.
The exploration of alternatives to the use of animal models and cell cultures has culminated in the creation of organ-on-a-chip systems in which organs in physio-pathological conditions and their reactions to the presence of external stimuli are simulated. In addition, they support the recreation of tissue interfaces such as tissue-air, tissue-liquid and tissue-tissue, which are very similar to those present in vivo, even through the presence of biomechanical stimuli. In this way they are best suited to mimic biological barriers, such as the skin, placenta, blood-brain barrier and others, which are characterized by tissue interface and their functioning is important to ensure the homeostasis of the organism. This review shows the different biological membranes that we can simulate within an organ-on-chip, also using induced pluripotent stem cells to act in the direction of personalized medicine. Different methods that can be used to detect barrier formation, including the integration of electrodes for real-time monitoring, are also explained, highlighting advantages and challenges.
Posted: 19 February 2025
Effects of Auxin and Its Inhibitors on Root Growth and Mineral Nutrient Absorption in Citrus (Trifoliate Orange) Seedlings
Yuwei Yang,
Yidong Shi,
Cuiling Tong,
Dejian Zhang
As an endogenous hormone, auxin plays a crucial role in regulating plants’ growth and development. Auxin synthesis and transport are mediated by gene expression regulation, but the regulatory mechanism is poorly understood. Therefore, we studied this problem using citrus (trifoliate orange, citrus rootstocks) as the experimental material. The experiment involved the treatment of two groups of trifoliate orange with exogenous auxin (indolebutyric acid, IBA) and auxin inhibitor (2-naphthoxyacetic acid, 2-NOA), respectively, in a sand culture system. The aim of this study is to investigate the regulatory mechanisms by which auxin affects seedling growth and mineral nutrition levels in trifoliate orange. The results showed that exogenous auxin significantly enhanced taproot elongation and lateral root density, while also markedly elevating the levels of phosphorus (P), cuprum (Cu), zinc (Zn), and other mineral nutrients in trifoliate orange leaves. In contrast, the auxin inhibitor produced the opposite effects. Exogenous auxin treatment significantly upregulated the expression of genes related to auxin synthesis and transport and led to a significant increase in auxin content. Exogenous auxin inhibitor treatment significantly reduced the expression levels of most auxin synthesis and transport genes and led to a significant decrease in auxin content. According to the results of this study, the synthesis and transport of auxin regulate trifoliate orange root growth, thereby further affecting its absorption of mineral nutrients.
As an endogenous hormone, auxin plays a crucial role in regulating plants’ growth and development. Auxin synthesis and transport are mediated by gene expression regulation, but the regulatory mechanism is poorly understood. Therefore, we studied this problem using citrus (trifoliate orange, citrus rootstocks) as the experimental material. The experiment involved the treatment of two groups of trifoliate orange with exogenous auxin (indolebutyric acid, IBA) and auxin inhibitor (2-naphthoxyacetic acid, 2-NOA), respectively, in a sand culture system. The aim of this study is to investigate the regulatory mechanisms by which auxin affects seedling growth and mineral nutrition levels in trifoliate orange. The results showed that exogenous auxin significantly enhanced taproot elongation and lateral root density, while also markedly elevating the levels of phosphorus (P), cuprum (Cu), zinc (Zn), and other mineral nutrients in trifoliate orange leaves. In contrast, the auxin inhibitor produced the opposite effects. Exogenous auxin treatment significantly upregulated the expression of genes related to auxin synthesis and transport and led to a significant increase in auxin content. Exogenous auxin inhibitor treatment significantly reduced the expression levels of most auxin synthesis and transport genes and led to a significant decrease in auxin content. According to the results of this study, the synthesis and transport of auxin regulate trifoliate orange root growth, thereby further affecting its absorption of mineral nutrients.
Posted: 19 February 2025
Histone Phosphorylation in DNA Damage Response
Ping Gong,
Zhaohui Guo,
Shengping Wang,
Shufeng Gao,
Qinhong Cao
Posted: 19 February 2025
Sem and Bacteriological Evidence of Laser-Activated Irrigation, Compared to Ultrasonic Activated Irrigation
David E. Jaramillo,
Ji Wook Jeong,
Enrico Divito
Posted: 19 February 2025
Purification and Inhibitor Screening of the Full-Length SARS-CoV-2 Nucleocapsid Protein
Chen Chen,
Zhengfu Zhang,
Qiao Zheng,
Yingshun Zhou,
Shujun Zhang
Posted: 19 February 2025
Comparative Mutational Analysis and the Glycosylation Patterns of a Peruvian Isolated Avian Influenza a Virus H5N1: Exploring Possible Viral Spillover Events Within One Health Approach
Sandra Landazabal-Castillo,
Lucero Alva-Alvarez,
Dilan Suarez-Agüero,
Enrique Mamani-Zapana,
Egma Mayta-Huatuco
(1) Background: The emergence of H5N1 Influenza A viruses clade 2.3.3.4b since 2020, have caused the mortality of thousands of birds/mammals worldwide, through evolu-tionary changes have been associated with acquired mutations and posttranslational modifications. (2) Methods: This study aimed to compare the mutational profile of H5N1 avian Influenza virus isolated from a Peruvian natural reserve, with recent data from other related international studies made in human and different species of domestic and wild birds and mammals. Briefly, the near complete protein sequences of Influenza virus coming from a Calidris alba were analyzed in a multisegmented level, altogether with 55 samples collected between 2022-2024 in different countries. Moreover, the glycosylation patterns were also predicted in silico. (3) Results: A total of 603 amino acid changes were found among H5N1 viruses analyzed, underscoring the detection of critical mutations HA:143T, HA:156A, HA:208K, NA: 71S, NP:52H, PA:336M, PA:36T, PA:85A/N, PB1-F2:66S, PB2:199S, PB2:292V, PB2:559T, as well as PA:86I, PA:432I, PA:558L, HA:492D, NA:70D, NS1-83P, PB1:515A, PA-X:57Q, PB1-F2:22E, NS1-21Q, NEP:67G, among others, considered of importance under One Health perspective. Similarly, changes in the N-linked glycosylation sites (NLGs) predicted in both HA and NA proteins were found, highlighting the loss/acquisition or changes in some NLGs sites such as 209NNTN, 100 NPTT, 302NSSM (HA) and 70NNTN, 68NISS, 50NGSV (NA). (4) Conclu-sions: This study provides our understanding about the evolution of current Influenza A viruses H5N1 HPAIV circulating globally. These findings outline the importance of sur-veillance updating mutational profiles and glycosylation patterns of these highly evolved virus.
(1) Background: The emergence of H5N1 Influenza A viruses clade 2.3.3.4b since 2020, have caused the mortality of thousands of birds/mammals worldwide, through evolu-tionary changes have been associated with acquired mutations and posttranslational modifications. (2) Methods: This study aimed to compare the mutational profile of H5N1 avian Influenza virus isolated from a Peruvian natural reserve, with recent data from other related international studies made in human and different species of domestic and wild birds and mammals. Briefly, the near complete protein sequences of Influenza virus coming from a Calidris alba were analyzed in a multisegmented level, altogether with 55 samples collected between 2022-2024 in different countries. Moreover, the glycosylation patterns were also predicted in silico. (3) Results: A total of 603 amino acid changes were found among H5N1 viruses analyzed, underscoring the detection of critical mutations HA:143T, HA:156A, HA:208K, NA: 71S, NP:52H, PA:336M, PA:36T, PA:85A/N, PB1-F2:66S, PB2:199S, PB2:292V, PB2:559T, as well as PA:86I, PA:432I, PA:558L, HA:492D, NA:70D, NS1-83P, PB1:515A, PA-X:57Q, PB1-F2:22E, NS1-21Q, NEP:67G, among others, considered of importance under One Health perspective. Similarly, changes in the N-linked glycosylation sites (NLGs) predicted in both HA and NA proteins were found, highlighting the loss/acquisition or changes in some NLGs sites such as 209NNTN, 100 NPTT, 302NSSM (HA) and 70NNTN, 68NISS, 50NGSV (NA). (4) Conclu-sions: This study provides our understanding about the evolution of current Influenza A viruses H5N1 HPAIV circulating globally. These findings outline the importance of sur-veillance updating mutational profiles and glycosylation patterns of these highly evolved virus.
Posted: 19 February 2025
Vesicular Glutamate Transporter 3 Is Involved in Glutamatergic Signaling in Podocytes
Naoko Nishii,
Tomoko Kawai,
Hiroki Yasuoka,
Tadashi Abe,
Nanami Tatsumi,
Yuika Harada,
Takaaki Miyaji,
Shunai Li,
Moemi Tsukano,
Masami Watanabe
Posted: 19 February 2025
Exploring Whether Education and Licensing of Horse-Owners Can Address Poor Horse Welfare in the UK
Aurelia Hall-Bromley,
Laura Dixon
Horse welfare concerns have been a subject of increased discussion for decades. The issue of compromised horse welfare in the UK, and across the globe, is complex as welfare concerns are varied, wide ranging and nuanced. Several solutions to combat compromised horse welfare have been suggested by existing research, but each of these have their limitations. In this study, existing literature regarding horse welfare, and education and licensing as potential solutions were analysed. Distress behaviour was the most cited welfare concern in the literature, narrowly followed by health issues and behavioural issues. The citations for causes of poor welfare were dominated by management and training practices. Analysis found that the highest cited barrier to good welfare was a lack of knowledge, followed by lack of understanding. Further research into horse welfare was most commonly suggested as the best step to address welfare concerns, and increased awareness of welfare issues was suggested as the best solution to prevent welfare issues. In terms of education, the most cited positive outcomes were increased knowledge, awareness or understanding. However, the most prominent limitation of education was an unclear effect on behaviour, as well as other notable factors such as availability. The most cited licensing success was use as a consumer tool, but licensing was limited by enforcement. Taking the relevant literature as a whole, there is no single evident solution that can solve the horse welfare problem, but there are areas identified that merit closer consideration.
Horse welfare concerns have been a subject of increased discussion for decades. The issue of compromised horse welfare in the UK, and across the globe, is complex as welfare concerns are varied, wide ranging and nuanced. Several solutions to combat compromised horse welfare have been suggested by existing research, but each of these have their limitations. In this study, existing literature regarding horse welfare, and education and licensing as potential solutions were analysed. Distress behaviour was the most cited welfare concern in the literature, narrowly followed by health issues and behavioural issues. The citations for causes of poor welfare were dominated by management and training practices. Analysis found that the highest cited barrier to good welfare was a lack of knowledge, followed by lack of understanding. Further research into horse welfare was most commonly suggested as the best step to address welfare concerns, and increased awareness of welfare issues was suggested as the best solution to prevent welfare issues. In terms of education, the most cited positive outcomes were increased knowledge, awareness or understanding. However, the most prominent limitation of education was an unclear effect on behaviour, as well as other notable factors such as availability. The most cited licensing success was use as a consumer tool, but licensing was limited by enforcement. Taking the relevant literature as a whole, there is no single evident solution that can solve the horse welfare problem, but there are areas identified that merit closer consideration.
Posted: 19 February 2025
Emerging Potential of Metabolomics in Thyroid Cancer- A Comprehensive Review
Sonam Kumari,
Andrew Makarewicz,
Joanna Klubo-Gwiezdzinska
Posted: 19 February 2025
From Parts to Whole: A Systems Approach to Decoding Milk Fever
Burim N. Ametaj
Posted: 19 February 2025
From Voluntary to Value: Stakeholder-Driven Mechanisms for Carbon Neutrality in China's Tea Industry
Jia Jiao,
ChenFeng Dai,
MiJu Su,
XiaoYue Fan,
LuTing Yu,
YingFeng Wang
Posted: 19 February 2025
The Novel Antigenic Epitopes of ASFV Inner Membrane p54 Protein Revealed by Monoclonal Antibodies
Jiajia Zhang,
Kaili Zhang,
Shaohua Sun,
Ping He,
Dafu Deng,
Hanrong Lv,
Mingwang Xie,
Pingping Zhang,
Wanglong Zheng,
Nanhua Chen
Posted: 19 February 2025
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