Ventral temporal and posteromedial sulcal morphology in autism spectrum disorder.

Two parallel research tracks link the morphology of small and shallow indentations, or sulci, of the cerebral cortex with functional features of the cortex and human cognition, respectively. The first track identified a relationship between the mid-fusiform sulcus (MFS) in ventral temporal cortex (VTC) and cognition in individuals with Autism Spectrum Disorder (ASD). The second track identified a new sulcus, the inframarginal sulcus (IFRMS), that serves as a tripartite landmark within the posteromedial cortex (PMC). As VTC and PMC are structurally and functionally different in ASD, here, we integrated these two tracks and tested if there are morphological differences in VTC and PMC sulci in a sample of young (5-17 years old) male participants (50 participants with ASD and 50 neurotypical controls). Our approach replicates and extends recent findings in four ways. First, regarding replication, the standard deviation (STD) of MFS cortical thickness (CT) was increased in ASD. Second, MFS length was shorter in ASD. Third, the CT STD effect extended to other VTC and to PMC sulci. Fourth, additional morphological features of VTC sulci (depth, surface area, gray matter volume) and PMC sulci (mean CT) were decreased in ASD, including putative tertiary sulci, which emerge last in gestation and continue to develop after birth. To our knowledge, this study is the most extensive comparison of the sulcal landscape (including putative tertiary sulci) in multiple cortical expanses between individuals with ASD and NTs based on manually defined sulci at the level of individual hemispheres, providing novel targets for future studies of neurodevelopmental disorders more broadly.

Untangling an insect's virome from its endogenous viral elements.

BACKGROUND: Insects are an important reservoir of viral biodiversity, but the vast majority of viruses associated with insects have not been discovered. Recent studies have employed high-throughput RNA sequencing, which has led to rapid advances in our understanding of insect viral diversity. However, insect genomes frequently contain transcribed endogenous viral elements (EVEs) with significant homology to exogenous viruses, complicating the use of RNAseq for viral discovery. METHODS: In this study, we used a multi-pronged sequencing approach to study the virome of an important agricultural pest and prolific vector of plant pathogens, the potato aphid Macrosiphum euphorbiae. We first used rRNA-depleted RNAseq to characterize the microbes found in individual insects. We then used PCR screening to measure the frequency of two heritable viruses in a local aphid population. Lastly, we generated a quality draft genome assembly for M. euphorbiae using Illumina-corrected Nanopore sequencing to identify transcriptionally active EVEs in the host genome. RESULTS: We found reads from two insect-specific viruses (a Flavivirus and an Ambidensovirus) in our RNAseq data, as well as a parasitoid virus (Bracovirus), a plant pathogenic virus (Tombusvirus), and two phages (Acinetobacter and APSE). However, our genome assembly showed that part of the 'virome' of this insect can be attributed to EVEs in the host genome. CONCLUSION: Our work shows that EVEs have led to the misidentification of aphid viruses from RNAseq data, and we argue that this is a widespread challenge for the study of viral diversity in insects.

Individual differences, missing sulci, and nomenclature: A comment on "On presentation of the human cerebral sulci from inside the cerebrum".

An average hemisphere of the human cerebral cortex contains over 100 individual folds (sulci). Many of these sulci have been overlooked by classic and modern atlases and neuroimaging tools. These sulci also show prominent individual differences: They can be broken into variable "complexes" and some sulci may not be present altogether.

Sulcal morphology of posteromedial cortex substantially differs between humans and chimpanzees.

Recent studies identify a surprising coupling between evolutionarily new sulci and the functional organization of human posteromedial cortex (PMC). Yet, no study has compared this modern PMC sulcal patterning between humans and non-human hominoids. To fill this gap in knowledge, we first manually defined over 2500 PMC sulci in 120 chimpanzee (Pan Troglodytes) hemispheres and 144 human hemispheres. We uncovered four new sulci, and quantitatively identified species differences in sulcal incidence, depth, and surface area. Interestingly, some sulci are more common in humans and others, in chimpanzees. Further, we found that the prominent marginal ramus of the cingulate sulcus differs significantly between species. Contrary to classic observations, the present results reveal that the surface anatomy of PMC substantially differs between humans and chimpanzees-findings which lay a foundation for better understanding the evolution of neuroanatomical-functional and neuroanatomical-behavioral relationships in this highly expanded region of the human cerebral cortex.

Defining putative tertiary sulci in lateral prefrontal cortex in chimpanzees using human predictions.

Similarities and differences in brain structure and function across species are of major interest in systems neuroscience, comparative biology, and brain mapping. Recently, increased emphasis has been placed on tertiary sulci, which are shallow indentations of the cerebral cortex that appear last in gestation, continue to develop after birth, and are largely either human or hominoid specific. While tertiary sulcal morphology in lateral prefrontal cortex (LPFC) has been linked to functional representations and cognition in humans, it is presently unknown if small and shallow LPFC sulci also exist in non-human hominoids. To fill this gap in knowledge, we leveraged two freely available multimodal datasets to address the following main question: Can small and shallow LPFC sulci be defined in chimpanzee cortical surfaces from human predictions of LPFC tertiary sulci? We found that 1-3 components of the posterior middle frontal sulcus (pmfs) in the posterior middle frontal gyrus are identifiable in nearly all chimpanzee hemispheres. In stark contrast to the consistency of the pmfs components, we could only identify components of the paraintermediate frontal sulcus (pimfs) in two chimpanzee hemispheres. Putative LPFC tertiary sulci were relatively smaller and shallower in chimpanzees compared to humans. In both species, two of the pmfs components were deeper in the right compared to the left hemisphere. As these results have direct implications for future studies interested in the functional and cognitive role of LPFC tertiary sulci, we share probabilistic predictions of the three pmfs components to guide the definitions of these sulci in future studies.

Why do viruses make aphids winged?

Aphids are hosts to diverse viruses and are important vectors of plant pathogens. The spread of viruses is heavily influenced by aphid movement and behaviour. Consequently, wing plasticity (where individuals can be winged or wingless depending on environmental conditions) is an important factor in the spread of aphid-associated viruses. We review several fascinating systems where aphid-vectored plant viruses interact with aphid wing plasticity, both indirectly by manipulating plant physiology and directly through molecular interactions with plasticity pathways. We also cover recent examples where aphid-specific viruses and endogenous viral elements within aphid genomes influence wing formation. We discuss why unrelated viruses with different transmission modes have convergently evolved to manipulate wing formation in aphids and whether this is advantageous for both host and virus. We argue that interactions with viruses are likely shaping the evolution of wing plasticity within and across aphid species, and we discuss the potential importance of these findings for aphid biocontrol.

Los áfidos albergan diversos virus y son vectores de importantes patógenos de plantas. La propagación de virus está fuertemente influenciada por el movimiento y el comportamiento de los áfidos. En consecuencia, la plasticidad de las alas (en la cual algunos individuos desarrollan alas dependiendo de las condiciones ambientales) es un factor importante en la propagación viral asociada a los áfidos. En este documento revisamos varios ejemplos fascinantes en los que virus de plantas transmitidos por áfidos interactúan con la plasticidad fenotípica de las alas, indirectamente manipulando la fisiología de la planta y directamente a través de interacciones moleculares con los mecanismos de plasticidad fenotípica del áfido. También describimos ejemplos recientes que demuestran como algunos virus específicos de áfidos y elementos virales endógenos localizados en los genomas de áfidos influyen en la formación de alas. Últimamente, discutimos por qué virus no relacionados con diferentes modos de transmisión han evolucionado convergentemente para manipular la formación de alas en áfidos y si este fenómeno es beneficioso para el insecto y el virus. Nosotros objetamos que las interacciones con virus están probablemente influenciando la evolución intra- e interespecífica de la plasticidad de las alas en áfidos, y discutimos el potencial de estos hallazgos para el control biológico de los áfidos.

Aphid facultative symbionts confer no protection against the fungal entomopathogen Batkoa apiculata.

Fungi in the family Entomophthoraceae are prevalent pathogens of aphids. Facultative symbiotic bacteria harbored by aphids, including Spiroplasma sp. and Regiella insecticola, have been shown to make their hosts more resistant to infection with the fungal pathogen Pandora neoaphidis. How far this protection extends against other species of fungi in the family Entomophthoraceae is unknown. Here we isolated a strain of the fungal pathogen Batkoa apiculata infecting a natural population of pea aphids (Acyrthosiphon pisum) and confirmed its identity by sequencing the 28S rRNA gene. We then infected a panel of aphids each harboring a different species or strain of endosymbiotic bacteria to test whether aphid symbionts protect against B. apiculata. We found no evidence of symbiont-mediated protection against this pathogen, and our data suggest that some symbionts make aphids more susceptible to infection. This finding is relevant to our understanding of this important model of host-microbe interactions, and we discuss our results in the context of aphid-microbe ecological and evolutionary dynamics.

Variation in density, immune gene suppression, and coinfection outcomes among strains of the aphid endosymbiont Regiella insecticola.

Many insects harbor heritable microbes that influence host phenotypes. Symbiont strains establish at different densities within hosts. This variation is important evolutionarily because within-host density has been linked to the costs and benefits of the symbiosis for both partners. Studying the factors shaping within-host density is important to our broader understanding of host-microbe coevolution. Here we focused on different strains of Regiella insecticola, a facultative symbiont of aphids. We first showed that strains of Regiella establish in pea aphids at drastically different densities. We then found that variation in density is correlated with the expression levels of two key insect immune system genes (phenoloxidase and hemocytin), with the suppression of immune gene expression correlating with higher Regiella density. We then performed an experiment where we established coinfections of a higher- and a lower-density Regiella strain, and we showed that the higher-density strain is better able to persist in coinfections than the lower-density strain. Together, our results point to a potential mechanism that contributes to strain-level variation in symbiont density in this system, and our data suggest that symbiont fitness may be increased by establishing at higher density within hosts. Our work highlights the importance of within-host dynamics shaping symbiont evolution.

Sulcal morphology of posteromedial cortex substantially differs between humans and chimpanzees.

Recent studies identify a surprising coupling between evolutionarily new sulci and the functional organization of human posteromedial cortex (PMC). Yet, no study has compared this modern PMC sulcal patterning between humans and non-human hominoids. To fill this gap in knowledge, we first manually defined 918 sulci in 120 chimpanzee ( Pan Troglodytes ) hemispheres and 1619 sulci in 144 human hemispheres. We uncovered four new PMC sulci, and quantitatively identified species differences in incidence, depth, and surface area. Interestingly, some PMC sulci are more common in humans and others, in chimpanzees. Further, we found that the prominent marginal ramus of the cingulate sulcus differs significantly between species. Contrary to classic observations, the present results reveal that the surface anatomy of PMC substantially differs between humans and chimpanzees â€" findings which lay a foundation for better understanding the evolution of neuroanatomical-functional and neuroanatomical-behavioral relationships in this highly expanded region of the human cerebral cortex.

Hominoid-specific sulcal variability is related to face perception ability.

The relationship among brain structure, brain function, and behavior is of major interest in neuroscience, evolutionary biology, and psychology. This relationship is especially intriguing when considering hominoid-specific brain structures because they cannot be studied in widely examined models in neuroscience such as mice, marmosets, and macaques. The fusiform gyrus (FG) is a hominoid-specific structure critical for face processing that is abnormal in individuals with developmental prosopagnosia (DPs)-individuals who have severe deficits recognizing the faces of familiar people in the absence of brain damage. While previous studies have found anatomical and functional differences in the FG between DPs and NTs, no study has examined the shallow tertiary sulcus (mid-fusiform sulcus, MFS) within the FG that is a microanatomical, macroanatomical, and functional landmark in humans, as well as was recently shown to be present in non-human hominoids. Here, we implemented pre-registered analyses of neuroanatomy and face perception in NTs and DPs. Results show that the MFS was shorter in DPs than NTs. Furthermore, individual differences in MFS length in the right, but not left, hemisphere predicted individual differences in face perception. These results support theories linking brain structure and function to perception, as well as indicate that individual differences in MFS length can predict individual differences in face processing. Finally, these findings add to growing evidence supporting a relationship between morphological variability of late developing, tertiary sulci and individual differences in cognition.

Functionally and structurally distinct fusiform face area(s) in over 1000 participants.

The fusiform face area (FFA) is a widely studied region causally involved in face perception. Even though cognitive neuroscientists have been studying the FFA for over two decades, answers to foundational questions regarding the function, architecture, and connectivity of the FFA from a large (N>1000) group of participants are still lacking. To fill this gap in knowledge, we quantified these multimodal features of fusiform face-selective regions in 1053 participants in the Human Connectome Project. After manually defining over 4,000 fusiform face-selective regions, we report five main findings. First, 68.76% of hemispheres have two cortically separate regions (pFus-faces/FFA-1 and mFus-faces/FFA-2). Second, in 26.69% of hemispheres, pFus-faces/FFA-1 and mFus-faces/FFA-2 are spatially contiguous, yet are distinct based on functional, architectural, and connectivity metrics. Third, pFus-faces/FFA-1 is more face-selective than mFus-faces/FFA-2, and the two regions have distinct functional connectivity fingerprints. Fourth, pFus-faces/FFA-1 is cortically thinner and more heavily myelinated than mFus-faces/FFA-2. Fifth, face-selective patterns and functional connectivity fingerprints of each region are more similar in monozygotic than dizygotic twins and more so than architectural gradients. As we share our areal definitions with the field, future studies can explore how structural and functional features of these regions will inform theories regarding how visual categories are represented in the brain.

Uncovering a tripartite landmark in posterior cingulate cortex.

Understanding brain structure-function relationships, and their development and evolution, is central to neuroscience research. Here, we show that morphological differences in posterior cingulate cortex (PCC), a hub of functional brain networks, predict individual differences in macroanatomical, microstructural, and functional features of PCC. Manually labeling 4511 sulci in 572 hemispheres, we found a shallow cortical indentation (termed the inframarginal sulcus; ifrms) within PCC that is absent from neuroanatomical atlases yet colocalized with a focal, functional region of the lateral frontoparietal network implicated in cognitive control. This structural-functional coupling generalized to meta-analyses consisting of hundreds of studies and thousands of participants. Additional morphological analyses showed that unique properties of the ifrms differ across the life span and between hominoid species. These findings support a classic theory that shallow, tertiary sulci serve as landmarks in association cortices. They also beg the question: How many other cortical indentations have we missed?

A Case of IgG4-Related Disease and Membranous Nephropathy Associated with Thrombospondin Type-1 Domain-Containing 7A.

Background: IgG4-related disease (IgG4-RD) is a systemic multi-organ inflammatory disorder which affects the kidney 20% of the time. Patients with intrinsic IgG4-related kidney disease (IgG4-RKD) often have tubulointerstitial nephritis (TIN) whereas glomerular lesions like membranous nephropathy (MN) are less common. Antibodies to thrombospondin type-1 domain-containing 7A (THSD7A) have been described in primary MN, but never in association with IgG4-RKD. Case Report: We report the first case of IgG4-MN associated with THSD7A antibodies in serum and positivity on glomerular staining, in a 57-year-old Caucasian male with IgG4-RD affecting the pancreas, liver, lacrimal glands, extraocular muscles, and kidneys. This patient presented initially with glomerular disease including significant proteinuria consistent with MN. Glomerular staining for THSD7A antigen and serum THSD7A antibody titres was positive. Treatment with corticosteroids and cyclophosphamide successfully induced remission with resolution of proteinuria, and improvement in renal function. However, despite maintenance azathioprine, the patient relapsed 39 months later. On relapse, there was minimal proteinuria but a significant rise in creatinine. Subsequent renal biopsy showed less glomerular disease and instead a TIN pattern. Subsequent treatment with Rituximab and corticosteroids successfully induced remission. Conclusion: The role of THSD7A autoantibodies in MN is emerging, and as both IgG4-MN and presence of THSD7A antibody are rare occurrences in themselves, we speculate that there may be an undiscovered association between THSD7A and IgG4-MN. Routine testing for THSD7A in IgG4-MN may help to identify the link.

Mechanisms and Evolution of Heritable Microbial Density in Insect Hosts.

Within-host density is a critically important aspect of vertically transmitted symbioses that influences the fitness of both hosts and microbes. I review recent studies of symbiont density in insects, including my laboratory's work on pea aphids and maternally transmitted bacteria. These studies used systems approaches to uncover the molecular mechanisms of how both hosts and microbes influence symbiont density, and they shed light on whether optimal density is different from the perspective of host and microbial fitness. Mounting empirical evidence suggests that antagonistic coevolution shapes vertically transmitted symbioses even when microbes provide clear benefits to hosts. This is potentially because of differing selective pressures at the host and within-host levels. Considering these contrasting evolutionary pressures will be critically important in efforts to use vertically transmitted symbionts for biocontrol and as lessons from model systems are applied to the study of more complex microbiomes.

Intraspecific variation in immune gene expression and heritable symbiont density.

Host genetic variation plays an important role in the structure and function of heritable microbial communities. Recent studies have shown that insects use immune mechanisms to regulate heritable symbionts. Here we test the hypothesis that variation in symbiont density among hosts is linked to intraspecific differences in the immune response to harboring symbionts. We show that pea aphids (Acyrthosiphon pisum) harboring the bacterial endosymbiont Regiella insecticola (but not all other species of symbionts) downregulate expression of key immune genes. We then functionally link immune expression with symbiont density using RNAi. The pea aphid species complex is comprised of multiple reproductively-isolated host plant-adapted populations. These 'biotypes' have distinct patterns of symbiont infections: for example, aphids from the Trifolium biotype are strongly associated with Regiella. Using RNAseq, we compare patterns of gene expression in response to Regiella in aphid genotypes from multiple biotypes, and we show that Trifolium aphids experience no downregulation of immune gene expression while hosting Regiella and harbor symbionts at lower densities. Using F1 hybrids between two biotypes, we find that symbiont density and immune gene expression are both intermediate in hybrids. We propose that in this system, Regiella symbionts are suppressing aphid immune mechanisms to increase their density, but that some hosts have adapted to prevent immune suppression in order to control symbiont numbers. This work therefore suggests that antagonistic coevolution can play a role in host-microbe interactions even when symbionts are transmitted vertically and provide a clear benefit to their hosts. The specific immune mechanisms that we find are downregulated in the presence of Regiella have been previously shown to combat pathogens in aphids, and thus this work also highlights the immune system's complex dual role in interacting with both beneficial and harmful microbes.

Wing plasticity and associated gene expression varies across the pea aphid biotype complex.

Developmental phenotypic plasticity is a widespread phenomenon that allows organisms to produce different adult phenotypes in response to different environments. Investigating the molecular mechanisms underlying plasticity has the potential to reveal the precise changes that lead to the evolution of plasticity as a phenotype. Here, we study wing plasticity in multiple host-plant adapted populations of pea aphids as a model for understanding adaptation to different environments within a single species. We describe the wing plasticity response of different "biotypes" to a crowded environment and find differences within as well as among biotypes. We then use transcriptome profiling to compare a highly plastic pea aphid genotype to one that shows no plasticity and find that the latter exhibits no gene expression differences between environments. We conclude that the loss of plasticity has been accompanied by a loss of differential gene expression and therefore that genetic assimilation has occurred. Our gene expression results generalize previous studies that have shown a correlation between plasticity in morphology and gene expression.

Intraspecific variation in symbiont density in an insect-microbe symbiosis.

Many insects host vertically transmitted microbes, which can confer benefits to their hosts but are costly to maintain and regulate. A key feature of these symbioses is variation: for example, symbiont density can vary among host and symbiont genotypes. However, the evolutionary forces maintaining this variation remain unclear. We studied variation in symbiont density using the pea aphid (Acyrthosiphon pisum) and the bacterium Regiella insecticola, a symbiont that can protect its host against fungal pathogens. We found that relative symbiont density varies both between two Regiella phylogenetic clades and among aphid "biotypes." Higher density symbiont infections are correlated with stronger survival costs, but variation in density has little effect on the protection Regiella provides against fungi. Instead, we found that in some aphid genotypes, a dramatic decline in symbiont density precedes the loss of a symbiont infection. Together, our data suggest that the optimal density of a symbiont infection is likely different from the perspective of aphid and microbial fitness. Regiella might prevent loss by maintaining high within-host densities, but hosts do not appear to benefit from higher symbiont numbers and may be advantaged by losing costly symbionts in certain environments. The standing variation in symbiont density observed in natural populations could therefore be maintained by antagonistic coevolutionary interactions between hosts and their symbiotic microbes.

Variation in intrinsic resistance of pea aphids to parasitoid wasps: A transcriptomic basis.

Evolutionary interactions between parasitoid wasps and insect hosts have been well studied at the organismal level, but little is known about the molecular mechanisms that insects use to resist wasp parasitism. Here we study the interaction between a braconid wasp (Aphidius ervi) and its pea aphid host (Acyrthosiphon pisum). We first identify variation in resistance to wasp parasitism that can be attributed to aphid genotype. We then use transcriptome sequencing to identify genes in the aphid genome that are differentially expressed at an early stage of parasitism, and we compare these patterns in highly resistant and susceptible aphid host lines. We find that resistant genotypes are upregulating genes involved in carbohydrate metabolism and several key innate immune system genes in response to parasitism, but that this response seems to be weaker in susceptible aphid genotypes. Together, our results provide a first look into the complex molecular mechanisms that underlie aphid resistance to wasp parasitism and contribute to a broader understanding of how resistance mechanisms evolve in natural populations.

Extreme developmental instability associated with wing plasticity in pea aphids.

A key focus of evolutionary developmental biology is on how phenotypic diversity is generated. In particular, both plasticity and developmental instability contribute to phenotypic variation among genetically identical individuals, but the interactions between the two phenomena and their general fitness impacts are unclear. We discovered a striking example of asymmetry in pea aphids: the presence of wings on one side and the complete or partial absence of wings on the opposite side. We used this asymmetric phenotype to study the connection between plasticity, developmental instability and fitness. We found that this asymmetric wing development (i) occurred equally on both sides and thus is a developmental instability; (ii) is present in some genetically unique lines but not others, and thus has a genetic basis; and (iii) has intermediate levels of fecundity, and thus does not necessarily have negative fitness consequences. We conclude that this dramatic asymmetry may arise from incomplete switching between developmental targets, linking plasticity and developmental instability. We suspect that what we have observed may be a more widespread phenomenon, occurring across species that routinely produce distinct, alternative phenotypes.