Influence of Genetic Variation on Birth Defects in Caenorhabditis elegans

In my Renee Crown Honors Capstone project, I studied how genetic variation influences birth defects that cause death in C. elegans embryos. I performed high-throughput hatching assay experiments of recombinant inbred advance intercross lines of C. elegans. These lines are genetically distinct from each other. I found significant variation in birth defects causing embryo death in these recombinant inbred advanced intercross lines. My results give evidence that gene interaction may play a significant role in causing birth defects resulting in death. My data also provides a starting point for studies making statistical arguments linking these birth defects to specific genetic interactions

Frequent expansion of Plasmodium vivax Duffy Binding Protein in Ethiopia and its epidemiological significance.

Plasmodium vivax invasion of human erythrocytes depends on the Duffy Binding Protein (PvDBP) which interacts with the Duffy antigen. PvDBP copy number has been recently shown to vary between P. vivax isolates in Sub-Saharan Africa. However, the extent of PvDBP copy number variation, the type of PvDBP multiplications, as well as its significance across broad samples are still unclear. We determined the prevalence and type of PvDBP duplications, as well as PvDBP copy number variation among 178 Ethiopian P. vivax isolates using a PCR-based diagnostic method, a novel quantitative real-time PCR assay and whole genome sequencing. For the 145 symptomatic samples, PvDBP duplications were detected in 95 isolates, of which 81 had the Cambodian and 14 Malagasy-type PvDBP duplications. PvDBP varied from 1 to >4 copies. Isolates with multiple PvDBP copies were found to be higher in symptomatic than asymptomatic infections. For the 33 asymptomatic samples, PvDBP was detected with two copies in two of the isolates, and both were the Cambodian-type PvDBP duplication. PvDBP copy number in Duffy-negative heterozygotes was not significantly different from that in Duffy-positives, providing no support for the hypothesis that increased copy number is a specific association with Duffy-negativity, although the number of Duffy-negatives was small and further sampling is required to test this association thoroughly

Computational algorithms and neural circuitry for compressed sensing in the mammalian main olfactory bulb

ABSTRACT A major challenge for many sensory systems is the representation of stimuli that vary along many dimensions. This problem is particularly acute for chemosensory systems because they require sensitivity to a large number of molecular features. Here we use a combination of computational modeling and in vivo electrophysiological data to propose a solution for this problem in the circuitry of the mammalian main olfactory bulb. We model the input to the olfactory bulb as an array of chemical features that, due to the vast size of chemical feature space, is sparsely occupied. We propose that this sparseness enables compression of the chemical feature array by broadly-tuned odorant receptors. Reconstruction of stimuli is then achieved by a supernumerary network of inhibitory granule cells. The main olfactory bulb may therefore implement a compressed sensing algorithm that presents several advantages. First, we demonstrate that a model of synaptic interactions between the granule cells and the mitral cells that constitute the output of the olfactory bulb, can store a highly efficient representation of odors by competitively selecting a sparse basis set of “expert” granule cells. Second, we further show that this model network can simultaneously learn separable representations of each component of an odor mixture without exposure to those components in isolation. Third, our model is capable of independent and odor-specific adaptation, which could be used by the olfactory system to perform background subtraction or sensitively compare a sample odor with an internal expectation. This model makes specific predictions about the dynamics of granule cell activity during learning. Using in vivo electrophysiological recordings, we corroborate these predictions in an experimental paradigm that stimulates memorization of odorants

Whole genome sequencing of Plasmodium vivax isolates reveals frequent sequence and structural polymorphisms in erythrocyte binding genes.

Plasmodium vivax malaria is much less common in Africa than the rest of the world because the parasite relies primarily on the Duffy antigen/chemokine receptor (DARC) to invade human erythrocytes, and the majority of Africans are Duffy negative. Recently, there has been a dramatic increase in the reporting of P. vivax cases in Africa, with a high number of them being in Duffy negative individuals, potentially indicating P. vivax has evolved an alternative invasion mechanism that can overcome Duffy negativity. Here, we analyzed single nucleotide polymorphism (SNP) and copy number variation (CNV) in Whole Genome Sequence (WGS) data from 44 P. vivax samples isolated from symptomatic malaria patients in southwestern Ethiopia, where both Duffy positive and Duffy negative individuals are found. A total of 123,711 SNPs were detected, of which 22.7% were nonsynonymous and 77.3% were synonymous mutations. The largest number of SNPs were detected on chromosomes 9 (24,007 SNPs; 19.4% of total) and 10 (16,852 SNPs, 13.6% of total). There were particularly high levels of polymorphism in erythrocyte binding gene candidates including merozoite surface protein 1 (MSP1) and merozoite surface protein 3 (MSP3.5, MSP3.85 and MSP3.9). Two genes, MAEBL and MSP3.8 related to immunogenicity and erythrocyte binding function were detected with significant signals of positive selection. Variation in gene copy number was also concentrated in genes involved in host-parasite interactions, including the expansion of the Duffy binding protein gene (PvDBP) on chromosome 6 and MSP3.11 on chromosome 10. Based on the phylogeny constructed from the whole genome sequences, the expansion of these genes was an independent process among the P. vivax lineages in Ethiopia. We further inferred transmission patterns of P. vivax infections among study sites and showed various levels of gene flow at a small geographical scale. The genomic features of P. vivax provided baseline data for future comparison with those in Duffy-negative individuals and allowed us to develop a panel of informative Single Nucleotide Polymorphic markers diagnostic at a micro-geographical scale

Perception and comprehension of concepts of the Brazilian Food Insecurity Scale in indigenous communities in the state of Amazonas, Brazil

OBJECTIVE: The objective was to evaluate the perception and comprehension of concepts and terminology related to food security and insecurity, especially those that comprise the Brazilian Food Insecurity Scale, in the context of indigenous socio-cultural reality. METHODS: Qualitative research techniques were used in Cacau, Flexeira and Mamori indigenous communities located in the Médio Juruá watershed, in the municipalities of Envira and Eirunepé (AM). The methods were based on a methodology used previously in Brazil and adapted to the present context in a meeting of specialists familiar with these indigenous communities. Next, focus groups were organized in each one of the three communities, with a total of 18 participants. RESULTS: Hunger appeared as a phenomenon experienced frequently by the participants. Many of the concepts and terms, such as food security, hunger, and good food, were well-understood, but others, such as varied food, sufficient food strategies to avoid problems with food were not. Everyday life depends on family relations that allow exchanges, which differs from studies conducted previously in urban and rural areas, where difficulties related to access to food were due to lack of financial resources. The subject of trading, or exchanges, appeared often during the focus groups, as well as a collective aspect of the experience of food security that had not emerged previously in focus groups conducted as part of the Brazilian Food Insecurity Scale validation. CONCLUSION: More in-depth qualitative and quantitative studies are needed to develop a food security measurement instrument that reflects the reality of these indigenous communities while, at the same time, provides results that are comparable to other indigenous communities as well as to results obtained using the Brazilian Food Insecurity Scale in other populations. To apprehend the situation of food security in these grups is necessary an instrument that takes into consideration the question of trading/exchange, the collective aspect, and the importance of the environment in their experiences related to food security and insecurity. It is recommended that, if questionnaires are to be used, that they should be kept as short and simple as possible.OBJETIVO: Este estudo teve como objetivo avaliar a percepção e a compreensão de conceitos e terminologia da segurança e insegurança alimentar, especialmente os que compõem a Escala Brasileira de Insegurança Alimentar, no contexto da realidade sócio-cultural indígena. MÉTODOS: Foram utilizados recursos de pesquisa qualitativa para a abordagem das comunidades indígenas Cacau, Flexeira e Mamori, situadas na bacia hidrográfica do Médio Juruá, nos municípios de Envira e Eirunepé (AM), baseando-se em metodologia já previamente utilizada no Brasil e adaptada ao presente contexto, em uma reunião com especialistas da área. Em seguida foram organizados grupos focais, com 18 participantes das três comunidades indígenas. RESULTADOS: A fome apareceu como situação vivenciada por muitos dos participantes dos grupos focais das três comunidades estudadas. Os conceitos e as terminologias como segurança alimentar, fome e comida boa foram bem compreendidos, no entanto, comida variada, comida suficiente e estratégia para evitar problemas com comida foram conceitos não compreendidos por eles. A rotina de vida desses povos baseia-se nas relações familiares que permitem trocas, diferindo de outros grupos focais da área urbana e rural, conduzidos como parte da validação da Escala Brasileira de Insegurança Alimentar, nos quais a dificuldade de acesso aos alimentos era conseqüência da falta de recursos financeiros. CONCLUSÃO: São necessários novos e aprofundados estudos, qualitativos e quantitativos, para o desenvolvimento de um instrumento de mensuração de insegurança alimentar que reflita a realidade desses povos, ao mesmo tempo em que busquem fornecer resultados comparáveis com aqueles de outros povos indígenas e mesmo os obtidos pela Escala Brasileira de Insegurança Alimentar em outras populações. Será necessário um instrumento que contemple a questão da troca, o aspecto coletivo, a importância e o uso do ambiente nas experiências de segurança ou insegurança alimentar. Sugere-se ainda que, para estudos quantitativos, o questionário deva ser mais resumido e simples.53s63

From Genes to Biomarkers: Understanding the Biology of Malaria Gametocytes and Their Detection

Each year, approximately 230 million malaria cases and 400,00 malaria deaths are reported worldwide. Malaria is a life-threatening disease caused by Plasmodium parasites that are transmitted from one individual to another through the bites of infected female Anopheles mosquitoes. Malaria parasites replicate asexually in the human host, and, in each replication cycle, a portion of the asexual stages develops into sexual gametocytes that permit transmission. The proportion of infections that carries gametocytes and the infectivity of gametocytes are indicators of human-to-mosquito transmission potential. In P. falciparum, gametocytes appear 10–14 days after infection, whereas in P. vivax gametocytes appear simultaneously with asexual schizonts. Such difference in development not only increases the length of time that an individual is infectious, but also increases the likelihood of transmission before treatment. The conversion from asexual parasites to gametocytes is also highly variable between infections. Differences in age, host immune response, parasite genetic composition, density of red blood cells, presence of co-infecting parasite strains, and antimalarial drug use could affect gametocytes production. In P. vivax, the unique ability to produce hypnozoites, a dormant liver stage of the parasite, may allow gametocytes to be produced periodically from relapse and contribute to transmission. In this chapter, we will provide an overview of the biology of Plasmodium gametocytes, existing tools for gametocyte detection, and features of gametocyte genes. The biological insights and genetic findings are essential to developing better detection biomarkers and effective strategies to reduce transmission in malaria-endemic countries

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Alternative Invasion Mechanisms and Host Immune Response to Plasmodium vivax Malaria: Trends and Future Directions

Plasmodium vivax malaria is a neglected tropical disease, despite being more geographically widespread than any other form of malaria. The documentation of P. vivax infections in different parts of Africa where Duffy-negative individuals are predominant suggested that there are alternative pathways for P. vivax to invade human erythrocytes. Duffy-negative individuals may be just as fit as Duffy-positive individuals and are no longer resistant to P.vivax malaria. In this review, we describe the complexity of P. vivax malaria, characterize pathogenesis and candidate invasion genes of P. vivax, and host immune responses to P. vivax infections. We provide a comprehensive review on parasite ligands in several Plasmodium species that further justify candidate genes in P. vivax. We also summarize previous genomic and transcriptomic studies related to the identification of ligand and receptor proteins in P. vivax erythrocyte invasion. Finally, we identify topics that remain unclear and propose future studies that will greatly contribute to our knowledge of P. vivax