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1.
Elife ; 122024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39120996

RESUMEN

In motor cortex, behaviorally relevant neural responses are entangled with irrelevant signals, which complicates the study of encoding and decoding mechanisms. It remains unclear whether behaviorally irrelevant signals could conceal some critical truth. One solution is to accurately separate behaviorally relevant and irrelevant signals at both single-neuron and single-trial levels, but this approach remains elusive due to the unknown ground truth of behaviorally relevant signals. Therefore, we propose a framework to define, extract, and validate behaviorally relevant signals. Analyzing separated signals in three monkeys performing different reaching tasks, we found neural responses previously considered to contain little information actually encode rich behavioral information in complex nonlinear ways. These responses are critical for neuronal redundancy and reveal movement behaviors occupy a higher-dimensional neural space than previously expected. Surprisingly, when incorporating often-ignored neural dimensions, behaviorally relevant signals can be decoded linearly with comparable performance to nonlinear decoding, suggesting linear readout may be performed in motor cortex. Our findings prompt that separating behaviorally relevant signals may help uncover more hidden cortical mechanisms.


Asunto(s)
Macaca mulatta , Corteza Motora , Neuronas , Corteza Motora/fisiología , Animales , Macaca mulatta/fisiología , Neuronas/fisiología , Conducta Animal/fisiología , Masculino , Movimiento/fisiología
2.
Malar J ; 23(1): 257, 2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39182094

RESUMEN

BACKGROUND: Plasmodium falciparum infection is associated with the human ABO blood group. However, there is a paucity of data on the role that ABO and Rhesus blood groups play in malaria clinical presentations. Therefore, the objective of this study was to assess the association of human ABO blood groups and the Rhesus blood (Rh) types with the severity of malaria. METHODS: This cross-sectional study was carried out at the Suhum Government Hospital in the Eastern region of Ghana. Conveniently, study participants with malaria, diagnosed by microscopy, were selected into the study. Subsequently, their ABO and Rh blood groups were determined (Accucare ABO/Rh monoclonal antibodies, Chennai, India). Malaria severity was assessed using the criteria for assessing severe malarial anaemia published by the World Health Organization. According to the criteria, severe malarial anaemia was classified as having haemoglobin (Hb) < 5 g/dL for children < 12 years and in patients ≥ 12 years, Hb level < 7 g/dL, with parasitaemia > 10,000/µL in both cases. Severe malarial anaemia was also classified as having plasma bilirubin > 50 µmol/L with parasitaemia ≥ 100,000/µL, for all ages. Chi square statistical analysis was used to test the association between the blood groups and the clinical or laboratory findings, while multivariate analysis was performed to identify which blood groups were more vulnerable to develop severe malarial anaemia. RESULTS: Of the total number of the study participants (n = 328), most of the patients had blood group O Rh positive (35.7%) while few of them had blood group AB Rh negative (2.1%). The types of Rhesus did not associate with malaria. However, compared to blood group O, the odds of developing severe malarial anaemia, in children < 12 years and in patients ≥ 12 years, were 16 times and 17.8 times higher among patients with blood group A, respectively. Furthermore, the odds of having bilirubin level > 50 µmol/L with parasitaemia ≥ 100,000 /µL was 10 times higher among patients with blood groups A and 2.6 times higher in patients with blood group B, compared to blood group O. Finally, in patients with blood group A majority (71.6%) of them developed high temperature (> 37.5 °C) while 43.3% of them vomited and had diarrhoea. However, pallor (group B = 46.2% vs group A = 37.3%), fever (group B = 84.6% vs group A = 79.1%) and nausea (group B = 46.2% vs group A = 25.4%) were more frequent in patients with blood group B than A. CONCLUSIONS: This study found that people with blood groups A and B were severely affected by malaria, with group A being the most vulnerable. It is recommended that blood group assessment be performed for all patients with malaria. Patients found to have blood group A or B must be promptly and efficiently managed to avoid the development of severe malaria anaemia.


Asunto(s)
Sistema del Grupo Sanguíneo ABO , Anemia , Malaria Falciparum , Sistema del Grupo Sanguíneo Rh-Hr , Humanos , Estudios Transversales , Masculino , Femenino , Preescolar , Niño , Ghana/epidemiología , Adulto , Malaria Falciparum/complicaciones , Malaria Falciparum/epidemiología , Malaria Falciparum/sangre , Anemia/etiología , Anemia/sangre , Anemia/epidemiología , Adolescente , Adulto Joven , Lactante , Persona de Mediana Edad , Anciano
3.
Hum Vaccin Immunother ; 20(1): 2374147, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-39090779

RESUMEN

Entamoeba histolytica, the causative agent of amebiasis, is one of the top three parasitic causes of mortality worldwide. However, no vaccine exists against amebiasis. Using a lead candidate vaccine containing the LecA fragment of Gal-lectin and GLA-3M-052 liposome adjuvant, we immunized rhesus macaques via intranasal or intramuscular routes. The vaccine elicited high-avidity functional humoral responses as seen by the inhibition of amebic attachment to mammalian target cells by plasma and stool antibodies. Importantly, antigen-specific IFN-γ-secreting peripheral blood mononuclear cells (PBMCs) and IgG/IgA memory B cells (BMEM) were detected in immunized animals. Furthermore, antigen-specific antibody and cellular responses were maintained for at least 8 months after the final immunization as observed by robust LecA-specific BMEM as well as IFN-γ+ PBMC responses. Overall, both intranasal and intramuscular immunizations elicited a durable and functional response in systemic and mucosal compartments, which supports advancing the LecA+GLA-3M-052 liposome vaccine candidate to clinical testing.


Asunto(s)
Administración Intranasal , Anticuerpos Antiprotozoarios , Entamoeba histolytica , Entamebiasis , Interferón gamma , Leucocitos Mononucleares , Liposomas , Macaca mulatta , Vacunas Antiprotozoos , Animales , Entamoeba histolytica/inmunología , Liposomas/inmunología , Liposomas/administración & dosificación , Vacunas Antiprotozoos/inmunología , Vacunas Antiprotozoos/administración & dosificación , Anticuerpos Antiprotozoarios/sangre , Anticuerpos Antiprotozoarios/inmunología , Leucocitos Mononucleares/inmunología , Entamebiasis/prevención & control , Entamebiasis/inmunología , Interferón gamma/inmunología , Interferón gamma/metabolismo , Inyecciones Intramusculares , Inmunogenicidad Vacunal , Adyuvantes de Vacunas/administración & dosificación , Adyuvantes Inmunológicos/administración & dosificación , Linfocitos B/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Inmunoglobulina A/inmunología , Inmunoglobulina A/sangre , Antígenos de Protozoos/inmunología , Inmunidad Humoral , Memoria Inmunológica , Proteínas Protozoarias/inmunología
4.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(4): 932-938, 2024 Jul 20.
Artículo en Chino | MEDLINE | ID: mdl-39170012

RESUMEN

Objective: Congenital cleft lip and palate is a common birth defect that seriously affects the lives of the afflicted children and their families. Previously, no research has been done to investigate the pathogenic characteristics of cleft lip and palate among ethnic minorities, for example, Tibetans, a minority ethnic group with a large population in China. This study aims to investigate the relationship between the occurrence of cleft lip and palate in Tibetans and Han Chinese in western China and the distribution of ABO blood groups and Rh blood groups to provide a theoretical basis for the precise prevention and treatment of cleft lip and palate. Methods: In this study, statistics on Tibetan patients with cleft lip and palate, some Han patients with cleft lip and palate, and normal controls from western China were retrospectively collected. All participants were patients from West China Stomatology Hospital, Sichuan University. All patients with cleft lip and palate received treatment at the hospital between January 2016 and September 2023. The normal controls were outpatients or inpatients who did not have cleft lip and palate, and who received treatment at the hospital between January 2020 and October 2023. Information on the A, B, O, and AB blood groups and Rh positive and negative blood groups of the patients was collected and compared with that of the normal controls. The incidence of different phenotypes, including cleft lip alone, cleft palate alone, and cleft lip with cleft palate, in patients of blood groups A, B, O and AB were statistically analyzed by Chi-square test. Results: A total of 1227 Tibetan patients with cleft lip and palate, 4064 Han patients with cleft lip and palate, and 5360 normal controls were included in the study. Among all the patients with cleft lip and palate, 1863 had cleft lip alone, 1425 had cleft palate alone, and 2003 had cleft lip with cleft palate. The ABO blood group distribution of Tibetan patients with cleft lip and palate was characterized as O>B>A>AB, with Rh positive blood group accounting for 100%, blood type O accounting for 41.15%, and blood type B accounting for 30.64%. The blood group distribution of the Han patients with cleft lip and palate was characterized as O>A>B>AB, with Rh positive blood group accounting for 99.58%, blood type O accounting for 35.78%, and type A accounting for 30.54%. There was a significant difference in ABO blood groups between Tibetan and Han patients with cleft lip and palate (P<0.005), but no significant difference in Rh blood groups. The ABO blood group distribution of the Tibetan patients with cleft lip and palate showed an obvious difference from that of the control group, while those of the Han patients with cleft lip and cleft palate and the control group did not show obvious differences. In the analysis of the subtypes, it was found that the blood group distribution in the subtypes of cleft lip alone, cleft palate alone, and cleft lip with cleft palate in the Tibetan population was O>B>A>AB, while that in the Han Chinese population was O>A>B>AB. There were differences in blood group distribution between Tibetans and Hans of the subtypes of cleft lip alone and cleft lip with cleft palate (P<0.001), but there was no difference in blood group distribution in the population of cleft palate-only subtype. The proportion of blood type O in Tibetan patients with cleft lip and palate was significantly higher than that in the Han patients with cleft lip and palate. The blood group distribution of Tibetan patients with cleft lip and palate in Sichuan Province, Xizang Autonomous Region, and Qinghai Province was always O>B>A>AB. Tibetan patients from Shiqu County and Baiyu County, Ganzi Tibetan Autonomous Prefecture and Chaya County, Qamdo City were predominantly of blood type B, and those from other regions were mainly of blood type O. Conclusion: There were significant differences in the phenotype composition and ABO blood group distribution between the Tibetan and Han populations with cleft lip and palate in western China. The distribution of blood group O in the population with cleft lip and palate was higher than that in the normal population, and the same trend was observed for different phenotypes. However, differences between Tibetan and Han populations in ABO blood group distribution were only found in the phenotypes of cleft lip only and cleft lip with palate. Tibetans with blood type O are more prone to cleft lip deformity than Han people, and the effect in the phenotype of cleft lip with palate is less pronounced than that in the phenotype of cleft lip only.


Asunto(s)
Sistema del Grupo Sanguíneo ABO , Labio Leporino , Fisura del Paladar , Sistema del Grupo Sanguíneo Rh-Hr , Centros de Atención Terciaria , Humanos , Labio Leporino/sangre , Fisura del Paladar/sangre , Tibet/epidemiología , China/epidemiología , Estudios Retrospectivos , Centros de Atención Terciaria/estadística & datos numéricos , Femenino , Masculino , Etnicidad , Pueblo Asiatico , Niño
5.
Natl Sci Rev ; 11(8): nwae213, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39183748

RESUMEN

The prefrontal cortex (PFC) is essential for higher-level cognitive functions. How epigenetic dynamics participates in PFC development and aging is largely unknown. Here, we profiled epigenomic landscapes of rhesus monkey PFCs from prenatal to aging stages. The dynamics of chromatin states, including higher-order chromatin structure, chromatin interaction and histone modifications are coordinated to regulate stage-specific gene transcription, participating in distinct processes of neurodevelopment. Dramatic changes of epigenetic signals occur around the birth stage. Notably, genes involved in neuronal cell differentiation and layer specification are pre-configured by bivalent promoters. We identified a cis-regulatory module and the transcription factors (TFs) associated with basal radial glia development, which was associated with large brain size in primates. These TFs include GLI3, CREB5 and SOX9. Interestingly, the genes associated with the basal radial glia (bRG)-associated cis-element module, such as SRY and SOX9, are enriched in sex differentiation. Schizophrenia-associated single nucleotide polymorphisms are more enriched in super enhancers (SEs) than typical enhancers, suggesting that SEs play an important role in neural network wiring. A cis-regulatory element of DBN1 is identified, which is critical for neuronal cell proliferation and synaptic neuron differentiation. Notably, the loss of distal chromatin interaction and H3K27me3 signal are hallmarks of PFC aging, which are associated with abnormal expression of aging-related genes and transposon activation, respectively. Collectively, our findings shed light on epigenetic mechanisms underlying primate brain development and aging.

6.
bioRxiv ; 2024 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-39131307

RESUMEN

Several age-related oral health problems have been associated with neurodegenerative diseases such as Alzheimer's Disease (AD), yet how oromotor dysfunction in healthy aging differ from those found in pathological aging is still unknown. This is partly because changes in the cortical and biomechanical ("neuromechanical") control of oromotor behavior in healthy aging are poorly understood. To this end, we investigated the natural feeding behavior of young and aged rhesus macaques (Macaca mulatta) to understand the age-related differences in tongue and jaw kinematics. We tracked tongue and jaw movements in 3D using high-resolution biplanar videoradiography and X-ray Reconstruction of Moving Morphology (XROMM). Older subjects exhibited a reduced stereotypy in tongue movements during chews and a greater lag in tongue movements relative to jaw movements compared to younger subjects. Overall, our findings reveal age-related changes in tongue and jaw kinematics, which may indicate impaired tongue-jaw coordination. Our results have important implications for the discovery of potential neuromechanical biomarkers for early diagnosis of AD.

7.
bioRxiv ; 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39131348

RESUMEN

T-cell Immunoglobulin and Mucin (TIM)-family proteins facilitate the clearance of apoptotic cells, are involved in immune regulation, and promote infection of enveloped viruses. These processes are frequently studied in experimental animals such as mice or rhesus macaques, but functional differences among the TIM orthologs from these species have not been described. Previously, we reported that while all three human TIM proteins bind phosphatidylserine (PS), only human TIM1 (hTIM1) binds phosphatidylethanolamine (PE), and that this PE-binding ability contributes to both phagocytic clearance of apoptotic cells and virus infection. Here we show that rhesus macaque TIM1 (rhTIM1) and mouse TIM1 (mTIM1) bind PS but not PE and that their inability to bind PE makes them less efficient than hTIM1. We also show that alteration of only two residues of mTIM1 or rhTIM1 enables them to bind both PE and PS, and that these PE-binding variants are more efficient at phagocytosis and mediating viral entry. Further, we demonstrate that the mucin domain also contributes to the binding of the virions and apoptotic cells, although it does not directly bind phospholipid. Interestingly, contribution of the hTIM1 mucin domain is more pronounced in the presence of a PE-binding head domain. These results demonstrate that rhTIM1 and mTIM1 are inherently less functional than hTIM1, owing to their inability to bind PE and their less functional mucin domains. They also imply that mouse and macaque models underestimate the activity of hTIM1.

8.
Cureus ; 16(7): e64464, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39135825

RESUMEN

Hydrops fetalis has classically been defined as the presence of extracellular fluid in at least two fetal body compartments. This fluid collection includes skin edema (> 5 mm thickness), pericardial effusion, pleural effusion, and ascites. Here we present a case of a 29-year-old female with antenatally diagnosed severe hydrops fetalis which was postnatally successfully managed. Despite recent advances, immune hydrops are still a challenge for healthcare workers in third-world nations.

9.
Am J Obstet Gynecol ; 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39153534

RESUMEN

Cell-free DNA (cfDNA) to determine the fetal RHD genotype from the maternal circulation was first described in 1993. High throughput assays using polymerase chain reaction technology were introduced in Europe and gained widespread acceptance in the management of the Rhesus alloimmunized pregnancy. The specificity and sensitivity of these assays approached 99%. As confidence was gained with these results, Scandinavian countries began to employ cfDNA for fetal RHD typing as an integral component of their introduction of antenatal Rhesus immune globulin (RhIG) in non-alloimmunized pregnancies. Since 40% of RhD-negative pregnant women will carry an RhD-negative fetus, doses of RhIG were conserved. Recently two U.S. companies have introduced cfDNA assays for RHD as part of their NIPT assays. Both utilize next generation sequencing and have developed methodologies to detect the aberrant RHD pseudogene and the hybrid RHD-CE-Ds genotype. In addition, excellent correlation studies with either neonatal genotyping or serology have been reported. The manufacturer of RhoGAM® has recently announced a national shortage. . Given the current availability of reliable cfDNA assays for determining the RHD status of the fetus, the time has come to implement this strategy to triage the antenatal use of Rhesus immune globulin in the U.S..

10.
Dev Comp Immunol ; 160: 105236, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39103005

RESUMEN

Interferon-lambda receptor 1 (IFNLR1) is the key to interferon-lambda's biological activities. Rhesus macaques (Macaca mulatta) are supposedly more suitable for translational studies on interferon lambda-associated human diseases, yet little is known about their IFNLR1 (mmuIFNLR1). In this study, we cloned the coding sequence of mmuIFNLR1, examined its variants, and determined the distribution of mmuIFNLR1 mRNA and immunoreactivity in the buccal mucosa and arm skin of normal and immunodeficiency virus (SHIV/SIV) infected rhesus macaques. It was found that mmuIFNLR1 has 93.1% amino acid sequence identity to that of humans; all the amino acid residues of mmuIFNLR1 signal peptide, transmembrane region, PxxLxF motif and those essential for ligand binding are identical to that of humans; 6 variants of mmuIFNLR1, including the ones corresponding to that of humans were detected; IFNLR1 immunoreactivity was localized in primarily the epithelia of buccal mucosa and arm skin; SHIV/SIV infection could affect the levels of mmuIFNLR1 mRNA and immunoreactivity. These data expanded our knowledge on mmuIFNLR1 and provided a scientific basis for rational use of rhesus macaques in studies of IFN-λ associated human diseases like AIDS. Future studies testing IFNLR1-targeting therapeutics in rhesus macaques were warranted.


Asunto(s)
Macaca mulatta , Mucosa Bucal , Síndrome de Inmunodeficiencia Adquirida del Simio , Virus de la Inmunodeficiencia de los Simios , Piel , Animales , Mucosa Bucal/inmunología , Mucosa Bucal/virología , Piel/virología , Piel/inmunología , Piel/metabolismo , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/virología , Virus de la Inmunodeficiencia de los Simios/inmunología , Virus de la Inmunodeficiencia de los Simios/fisiología , Humanos , Secuencia de Aminoácidos , Receptores de Interferón/genética , Receptores de Interferón/metabolismo , Clonación Molecular
11.
Comput Methods Programs Biomed ; 255: 108354, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39111194

RESUMEN

BACKGROUND AND OBJECTIVE: Viral respiratory infections stand as a considerable global health concern, presenting significant risks to the health of both humans and animals. This study aims to conduct a preliminary analysis of the time series of viral load in the nasal cavity-nasopharynx (NC-NP) of the human and rhesus macaque (RM). METHODS: Taking into account the random uniform distribution of virus-laden droplets with a diameter of 10 µm in the mucus layer, this study applies the computational fluid dynamics-host cell dynamics (CFD-HCD) method to 3D-shell NC-NP models of human and RM, analyzing the impact of initial distribution of droplets on the viral dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), estimating parameters in the HCD model based on experimental data, integrating them into simulations to predict the time series of viral load and cell counts, and being visualized. The reproductive number (R0) are calculated to determine the occurrence of infection. The study also considers cross-parameter combinations and cross-experimental datasets to explore potential correlations between the human and RM. RESULTS: The research findings indicate that the uniform distribution of virus-laden droplets throughout the whole NC-NP models of human and RM is reasonable for simulating and predicting viral dynamics. The visualization results offer dynamic insights into virus infection over a period of 20 days. Studies involving parameter and dataset exchanges between the two species underscore certain similarities in predicting virus infections between the human and RM. CONCLUSIONS: This study lays the groundwork for further exploration into the parallels and distinctions in respiratory virus dynamics between humans and RMs, thus aiding in making more informed decisions in research and experimentation.


Asunto(s)
COVID-19 , Macaca mulatta , Cavidad Nasal , Nasofaringe , SARS-CoV-2 , Carga Viral , Humanos , Animales , Cavidad Nasal/virología , Nasofaringe/virología , COVID-19/virología , Hidrodinámica , Simulación por Computador , Moco/virología , Modelos Biológicos
12.
Biomedicines ; 12(8)2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39200249

RESUMEN

Rapid and reliable Rhesus D typing is crucial for blood donation centers. In instances of massive blood transfusion or reduced antigen expression, DNA-based phenotype prediction becomes mandatory. Our molecular RHD typing approach involves an initial real-time PCR for the most common aberrant RHD types in our region, RHD*01W.1 (weak D type 1), RHD*01W.2 (weak D type 2), RHD*01W.3 (weak D type 3), and RHD*07.01 (DVII). For comprehensive coverage, Sanger sequencing of RHD coding regions is performed in the case of PCR target-negative results. We evaluated the specificity and accuracy of these methods using the recently launched LightCycler® PRO real-time platform. All findings demonstrated remarkable accuracy. Notably, the LightCycler® PRO instrument offers a distinct advantage in data interpretation and integration via the HL7 interface. This study underlines the importance of including advanced molecular techniques in blood typing protocols, especially in scenarios where conventional serological methods may be insufficient.

13.
Microbiol Resour Announc ; : e0056724, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39190670

RESUMEN

Clostridium perfringens is a leading cause of human gastroenteritis. The genome sequence of C. perfringens CP201 from an asymptomatic rhesus monkey, Macaca mulatta, consists of one chromosome (3,241,413 bp; 30.22% G + C) and one plasmid (92,983 bp; 28.43% G + C), encoding 2,935 genes, 94 tRNAs, 30 rRNAs, and 1 CRISPR array.

14.
Bull Exp Biol Med ; 177(3): 379-382, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39134810

RESUMEN

Variable number tandem repeat (VNTR) polymorphisms of the human neonatal IgG Fc receptor α-chain gene (FCGRT) are known to influence the expression levels of FCGRT and IgG in serum. Monkeys are considered to be a relevant biological model for studying the effects of immunobiological drugs. The study determined the functional VNTR polymorphisms of the FCGRT gene in 109 male rhesus macaques from the nursery of the Kurchatov Complex of Medical Primatology. PCR amplification of samples was carried out followed by electrophoretic separation of DNA fragments in a 2% agarose gel. Individual DNA amplification products were sequenced (according to Sanger system) in forward and reverse directions to confirm the specificity. The genotyping showed that the VNTR polymorphism of the FCGRT gene in the studied population of rhesus macaques is presented by 9 variants. The frequency of the VNTR5 allele associated with lower IgG levels was 14.2%, and the most common one was the VNTR7 allele (25.2%). We also identified alleles that have not been previously reported: VNTR3, VNTR4, VNTR6, VNTR8, and VNTR9. The study allows to consider rhesus macaques as a potential model for studying the immunological response depending on the genetic VNTR variant of FCGRT.


Asunto(s)
Alelos , Macaca mulatta , Repeticiones de Minisatélite , Polimorfismo Genético , Animales , Macaca mulatta/genética , Repeticiones de Minisatélite/genética , Polimorfismo Genético/genética , Masculino , Frecuencia de los Genes/genética , Inmunoglobulina G/sangre , Inmunoglobulina G/genética , Receptores Fc/genética , Genotipo , Antígenos de Histocompatibilidad Clase I
15.
Int J Mol Sci ; 25(15)2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39126016

RESUMEN

A thorough characterization of induced pluripotent stem cells (iPSCs) used with in vitro models or therapeutics is essential. Even iPSCs derived from a single donor can exhibit variability within and between cell lines, which can lead to heterogeneity in results and hinder the promising future of cell replacement therapies. In this study, the cell seeding density of human and rhesus monkey iPSCs was tested to maximize the cell line-specific yield of the generated cardiomyocytes. We found that, despite using the same iPSC generation and differentiation protocols, the cell seeding density for the cell line-specific best differentiation efficiency could differ by a factor of four for the four cell lines used here. In addition, the cell lines showed differences in the range of cell seeding densities that they could tolerate without the severe loss of differentiation efficiency. Overall, our data show that the cell seeding density is a critical parameter for the differentiation inefficiency of primate iPSCs to cardiomyocytes and that iPSCs generated with the same episomal approach still exhibit considerable heterogeneity. Therefore, individual characterization of iPSC lines is required, and functional comparability with in vivo processes must be ensured to warrant the translatability of in vitro research with iPSCs.


Asunto(s)
Diferenciación Celular , Células Madre Pluripotentes Inducidas , Macaca mulatta , Miocitos Cardíacos , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/metabolismo , Miocitos Cardíacos/citología , Humanos , Animales , Línea Celular , Recuento de Células , Técnicas de Cultivo de Célula/métodos , Células Cultivadas
16.
Saudi J Med Med Sci ; 12(3): 210-215, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39055072

RESUMEN

Background: The RHD gene is one of the most complex blood group genes. The molecular background of the RHD gene in RhD-negative and RhD-positive individuals varies within and among different populations. Knowing the molecular basis of the RHD gene in a specific population is required to establish effective genotyping methods. While the molecular basis has been revealed in many ethnicities, such as Caucasians and Black Africans, it still requires elucidation in Arabs. Objectives: The aim of this study was to gain insights into the molecular basis of RhD-positive and RhD-negative phenotypes in Saudi donors. Materials and Methods: Conventional serological tests were used to determine the Rh phenotypes in 136 Saudi donors by typing D, C, c, E, and e antigens. Multiplex-PCR and Single Specific Primer-PCR were used to detect the presence of exons 3, 4, and 7 and the hybrid Rhesus box gene, respectively, in RhD-negative and/or RhD-positive samples. Results: Of the 136 samples, 70 were RhD positive and 66 were RhD negative. None of the RhD-negative donors had any of the three tested exons, whereas the hybrid Rhesus box gene was detected in all, indicating the zygosity status of the RHD deletion allele. The hybrid Rhesus box gene was detected in 79% of the RhD-positive individuals, suggesting high frequencies of RHD-negative haplotypes. Conclusions: The study findings indicate that Saudis with the RhD-negative phenotype are likely to have an entire RHD deletion in the homozygous state. However, a more comprehensive analysis of variant RHD alleles in the Saudi population is required to implement effective and dedicated molecular RHD typing strategies.

17.
Elife ; 132024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39083414

RESUMEN

Body movement does not significantly increase neuronal activity in the primary visual cortex of marmosets, in contrast to the effects observed in mice.


Asunto(s)
Callithrix , Animales , Ratones , Callithrix/fisiología , Corteza Visual Primaria/fisiología , Neuronas/fisiología , Movimiento/fisiología , Corteza Visual/fisiología
18.
Sci Rep ; 14(1): 15677, 2024 07 08.
Artículo en Inglés | MEDLINE | ID: mdl-38977718

RESUMEN

Liver fibrosis is an important pathological process in chronic liver disease and cirrhosis. Recent studies have found a close association between intestinal microbiota and the development of liver fibrosis. To determine whether there are differences in the intestinal microbiota between rhesus macaques with liver fibrosis (MG) and normal rhesus macaques (MN), fecal samples were collected from 8 male MG and 12 male MN. The biological composition of the intestinal microbiota was then detected using 16S rRNA gene sequencing. The results revealed statistically significant differences in ASVs and Chao1 in the alpha-diversity and the beta-diversity of intestinal microbiota between MG and MN. Both groups shared Prevotella and Lactobacillus as common dominant microbiota. However, beneficial bacteria such as Lactobacillus were significantly less abundant in MG (P = 0.02). Predictive functional analysis using PICRUSt2 gene prediction revealed that MG exhibited a higher relative abundance of functions related to substance transport and metabolic pathways. This study may provide insight into further exploration of the mechanisms by which intestinal microbiota affect liver fibrosis and its potential future use in treating liver fibrosis.


Asunto(s)
Microbioma Gastrointestinal , Cirrosis Hepática , Macaca mulatta , Metagenómica , ARN Ribosómico 16S , Animales , Macaca mulatta/microbiología , Microbioma Gastrointestinal/genética , Cirrosis Hepática/microbiología , Cirrosis Hepática/genética , Cirrosis Hepática/patología , Masculino , ARN Ribosómico 16S/genética , Metagenómica/métodos , Heces/microbiología , Metagenoma , Bacterias/genética , Bacterias/clasificación , Bacterias/aislamiento & purificación
19.
Elife ; 132024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38984395

RESUMEN

Subpopulations of neurons in the subthalamic nucleus have distinct activity patterns that relate to the three hypotheses of the Drift Diffusion Model.


Asunto(s)
Neuronas , Núcleo Subtalámico , Núcleo Subtalámico/fisiología , Neuronas/fisiología , Humanos , Animales , Modelos Neurológicos
20.
Elife ; 132024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38968311

RESUMEN

Object classification has been proposed as a principal objective of the primate ventral visual stream and has been used as an optimization target for deep neural network models (DNNs) of the visual system. However, visual brain areas represent many different types of information, and optimizing for classification of object identity alone does not constrain how other information may be encoded in visual representations. Information about different scene parameters may be discarded altogether ('invariance'), represented in non-interfering subspaces of population activity ('factorization') or encoded in an entangled fashion. In this work, we provide evidence that factorization is a normative principle of biological visual representations. In the monkey ventral visual hierarchy, we found that factorization of object pose and background information from object identity increased in higher-level regions and strongly contributed to improving object identity decoding performance. We then conducted a large-scale analysis of factorization of individual scene parameters - lighting, background, camera viewpoint, and object pose - in a diverse library of DNN models of the visual system. Models which best matched neural, fMRI, and behavioral data from both monkeys and humans across 12 datasets tended to be those which factorized scene parameters most strongly. Notably, invariance to these parameters was not as consistently associated with matches to neural and behavioral data, suggesting that maintaining non-class information in factorized activity subspaces is often preferred to dropping it altogether. Thus, we propose that factorization of visual scene information is a widely used strategy in brains and DNN models thereof.


When looking at a picture, we can quickly identify a recognizable object, such as an apple, applying a single word label to it. Although extensive neuroscience research has focused on how human and monkey brains achieve this recognition, our understanding of how the brain and brain-like computer models interpret other complex aspects of a visual scene ­ such as object position and environmental context ­ remains incomplete. In particular, it was not clear to what extent object recognition comes at the expense of other important scene details. For example, various aspects of the scene might be processed simultaneously. On the other hand, general object recognition may interfere with processing of such details. To investigate this, Lindsey and Issa analyzed 12 monkey and human brain datasets, as well as numerous computer models, to explore how different aspects of a scene are encoded in neurons and how these aspects are represented by computational models. The analysis revealed that preventing effective separation and retention of information about object pose and environmental context worsened object identification in monkey cortex neurons. In addition, the computer models that were the most brain-like could independently preserve the other scene details without interfering with object identification. The findings suggest that human and monkey high level ventral visual processing systems are capable of representing the environment in a more complex way than previously appreciated. In the future, studying more brain activity data could help to identify how rich the encoded information is and how it might support other functions like spatial navigation. This knowledge could help to build computational models that process the information in the same way, potentially improving their understanding of real-world scenes.


Asunto(s)
Imagen por Resonancia Magnética , Redes Neurales de la Computación , Animales , Humanos , Masculino , Macaca mulatta/fisiología , Vías Visuales/fisiología , Percepción Visual/fisiología , Corteza Visual/fisiología , Femenino , Estimulación Luminosa , Modelos Neurológicos
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