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Местный контроль за судьбой клеток Т в лимфатических узлах безопасно и надежно меняет автоматический иммунитет миелина.

Развитие толерогенных антигенных иммунотерапий может преодолеть ограничения существующих методов лечения подстрекательских аутоиммунных заболеваний путем достижения мощной и долговременной ремиссии без воздействия на здоровый иммунный надзор. Здесь мы поставляем полимерные хранилища с ограниченной диффузией на лимфатические узлы для местного руководства судьбами клеток Т для лечения множественного склероза (MS), аутоиммунного заболевания, которое происходит, когда иммунная система ошибочно атакует миелин. В доклинических моделях MS депо, нагруженные миелином самоантигеном и терпимое отношение

Совпадение в аннотации оригинала
Development of tolerogenic, antigen-specific immunotherapies could overcome limitations of existing treatments for inflammatory autoimmune d … ts offer favorable chemistry and manufacturing control features and are well tolerated in non-human primates. This work supports a clinically feasible concept for inducing safe, effective, antigen-specific tolerance without systemic or repeated dosing.

Estrogen receptor activation remodels TEAD1 gene expression to alleviate hepatic steatosis.

Sex-based differences in obesity-related hepatic malignancies suggest the protective roles of estrogen. Using a preclinical model, we dissected estrogen receptor (ER) isoform-driven molecular responses in high-fat diet (HFD)-induced liver diseases of male and female mice treated with or without an estrogen agonist by integrating liver multi-omics data. We found that selective ER activation recovers HFD-induced molecular and physiological liver phenotypes. HFD and systemic ER activation altered core liver pathways, beyond lipid metabolism, that are consistent between mice and primates. By inclu…

Regulatory Considerations in the Approval of Rezafungin (Rezzayo) for the Treatment of Candidemia and Invasive Candidiasis in Adults.

On 22 March 2023, the FDA approved rezafungin (Rezzayo) for the treatment of candidemia and invasive candidiasis in adults with limited or n … fungin is noninferior to the comparator echinocandin. Nonclinical studies of rezafungin in nonhuman primates identified a neurotoxicity safety signal; however, rezafungin's safety profile in the completed clinical studies was similar to other Food and Drug Administration-approved echinocandins. Here we describe the rationale for this approval and important …

Oesophagostomum stephanostomum causing parasitic granulomas in wild chimpanzees (Pan troglodytes verus) of Taï National Park, Côte d'Ivoire.

Nematodes belonging to the genus Oesophagostomum frequently infect wild chimpanzees (Pan troglodytes) across widely separated field sites. N … ences from this study were identical to the only other published sequences from nodules in nonhuman primates-those from the wild chimpanzees of Gombe, Tanzania.

An intranasal nanoparticle STING agonist protects against respiratory viruses in animal models.

Respiratory viral infections cause morbidity and mortality worldwide. Despite the success of vaccines, vaccination efficacy is weakened by t … al interferon-dependent and interferon-independent pathways in mice, hamsters, as well as non-human primates. Our results thus implicate NanoSTING as a broad-spectrum immune activator for controlling respiratory virus infection.

Human Stem Cell-Derived Cardiomyocytes Integrate Into the Heart of Monkeys With Right Ventricular Pressure Overload.

Cardiac ventricular pressure overload affects patients with congenital heart defects and can cause cardiac insufficiency. Grafts of stem cel … esults demonstrate that grafted cardiomyocytes mature and integrate into the myocardium of nonhuman primates modeling right ventricular pressure overload.

Size-reduced DREADD derivatives for AAV-assisted multimodal chemogenetic control of neuronal activity and behavior.

Designer receptors exclusively activated by designer drugs (DREADDs) are engineered G-protein-coupled receptors that afford reversible manip … nity for multiplexed interrogation and/or intervention in neuronal regulation in mice and non-human primates.

Conserved transcriptional regulation by BRN1 and BRN2 in neocortical progenitors drives mammalian neural specification and neocortical expansion.

The neocortex varies in size and complexity among mammals due to the tremendous variability in the number and diversity of neuronal subtypes … ically modified macaques provides evidence that these molecular pathways are conserved in non-human primates. Our findings thus demonstrate that BRN1/2 are central regulators of gene expression programs in neocortical progenitors critical to determine brain size during evolution.

Contribution of ultrasound examination in diagnosing platynosomiasis and correlation with macro and microscopic findings in callitrichids kept under human care.

BACKGROUND: Platynosomiasis in non-human primates kept under human care causes chronic disease of the bile ducts and liver, which initially presents with nonspecific signs and can culminate in the death of the animal. Diagnosing this disease is a challenge, and an ultrasound examination can be an excellent tool when it is suspected. METHODS: This study describes the ultrasound findings from 57 marmosets with suspected infection by Platynosomum sp., the correlated hepatobiliary changes, and the anatomopathological findings that confirmed the occurrence of platynosomiasis. RESULTS: In six marm…

Detection of Mycobacterium bovis in Free-Ranging Sapajus nigritus, Argentina.

Mycobacterium bovis and Mycobacterium tuberculosis are the most relevant among pathogenic mycobacteria, both belonging to the M. tuberculosi … ultiplex PCR further validated the presence of M. bovis genes. Cases of tuberculosis in platyrrhine primates have only been reported in animals maintained in captivity. We describe for the first time the pathological and molecular findings of M. bovis infection in a free-ranging platyrrhine monkey within an area of intense human-wildlife interaction, which …

Perception and Memory in the Ventral Visual Stream and Medial Temporal Lobe.

Perception and memory are traditionally thought of as separate cognitive functions, supported by distinct brain regions. The canonical persp … l perceptual processing. In this article, we review relevant research conducted in humans, nonhuman primates, and rodents. We conclude that the evidence is largely inconsistent with theoretical proposals that draw sharp functional boundaries between perceptual and memory systems in the brain. Instead, the weight of the empirical findings is best captured b …

Rhesus monkeys exhibiting spontaneous ritualistic behaviors resembling obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a chronic and debilitating psychiatric disorder that affects ∼2%-3% of the population globally. Studying spontaneous OCD-like behaviors in non-human primates may improve our understanding of the disorder. In large rhesus monkey colonies, we found 10 monkeys spontaneously exhibiting persistent sequential motor behaviors (SMBs) in individual-specific sequences that were repetitive, time-consuming and stable over prolonged periods. Genetic analysis revealed severely damaging mutations in genes associated with OCD risk in humans. Brain imaging showed that mon…

Clinical and histopathological investigation of symmetrical alopecia with associated chronic pruritus in tufted capuchin monkeys (Sapajus apella apella).

BACKGROUND: Symmetrical alopecia is a common symptom of endocrine and autoimmune diseases, which are rarely manifested with pruritus. Increased levels of stress in primates have been presented with increased levels of pruritus and alopecia appearance. METHODS: A pruritic and alopecic disease was investigated in a group of tufted capuchin monkeys (N = 12), but due to ethical reasons, four random animals were further investigated by numerous diagnostic methods. The impact of food and enclosure enrichment was assessed and observed over a 2-year period. RESULTS: Histopathology of four random tuf…

Multitargeted Opioid Ligand Discovery as a Strategy to Retain Analgesia and Reduce Opioid-Related Adverse Effects.

The global "opioid crisis" has placed enormous pressure on the opioid ligand discovery community to produce novel opioid analgesics with sup … tial agonists have superior preclinical therapeutic indices to morphine and/or fentanyl in nonhuman primates and are also considered promising. Based on the poor preclinical and clinical therapeutic indices of cebranopadol, which is a full agonist at MOP, DOP, and NOP receptors and a partial agonist at the KOP receptor, this pharmacologic template should b …

A Library of Polymer-based Microelectrode Array Designs for Recording from the Brain of Different Animal Models.

Large-scale network recording technology is critical in linking neural activity to behavior. Stable, long-term recordings collected from beh … foreign body response and prolong the lifetime of neural interfacing devices. Rodents and nonhuman primates (NHP) are commonly used animal models in neuroscience and neuroengineering studies. Specially designed MEAs that capture morphological features of different animal brains and various brain structures are powerful tools to simultaneously obtain neura …

Hominoid SVA-lncRNA AK057321 targets human-specific SVA retrotransposons in SCN8A and CDK5RAP2 to initiate neuronal maturation.

SINE-VNTR-Alu (SVA) retrotransposons arose and expanded in the genome of hominoid primates concurrent with the slowing of brain maturation. We report genes with intronic SVA transposons are enriched for neurodevelopmental disease and transcribed into long non-coding SVA-lncRNAs. Human-specific SVAs in microcephaly CDK5RAP2 and epilepsy SCN8A gene introns repress their expression via transcription factor ZNF91 to delay neuronal maturation. Deleting the SVA in CDK5RAP2 initiates multi-dimensional and in SCN8A selective sodium current neuronal maturation by upregulating these genes. SVA-lncRNA AK…

Downclimbing and the evolution of ape forelimb morphologies.

The forelimbs of hominoid primates (apes) are decidedly more flexible than those of monkeys, especially at the shoulder, elbow and wrist joints. It is tempting to link the greater mobility of these joints to the functional demands of vertical climbing and below-branch suspension, but field-based kinematic studies have found few differences between chimpanzees and monkeys when comparing forelimb excursion angles during vertical ascent (upclimbing). There is, however, a strong theoretical argument for focusing instead on vertical descent (downclimbing), which motivated us to quantify the effects…

Gastrointestinal and respiratory parasites in captive mammals at Rabat zoo, with the first record of Capillaria spp. in the Fennec fox (Vulpes zerda).

The aim of the present study was to broaden the understanding of parasitism in captive wild mammals in Morocco. For this purpose, an investigation on gastrointestinal and respiratory parasites in African mammals from Rabat Zoo was carried out. A total of 47 fecal samples were collected from 30 species from November 2021 to March 2022 and examined macroscopically and microscopically. Parasites were detected in 21 species at a prevalence of 70%, with a parasite positivity rate of 89% in artiodactyls, 50% in perissodactyls, 67% in both carnivores and primates. No parasitic infection was detected …

AAV-Vectored Expression of Marburg Virus-Neutralizing Antibody MR191 Provides Complete Protection From Challenge in a Guinea Pig Model.

Although there are no approved countermeasures available to prevent or treat disease caused by Marburg virus (MARV), potently neutralizing monoclonal antibodies (mAbs) derived from B cells of human survivors have been identified. One such mAb, MR191, has been shown to provide complete protection against MARV in nonhuman primates. We previously demonstrated that prophylactic administration of an adeno-associated virus (AAV) expressing MR191 protected mice from MARV. Here, we modified the AAV-MR191 coding sequence to enhance efficacy and reevaluated protection in a guinea pig model. Remarkably, …

Effects of adjuvants in a rabies-vectored Ebola virus vaccine on protection from surrogate challenge.

Ebola virus is the primary contributor to the global threat of filovirus severe hemorrhagic fever, and Ebola virus disease has a case fatality rate of 50-90%. An inactivated, bivalent filovirus/rabies virus vaccine, FILORAB1, consists of recombinant rabies virus virions expressing the Ebola virus glycoprotein. FILORAB1 is immunogenic and protective from Ebola virus challenge in mice and non-human primates, and protection is enhanced when formulated with toll-like receptor 4 agonist Glucopyranosyl lipid adjuvant (GLA) in a squalene oil-in-water emulsion (SE). Through an adjuvant comparison in m…