ResearchPad - monkeys https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Conservation laws by virtue of scale symmetries in neural systems]]> https://www.researchpad.co/article/elastic_article_14657 Considerations of the way in which a dynamical system changes under transformation of scale offer insight into its operational principles. Scale freeness is a paradigm that has been observed in a variety of physical and biological phenomena and describes a situation in which appropriately scaling the space and time coordinates of any evolution of the system yields another possible evolution. In the brain, scale freeness has drawn considerable attention, as it has been associated with optimal information transmission capabilities. Scale symmetry describes a special case of scale freeness, in which a system is perfectly unchanged under transformation of scale. Noether’s theorem tells us that in a system that possesses such a symmetry, an associated conservation law must also exist. Here we show that scale symmetry can be identified, and the related conserved quantities measured, in both simulations and real-world data. We achieve this by deriving a generalised equation of motion that leaves the action invariant under spatiotemporal scale transformations and using a modified version of Noether’s theorem to write the associated family of conservation laws. Our contribution allows for the first such statistical characterisation of the quantity that is conserved purely by virtue of scale symmetry.

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<![CDATA[Single-cell transcription analysis of <i>Plasmodium vivax</i> blood-stage parasites identifies stage- and species-specific profiles of expression]]> https://www.researchpad.co/article/elastic_article_14651 Analysis of individual Plasmodium vivax parasites reveals the tight control of the expression of most genes during the intra-erythrocytic cycle and the differentiation of male and female gametocytes, and highlights differences between the development of P. vivax and P. falciparum.

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<![CDATA[Two halves are less than the whole: Evidence of a length bisection bias in fish (<i>Poecilia reticulata</i>)]]> https://www.researchpad.co/article/elastic_article_14632 The horizontal-vertical (HV) illusion is characterized by a tendency to overestimate the length of vertically-arranged objects. Comparative research is primarily confined to primates, a range of species that, although arboreal, often explore their environment moving along the horizontal axis. Such behaviour may have led to the development of asymmetrical perceptual mechanisms to make relative size judgments of objects placed vertically and horizontally. We observed the susceptibility to the HV illusion in fish, whose ability to swim along the horizontal and vertical plane permits them to scan objects’ size equally on both axes. Guppies (Poecilia reticulata) were trained to select the longer orange line to receive a food reward. In the test phase, two arrays, containing two same-sized lines were presented, one horizontally and the other vertically. Black lines were also included in each pattern to generate the perception of an inverted T-shape (where a horizontal line is bisected by a vertical one) or an L-shape (no bisection). No bias was observed in the L-shape, which supports the idea of differential perceptual mechanisms for primates and fish. In the inverted T-shape, guppies estimated the bisected line as shorter, providing the first evidence of a length bisection bias in a fish species.

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<![CDATA[Maximizing viral detection with SIV droplet digital PCR (ddPCR) assays]]> https://www.researchpad.co/article/elastic_article_14590 Highly sensitive detection of HIV-1 nucleic acids is of critical importance for evaluating treatment interventions superimposed on combination antiretroviral therapy (cART) in HIV-1 infected individuals. SIV infection of rhesus macaques models many key aspects of human HIV-1 infection and plays a key role in evaluation of approaches for prevention, treatment and attempted eradication of HIV infection. Here we describe two droplet digital PCR (ddPCR) assays, a ddPCR DNA assay and an RT-ddPCR RNA assay for detecting simian immunodeficiency virus (SIV) on the RainDance platform. We demonstrate that RainDance ddPCR can tolerate significantly higher cell DNA input without inhibition on a per reaction basis (compared to both qPCR and Bio-Rad ddPCR), thus allowing a large quantity of sample to be analyzed in each reaction. In addition, the combination of a high processivity RT enzyme and RainDance ddPCR could overcome inhibition in severely inhibited (99.99% inhibition in qPCR quantification) viral RNA samples. These assays offer valuable tools for assessing low level viral production/replication and strategies for targeting residual virus in the setting of cART suppression of viral replication. The methodologies presented here can be adapted for a broad range of applications where highly sensitive nucleic acid detection is required.

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<![CDATA[Increasing sika deer population density may change resource use by larval dung beetles]]> https://www.researchpad.co/article/N8cd3ee58-c057-4e17-9e0d-6a1ba00b0cfd

Because animal feces contain organic matter and plant seeds, dung beetles (Scarabaeinae) are important for the circulation of materials and secondary seed dispersal through burying feces. Dung beetles are usually generalists and use the feces of various mammals. Additionally, the larval stages have access to feces from only one mammal species leaving them susceptible to changes in animal fauna and variations in animal populations. Here, we explain the effects of resource availability changes associated with sika deer (Cervus nippon) overabundance on dung beetle larvae feeding habits in Japan. δ15N values were notably higher in raccoon dog and badger dung than in that of other mammals. A dung beetle breeding experiment revealed that the δ15N values of dung beetle exoskeletons that had fed on deer feces during their larval stage were significantly lower than those of beetles that had fed on raccoon dog feces. The δ15N values of the adult exoskeleton were significantly lower in a deer high-density area than in a low-density area in large dung beetles only. It is possible that the high-quality feces, such as those of omnivores, preferred by the large beetles decrease in availability with an increase in deer dung; large beetles may therefore be unable to obtain sufficient high-quality feces and resort to using large amounts of low-quality deer feces. Small dung beetles may use the easily obtained feces that is in high abundance and they may also use deer feces more frequently with increases in deer density. These findings suggest that a larval resource shift associated with deer overabundance may affect ecosystem functions such as soil nutrient cycling and seed dispersal.

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<![CDATA[Structure and variability of delay activity in premotor cortex]]> https://www.researchpad.co/article/5c990204d5eed0c484b9749c

Voluntary movements are widely considered to be planned before they are executed. Recent studies have hypothesized that neural activity in motor cortex during preparation acts as an ‘initial condition’ which seeds the proceeding neural dynamics. Here, we studied these initial conditions in detail by investigating 1) the organization of neural states for different reaches and 2) the variance of these neural states from trial to trial. We examined population-level responses in macaque premotor cortex (PMd) during the preparatory stage of an instructed-delay center-out reaching task with dense target configurations. We found that after target onset the neural activity on single trials converges to neural states that have a clear low-dimensional structure which is organized by both the reach endpoint and maximum speed of the following reach. Further, we found that variability of the neural states during preparation resembles the spatial variability of reaches made in the absence of visual feedback: there is less variability in direction than distance in neural state space. We also used offline decoding to understand the implications of this neural population structure for brain-machine interfaces (BMIs). We found that decoding of angle between reaches is dependent on reach distance, while decoding of arc-length is independent. Thus, it might be more appropriate to quantify decoding performance for discrete BMIs by using arc-length between reach end-points rather than the angle between them. Lastly, we show that in contrast to the common notion that direction can better be decoded than distance, their decoding capabilities are comparable. These results provide new insights into the dynamical neural processes that underline motor control and can inform the design of BMIs.

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<![CDATA[High capacity reversible data hiding with interpolation and adaptive embedding]]> https://www.researchpad.co/article/5c897722d5eed0c4847d2525

A new Interpolation based Reversible Data Hiding (IRDH) scheme is reported in this paper. For different applications of an IRDH scheme to the digital image, video, multimedia, big-data and biological data, the embedding capacity requirement usually varies. Disregarding this important consideration, existing IRDH schemes do not offer a better embedding rate-distortion performance for varying size payloads. To attain this varying capacity requirement with our proposed adaptive embedding, we formulate a capacity control parameter and propose to utilize it to determine a minimum set of embeddable bits in a pixel. Additionally, we use a logical (or bit-wise) correlation between the embeddable pixel and estimated versions of an embedded pixel. Thereby, while a higher range between an upper and lower limit of the embedding capacity is maintained, a given capacity requirement within that limit is also attained with a better-embedded image quality. Computational modeling of all new processes of the scheme is presented, and performance of the scheme is evaluated with a set of popular test-images. Experimental results of our proposed scheme compared to the prominent IRDH schemes have recorded a significantly better-embedding rate-distortion performance.

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<![CDATA[Late effects of total body irradiation on hematopoietic recovery and immune function in rhesus macaques]]> https://www.researchpad.co/article/5c6dc9f6d5eed0c48452a5fd

While exposure to radiation can be lifesaving in certain settings, it can also potentially result in long-lasting adverse effects, particularly to hematopoietic and immune cells. This study investigated hematopoietic recovery and immune function in rhesus macaques Cross-sectionally (at a single time point) 2 to 5 years after exposure to a single large dose (6.5 to 8.4 Gray) of total body radiation (TBI) derived from linear accelerator-derived photons (2 MeV, 80 cGy/minute) or Cobalt 60-derived gamma irradiation (60 cGy/min). Hematopoietic recovery was assessed through measurement of complete blood counts, lymphocyte subpopulation analysis, and thymus function assessment. Capacity to mount specific antibody responses against rabies, Streptococcus pneumoniae, and tetanus antigens was determined 2 years after TBI. Irradiated macaques showed increased white blood cells, decreased platelets, and decreased frequencies of peripheral blood T cells. Effects of prior radiation on production and export of new T cells by the thymus was dependent on age at the time of analysis, with evidence of interaction with radiation dose for CD8+ T cells. Irradiated and control animals mounted similar mean antibody responses to proteins from tetanus and rabies and to 10 of 11 serotype-specific pneumococcal polysaccharides. However, irradiated animals uniformly failed to make antibodies against polysaccharides from serotype 5 pneumococci, in contrast to the robust responses of non-irradiated controls. Trends toward decreased serum levels of anti-tetanus IgM and slower peak antibody responses to rabies were also observed. Taken together, these data show that dose-related changes in peripheral blood cells and immune responses to both novel and recall antigens can be detected 2 to 5 years after exposure to whole body radiation. Longer term follow-up data on this cohort and independent validation will be helpful to determine whether these changes persist or whether additional changes become evident with increasing time since radiation, particularly as animals begin to develop aging-related changes in immune function.

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<![CDATA[Monotherapy with a low-dose lipopeptide HIV fusion inhibitor maintains long-term viral suppression in rhesus macaques]]> https://www.researchpad.co/article/5c61e93ed5eed0c48496fa7b

Combination antiretroviral therapy (cART) dramatically improves survival of HIV-infected patients, but lifelong treatment can ultimately result in cumulative toxicities and drug resistance, thus necessitating the development of new drugs with significantly improved pharmaceutical profiles. We recently found that the fusion inhibitor T-20 (enfuvirtide)-based lipopeptides possess dramatically increased anti-HIV activity. Herein, a group of novel lipopeptides were designed with different lengths of fatty acids, identifying a stearic acid-modified lipopeptide (LP-80) with the most potent anti-HIV activity. It inhibited a large panel of divergent HIV subtypes with a mean IC50 in the extremely low picomolar range, being > 5,300-fold more active than T-20 and the neutralizing antibody VRC01. It also sustained the potent activity against T-20-resistant mutants and exhibited very high therapeutic selectivity index. Pharmacokinetics of LP-80 in rats and monkeys verified its potent and long-acting anti-HIV activity. In the monkey, subcutaneous administration of 3 mg/kg LP-80 yielded serum concentrations of 1,147 ng/ml after injection 72 h and 9 ng/ml after injection 168 h (7 days), equivalent to 42,062- and 330-fold higher than the measured IC50 value. In SHIV infected rhesus macaques, a single low-dose LP-80 (3 mg/kg) sharply reduced viral loads to below the limitation of detection, and twice-weekly monotherapy could maintain long-term viral suppression.

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<![CDATA[Orangutans (Pongo abelii) make flexible decisions relative to reward quality and tool functionality in a multi-dimensional tool-use task]]> https://www.researchpad.co/article/5c6dca02d5eed0c48452a6b6

Making economic decisions in a natural foraging situation that involves the use of tools may require an animal to consider more levels of relational complexity than merely deciding between an immediate and a delayed food option. We used the same method previously used with Goffin´s cockatoos to investigate the orangutans’ flexibility for making the most profitable decisions when confronted with five different settings that included one or two different apparatuses, two different tools and two food items (one more preferred than the other). We found that orangutans made profitable decisions relative to reward quality, when the task required the subjects to select a tool over an immediately accessible food reward. Furthermore, most subjects were sensitive to work-effort when the immediate and the delayed option (directly accessible by using a tool) led to the same outcome. Most subjects continued to make profitable decisions that required taking into account the tool functionality. In a final multidimensional task design in which subjects had to simultaneously focus on two apparatuses, two reward qualities and two different tools, the orangutans chose the functional tool to access the high quality reward.

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<![CDATA[Information integration in large brain networks]]> https://www.researchpad.co/article/5c65dcadd5eed0c484dec021

An outstanding problem in neuroscience is to understand how information is integrated across the many modules of the brain. While classic information-theoretic measures have transformed our understanding of feedforward information processing in the brain’s sensory periphery, comparable measures for information flow in the massively recurrent networks of the rest of the brain have been lacking. To address this, recent work in information theory has produced a sound measure of network-wide “integrated information”, which can be estimated from time-series data. But, a computational hurdle has stymied attempts to measure large-scale information integration in real brains. Specifically, the measurement of integrated information involves a combinatorial search for the informational “weakest link” of a network, a process whose computation time explodes super-exponentially with network size. Here, we show that spectral clustering, applied on the correlation matrix of time-series data, provides an approximate but robust solution to the search for the informational weakest link of large networks. This reduces the computation time for integrated information in large systems from longer than the lifespan of the universe to just minutes. We evaluate this solution in brain-like systems of coupled oscillators as well as in high-density electrocortigraphy data from two macaque monkeys, and show that the informational “weakest link” of the monkey cortex splits posterior sensory areas from anterior association areas. Finally, we use our solution to provide evidence in support of the long-standing hypothesis that information integration is maximized by networks with a high global efficiency, and that modular network structures promote the segregation of information.

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<![CDATA[Zika virus infection at mid-gestation results in fetal cerebral cortical injury and fetal death in the olive baboon]]> https://www.researchpad.co/article/5c4b7f5dd5eed0c4848412b9

Zika virus (ZIKV) infection during pregnancy in humans is associated with an increased incidence of congenital anomalies including microcephaly as well as fetal death and miscarriage and collectively has been referred to as Congenital Zika Syndrome (CZS). Animal models for ZIKV infection in pregnancy have been developed including mice and non-human primates (NHPs). In macaques, fetal CZS outcomes from maternal ZIKV infection range from none to significant. In the present study we develop the olive baboon (Papio anubis), as a model for vertical transfer of ZIKV during pregnancy. Four mid-gestation, timed-pregnant baboons were inoculated with the French Polynesian ZIKV isolate (104 ffu). This study specifically focused on the acute phase of vertical transfer. Dams were terminated at 7 days post infection (dpi; n = 1), 14 dpi (n = 2) and 21 dpi (n = 1). All dams exhibited mild to moderate rash and conjunctivitis. Viremia peaked at 5–7 dpi with only one of three dams remaining mildly viremic at 14 dpi. An anti-ZIKV IgM response was observed by 14 dpi in all three dams studied to this stage, and two dams developed a neutralizing IgG response by either 14 dpi or 21 dpi, the latter included transfer of the IgG to the fetus (cord blood). A systemic inflammatory response (increased IL2, IL6, IL7, IL15, IL16) was observed in three of four dams. Vertical transfer of ZIKV to the placenta was observed in three pregnancies (n = 2 at 14 dpi and n = 1 at 21 dpi) and ZIKV was detected in fetal tissues in two pregnancies: one associated with fetal death at ~14 dpi, and the other in a viable fetus at 21 dpi. ZIKV RNA was detected in the fetal cerebral cortex and other tissues of both of these fetuses. In the fetus studied at 21 dpi with vertical transfer of virus to the CNS, the frontal cerebral cortex exhibited notable defects in radial glia, radial glial fibers, disorganized migration of immature neurons to the cortical layers, and signs of pathology in immature oligodendrocytes. In addition, indices of pronounced neuroinflammation were observed including astrogliosis, increased microglia and IL6 expression. Of interest, in one fetus examined at 14 dpi without detection of ZIKV RNA in brain and other fetal tissues, increased neuroinflammation (IL6 and microglia) was observed in the cortex. Although the placenta of the 14 dpi dam with fetal death showed considerable pathology, only minor pathology was noted in the other three placentas. ZIKV was detected immunohistochemically in two placentas (14 dpi) and one placenta at 21 dpi but not at 7 dpi. This is the first study to examine the early events of vertical transfer of ZIKV in a NHP infected at mid-gestation. The baboon thus represents an additional NHP as a model for ZIKV induced brain pathologies to contrast and compare to humans as well as other NHPs.

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<![CDATA[The molecular biology and HPV drug responsiveness of cynomolgus macaque papillomaviruses support their use in the development of a relevant in vivo model for antiviral drug testing]]> https://www.researchpad.co/article/5c57e6c2d5eed0c484ef3d31

Due to the extreme tissue and species restriction of the papillomaviruses (PVs), there is a great need for animal models that accurately mimic PV infection in humans for testing therapeutic strategies against human papillomaviruses (HPVs). In this study, we present data that demonstrate that in terms of gene expression during initial viral DNA amplification, Macaca fascicularis PV (MfPV) types 5 and 8 appear to be similar to mucosal oncogenic HPVs, while MfPV1 (isolated from skin) resembles most high-risk cutaneous beta HPVs (HPV5). Similarities were also observed in replication properties during the initial amplification phase of the MfPV genomes. We demonstrate that high-risk mucosal HPV-specific inhibitors target the transient replication of the MfPV8 genomes, which indicates that similar pathways are used by the high-risk HPVs and MfPVs during their genome replication. Taking all into account, we propose that Macaca fascicularis may serve as a highly relevant model for preclinical tests designed to evaluate therapeutic strategies against HPV-associated lesions.

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<![CDATA[Initiation of feeding by four sympatric Neotropical primates (Ateles belzebuth, Lagothrix lagotricha poeppigii, Plecturocebus (Callicebus) discolor, and Pithecia aequatorialis) in Amazonian Ecuador: Relationships to photic and ecological factors]]> https://www.researchpad.co/article/5c52187ed5eed0c484798996

We examined photic and ecological factors related to initiation of feeding by four sympatric primates in the rain forest of Amazonian Ecuador. With rare exceptions, morning activities of all taxa began only after the onset of nautical twilight, which occurred 47–48 min before sunrise. The larger spider and woolly monkeys, Ateles belzebuth and Lagothrix lagotricha poeppigii, left their sleeping trees before sunrise about half the time, while the smaller sakis and titi monkeys, Pithecia aequatorialis and Plecturocebus (formerly Callicebus) discolor, did not emerge until sunrise or later. None of the four taxa routinely began feeding before sunrise. Pithecia began feeding a median 2.17 h after sunrise, at least 0.8 h later than the median feeding times of the other three taxa. The early movement of Ateles and Lagothrix, and late initiation of feeding by Pithecia are consistent with temporal niche partitioning. Among most New World primate species, all males and many females, have dichromatic color vision, with only two cone photopigments, while some females are trichromats with three cone photopigments. Current evidence indicates that the dichromats have a foraging advantage in dim light, which could facilitate utilization of twilight periods and contribute to temporal niche partitioning. However, in our study, dichromatic males did not differentially exploit the dim light of twilight, and times of first feeding bouts of female Ateles and Lagothrix were similar to those of males. First feeding bouts followed a seasonal pattern, occurring latest in May-August, when ripe fruit abundance and ambient temperature were both relatively low. The most frugivorous taxon, Ateles, exhibited the greatest seasonality, initiating feeding 1.4 h later in May-August than in January-April. This pattern may imply a strategy of conserving energy when ripe fruit is scarcer, but starting earlier to compete successfully when fruit is more abundant. Lower temperatures were associated with later feeding of Ateles (by 26 min / °C) and perhaps Pithecia, but not Lagothrix or Plecturocebus. The potential for modification of temporal activity patterns and temporal niche partitioning by relatively small changes in temperature should be considered when predicting the effects of climate change.

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<![CDATA[A viral video and pet lemurs on Twitter]]> https://www.researchpad.co/article/5c3fa5b1d5eed0c484ca76f7

Content shared on social media platforms can impact public perceptions of wildlife. These perceptions, which are in part shaped by context (e.g. non-naturalistic setting, presence of a human), can influence people’s desires to interact with or acquire wild animals as pets. However, few studies have examined whether this holds true for wild animals featured in viral videos. This study reports on opportunistic data collected on Twitter before, during, and after a video that featured a habituated ring-tailed lemur (Lemur catta), called “Sefo”, in southern Madagascar went ‘viral’ (i.e. circulated rapidly on the internet). Our dataset of 13,953 tweets (from an 18.5-week time period in early 2016) referencing lemurs was collected using targeted keywords on the Twitonomy Service. We identified 613 individual tweets about people wanting a lemur as a pet. In addition, 744 tweets that were captured in our dataset linked to the Sefo viral video. We found that as the number of tweets about the viral video increased, so did the number of tweets where an individual wanted to have a lemur as a pet. Most tweets (91%) did not make reference to a specific species of lemur, but when they did, they often (82%) referenced ring-tailed lemurs (L. catta), ruffed lemurs (Varecia spp.), and mouse lemurs (Microcebus spp.). This study serves as a case study to consider how viral content can impact how wild animals are perceived. We close by noting that social media sites like Twitter, which are increasingly providing their users with news and information, should carefully consider how information about wild animals is shared on their platforms, as it may impact animal welfare.

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<![CDATA[Using physical contact heterogeneity and frequency to characterize dynamics of human exposure to nonhuman primate bodily fluids in central Africa]]> https://www.researchpad.co/article/5c2e7fd9d5eed0c48451bb6f

Emerging infectious diseases of zoonotic origin constitute a recurrent threat to global health. Nonhuman primates (NHPs) occupy an important place in zoonotic spillovers (pathogenic transmissions from animals to humans), serving as reservoirs or amplifiers of multiple neglected tropical diseases, including viral hemorrhagic fevers and arboviruses, parasites and bacteria, as well as retroviruses (simian foamy virus, PTLV) that are pathogenic in human beings. Hunting and butchering studies in Africa characterize at-risk human social groups, but overlook critical factors of contact heterogeneity and frequency, NHP species differences, and meat processing practices. In southeastern Cameroon, a region with a history of zoonotic emergence and high risk of future spillovers, we conducted a novel mixed-method field study of human physical exposure to multiple NHP species, incorporating participant-based and ecological methodologies, and qualitative interviews (n = 25). We find frequent physical contact across adult human populations, greater physical contact with monkeys than apes, especially for meat handling practices, and positive correlation of human exposure with NHP species abundance and proximity to human settlement. These fine-grained results encourage reconsideration of the likely dynamics of human-NHP contact in past and future NTD emergence events. Multidisciplinary social science and ecological approaches should be mobilized to generate more effective human and animal surveillance and risk communications around neglected tropical diseases. At a moment when the WHO has included “Disease X”, a presumably zoonotic pathogen with pandemic potential, on its list of blueprint priority diseases as, new field-based tools for investigating zoonotic disease emergence, both known and unknown, are of critical importance.

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<![CDATA[Methods for detecting Zika virus in feces: A case study in captive squirrel monkeys (Saimiri boliviensis boliviensis)]]> https://www.researchpad.co/article/5c2544e6d5eed0c48442baef

A strain of Zika virus (ZIKV) of Asian origin associated with birth defects and neurological disorders has emerged and spread through the Americas. ZIKV was first isolated in the blood of nonhuman primates in Africa and has been detected in the blood, saliva, and urine of a few catarrhine species in both Africa and Asia, suggesting that nonhuman primates may serve as both a source and a reservoir of the virus. The recent introduction of ZIKV to human populations in the Americas presents the potential for the virus to spread into nonhuman primate reservoirs. Thus, it is critical to develop efficient and noninvasive detection methods to monitor the spread of the virus in wild nonhuman primate populations. Here, we describe a method for ZIKV detection in noninvasively collected fecal samples of a Neotropical primate. Fecal samples were collected from two captive squirrel monkeys (Saimiri boliviensis boliviensis) that were experimentally infected with ZIKV (Strain Mexico_1_44) and an additional two uninfected squirrel monkeys. Nucleic acids were extracted from these samples, and RT-qPCR was used to assay for the presence of ZIKV using primers flanking a 101 bp region of the NS5 gene. In both ZIKV-inoculated animals, ZIKV was detected 5–11 days post-infection, but was not detected in the uninfected animals. We compare the fecal results to ZIKV detection in serum, saliva, and urine samples from the same individuals. Our results indicate that fecal detection is a cost-effective, noninvasive method for monitoring wild populations of Neotropical primates as possible ZIKV reservoirs.

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<![CDATA[Coastal complexity: Ancient human diets inferred from Bayesian stable isotope mixing models and a primate analogue]]> https://www.researchpad.co/article/5c2544e3d5eed0c48442baa9

An extensive ecological literature applies stable isotope mixing models to derive quantitative dietary reconstructions from isotope ratios of consumer tissues. While this approach works well for some organisms, it is challenging for consumers with complex, varied diets, including humans; indeed, many archaeologists have avoided the use of mixing models because uncertainties in model outputs are sufficiently large that the findings are not helpful in understanding ancient lifeways. Here, we exploit an unparalleled opportunity to evaluate the feasibility of dietary quantification in a nutritionally and isotopically complex context on the Cape Peninsula, South Africa. Delta values (δ13C and δ15N) of 213 indigenous food samples enable us to characterise four food groups: terrestrial plants, terrestrial vertebrates, marine invertebrates and marine vertebrates. A recent study of baboons that consumed marine and terrestrial foods provides insight into the relationship between such foods and consumer tissue isotopes. We use this information to refine our interpretation of δ15N and especially δ13C in bone collagen from 35 archaeological hunter-gatherers, achieving better estimates of the relative importance of marine and terrestrial foods in the diet than has hitherto been possible. Based on Bayesian stable isotope mixing model (SIMM) outputs, we infer that the trophic enrichment factor (TEF) for δ13Cbone collagen in these coastal humans is closer to +3 than +5‰. In the most 13C- and 15N-rich individuals, 65–98% of bone collagen (95% credible intervals) derived from marine foods. Conversely, in 13C and 15N-poor individuals, 7–44% of bone collagen derived from marine foods. The uncertainties discussed here highlight the need for caution when implementing SIMMs in studies of consumers with complex diets. To our knowledge, this work constitutes the most detailed and most tightly constrained study of this problem to date.

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<![CDATA[Detection and analysis of spatiotemporal patterns in brain activity]]> https://www.researchpad.co/article/5c0ed751d5eed0c484f13ef0

There is growing evidence that population-level brain activity is often organized into propagating waves that are structured in both space and time. Such spatiotemporal patterns have been linked to brain function and observed across multiple recording methodologies and scales. The ability to detect and analyze these patterns is thus essential for understanding the working mechanisms of neural circuits. Here we present a mathematical and computational framework for the identification and analysis of multiple classes of wave patterns in neural population-level recordings. By drawing a conceptual link between spatiotemporal patterns found in the brain and coherent structures such as vortices found in turbulent flows, we introduce velocity vector fields to characterize neural population activity. These vector fields are calculated for both phase and amplitude of oscillatory neural signals by adapting optical flow estimation methods from the field of computer vision. Based on these velocity vector fields, we then introduce order parameters and critical point analysis to detect and characterize a diverse range of propagating wave patterns, including planar waves, sources, sinks, spiral waves, and saddle patterns. We also introduce a novel vector field decomposition method that extracts the dominant spatiotemporal structures in a recording. This enables neural data to be represented by the activity of a small number of independent spatiotemporal modes, providing an alternative to existing dimensionality reduction techniques which separate space and time components. We demonstrate the capabilities of the framework and toolbox with simulated data, local field potentials from marmoset visual cortex and optical voltage recordings from whole mouse cortex, and we show that pattern dynamics are non-random and are modulated by the presence of visual stimuli. These methods are implemented in a MATLAB toolbox, which is freely available under an open-source licensing agreement.

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<![CDATA[Vectored delivery of anti-SIV envelope targeting mAb via AAV8 protects rhesus macaques from repeated limiting dose intrarectal swarm SIVsmE660 challenge]]> https://www.researchpad.co/article/5c117b9ed5eed0c484699e2f

Gene based delivery of immunoglobulins promises to safely and durably provide protective immunity to individuals at risk of acquiring infectious diseases such as HIV. We used a rhesus macaque animal model to optimize delivery of naturally-arising, autologous anti-SIV neutralizing antibodies expressed by Adeno-Associated Virus 8 (AAV8) vectors. Vectored transgene expression was confirmed by quantitation of target antibody abundance in serum and mucosal surfaces. We tested the expression achieved at varying doses and numbers of injections. Expression of the transgene reached a saturation at about 2 x 1012 AAV8 genome copies (gc) per needle-injection, a physical limitation that may not scale clinically into human trials. In contrast, expression increased proportionately with the number of injections. In terms of anti-drug immunity, anti-vector antibody responses were universally strong, while those directed against the natural transgene mAb were detected in only 20% of animals. An anti-transgene antibody response was invariably associated with loss of detectable plasma expression of the antibody. Despite having atypical glycosylation profiles, transgenes derived from AAV-directed muscle cell expression retained full functional activity, including mucosal accumulation, in vitro neutralization, and protection against repeated limiting dose SIVsmE660 swarm challenge. Our findings demonstrate feasibility of a gene therapy-based passive immunization strategy against infectious disease, and illustrate the potential for the nonhuman primate model to inform clinical AAV-based approaches to passive immunization.

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