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Biology subjects

Perez, O.

Publications and source records attributed to Perez, O..

7 recordsLinked to original sources

Oral Administration of Hyperimmune Eggs Induces Mucosal IgA Responses, Anti-Idiotypic Antibodies, and HIV-1 Neutralizing Activity: A Proof-of-Concept Preclinical Study

The development of effective mucosal vaccination strategies against human immunodeficiency virus type 1 (HIV-1) remains a major challenge. This study investigated whether oral administration of hyperimmune anti-HIV-1 gp120 immunoglobulin Y (IgY) could induce mucosal and systemic immune responses in outbred felines through an anti-idiotypic network mechanism. A controlled immunization study involving 42 cats (18 immunized and 24 controls) was conducted to evaluate mucosal anti-gp120 IgA responses. In addition, a proof-of-concept cohort was used to investigate anti-idiotypic antibody (Ab-3) induction, competitive inhibition, and HIV-1 neutralization. Anti-gp120 IgA antibodies were detected in saliva from immunized animals but were absent or present at low levels in controls, indicating activation of mucosal immunity. All immunized cats developed detectable Ab-3 responses against HIV-1 gp120. Competitive inhibition assays demonstrated specific in hibition of gp120-related interactions, supporting the presence of biologically relevant anti-idiotypic antibodies. Furthermore, sera from immunized animals significantly reduced HIV-1 infectivity in a TZM-bl luciferase-based neutralization assay, with viral inhibition exceeding 60% at selected dilutions. Collectively, these findings demonstrate that oral administration of hyperimmune anti-gp120 IgY can induce mucosal IgA responses, systemic anti-idiotypic antibodies, and functional HIV-1 neutralizing activity. This preclinical proof-of-concept study supports further investigation of IgY-based oral immunization as a potential platform for HIV vaccine development. However, the Ab3, competitive inhibition assay using Ab3, and HIV-1 neutralization studies should be regarded as exploratory proof-of-concept investigations designed to establish biological plausibility rather than definitive efficacy.

immunology↗

Flexible tapping synchronization in macaques: dynamic switching of timing strategies within rhythmic sequences

The ability to synchronize bodily movements with regular auditory rhythm across a broad range of tempos underlies humans capacity for playing music and dancing. This capability is prevalent across human cultures but relatively uncommon among non-human species. Recent research indicates that monkeys can predictively synchronize to regular, isochronous metronomes, exhibiting a preference for visual rather than auditory sequences. In this study, we trained macaques to perform a visual synchronization tapping task, testing their synchronization abilities over a wide tempo range and characterizing their precision and accuracy in timing intervals throughout rhythmic sequences. Additionally, we investigated whether the macaques employed priors or error correction strategies to maintain synchrony with the metronome. Our findings demonstrate that, following sufficient training, macaques exhibit a remarkable capability to synchronize across diverse tempos. Through an inference model analysis, we identified two distinct timing control strategies used by the macaques: an initial strong regression-to-the-mean effect transitioning dynamically into a more precise error correction approach at their preferred tempo. These results provide compelling evidence that primates possess sophisticated rhythmic timing mechanisms, effectively leveraging internal and external cues to regulate their tapping behavior according to task demands. NEW & NOTEWORTHYWe trained macaques in a visual synchronization tapping task and using an inference model we found that they are highly precise and accurate in their rhythmic performance. The model also captured a dynamic switch in behavior. At the beginning of the task, the monkeys used their prior knowledge about the interval statistics and then switched to an error correction mechanism to generate intervals depending on the previously produced duration.

neuroscience↗

Rhythmic tapping to a moving beat: motion kinematics overrules motion naturalness.

Beat induction is the cognitive ability that allow humans to listen to a regular pulse in music and move in synchrony with it. Although auditory rhythmic cues are known to induce more consistent synchronization than flashing visual metronomes, this asymmetry can be canceled out by visual moving metronomes. Here, we investigated whether the naturalness of the visual motion or its kinematics could provide a synchronization advantage over flashing metronomes. Subjects tap in sync with visual isochronous metronomes defined by vertically or horizontally accelerating and decelerating motion, either congruent or not with natural gravity, and then continue tapping with no metronome. We found that motion kinematics was the predominant factor determining rhythm synchronization, as accelerating moving metronomes in either cardinal direction produced more precise and predictive tapping than decelerating or flashing conditions. Notably, a Bayesian observer model revealed that error correction during tapping synchronization and regression towards the mean in accuracy during tapping continuation in the absence of external cues are optimal control strategies independently of the moving properties of the visual metronomes. Our results support the notion that accelerating visual metronomes convey a strong sense of beat as seen in the cueing movements of an orchestra director.

neuroscience↗

Different time encoding strategies within the medial premotor areas of the primate

The measurement of time in the subsecond scale is critical for many sophisticated behaviors, yet its neural underpinnings are largely unknown. Recent neurophysiological experiments from our laboratory have shown that the neural activity in the medial premotor areas (MPC) of macaques can represent different aspects of temporal processing. During interval categorization, we found that preSMA encodes a subjective category limit by reaching a peak of activity at a time that divides the set of test intervals into short and long. We also observed neural signals associated with the category selected by the subjects and the reward outcomes of the perceptual decision. On the other hand, we have studied the behavioral and neurophysiological basis of rhythmic timing. First, we have shown in different tapping tasks that macaques are able to produce predictively and accurately intervals that are cued by auditory or visual metronomes or when intervals are produced internally without sensory guidance. In addition, we found that the rhythmic timing mechanism in MPC is governed by different layers of neural clocks. Next, the instantaneous activity of single cells shows ramping activity that encode the elapsed or remaining time for a tapping movement. In addition, we found MPC neurons that build neural sequences, forming dynamic patterns of activation that flexibly cover all the produced interval depending on the tapping tempo. This rhythmic neural clock resets on every interval providing an internal representation of pulse. Furthermore, the MPC cells show mixed selectivity, encoding not only elapsed time, but also the tempo of the tapping and the serial order element in the rhythmic sequence. Hence, MPC can map different task parameters, including the passage of time, using different cell populations. Finally, the projection of the time varying activity of MPC hundreds of cells into a low dimensional state space showed circular neural trajectories whose geometry represent the internal pulse and the tapping tempo. Overall, these findings support the notion that MPC is part of the core timing mechanism for both single interval and rhythmic timing, using neural clocks with different encoding principles, probably to flexibly encode and mix the timing representation with other task parameters.

neuroscience↗

Premotor population dynamics as neural substrate for auditory and visual rhythmic entrainment

The neural substrate for beat extraction and response entrainment to auditory and visual rhythms is still unknown. Here we analyzed the population activity of hundreds of medial premotor neurons of monkeys performing an isochronous tapping guided by brief flashing stimuli or auditory tones. The animals showed a strong bias towards visual than auditory metronomes, with rhythmic tapping that was more precise and accurate on the former. The population dynamics shared the following properties across modalities: the circular dynamics of the neural trajectories formed a regenerating loop for every produced interval; the trajectories converged in similar state space at tapping times resetting the clock; the tempo of the synchronized tapping was encoded in the trajectories by a combination of amplitude modulation and temporal scaling. In addition, the modality induced a displacement in the neural trajectories in auditory and visual subspaces without greatly altering time keeping mechanism. These results suggest that the interaction between the MPC amodal internal representation of pulse and a modality specific external input generates a neural rhythmic clock whose dynamics governs rhythmic tapping execution across senses.

neuroscience↗

In vivo administration of anti-HIV hyper-immune eggs induces anti-anti-idiotypic antibodies against HIV gp120 peptides (fragments 308-331 and 421-438) and against HIV gp41 peptide (fragment 579-601) which have demonstrable protective capacity.

Isolation of antibodies from the egg yolk of chickens is of particular interest as a source of specific antibodies for oral administration to prevent infections and use them as immunodiagnostic reagents. The use of birds in antibody production results in a reduction in the use of laboratory animals. Immunized chickens produce larger quantities of antibodies (2000 mg IgY/month) than rodents (200 mg IgG/month) in the laboratory. According to Jernes network theory, it is possible to produce an antibody against the antigen-binding site of another antibody. This study assessed the hypothesis that immunization with viral peptides (immunogens) could provide a potent immune response that could be evaluated in chicken eggs. Human immunodeficiency virus 1(HIV-1) is used as an immunogen. The second hypothesis was that an orally administered antibody stimulates the production of a complementary antibody, the so-called anti-idiotypic antibody, which can potentially be therapeutical. This study reports and analyzes the use of eggs as therapeutic agents. We wanted to test the hypothesis that feeding chicks with hyperimmune eggs stimulates the production of anti-anti-idiotypic antibodies that neutralize the original HIV antigen fragments 308-331 or 421-438 of gp120 or fragment 579-601 of gp41. Future research could entail an anti-idiotype strategy for prophylactic vaccines. It is vital to note that it may need an anti-idiotype response to prime immunity against an HIV viral epitope, which may be used as a secondary element. The use of anti-idiotype immune responses in infected individuals may shift the balance of the immune system, allowing the organism to manage HIV infection. Therefore, it may be an avenue for immunotherapy to improve the fight against HIV infections. However, more studies and clinical trials are required to demonstrate similar human immune responses as observed in birds.

immunology↗

A 3500-year-old leaf from a Pharaonic tomb reveals that New Kingdom Egyptians were cultivating domesticated watermelon

Domestication of the watermelon (Citrullus lanatus) has alternatively been placed in South Africa, the Nile valley, or more recently West Africa, with the oldest archeological evidence coming from Libya and Egypt. The geographic origin and domestication of watermelons has therefore remained unclear. Using extensive nuclear and plastid genomic data from a 3,560-year-old Citrullus leaf from a mummys sarcophagus and skimmed genomes for representatives of the seven extant species of Citrullus, we show that modern cultivars and the ancient plant uniquely share mutations in a lycopene metabolism gene (LYCB) affecting pulp color and a stop codon in a transcription factor regulating bitter cucurbitacin compounds. This implies that the plant we sequenced had red-fleshed and sweet fruits and that New Kingdom Egyptians were cultivating domesticated watermelons. The genomic data also identify extant Sudanese watermelons with white, sweet pulp as the closest relatives of domesticated watermelons.\n\nSignificance statementWith some 197.8 million tons in 2017, watermelon, Citrullus lanatus, is among the Worlds most important crops, yet its area of origin and domestication have remained unclear, with competing hypotheses favoring South Africa, West Africa, Central Africa, or the Nile valley. We generated extensive nuclear and plastid genomic data from a 3500-year-old leaf from a Pharaonic sarcophagus and performed genome skimming for representatives of all other Citrullus species to compare key genes involved in fruit bitterness and color. White-fleshed, non-bitter melons from southern Sudan are the closest relatives of domesticated watermelon, and the ancient genome shares unique alleles with a red-fleshed, non-bitter domesticated form (but no wild forms), implying that 18th Dynasty Egyptians were cultivating domesticated watermelon by 3500 years ago.

evolutionary biology↗