Stereotyped B-Cell Receptor Immunoglobulins in B-Cell Lymphomas.

Thorough examination of clonotypic B-cell receptor immunoglobulin (BcR IG) gene rearrangement sequences in patients with mature B-cell malignancies has revealed significant repertoire restrictions, leading to the identification of subsets of patients expressing highly similar, stereotyped BcR IG. This discovery strongly suggests selection by common epitopes or classes of structurally similar epitopes in the development of these tumors. Initially observed in chronic lymphocytic leukemia (CLL), where the stereotyped fraction accounts for a substantial fraction of patients, stereotyped BcR IGs have also been identified in other mature B-cell malignancies, including mantle cell lymphoma (MCL) and splenic marginal zone lymphoma (SMZL).Further comparisons across different entities have indicated that stereotyped IGs are predominantly "disease-biased," indicating distinct immune pathogenetic trajectories. Notably, accumulating evidence suggests that molecular subclassification of mature B-cell malignancies based on BcR IG stereotypy holds biological and clinical relevance. Particularly in CLL, patients belonging to the same subset due to the expression of a specific stereotyped BcR IG exhibit consistent biological backgrounds and clinical courses, especially for major and extensively studied subsets. Therefore, robust assignment to stereotyped subsets may aid in uncovering mechanisms underlying disease initiation and progression, as well as refining patient risk stratification. In this chapter, we offer an overview of recent studies on BcR IG stereotypy in mature B-cell malignancies and delineate past and present methodological approaches utilized for the identification of stereotyped BcR IG.

Influencia de la edad en el contenido de fenoles y ligninas en Gmelina arborea (Lamiaceae) / The influence of age on the phenolic contents and lignins of Gmelina arborea (Lamiaceae)

Resumen Introducción: La melina (Gmelina arborea), es una especie de gran interés por su madera y propiedades medicinales. En Costa Rica, existen clones genéticamente superiores que se propagan sin el conocimiento de la edad ontogénica y fisiológica de los materiales. Objetivo: Evaluar la relación del contenido de fenoles y ligninas en hojas, peciolos, tallos y raíces de plantas con diferentes edades. Métodos: Los contenidos de fenoles y ligninas totales se determinaron mediante el método colorimétrico de Folin-Ciocalteu y el método de extracción alcalina, respectivamente. Para la investigación se eligieron plantas in vitro "año cero" y árboles de año y medio, cuatro, siete y 20 años. El muestreo se realizó en marzo y abril del 2021. Resultados: Se demostró que todas las partes de la planta analizadas contienen compuestos fenólicos y ligninas, independientemente de su edad. No hubo una correlación positiva entre la edad con el contenido de fenoles y ligninas para ninguna condición de desarrollo, pues los valores más altos no se obtuvieron en los árboles más longevos. Los extractos de hojas de las plantas in vitro y los árboles de siete años mostraron, respectivamente, los contenidos más altos de fenoles y ligninas para todas las condiciones (P < 0.05). Los valores promedio más bajos de compuestos fenólicos para todas las condiciones se obtuvieron en los árboles de cuatro años. Respecto a las ligninas, el contenido más bajo se presentó en las raíces más longevas, aunque la tendencia no se mantuvo para el resto de las partes de la planta. Conclusiones: La investigación muestra los primeros resultados del contenido de compuestos fenólicos y ligninas presentes en diferentes tejidos de una especie forestal de edades diferentes. Por lo tanto, son los primeros valores de referencia acerca del compromiso bioquímico para la síntesis fenólica según la edad y el estado de desarrollo específico de una planta leñosa.

Abstract Introduction: Melina (Gmelina arborea) is a tree species of great interest for its wood and medicinal properties. In Costa Rica, there are genetically superior clones that are propagated without knowledge of the ontogenic and physiological age of the materials. Objective: To evaluate how age influences the content of phenols and lignins in leaves, petioles, stems, and roots of melina plants. Methods: The total phenolic and lignins contents were determined using Folin-Ciocalteu colorimetric method and alkaline extraction method, respectively. Plants of five different ages were chosen for the investigation (in vitro plants "year 0" and trees of a year and a half, four, seven and 20 years). Sampling was done in March and April 2021. Results: All parts of the plant analyzed contain phenolic compounds and lignins, regardless of their age. There was no positive correlation between age and phenol and lignin content for any development condition, since the highest values were not obtained in the oldest trees. Leaf extracts from in vitro plants and seven-year-old trees showed, respectively, the highest phenol and lignin contents for all conditions (P < 0.05). The lowest average values of phenolic compounds for all conditions were obtained in four-year-old trees. Regarding lignins, the lowest content occurred in the oldest roots, although the trend was not maintained for the rest of the plant parts. Conclusions: This study provides the first results of the content of phenolic compounds and lignins present in different tissues of a forest species of different ages. Therefore, they are the first reference values about the biochemical commitment for phenolic synthesis according to the age and the specific developmental stage of a woody plant.

Border-Associated Macrophages: From Embryogenesis to Immune Regulation.

Border-associated macrophages (BAMs) play a pivotal role in maintaining brain homeostasis and responding to pathological conditions. Understanding their origins, characteristics, and roles in both healthy and diseased brains is crucial for advancing our knowledge of neuroinflammatory and neurodegenerative diseases. This review addresses the ontogeny, replenishment, microenvironmental regulation, and transcriptomic heterogeneity of BAMs, highlighting recent advancements in lineage tracing and fate-mapping studies. Furthermore, we examine the roles of BAMs in maintaining brain homeostasis, immune surveillance, and responses to injury and neurodegenerative diseases. Further research is crucial to clarify the dynamic interplay between BAMs and the brain's microenvironment in health and disease. This effort will not only resolve existing controversies but also reveal new therapeutic targets for neuroinflammatory and neurodegenerative disorders, pushing the boundaries of neuroscience.

Exploring the Impact of Developmental Clearance Saturation on Propylene Glycol Exposure in Adults and Term Neonates Using Physiologically Based Pharmacokinetic Modeling.

Propylene glycol (PG) is a pharmaceutical excipient which is generally regarded as safe (GRAS), though clinical toxicity has been reported. PG toxicity has been attributed to accumulation due to saturation of the alcohol dehydrogenase (ADH)-mediated clearance pathway. This study aims to explore the impact of the saturation of ADH-mediated PG metabolism on its developmental clearance in adults and neonates and assess the impact of a range of doses on PG clearance saturation and toxicity. Physiologically based pharmacokinetic (PBPK) models for PG in adults and term neonates were developed using maximum velocity (Vmax) and Michaelis-Menten's constant (Km) of ADH-mediated metabolism determined in vitro in human liver cytosol, published physicochemical, drug-related and ADH ontogeny parameters. The models were validated and used to determine the impact of dosing regimen on PG clearance saturation and toxicity in adults and neonates. The Vmax and Km of PG in human liver cytosol were 1.57 nmol/min/mg protein and 25.1 mM, respectively. The PG PBPK model adequately described PG PK profiles in adults and neonates. The PG dosing regimens associated with saturation and toxicity were dependent on both dose amount and cumulative in standard dosing frequencies. Doses resulting in saturation were higher than those associated with clinically observed toxicity. In individuals without impaired clearance or when PG exposure is through formulations that contain excipients with possible interaction with PG, a total daily dose of 100-200 mg/kg/day in adults and 25-50 mg/kg/day in neonates is unlikely to result in toxic PG levels or PG clearance saturation.

Captive Breeding and Early Developmental Dynamics of Cirrhinus mrigala: Implications for Sustainable Seed Production.

Cirrhinus mrigala is an important edible fish with a significant aquaculture contribution in Southeast Asian countries. The current study aims to enhance our understanding of the developmental biology of Cirrhinus mrigala, which is crucial for implementing sustainable fish farming practices. To induce spermiation and ovulation in Cirrhinus mrigala brooders, the synthetic hormone Ovaprim® (GnRH + dopamine inhibitor) was administrated as a single injection dose of 0.2 mL/kg to males and 0.4 mL/kg to females. After induction, the fish spawned, and the eggs produced were fertilized artificially and cell division commenced successfully. The characteristics of each larval developmental stage were closely observed and recorded using a time-lapse imaging technique. The fertilized eggs were spherical, demersal, and non-adhesive throughout their incubation period. The spawned eggs ranged in diameter from 2.1 mm to 2.13 mm and possessed circular yolk sacs. The gastrula stage initiated approximately 4 h after fertilization, with 25% of the yolk sphere covered by blastoderm, reaching 75% coverage at the end of the gastrula stage, approximately 6 h post fertilization. Organogenesis was marked by the formation of notochord and the visibility of rudimentary organs such as the heart, eyes, and gills, followed by tail movement, which was observed at the time of hatching. Compared to other cyprinid fishes, C. mrigala exhibited distinct features at certain stages of embryonic development. Blood circulation was observed to start at the onset of hatching. The lengths of the newly hatched larvae ranged from 2.9 to 3.2 mm, smaller than other reports on induced breeding in carps. The findings of the present study provide a detailed reference for the embryonic development of C. mrigala, which will assist its future research endeavors and large-scale seed production for sustainable aquaculture.

Effect of Different Early Weaning Diets on Survival, Growth, and Digestive Ontogeny of Channa striatus (Bloch, 1793) Larvae.

The present study was carried out to evaluate the survival, growth, and digestive ontogeny of C. striatus larvae fed with different experimental diets from 4 days post-hatch (dph) to 32 dph at three-day intervals. A total of 24,000 larvae, with 1600 larvae per tank in triplicate and an initial mean weight of 0.64 ± 0.01 mg at 4 days post hatch (dph) were subjected to five different early weaning diets, namely Artemia nauplii (T1), co-feed diet comprising Artemia nauplii and formulated micro diet (T2), formulated micro diet (T3), formulated micro diet with protease supplementation (T4), and a commercial diet (T5). All the early weaning diets significantly affected the survival, growth, and ontogeny of the digestive system. Initially at 8 dph, C. striatus fed with T1 showed better survival and growth performance compared to other treatments. By 12 dph, the larvae fed with T1 and T2 showed similar results in terms of survival and growth performance, outperforming other treatments. However, the larvae fed with T2 and T4 outperformed T1 in survival and growth performance at 16 dph. By 24-32 dph, the larvae fed with all treatments met the basic nutritional needs for survival, with T4 fed larvae showing better growth compared to other treatments. At the end of the trial, cumulative mortality was lowest in larvae fed with T1 and highest in the larvae fed with T3 and T5. Similarly, the larvae fed with T4 showed significantly higher weight gain, specific growth rate (SGR), and average daily growth (ADG), while T1 fed larvae exhibited better feed conversion ratio (FCR) and protein efficiency ratio (PER). The enzyme activity fluctuated throughout the experimental duration. Lavae fed with T1 and T2 showed higher enzyme activities initially. However, T4 fed larvae showed higher trypsin and chymotrypsin specific activity at 16 dph along with well-developed intestinal folds with dense microvilli, higher pepsin-specific activity at 20 dph onwards with fully developed gastric glands and thicker gastric mucosal epithelium, and higher amylase and lipase activity at 16 dph with large and prominent zymogen granules in the exocrine pancreas. Peaking at 4 dph, the activity of protein metabolic enzymes (AST and ALT) sharply declined at 8 dph and increased until 32 dph. Larvae fed with T1 showed higher AST and ALT activity along with increased lipid deposits, followed by those fed with T2 and the larvae fed with T4 showing higher activity without fat accumulation but significantly lower than those fed T1 and T2. From the present research findings, it is recommended to initiate weaning for Channa striatus larvae with Artemia nauplii (from 4 dph to 8 dph) followed by a co-feeding regime (Artemia nauplii and formulated diet) between 9 and 16 dph and transition to protease-supplemented micro diet (T4) from 17 dph onwards.

Apneic uptake of atmospheric O2 by deeply hypothermic nestlings of the white-footed mouse (Peromyscus leucopus): circulation and lungs.

Nestling white-footed mice (Peromyscus leucopus) are born in the earliest days of spring in cold climates. If the nestlings are by accident exposed to ambient temperatures near freezing (0-7 °C) at early ages (2-10 days old), they may experience body temperatures (Tbs) equally low. During such hypothermia, although their heart keeps beating, they become apneic (cease inhaling and exhaling). However, they have an exceptional ability (e.g., compared to Mus musculus) to tolerate these conditions for at least several hours, after which they revive if rewarmed by parents. This paper addresses the physiology of the apneic period. We show that apneic, hypothermic nestlings undergo physiologically important exchanges of gases with the atmosphere. These gas exchanges do not occur across the skin. Instead they occur via the trachea and lungs even though the animals are apneic. Most significantly, when hypothermic neonates are in apnea in ordinary air, they take up O2 steadily from the atmosphere throughout the apneic period, and the evidence available indicates that this O2 uptake is essential for the nestlings' survival. At Tbs of 2-7 °C, the nestlings' rate of O2 consumption varies quasi-exponentially with Tb and averages 0.04 mL O2 g- 1 h- 1, closely similar to the rate expressed by adult mammalian hibernators in hibernation at similar Tbs. Morphometric analysis indicates that, at all focal ages, O2 transport along the full length of the trachea can take place by diffusion at rates adequate to meet the measured rates of metabolic O2 consumption.

Plasma adenosine deaminase-1 and -2 activities are lower at birth in Papua New Guinea than in The Gambia but converge over the first weeks of life.

Introduction: Dynamic cellular and molecular adaptations in early life significantly impact health and disease. Upon birth, newborns are immediately challenged by their environment, placing urgent demands on the infant immune system. Adenosine deaminases (ADAs) are enzymatic immune modulators present in two isoforms - ADA-1 and ADA-2. Infants exhibit low ADA activity, resulting in high plasma adenosine concentrations and a consequent anti-inflammatory/anti-Th1 bias. While longitudinal studies of plasma ADA have been conducted in infants in The Gambia (GAM), little is known regarding ADA trajectories in other parts of the world. Methods: Herein, we characterized plasma ADA activity in an infant cohort in Papua New Guinea (PNG; n=83) and compared to ontogeny of ADA activity in a larger cohort in GAM (n=646). Heparinized peripheral blood samples were collected at day of life (DOL) 0, DOL7, DOL30, and DOL128. Plasma ADA-1, ADA-2, and total ADA activities were measured by chromogenic assay. Results: Compared to GAM infants, PNG infants had significantly lower ADA-1 (0.9-fold), ADA-2 (0.42-fold), and total ADA (0.84-fold) activities at birth which converged by DOL30. Discussion: Overall, discovery of a distinct baseline and a consistent pattern of increasing plasma ADA activity in early life in two genetically and geographically distinct populations validates and extends previous findings on the robustness of early life immune ontogeny.

Elephants develop wrinkles through both form and function.

The trunks of elephants have prominent wrinkles from their base to the very tip. But neither the obvious differences in wrinkles between elephant species nor their development have been studied before. In this work, we characterize the lifelong development of trunk wrinkles in Asian and African elephants. Asian elephants have more dorsal major, meaning deep and wide, trunk wrinkles (approx. 126 ± 25 s.d.) than African elephants (approx. 83 ± 13 s.d.). Both species have more dorsal than ventral major trunk wrinkles and a closer wrinkle spacing distally than proximally. In Asian elephants, wrinkle density is high in the 'trunk wrapping zone'. Wrinkle numbers on the left and right sides of the distal trunk differed as a function of trunk lateralization, with frequent bending in one direction causing wrinkle formation. Micro-computed tomography (microCT) imaging and microscopy of newborn elephants' trunks revealed a constant thickness of the putative epidermis, whereas the putative dermis shrinks in the wrinkle troughs. During fetal development, wrinkle numbers double every 20 days in an early exponential phase. Later wrinkles are added slowly, but at a faster rate in Asian than African elephants. We discuss the relationship of species differences in trunk wrinkle distribution and number with behavioural, environmental and biomechanical factors.

Extraembryonic Membranes and Placentation in the Mexican Snake Conopsis lineata.

Extraembryonic membranes provide protection, oxygen, water, and nutrients to developing embryos, and their study generates information on the origin of the terrestrial egg and the evolution of viviparity. In this research, the morphology of the extraembryonic membranes and the types of placentation in the viviparous snake Conopsis lineata are described through optical microscopy during early and late gestation. When embryos develop inside the uterus, they become surrounded by a thin eggshell membrane. In early gestation, during stages 16 and 18, the embryo is already surrounded by the amnion and the chorion, and in a small region by the chorioallantois, which is product of the contact between the chorion and the growing allantois. A trilaminar omphalopleure covers the yolk sac from the embryonic hemisphere to the level of the equator where the sinus terminalis is located, and from there a bilaminar omphalopleure extends into the abembryonic hemisphere. Thus, according to the relationship of these membranes with the uterine wall, the chorioplacenta, the choriovitelline placenta, and the chorioallantoic placenta are structured at the embryonic pole, while the omphaloplacenta is formed at the abembryonic pole. During late gestation (stages 35, 36, and 37), the uterus and allantois are highly vascularized. The allantois occupies most of the extraembryonic coelom and at the abembryonic pole, it contacts the omphaloplacenta and form the omphalallantoic placenta. This is the first description of all known placenta types in Squamata for a snake species member of the subfamily Colubrinae; where an eggshell membrane with 2.9 µm in width present throughout development is also evident. The structure of extraembryonic membranes in C. lineata is similar to that of other oviparous and viviparous squamate species. The above indicates not only homology, but also that the functional characteristics have been maintained throughout the evolution of the reproductive type.

Acorn ant exhibits age-dependent induced defence in response to parasitic raids.

When risk is unpredictable, organisms may evolve induced defenses, which are activated after an indication of increased risk. In colonies with behavioural specialization, investment in defence may not be uniformly beneficial among group members. Instead, it should depend on the individual's likelihood of participating in defence. The ant Temnothorax longispinosus uses venom to defend against raids by the social parasite Temnothorax americanus. We tested whether T. longispinosus upregulate investment in venom after experiencing a raid, investigating the relationship between venom volume and worker behavioural caste. Overall, raided colonies had more venom per capita than unraided colonies. When divided into behavioural castes, foragers had more venom after experiencing a raid, while nurses did not. These results demonstrate that T. longispinosus have an induced chemical defence against parasitic raids. However, instead of this defence being deployed uniformly among all workers, the induction of the defence depends on the behavioural caste, and therefore age, of the worker, implying that plasticity in venom production increases with age. Since older social insect workers tend to perform riskier tasks, inducibility may align with an increase in expected risk of death, especially if foragers are more likely to defend the colony against parasites than younger workers.

Reverse development in the ctenophore Mnemiopsis leidyi.

Reverse development, or the ability to rejuvenate by morphological reorganization into the preceding life cycle stage is thought to be restricted to a few species within Cnidaria. To date, Turritopsis dohrnii is the only known species capable of undergoing reverse development after the onset of sexual reproduction. Here, we demonstrate that the ctenophore Mnemiopsis leidyi is capable of reversal from mature lobate to early cydippid when fed following a period of stress. Our findings illuminate central aspects of ctenophore development, ecology, and evolution and show the high potential of M. leidyi as a unique model system to study reverse development and rejuvenation. Besides shedding light on the plasticity of developmental programs, these results raise fundamental questions about early animal development, body plans, and life cycles.

Predictive gene expression signature diagnoses neonatal sepsis before clinical presentation.

BACKGROUND: Neonatal sepsis is a deadly disease with non-specific clinical signs, delaying diagnosis and treatment. There remains a need for early biomarkers to facilitate timely intervention. Our objective was to identify neonatal sepsis gene expression biomarkers that could predict sepsis at birth, prior to clinical presentation. METHODS: Among 720 initially healthy full-term neonates in two hospitals (The Gambia, West Africa), we identified 21 newborns who were later hospitalized for sepsis in the first 28 days of life, split into early-onset sepsis (EOS, onset ≤7 days of life) and late-onset sepsis (LOS, onset 8-28 days of life), 12 neonates later hospitalized for localized infection without evidence of systemic involvement, and 33 matched control neonates who remained healthy. RNA-seq was performed on peripheral blood collected at birth when all neonates were healthy and also within the first week of life to identify differentially expressed genes (DEGs). Machine learning methods (sPLS-DA, LASSO) identified genes expressed at birth that predicted onset of neonatal sepsis at a later time. FINDINGS: Neonates who later developed EOS already had ∼1000 DEGs at birth when compared to control neonates or those who later developed a localized infection or LOS. Based on these DEGs, a 4-gene signature (HSPH1, BORA, NCAPG2, PRIM1) for predicting EOS at birth was developed (training AUC = 0.94, sensitivity = 0.93, specificity = 0.92) and validated in an external cohort (validation AUC = 0.72, sensitivity = 0.83, and specificity = 0.83). Additionally, during the first week of life, EOS disrupted expression of >1800 genes including those influencing immune and metabolic transitions observed in healthy controls. INTERPRETATION: Despite appearing healthy at birth, neonates who later developed EOS already had distinct whole blood gene expression changes at birth, which enabled the development of a 4-gene predictive signature for EOS. This could facilitate early recognition and treatment of neonatal sepsis, potentially mitigating its long-term sequelae. FUNDING: CIHR and NIH/NIAID.

Differential temporal decline of cerebral oxytocin and µ-opioid receptor density during the aging process in mice.

Aging is often associated with changes in social, sexual, emotional and pain functioning, as well as with the increased prevalence of certain psychopathologies. However, the neurodevelopmental basis underpinning these age-related changes remains to be determined. Considering the key roles of oxytocin (OTR) and µ-opioid (MOPr) receptor systems in regulating social, sexual, pain, reward and emotional processing, it seems plausible that they are also implicated in age-related behavioural alterations. Although the ontogeny of both receptors has been well characterized in rodent brains from early development till adulthood, little is known concerning the neuroadaptations occurring from middle age to old age. Therefore, we mapped the neuroadaptations in OTR and MOPr in the brains of mice at those developmental endpoints. Quantitative OTR and MOPr autoradiographic binding was carried out in the brains of male mice at 2, 6, 9, 12 and 18 months of age. A significant whole brain decline in OTR density was detected between 2 and 6 months of age, with no additional decline thereafter. Interestingly, for MOPrs, the decline in density was not detected until 9 months of age. Region-specific age-related decline in OTR density was concentrated in the lateral anterior olfactory nuclei (AOL) and, for MOPr, in the AOL and the nucleus accumbens for MOPr. Identifying the tipping point of these age-related variations in both receptors may assist with our understanding of the neurobiology underlining age-related changes in social, pain and emotional functioning/processing. It may also help us target interventions to specific developmental windows to abrogate certain age-related psychopathologies.

Effects of development and parental care on Hamilton's force of selection.

The force of selection describes the sensitivity of population growth to changes in life history parameters, with a focus usually on the survival probabilities from one age class to the next. Importantly, according to Hamilton the force of selection generally decreases after the onset of reproduction, thereby providing a possible explanation for patterns of senescence. A second characteristic feature is that the force of selection remains constant up to the age of first re- production. This latter observation, however, rests on the assumption that offspring become independent from their parents right after birth. I show here in a minimal model that if offspring are fully reliant on their parents, either during early embryonal development or via parental care at later stages, and during this time prevent their parents from entering a new bout of repro- duction, the force of selection on offspring survival generally increases up until the age at which offspring become independent. This provides a possible explanation for the commonly observed pattern of decreasing mortality during early ontogeny. Further, genes acting during recurrent life stages are observed to experience a heightened force of selection compared to genes that act strictly age-specifically, demonstrating the need to develop a mechanistic understanding of gene activation patterns through which to consider life history evolution.

Tooth eruption status and bite force determine dental microwear texture gradients in albino rats (Rattus norvegicus forma domestica).

Dental microwear texture analysis (DMTA) is widely applied for inferring diet in vertebrates. Besides diet and ingesta properties, factors like wear stage and bite force may affect microwear formation, potentially leading to tooth position-specific microwear patterns. We investigated DMTA consistency along the upper cheek tooth row in young adult female rats at different growth stages, but with erupted adult dentitions. Bite forces for each molar (M) position were determined using muscle cross-sectional areas and lever arm mechanics. Rats were categorized into three size classes based on increasing skull length. Maximum bite force increased with size, while across all size classes, M3 bite force was almost 1.4 times higher than M1 bite force. In size class 1, M1 and M2 showed higher values than M3 for DMTA complexity, height, and volume parameters, while in size class 3, M1 had the lowest values. Comparing the same tooth position between size classes revealed opposing trends: M1 and M2 showed, for most parameters, decreasing roughness and complexity from size class 1-3, while M3 displayed the opposite trend, with size class 1 showing lowest, and either size class 2 or 3 the highest roughness and complexity values. This suggests that as rats age and M3 fully occludes, it becomes more utilized during mastication. DMTA, being a short-term diet proxy, is influenced by eruption and occlusion status changes. Our findings emphasize the importance of bite force and ontogenetic stage when interpreting microwear patterns and advise to select teeth in full occlusion for diet reconstruction.

A gut check: understanding the interplay of the gastrointestinal microbiome and the developing immune system towards the goal of pediatric HIV remission.

Despite the efficacy of antiretroviral therapy (ART) in reducing the global incidence of vertical HIV transmissions, more than 120,000 children are still infected with the virus each year. Since ART cannot clear the HIV reservoir that is established soon after infection, children living with HIV (CLWH) are forced to rely on therapy for their lives and suffer from long-term drug-related complications. Pediatric HIV infection, like adult infection, is associated with gut microbial dysbiosis, loss of gut epithelial integrity, bacterial translocation, CD4 + T cell depletion, systemic immune activation, and viral reservoir establishment. However, unlike in adults, HIV that is vertically acquired by infants interacts with a gut microbiome that is continuously evolving while concomitantly shaping the infant's immune ontogeny. Therefore, to determine whether there may be interventions that target the HIV reservoir through microbiome-directed approaches, understanding the complex tripartite interactions between the transmitted HIV, the maturing gut microbiome, and the developing immune system during early life is crucial. Importantly, early life is the time when the gut microbiome of an individual is highly dynamic, and this temporal development of the gut microbiome plays a crucial role in educating the maturing immune system of a child. Therefore, manipulation of the gut microbiome of CLWH to a phenotype that can reduce HIV persistence by fostering an antiviral immune system might be an opportune strategy to achieve ART-free viral suppression in CLWH. This review summarizes the current state of knowledge on the vertical transmission of HIV, the developing gut microbiome of CLWH, and the immune landscape of pediatric elite controllers, and explores the prospect of employing microbial modulation as a potential therapeutic approach to achieve ART-free viral suppression in the pediatric population.

Homing pigeon navigational ontogeny: no evidence that exposure to a novel release site is sufficient for learning.

The navigational mechanisms of homing pigeons, Columba livia, have been extensively studied and represent a useful model for the navigation of birds and other animals. Pigeons navigate with an olfactory map and sun compass from unfamiliar areas and, in familiar areas, are largely guided by visual landscape cues, following stereotyped and idiosyncratic routes. However, the mechanisms by which they gain familiarity, improve their navigation and transition between navigational strategies during learning are not fully understood. Addressing these outstanding questions in this navigational model will help to improve our understanding of navigational ontogeny. We sought to investigate whether passive exposure to the cues at a site, without release, was sufficient for navigational learning, given that pigeons can determine the home direction before taking off. We exposed pigeons to cues at a novel site before returning them to the site the next day and releasing them alongside controls. We found no differences in the directional distributions, mean vector lengths, virtual vanishing times, efficiency indices or homing efficiency indices between birds that had and had not previously visited the site. We therefore found no evidence to suggest that passive exposure to the cues at a novel site was sufficient to facilitate a detectable improvement in navigational performance. There are three possible explanations for this result: first, a larger sample size would have detected a weak effect of learning; second, passive exposure to a release site is insufficient to generate navigational learning; and third, pigeons learn from passive exposure but do not rely upon this information, showing no difference in performance, despite learning. We discuss these three explanations with reference to previous findings on navigational learning in homing pigeons. We suggest that experiments should continue to examine navigational ontogeny in homing pigeons to help address this major problem for the field of navigation.

Androgen-mediated maternal effects and trade-offs: postnatal hormone development, growth, and survivorship in wild meerkats.

Introduction: Mammalian reproductive and somatic development is regulated by steroid hormones, growth hormone (GH), and insulin-like growth factor-1 (IGF-1). Based largely on information from humans, model organisms, and domesticated animals, testosterone (T) and the GH/IGF-1 system activate sexually differentiated development, promoting male-biased growth, often at a cost to health and survivorship. To test if augmented prenatal androgen exposure in females produces similar developmental patterns and trade-offs, we examine maternal effects in wild meerkats (Suricata suricatta), a non-model species in which adult females naturally, albeit differentially by status, express exceptionally high androgen concentrations, particularly during pregnancy. In this cooperative breeder, the early growth of daughters predicts future breeding status and reproductive success. Methods: We examine effects of normative and experimentally induced variation in maternal androgens on the ontogenetic patterns in offspring reproductive hormones (androstenedione, A4; T; estradiol, E2), IGF-1, growth from pup emergence at 1 month to puberty at 1 year, and survivorship. Specifically, we compare the male and female offspring of dominant control (DC or high-T), subordinate control (SC or lower-T), and dominant treated (DT or blocked-T) dams, the latter having experienced antiandrogen treatment in late gestation. Results: Meerkat offspring showed sex differences in absolute T and IGF-1 concentrations, developmental rates of A4 and E2 expression, and survivorship - effects that were sometimes socially or environmentally modulated. Atypical for mammals were the early male bias in T that disappeared by puberty, the absence of sex differences in A4 and E2, and the female bias in IGF-1. Food availability was linked to steroid concentrations in females and to IGF-1, potentially growth, and survival in both sexes. Maternal treatment significantly affected rates of T, E2, and IGF-1 expression, and weight, with marginal effects on survivorship; offspring of DT dams showed peak IGF-1 concentrations and the best survivorship. Discussion: Maternal effects thus impact offspring development in meerkats, with associated trade-offs: Whereas prenatal androgens modify postnatal reproductive and somatic physiology, benefits associated with enhanced competitiveness in DC lineages may have initial costs of reduced IGF-1, delay in weight gain, and decreased survivorship. These novel data further confirm the different evolutionary and mechanistic pathways to cooperative breeding and call for greater consideration of natural endocrine variation in both sexes.

Effects of different temperatures on the embryonic development of the Lebranche mullet Mugil liza.

We herein investigated the influence of temperature on the embryonic development (from fertilisation to hatching) of Mugil liza larvae. For this purpose, oocytes (>600 µm) and sperm were obtained from breeding stock at the laboratory of marine fish culture (LAPMAR). After fertilisation, 1200 eggs were distributed in 12 cylindrical experimental units of 400 mL under four different temperatures 18, 22, 26 and 30 ºC, all in triplicate. Every 15 min until hatching, about 10 eggs were randomly sampled in each treatment. The eggs were visualized and photographed, and the classification of embryonic stages was performed. Temperature influenced the main events of the embryonic development of M. liza. More accelerated development was observed according to the increase in temperature until the gastrula phase. At temperatures of 22 and 26 °C, embryonic development occurred from fertilisation to hatching of the larvae. In the 18 °C treatment, it was verified that most of the embryos ceased development during the final phase of cleavage and the beginning of blastula formation, while in the 30 °C treatment patterns of embryo malformation were also verified, with erratic divisions of the blastomeres, resulting in irregular cells. Unlike what was observed at a temperature of 18 °C, none of the embryos incubated at 30 °C reached the blastopore closure phase, stopping in the gastrula. The larvae hatched in the treatments at 22 and 26 °C were viable and exhibited intense swimming, with a large amount of reserve material (yolk) and an evident drop of oil.