Secretion of endocrine signals by the primate embryo during the peri-implantation period

Development of preimplantation embryos and blastocyst implantation are critical early events in the establishment of pregnancy. In primates, embryonic signals, secreted during the peri-implantation period, are believed to play a major role in the regulation of embryonic differentiation and implantation. However, only limited progress has been made in the molecular and functional characterization of embryonic signals, partly due to severe paucity of primate embryos and the lack of optimal culture conditions to obtain viable embryo development. Two embryonic (endocrine) secretions, i.e. chorionic gonadotrophin (CG) and gonadotrophin releasing hormone (GnRH) are being studied. This article reviews the current status of knowledge on the recovery and culture of embryos, their secretion of CG, GnRH and other potential endocrine signals and their regulation and physiological role(s) during the peri-implantation period in primates, including humans.

Is there a role for estrogen in follicular maturation in the primate

The present study focusses attention on the effects of blocking estrogen synthesis, during follicular phase, on follicular maturation in the adult female bonnet monkey (Macaca radiata). Administration of cycling females (n = 4) with an aromatase inhibitor CGS 16949A (AI) by Alzet mini-pump (2.5 mg/day) from day 3 of cycle resulted in significant reduction in basal (by 53%) and surge levels of estrogen (by 70%) but this had no effect on follicular maturation, ovulation and luteal function as assessed by serum hormone profiles as well as laparotomy. This lack of need for estrogen for completion of follicular maturation process was confirmed by administering cycling monkeys hFSH (25 IU/day) from day 3 till day 8 of the cycle along with (5 mg AI/day) or without Al (n = 3/group). Administration of Al resulted in suppression of FSH induced increase in serum estrogen (by 100%) and elevation in circulating androstenedione. Aromatase inhibitor treatment had no effect on either the number of follicles developed or their size relative to control. Testing the ability of both granulosa and thecal cells, removed on day 9 of treatment cycle, to respond to gonadotropins in vitro showed no change indicating that cellular development and maturation of follicular cells had occurred normally. It is concluded that follicular maturation in the primate can occur even when increase in estrogen synthesis is blocked.

Viral Kinetics Suggests a Reconciliation of the Disparate Observations of the Modulation of Claudin-1 Expression on Cells Exposed to Hepatitis C Virus

The tight junction protein claudin-1 (CLDN1) is necessary for hepatitis C virus (HCV) entry into target cells. Recent studies have made disparate observations of the modulation of the expression of CLDN1 on cells following infection by HCV. In one study, the mean CLDN1 expression on cells exposed to HCV declined, whereas in another study HCV infected cells showed increased CLDN1 expression compared to uninfected cells. Consequently, the role of HCV in modulating CLDN1 expression, and hence the frequency of cellular superinfection, remains unclear. Here, we present a possible reconciliation of these disparate observations. We hypothesized that viral kinetics and not necessarily HCV-induced receptor modulation underlies these disparate observations. To test this hypothesis, we constructed a mathematical model of viral kinetics in vitro that mimicked the above experiments. Model predictions provided good fits to the observed evolution of the distribution of CLDN1 expression on cells following exposure to HCV. Cells with higher CLDN1 expression were preferentially infected and outgrown by cells with lower CLDN1 expression, resulting in a decline of the mean CLDN1 expression with time. At the same time, because the susceptibility of cells to infection increased with CLDN1 expression, infected cells tended to have higher CLDN1 expression on average than uninfected cells. Our study thus presents an explanation of the disparate observations of CLDN1 expression following HCV infection and points to the importance of considering viral kinetics in future studies of receptor expression on cells exposed to HCV.

Single nucleotide polymorphisms in genes that are common targets of luteotropin and luteolysin in primate corpus luteum: Computational exploration

Luteal insufficiency affects fertility and hence study of mechanisms that regulate corpus luteum (CL) function is of prime importance to overcome infertility problems. Exploration of human genome sequence has helped to study the frequency of single nucleotide polymorphisms (SNPs). Clinical benefits of screening SNPs in infertility are being recognized well in recent times. Examining SNPs in genes associated with maintenance and regression of CL may help to understand unexplained luteal insufficiency and related infertility. Publicly available microarray gene expression databases reveal the global gene expression patterns in primate CL during the different functional state. We intend to explore computationally the deleterious SNPs of human genes reported to be common targets of luteolysin and luteotropin in primate CL Different computational algorithms were used to dissect out the functional significance of SNPs in the luteinizing hormone sensitive genes. The results raise the possibility that screening for SNPs might be integrated to evaluate luteal insufficiency associated with human female infertility for future studies. (C) 2012 Elsevier B.V. All rights reserved,

Computational interrogation of cis-regulatory elements of genes that are common targets of luteotropin and luteolysin in the primate corpus luteum

The rapid recent increase in microarray-based gene expression studies in the corpus luteum (CL) utilizing macaque models gathered increasing volume of data in publically accessible microarray expression databases. Examining gene pathways in different functional states of CL may help to understand the factors that control luteal function and hence human fertility. Co-regulation of genes in microarray experiments may imply common transcriptional regulation by sequence-specific DNA-binding transcriptional factors. We have computationally analyzed the transcription factor binding sites (TFBS) in a previously reported macaque luteal microarray gene set (n = 15) that are common targets of luteotropin (luteinizing hormone (LH) and human chorionic gonadotropin (hCG)) and luteolysin (prostaglandin (PG) F-2 alpha). This in silico approach can reveal transcriptional networks that control these important genes which are representative of the interplay between luteotropic and luteolytic factors in the control of luteal function. Our computational analyses revealed 6 matrix families whose binding sites are significantly over-represented in promoters of these genes. The roles of these factors are discussed, which might help to understand the transcriptional regulatory network in the control of luteal function. These factors might be promising experimental targets for investigation of human luteal insufficiency. (C) 2012 Elsevier B.V. All rights reserved.

Primates, Provisioning and Plants: Impacts of Human Cultural Behaviours on Primate Ecological Functions

Human provisioning of wildlife with food is a widespread global practice that occurs in multiple socio-cultural circumstances. Provisioning may indirectly alter ecosystem functioning through changes in the eco-ethology of animals, but few studies have quantified this aspect. Provisioning of primates by humans is known to impact their activity budgets, diets and ranging patterns. Primates are also keystone species in tropical forests through their role as seed dispersers; yet there is no information on how provisioning might affect primate ecological functions. The rhesus macaque is a major human-commensal species but is also an important seed disperser in the wild. In this study, we investigated the potential impacts of provisioning on the role of rhesus macaques as seed dispersers in the Buxa Tiger Reserve, India. We studied a troop of macaques which were provisioned for a part of the year and were dependent on natural resources for the rest. We observed feeding behaviour, seed handling techniques and ranging patterns of the macaques and monitored availability of wild fruits. Irrespective of fruit availability, frugivory and seed dispersal activities decreased when the macaques were provisioned. Provisioned macaques also had shortened daily ranges implying shorter dispersal distances. Finally, during provisioning periods, seeds were deposited on tarmac roads that were unconducive for germination. Provisioning promotes human-primate conflict, as commensal primates are often involved in aggressive encounters with humans over resources, leading to negative consequences for both parties involved. Preventing or curbing provisioning is not an easy task as feeding wild animals is a socio-cultural tradition across much of South and South-East Asia, including India. We recommend the initiation of literacy programmes that educate lay citizens about the ill-effects of provisioning and strongly caution them against the practice.

Analog VLSI-based, neuromorphic sensorimotor systems: modeling the primate oculomotor system

Using neuromorphic analog VLSI techniques for modeling large neural systems has several advantages over software techniques. By designing massively-parallel analog circuit arrays which are ubiquitous in neural systems, analog VLSI models are extremely fast, particularly when local interactions are important in the computation. While analog VLSI circuits are not as flexible as software methods, the constraints posed by this approach are often very similar to the constraints faced by biological systems. As a result, these constraints can offer many insights into the solutions found by evolution. This dissertation describes a hardware modeling effort to mimic the primate oculomotor system which requires both fast sensory processing and fast motor control. A one-dimensional hardware model of the primate eye has been built which simulates the physical dynamics of the biological system. It is driven by analog VLSI circuits mimicking brainstem and cortical circuits that control eye movements. In this framework, a visually-triggered saccadic system is demonstrated which generates averaging saccades. In addition, an auditory localization system, based on the neural circuits of the barn owl, is used to trigger saccades to acoustic targets in parallel with visual targets. Two different types of learning are also demonstrated on the saccadic system using floating-gate technology allowing the non-volatile storage of analog parameters directly on the chip. Finally, a model of visual attention is used to select and track moving targets against textured backgrounds, driving both saccadic and smooth pursuit eye movements to maintain the image of the target in the center of the field of view. This system represents one of the few efforts in this field to integrate both neuromorphic sensory processing and motor control in a closed-loop fashion.

Connectivity and Function of the Primate Insula

The insula is a mammalian cortical structure that has been implicated in a wide range of low- and high-level functions governing one’s sensory, emotional, and cognitive experiences. One particular role of this region is considered to be processing of olfactory stimuli. The ability to detect and evaluate odors has significant effects on an organism’s eating behavior and survival and, in case of humans, on complex decision making. Despite such importance of this function, the mechanism in which olfactory information is processed in the insula has not been thoroughly studied. Moreover, due to the structure’s close spatial relationship with the neighboring claustrum, it is not entirely clear whether the connectivity and olfactory functions attributed to the insula are truly those of the insula, rather than of the claustrum. My graduate work, consisting of two studies, seeks to help fill these gaps. In the first, the structural connectivity patterns of the insula and the claustrum in a non-human primate brain is assayed using an ultra-high-quality diffusion magnetic resonance image, and the results suggest dissociation of connectivity — and hence function — between the two structures. In the second study, a functional neuroimaging experiment investigates the insular activity during odor evaluation tasks in humans, and uncovers a potential spatial organization within the anterior portion of the insula for processing different aspects of odor characteristics.

The impact of chromosome sorting and painting on the comparative analysis of primate genomes

Chromosome sorting by flow cytometry is the main source of chromosome-specific DNA for the production of painting probes. These probes have been used for cross-species in situ hybridization in the construction of comparative maps, in the study of karyotype evolution and phylogenetics, in delineating territories in interphase nuclei, and in the analysis of chromosome breakpoints. We review here the contributions that this technology has made to the analysis of primate genomes. Copyright (C) 2005 S. Karger AG, Basel.

Chromosome painting between human and lorisiform prosimians: Evidence for the HSA 7/16 Synteny in the primate ancestral karyotype

Multidirectional chromosome painting with probes derived from flow-sorted chromosomes of humans (Homo sapiens, HSA, 2n = 46) and galagos (Galago moholi, GMO, 2n = 38) allowed us to map evolutionarily conserved chromosomal segments among humans, galagos, a

Genetic evidence of a strong functional constraint of neurotrypsin during primate evolution

Neurotrypsin is one of the extra-cellular serine proteases that are predominantly expressed in the brain and involved in neuronal development and function. Mutations in humans are associated with autosomal recessive non-syndromic mental retardation (MR). We studied the molecular evolution of neurotrypsin by sequencing the coding region of neurotrypsin in 11 representative non-human primate species covering great apes, lesser apes, Old World monkeys and New World monkeys. Our results demonstrated a strong functional constraint of neurotrypsin that was caused by strong purifying selection during primate evolution, an implication of an essential functional role of neurotrypsin in primate cognition. Further analysis indicated that the purifying selection was in fact acting on the SRCR domains of neurotrypsin, which mediate the binding activity of neurotrypsin to cell surface or extracellular proteins. In addition, by comparing primates with three other mammalian orders, we demonstrated that the absence of the first copy of the SRCR domain (exon 2 and 3) in mouse and rat was due to the deletion of this segment in the murine lineage. Copyright (C) 2005 S. Karger AG, Basel.

Molecular evolution of a primate-specific microRNA family

Lineage-specific microRNA (miRNA) families may contribute to developmental novelties during evolution. However, little is known about the origin and evolution of new miRNA families. We report evidence of an Alu-mediated rapid expansion of miRNA genes in a

Adaptive evolution of primate TRIM5 alpha, a gene restricting HIV-1 infection

Recent studies showed that nonhuman primate TRIM5 alpha can efficiently block HIV-1 infection in human cell lines. It can also restrict other retroviruses, therefore, suggested as a general defender against retrovirus infection. Here, we present an evolutionary analysis of TRIM5 alpha in primates. Our results demonstrated that TRIM5a has been evolving rapidly in primates, which is likely caused by Darwinian positive selection. The SPRY domain of TRM5 alpha, which may be responsible for recognition of incoming viral capsids showed higher nonsynonymous/synonymous substitution ratios than the non-SPRY domain, indicating that the adaptive evolution of TRIM5a ill primates might be an innate strategy developed in defending retrovirus infection during primate evolution. In addition, the comparative protein sequence analysis suggested that the amino acid substitution pattern at a single site (344R/Q/P) located in the SPRY domain may explain the differences in Susceptibilities of HIV-1 infection in diverse primate species. (c) 2005 Elsevier B.V. All rights reserved.

Genotyping of TRIM5 locus in northern pig-tailed macaques (Macaca leonina), a primate species susceptible to Human Immunodeficiency Virus type 1 infection

Background: The pig-tailed macaques are the only Old World monkeys known to be susceptible to human immunodeficiency virus type 1 (HIV-1) infection. We have previously reported that the TRIM5-Cyclophilin A (TRIMCyp) fusion in pig-tailed macaques (Macaca n