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Biology subjects

Ramirez, A. L.

Publications and source records attributed to Ramirez, A. L..

7 recordsLinked to original sources

Temperature alters specificity in a host-parasite interaction

The Red Queen Hypothesis proposes that genetic variation is maintained in populations through antagonistic coevolution of hosts and parasites. A major assumption of the Red Queen Hypothesis is tight genetic specificity for infection. However, it has been argued that this genetic interaction of host and parasite (GHxGP) is sensitive to environmental context (GHxGPxE). Environmental change could accordingly disrupt coevolutionary oscillations on relevant time scales, calling into question antagonistic coevolution as a general and robust explanation for the maintenance of genetic diversity. To evaluate this critique, we used the plant-parasitic nematode Meloidogyne arenaria and its natural bacterial parasite Pasteuria penetrans to determine if specificity is altered by temperature. We exposed six isofemale host lines to five parasite sources at three ecologically relevant temperatures. We found that, at two of three temperatures, susceptibility to infection depended on the specific combination of host line and parasite source (GHxGP). This specificity varied across temperatures, consistent with a GHxGPxE effect. This three-way interaction was driven both by quantitative changes in the strength of specificity across temperatures and shifts in the susceptibility rankings of host-parasite combinations. Our study contributes a rare experimental test of a proposed challenge to the Red Queen Hypothesis and suggests the potential for environmental context to change host-parasite specificity.

evolutionary biology↗

Impaired perception of isoluminant contrast modulation stimuli: Evidence for a magnocellular pathway mechanism

Contrast modulation (CM) stimuli have been previously used to reveal nonlinear contributions of Y-like retinal ganglion cells (RGCs) such as parasol cells to cortical responses and perception. To test whether CMs are selectively processed within the magnocellular pathway, we assessed envelope motion discrimination and detection for achromatic (yellow-black) and chromatic (red-green) CMs in the presence of luminance masking noise to disrupt luminance-based mechanisms of motion processing. Compared to achromatic CMs, perception of chromatic CMs was more sensitive to luminance masking noise, suggesting that CM envelope motion perception relied predominantly on luminance signals. Specifically, envelope motion discrimination performance was better maintained for achromatic CMs than chromatic CMs, even at high masking noise levels. Notably, luminance masking noise greatly impaired envelope direction discrimination for chromatic CMs but had minimal impact on their detection, suggesting that chromatic aberrations may enhance envelope motion perception for chromatic CMs by introducing luminance signals. These findings collectively emphasize that CM stimuli selectively activate Y-like/parasol RGCs of the retino-geniculate magnocellular pathway, underscoring their potential to specifically target this pathway. This might have clinical advantages for early diagnosis in disorders such as glaucoma or dyslexia, where magnocellular pathway dysfunction is predominant.

neuroscience↗

A microbiome-derived transfer RNA modification underlies behavioral optimums and predator avoidance in mosquito larvae

The gut microbiome is a rich source of nutrients that are critical to the development and biology of eukaryotes. Transfer RNAs (tRNAs) are essential components of protein synthesis, and some chemical modifications to tRNA rely on the availability of microbiome-derived nutrients. In eukaryotes, the micronutrient queuosine (Q) is salvaged from the microbiome or diet and then incorporated into eukaryotic tRNA to influence the speed and efficiency of protein synthesis. Here, we examine the role of microbiome-derived Q in mosquito larval development and behavior. When mosquito larvae are grown with a microbiome incapable of synthesizing Q, there is a significant impact on tyrosine levels and processes, which correlate with defects in behavior and cuticle formation. Due to defects in movement and behavioral responses, Q-deficient larvae demonstrate impaired predator evasion, leading to higher instances of capture by predaceous beetle larvae. The broad effects of Q-deficiency in mosquito larvae highlight the importance of microbiome-derived nutrients for eukaryotic physiology and behavior.

physiology↗

Microbes reduce susceptibility of Aedes aegypti to Zika virus by enhancing blood digestion and limiting midgut cell infection

The worldwide expansion of mosquito-borne pathogens necessitates improved control measures, including approaches to reduce transmission by mosquito vectors. Reducing transmission is challenging because determinants of vector competence for viruses like Zika (ZIKV) are poorly understood. Our previous work established that Aedes (Ae.) aegypti larvae reared in environmental water containing microbes are less susceptible to ZIKV as adults compared to cohorts reared in laboratory tap water with fewer microbial species and lower microbial abundance. Here, we identify a process by which environment-derived microbes reduce susceptibility of Ae. aegypti for ZIKV. Provided that the midgut represents the first barrier to mosquito infection, we hypothesized that microbial exposure modulates midgut infection by ZIKV. Since mosquitoes live in water as larvae and pupae and then transition to air as adults, we also define the stage in the life of a mosquito when microbial exposure reduces ZIKV susceptibility. Ae. aegypti larvae were reared in water containing microbes and then treated with antibiotics during the pupal and adult stages, adult stage only, or provided no antibiotics at any stage. Vector competence was next evaluated in mosquitoes that ingested ZIKV-spiked bloodmeals. Antibiotic treated mosquitoes with reduced microbiota showed enhanced ZIKV infection rates in Ae. aegypti treated as both pupae and adults. Antibiotic treatment to disrupt microbes in pupal and adult mosquitoes also resulted in increased midgut epithelium permeability, higher numbers of ZIKV-infected midgut cells, and impaired bloodmeal digestion. Parallel control experiments with antibiotic-treated or gnotobiotic mosquitoes reared in laboratory water showed that the dysbiotic state created by antibiotic use does not influence ZIKV vector competence or midgut permeability and that more than the bacterial species in gnotobiotic mosquitoes is responsible for reducing ZIKV vector competence. Ae. aegypti with disrupted microbiota via antibiotic treatment as pupae and adults that ingested ZIKV in bloodmeals showed reduced expression of genes associated with bloodmeal digestion and metabolism relative to mosquitoes whose microbes were not reduced with antibiotics. Together, these data show that exposure to microbes throughout the life of Ae. aegypti restricts ZIKV infection by facilitating blood digestion and reducing midgut cell infection. Understanding the connections between mosquito microbiota, midgut physiology, and arbovirus susceptibility can lead to novel approaches to decrease mosquito transmission and will improve understanding of vector competence in environmental habitats containing microbes. Author SummaryMosquito-transmitted viruses like Zika continue to threaten human health. Absent vaccines or treatments, controlling mosquitoes or limiting their ability to transmit viruses represents a primary way to prevent mosquito-borne viral diseases. The role mosquito microbiota play in shaping transmission of Zika virus has been limited to association-based studies. Our prior work showed that Aedes aegypti mosquito larvae that develop in water containing bacteria are less susceptible to Zika virus compared to larvae reared in laboratory tap water with fewer numbers and species of bacteria. Here we identify a process that explains this association. Since mosquitoes are aquatic as larvae and pupae and terrestrial as adults, we also define the life stage when microbes need be present to reduce Zika virus susceptibility. We used antibiotics to reduce environmental water-derived microbes at pupal and adult or only adult stages and observed that microbial disruption via antibiotic treatment increases Zika virus infection and midgut permeability and impairs bloodmeal digestion. These findings advance understanding of microbiota-mosquito-virus interactions and further implicate microbes as a means to restrict virus infection of mosquitoes.

microbiology↗

Human influenza A virus H1N1 1 in marine mammals in California, 2019

From 2011-2018, we conducted surveillance in marine mammals along the California coast for influenza A virus (IAV), frequently detecting anti-influenza antibodies and intermittently detecting IAV. In spring 2019, this pattern changed. Despite no change in surveillance intensity, we detected IAV RNA in 10 samples in March and April, mostly in nasal and rectal swabs from northern elephant seals (Mirounga angustirostris). Although virus isolation was unsuccessful, IAV sequenced from one northern elephant seal nasal swab showed close genetic identity with pandemic H1N1 IAV subclade 6B.1A.1 that was concurrently circulating in humans in the 2018/19 influenza season. This represents the first report of human A(H1N1)pdm09 IAV in northern elephant seals since 2010, suggesting IAV continues to spill over from humans to pinnipeds.

microbiology↗

Behavioral signatures of Y-like neuronal responses in human vision

Retinal ganglion cells initiating the magnocellular/Y-cell visual pathways respond nonlinearly to high spatial frequencies (SFs) and temporal frequencies (TFs). This nonlinearity is implicated in the processing of contrast modulation (CM) stimuli in cats and monkeys, but its contribution to human visual perception is not well understood. Here, we evaluate human psychophysical performance for CM stimuli, consisting of a high SF grating carrier whose contrast is modulated by a low SF sinewave envelope. Subjects reported the direction of motion of CM envelopes or luminance modulation (LM) gratings at different eccentricities. The performance on SF (for LMs) or carrier SF (for CMs) was measured for different TFs (LMs) or carrier TFs (CMs). The best performance for LMs was at lower TFs and SFs, decreasing systematically with eccentricity. However, performance with CMs was bandpass with carrier SF, largely independent of carrier TF, and at the highest carrier TF (20 Hz) decreased minimally with eccentricity. Since the nonlinear subunits of Y-cells respond better at higher TFs compared to the linear response components and respond best at higher SFs that are relatively independent of eccentricity, these results suggest that behavioral tasks employing CM stimuli might reveal nonlinear contributions of retinal Y-like cells to human perception.

neuroscience↗

Two sides of a coin: a Zika virus mutation selected in pregnant rhesus macaques promotes fetal infection in mice but at a cost of reduced fitness in nonpregnant macaques and diminished transmissibility by vectors

Although fetal death is now understood to be a severe outcome of congenital Zika syndrome, the role of viral genetics is still unclear. We sequenced Zika virus (ZIKV) from a rhesus macaque fetus that died after inoculation and identified a single intra-host mutation, M1404I, in the ZIKV polyprotein, located in NS2B. Targeted sequencing flanking position 1404 in 9 additional macaque mothers and their fetuses identified M1404I at sub-consensus frequency in the majority (5 of 9, 56%) of animals and some of their fetuses. Despite its repeated presence in pregnant macaques, M1404I occurs rarely in humans since 2015. Since the primary ZIKV transmission cycle is human-mosquito-human, mutations in one host must be retained in the alternate host to be perpetuated. We hypothesized that ZIKV I1404 increases fitness in non-pregnant macaques and pregnant mice but is less efficiently transmitted by vectors, explaining its low frequency in humans during outbreaks. By examining competitive fitness relative to M1404, we observed that I1404 produced lower viremias in non-pregnant macaques and was a weaker competitor in tissues. In pregnant wildtype mice ZIKV I1404 increased the magnitude and rate of placental infection and conferred fetal infection, contrasting with M1404, which was not detected in fetuses. Although infection and dissemination rates were not different, Ae. aegypti transmitted ZIKV I1404 more poorly than M1404. Our data highlight the complexity of arbovirus mutation-fitness dynamics, and suggest that intrahost ZIKV mutations capable of augmenting fitness in pregnant vertebrates may not necessarily spread efficiently via mosquitoes during epidemics. IMPORTANCEAlthough Zika virus infection of pregnant women can result in congenital Zika syndrome, the factors that cause the syndrome in some but not all infected mothers are still unclear. We identified a mutation that was present in some ZIKV genomes in experimentally inoculated pregnant rhesus macaques and their fetuses. Although we did not find an association between the presence of the mutation and fetal death, we performed additional studies with it in non-pregnant macaques, pregnant mice, and mosquitoes. We observed that the mutation increased the ability of the virus to infect mouse fetuses but decreased its capacity to produce high levels of virus in the blood of non-pregnant macaques and to be transmitted by mosquitoes. This study shows that mutations in mosquito-borne viruses like ZIKV that increase fitness in pregnant vertebrates may not spread in outbreaks when they compromise transmission via mosquitoes and fitness in non-pregnant hosts.

microbiology↗