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Tuberculosis (TB), a deadly disease caused by Mycobacterium tuberculosis (Mtb) infection, remains one of the top killers among infectious diseases worldwide. How to increase targeting effects of current anti-TB chemotherapeutics and enhance anti-TB immunological responses remains a big challenge in TB and drug-resistant TB treatment. Here, mannose functionalized and polyetherimide protected graphene oxide system (GO-PEI-MAN) was designed for macrophage-targeted antibiotic (rifampicin) and autophagy inducer (carbamazepine) delivery to achieve more effective Mtb killings by combining targeted drug killing and host immunological clearance. GO-PEI-MAN system demonstrated selective uptake by in vitro macrophages and ex vivo macrophages from macaques. The endocytosed GO-PEI-MAN system would be transported into lysosomes, where the drug loaded Rif@Car@GO-PEI-MAN system would undergo accelerated drug release in acidic lysosomal conditions. Rif@Car@GO-PEI-MAN could significantly promote autophagy and apoptosis in Mtb infected macrophages, as well as induce anti-bacterial M1 polarization of Mtb infected macrophages to increase anti-bacterial IFN-γ and nitric oxide production. Collectively, Rif@Car@GO-PEI-MAN demonstrated effectively enhanced intracellular Mtb killing effects than rifampicin, carbamazepine or GO-PEI-MAN alone in Mtb infected macrophages, and could significantly reduce mycobacterial burdens in the lung of infected mice with alleviated pathology and inflammation without systemic toxicity. This macrophage targeted nanosystem synergizing increased drug killing efficiency and enhanced host immunological defense may be served as more effective therapeutics against TB and drug-resistant TB., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Sulawesi crested macaques (Macaca nigra) (SCMs) are critically endangered and frequently suffer from chronic intestinal disease in captivity. Often, despite routine diagnostic investigations and confirmation of intestinal inflammation, an aetiology cannot be identified, leading to a non-specific categorization as chronic enterocolitis rather than an aetiological diagnosis. This study evaluates the histological features of gastrointestinal tissues from 23 SCMs, comparing animals with a clinical history suggestive of chronic enterocolitis (n = 14) with those without gastrointestinal clinical signs (n = 9). Tissues were graded according to the Nancy index (NI), a scoring system used in human medicine to evaluate disease activity in ulcerative colitis, a common form of human inflammatory bowel disease (IBD). Additionally, inflammatory cells in the colonic lamina propria were visually identified by type, counted and subsequently compared between diseased and control animals. Moderate to severe lymphoplasmacytic inflammation and structural changes were most common in the colons of affected SCMs, whereas histopathological changes were absent or mild in all examined small intestine (n = 17) and stomach (n = 11) tissues. The colonic NI had a significant positive correlation with clinical disease severity and 57% (n = 8) of animals with clinical signs had a NI grade of ≥2, consistent with moderate to severe, active IBD. Half of SCMs with recurrent rectal prolapse (n = 6) had a NI grade of 0, suggesting that intestinal inflammation is not always part of this condition's pathogenesis. The numbers of colonic lymphocytes, plasma cells, neutrophils, macrophages and total leucocytes were significantly higher in diseased animals. This study validated the use of the NI in SCMs, enabling a more standardized histopathological evaluation of the colon in this species., Competing Interests: Declaration of competing interests The authors declared no conflicts of interest in relation to the research, authorship or publication of this article., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Although 'Candidatus Mycoplasma haematomacacae' (formerly known as 'Candidatus Mycoplasma haemomacaque') has been reported on extensively in macaques from Thailand, the USA, Japan, and Brazil, its genetic characterization has primarily been restricted to the 16S rRNA sequences with no exploration on multi-locus sequence analysis. The primary goal of this study was to characterize 'Ca. M. haematomacacae' among Thai macaques based on multiple genetic markers. Between April 2018 and November 2021, blood samples were taken from 580 free-ranging macaques (560 Macaca fascicularis and 20 Macaca nemestrina) in 15 locations encompassing 10 provinces throughout Thailand. Using the conventional PCR assay targeting the 16S ribosomal RNA (16S rRNA) gene, 338 out of 580 macaques (58.27 %) tested hemoplasma-positive. Of these, 40 positive samples were further subjected to DNA sequencing, and all were identified as 'Ca. M. haematomacacae'. Subsequently, the partial nucleotide sequences of 23S ribosomal RNA (23S rRNA) and RNase P RNA (rnpB) genes of this particular hemoplasma species were amplified through nested PCR assay. The analysis of multi-locus genetic markers revealed that the 23S rRNA and rnpB sequences exhibited higher levels of genetic diversity than the 16S rRNA sequences. Furthermore, the 16S rRNA analyses demonstrated that 'Ca. M. haematomacacae' infecting Old World monkeys (Macaca spp.) was most closely related to hemotropic Mycoplasma spp. in black-capped capuchins (Sapajus apella) and Marcgrave's capuchins (Sapajus flavius) from Brazil, as well as establishing a common ancestor clade with hemotropic Mycoplasma spp. from the Neotropical bats in Belize and Peru and an Old World bat in Spain. The 23S rRNA analyses likewise evidenced that 'Ca. M. haematomacacae' formed a sister clade with hemotropic Mycoplasma spp. in Neotropical bats from Belize and Panama. Thus, the present findings, based on multi-locus sequence analysis, suggest a potential origin of 'Ca. M. haematomacacae' from Neotropical and Old World bats. To the best of the authors' knowledge, this study provided the largest dataset so far of multi-locus genetic sequences of 'Ca. M. haematomacacae' isolated from Thai macaques and enhanced the accuracy of phylogenetic analyses, providing insights into their origins among hemotropic Mycoplasma spp. discovered worldwide., Competing Interests: Declaration of competing interest The authors declare no conflict of interest. We also confirm that our work is original and has not been submitted elsewhere., (Copyright © 2024 Elsevier B.V. All rights reserved.)

For animals, including humans, to have self-awareness, the ability to reflect on one's own perceptions and cognitions, which is known as metacognition, and an understanding of consistency of the self from the past to the present and into the future based on metacognition is essential. Through the mediation of self-consciousness, animals are thought to be able to proactively act to change their environment rather than passively responding to changes in their environment. However, it has not been known whether animals have self-awareness, and, if so, how it is implemented neurobiologically. In this review article, I introduce our studies examining the neural basis of metacognitive abilities for past, present, and future actions in macaque monkeys and humans, and explore the evolutionary origins of self-awareness., (Copyright © 2024. Published by Elsevier B.V.)

Viral hemorrhagic fevers (HF) are a group of acute febrile diseases with high mortality rates. Although hemostatic dysfunction appears to be a major determinant of the severity of the disease, it is still unclear what pathogenic mechanisms lead to it. In clinical studies it is found that arenaviruses, such as Lassa, Machupo, and Guanarito viruses cause HF that vary in symptoms and biological alterations. In this study we aimed to characterize the hemostatic dysfunction induced by arenaviral HF to determine its implication in the severity of the disease and to elucidate the origin of this syndrome. We found that lethal infection with Machupo, Guanarito, and Lassa viruses is associated with cutaneomucosal, cerebral, digestive, and pulmonary hemorrhages. The affected animals developed a severe alteration of the coagulation system, which was concomitant with acute hepatitis, minor deficit of hepatic factor synthesis, presence of a plasmatic inhibitor of coagulation, and dysfunction of the fibrinolytic system. Despite signs of increased vascular permeability, endothelial cell infection was not a determinant factor of the hemorrhagic syndrome. There were also alterations of the primary hemostasis during lethal infection, with moderate to severe thrombocytopenia and platelet dysfunction. Finally, we show that lethal infection is accompanied by a reduced hematopoietic potential of the bone marrow. This study provides an unprecedented characterization of the hemostasis defects induced by several highly pathogenic arenaviruses., (© 2023 by The American Society of Hematology.)

Combining multimodal approaches with functional magnetic resonance imaging (fMRI) has catapulted the research on brain circuitries of non-human primates (NHPs) into a new era. However, many studies are constrained by a lack of appropriate RF coils. In this study, a single loop transmit and 16-channel receive array coil was constructed for brain imaging of macaques at 7 Tesla (7 T). The 16 receive channels were mounted on a 3D-printed helmet-shaped form closely fitting the macaque head, with fourteen openings arranged for multimodal devices around the cortical regions. Coil performance was evaluated by quantifying and comparing signal-to-noise ratio (SNR) maps, noise correlations, g-factor maps and flip-angle maps with a 28-channel commercial knee coil. The in vivo results suggested that the macaque coil has higher SNR in cortical regions and better acceleration ability in parallel imaging, which may benefit revealing mesoscale organizations in the brain., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In human and nonhuman primates, the amygdala paralaminar nucleus (PL) contains immature neurons. To explore the PL's potential for cellular growth during development, we compared PL neurons in (1) infant and adolescent macaques (control, maternally-reared), and in (2) infant macaques that experienced separation from their mother in the first month of life compared to control maternally-reared infants. In maternally-reared animals, the adolescent PL had fewer immature neurons, more mature neurons, and larger immature soma volumes compared to infant PL. There were also fewer total neurons (immature plus mature) in adolescent versus infant PL, suggesting that some neurons move out of the PL by adolescence. Maternal separation did not change mean immature or mature neuron counts in infant PL. However, across all infant animals, immature neuron soma volume was strongly correlated with mature neuron counts. TBR1 mRNA, a transcript required for glutamatergic neuron maturation, is significantly reduced in the maternally-separated infant PL (DeCampo et al., 2017), and was also positively correlated with mature neuron counts in infant PL. We conclude that immature neurons gradually mature by adolescence, and that the stress of maternal separation may shift this trajectory, as revealed by correlations between TBR1 mRNA and mature neuron numbers across animals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Conflict of interest statement The authors declare no competing financial interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Systemic amyloidosis has been described in many animals and the most common form is reactive systemic AA amyloidosis. However, cardiac amyloidosis leading to heart failure is rare in animals. We now describe systemic and cardiac amyloidosis in two captive endangered Celebes crested macaques (Macaca nigra) at the Singapore Zoo. Both animals were geriatric and had chronic morbidities. Physical examination, radiography and ultrasonography revealed cardiac arrhythmia, pleural effusion, pulmonary oedema and ascites, consistent with cardiac failure. Amyloidosis was suspected and confirmed as type AA by immunohistochemistry., Competing Interests: Conflict of Interest Statement The authors declared no potential conflicts of interest in relation to the research, authorship or publication of this article., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Non-human primates are important models for investigations of neural development and evolution, and the use of Japanese macaque monkeys has especially contributed to the advancement of neuroscience studies. However, these studies are restricted by the number of animals able to be evaluated and the invasiveness of the methodologies. Induced pluripotent stem cells (iPSCs) can provide an alternative strategy for investigating neural development in vitro. We have established direct neurosphere (dNS) formation cultures of primate iPSCs as an in vitro model of early neurodevelopment in primate species. Here, we used dNS formation and neuronal differentiation cultures established from Japanese macaque iPSCs (jm-iPSCs) to investigate the usefulness of these cells as an in vitro model of early neural development. Time-course analyses of developmental potency and gene expression kinetics were performed during dNS formation culture of jm-iPSCs. During a 1-week culture, jm-iPSC-derived dNSs became neurogenic by day 3 and underwent stepwise expression changes of key developmental regulators along early neural development in a similar manner to chimpanzee dNS formation previously reported. Meanwhile, a subset of genes, including CYP26A1 and NPTX1, showed differential expression propensity in Japanese macaque, chimpanzee, and human iPSC-derived dNSs. Spontaneous upregulation of NOTCH signaling-associated genes HES5 and DLL1 was also observed in neuronal differentiation cultures of Japanese macaque but not chimpanzee dNSs, possibly reflecting the earlier neurogenic competence in Japanese macaques. The use of jm-iPSCs provides an alternative approach to neurological studies of primate development. Furthermore, jm-iPSCs can be used to investigate species differences in early neural development that are key to primate evolution., Competing Interests: Declaration of competing interest The authors have no competing interests., (Copyright © 2022 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.)

Background: In monkey neuroimaging, particularly magnetic resonance imaging (MRI) studies, quick and accurate automatic macaque brain segmentation is essential. However, there are few processing and analysis tools dedicated to automatic brain tissue segmentation and labeling of the macaque brain on a subject-specific basis. As a result, currently most adopted methods are through direct implementation of existing tools that have been designed for human brain. However, the operation steps combining different functional modules of a variety of processing and analysis tool software are inevitably complicated, cumbersome, time-consuming and labor-intensive., New Method: In this study, we proposed a novel quick and accurate automatic macaque brain segmentation method based on multi-atlas registration and majority-vote algorithm. First, the single-atlas method based on S-HAMMER is used to register each template image of the reference atlas set (including brain tissue labeled images and brain anatomical structure labeled images) to the preprocessed image to be segmented. Thus, we obtain the corresponding deformation field and spatially transform the labeled image, and then get multiple segmentation results by local weighted voting method, which perform label fusion to obtain the final labeled images of brain structures segmentation result., Results: By collecting high SNR and high spatial resolution images of macaque brain images from our 7T human MRI scanner, we have constructed two brain templates for each individual macaque subject, and macaque brain tissues and brain anatomical structure by one-atlas method. However, segmentation result of single-atlas method is not much accurate in some brain tissue area. It takes about 2 h and need more manual correction for segmentation. Automatic segmentation of macaque brain structure based on multi-atlas method was reasonably successful, the accuracy of segmentation was greatly improved without manual correction. Also, the proposed method provided good tissue fitting to V1 with smooth and continuous boundary. The Dice similarity of multi-atlas method showing 3.24%, 4.24%, 2.55%, 2.85%, 3.05%, and 0.35% improvement in image slices of 63, 66, 70, 71, 99 and 100, respectively. The entire processing time for the construction of a single template map took ~40 min., Conclusions: This study proposed a novel automatic segmentation method of individual macaque brain structure based on multi-atlas registration method, which is concise and reliable. It may offer a valuable tool to applications in the field of brain and neuroscience research using the macaque as an experimental animal model., (Copyright © 2022. Published by Elsevier Inc.)

Repetitive transcranial magnetic stimulation (rTMS) is now widely used as a means of neuromodulation, but the details of the mechanisms by which rTMS works remain unclarified. As a step forward to unveiling the neural phenomena occurring underneath the TMS coil, we conducted an electrophysiological study using awake and unanesthetized monkeys with subdural electrocorticogram (ECoG) electrodes implanted over the primary motor cortex (MI). We evaluated the effects of low-frequency (1 Hz) and high-frequency (10 Hz) rTMS on the resting-state ECoG signals in the stimulated MI, as well as the motor evoked potentials (MEPs) in the contralateral hand. Following the 1-Hz rTMS application, the ECoG beta band power and the MEP amplitude were significantly decreased. Following the 10-Hz rTMS application, the ECoG high-gamma power and the MEP amplitude significantly increased. Given that beta and high-gamma activities in the ECoG reflect the synchronous firing and the firing frequency of cell assemblies, respectively, in local neural circuits, these results suggest that low-frequency rTMS inhibits neural activity by desynchronizing the firing activity of local circuits, whereas high-frequency rTMS facilitates neural activity by increasing the firing rate of cell assemblies in the local circuits., (Copyright © 2021 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.)

We quantitatively investigated temporal changes of macrophages and microglia (MΦ/MG) after focal infarction of the internal capsule using a macaque model we recently established. Immunoreactivity for Iba1, a general marker for MΦ/MG, in the periinfarct core gradually increased from 0 days to 2-3 weeks after infarction, and the increased immunoreactivity continued at least until 6 months; no study in rodents has reported increased Iba1-immunoreactive cells for so long. Retrograde atrophy or degeneration of neurons in layer V of the primary motor cortex, where the descending motor tract originates, was seen as secondary damage. Here we found that Iba1-positive MΦ/MG transiently increased in layer V during several weeks after the infarction. Therefore, the time course of MΦ/MG activation differs between the perilesional area and the remote brain area where secondary damage occurs to tissue initially preserved after the infarct. Detailed analyses using the functional phenotype markers CD68, CD86, and CD206, as well as cytokines released by cells with each phenotype, suggest an anti-inflammatory role for activated MΦ/MG both in the periinfarct core during the chronic phase and in the primary motor cortex., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2020 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.)

Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections are characterized by dramatic alterations in the mucosal CD4 T cell compartment. Though viremia is effectively suppressed, and peripheral CD4 T cell numbers recover to near healthy levels after highly active anti-retroviral therapy (HAART), some of the dysfunctional consequences of HIV infection continue to persist during therapy. We hypothesized that CD4 T follicular helper (Tfh) cell deficiencies may play a role in this process. Using the macaque model we show that SIV infection was associated with a significant loss of Tfh cells in the GALT that drain the mesentery lining the gastrointestinal tract (GIT). Loss of Tfh cells significantly correlated with the depletion of the overall memory CD4 T cell compartment; most Tfh cells in the GALT expressed a CD95+CD28+ memory phenotype suggesting that infection of the memory compartment likely drives the loss of GALT Tfh cells during infection. Continuous anti-retroviral therapy (cART) was accompanied by a significant repopulation of Tfh cells in the GALT to levels similar to those of uninfected animals. Repopulating Tfh cells displayed significantly higher capacity to produce IL-21 as compared to SIV infected animals suggesting that cART fully restores Tfh cells that are functionally capable of supporting GC reactions in the GALT., (Published by Elsevier Inc.)

Several gastrointestinal epithelial cells are involved in taste signal transduction. Although rodent tissues are extensively used as a human gut model, recent studies show that the chemical sensing system in rodents differs from that in humans. Nonhuman primates in biomedical research are valuable animal models to advance our understanding of biological responses in humans. The 3D organoid culture produces functional gastrointestinal epithelial cells in vitro and can be generated from animal and human tissues. Here, we report the generation of intestinal chemosensory cells from nonhuman primates, macaques, using an organoid culture system. We were able to maintain macaque intestinal organoids in the proliferation medium for more than six months. Upon switching to differentiation medium, we observed a drastic change in organoid morphology and chemosensory cell marker protein expression. This switch from proliferation to differentiation was confirmed by transcriptome analysis of the duodenum, jejunum, and ileum organoids. We further observed that the supplementation of culture media with interleukin (IL)-4 or the Notch inhibitor dibenzazepine (DBZ) accelerated terminal cell differentiation into chemosensory cells. Overall, we generated monkey intestinal organoids for the first time. These organoids are suitable for studying the function of primate chemosensory cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

An effective prophylactic HIV-1 vaccine is essential in order to contain the HIV/AIDS global pandemic. The discovery of different broadly neutralizing antibodies (bnAbs) in the last decades has enabled the characterization of several minimal epitopes on the HIV envelope (Env) spike, including glycan-dependent fragments. Herein, we provide a brief overview of the progress made on the development of synthetic carbohydrate-based epitope mimics for the elicitation of bnAbs directed to certain regions on Env gp120 protein: the outer domain high-mannose cluster and the variable loops V1V2 and V3. We focus on the design, synthesis and biological evaluation of minimal immunogens and discuss key aspects towards the development of a successful protective vaccine against HIV-1., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

IgA antibodies are key immune effectors against invading pathogens but also possess essential immunoregulatory functions. Detecting and quantifying human IgA + B-cell subsets and secreted IgA molecules is needed for investigating the protective, modulatory and pathophysiologic roles of IgAs. Here, we produced a recombinant tagged trimeric form of the streptococcal IgA-binding peptide (SAP) by transient transfection-based eukaryotic expression system. The trimeric SAP (tSAP) probe had a higher production yield and apparent binding affinity to human IgA1 and IgA2 immunoglobulins when compared to the dimeric SAP molecule classically used to purify IgAs. tSAP bound both monomeric and dimeric IgAs, and allowed immunoblot detection and ELISA quantification of serum IgA antibodies in humans and non-human primates. Fluorescently labeled tSAP also permitted an accurate quantification of circulating human blood IgA-expressing memory B cells by flow-cytometric analyses. Thus, the easy-to-produce high affinity recombinant tSAP probe we developed is a versatile and valuable tool to quantify secreted and membrane-bound human but also primate IgA immunoglobulins., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Human butyrylcholinesterase (HuBChE) is a stoichiometric bioscavenger that protects from the toxicity of nerve agents. Non-human primates are suitable models for toxicity studies that cannot be performed in humans. We evaluated the biochemical properties of native macaque (MaBChE) tetramers, compared to recombinant MaBChE monomers, PEGylated recombinant MaBChE tetramers and monomers, and native HuBChE tetramers. K m and k cat values for butyrylthiocholine were independent of subunit assembly status. The K m for all forms of MaBChE was about 70 μM, compared to 13 μM for HuBChE. The k cat was about 100,000 min -1 for MaBChE and 30,000 min -1 for HuBChE. The reversible inhibitor ethopropazine had similar K i values of 0.05 μM for all MaBChE forms and HuBChE. The bimolecular rate constant, ki, for inhibition by diisopropylfluorophosphate (DFP), an analog of sarin, was 2.2 to 2.5 × 10 7  M -1  min -1 for all MaBChE forms and for HuBChE. A major difference between MaBChE and HuBChE was the rate of reactivation by 2-PAM. The second order rate constant for reactivation of DFP-inhibited MaBChE by 2-PAM was 1.4 M -1  min -1 , but was 380 fold faster for DFP-inhibited HuBChE (k r 531 M -1  min -1 ). The acyl pocket of MaBChE has Leu285 in place of Pro285 in HuBChE. The reactivation rate of DFP-inhibited HuBChE mutant P285L by 2-PAM was reduced 5.8-fold (k r 92 M -1  min -1 ) indicating that P285 determines whether 2-PAM binds in an orientation that favors release of diisopropylphosphate. DFP-inhibited MaBChE treated with 0.2 M 2-PAM recovered 10% of its original activity, whereas DFP-inhibited HuBChE recovered 80% activity. It was concluded that the biochemical properties of MaBChE are similar to those of HuBChE except for the reactivation of DFP-inhibited BChE., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Non-human primates (NHPs) are vital models for neuroscience research. These animals have been widely used in behavioral, electrophysiological, molecular, and more recently, multimodal neuroimaging and neuro-engineering studies. Several RF coil arrays have been designed for functional, high-resolution brain magnetic resonance imaging (MRI), but few have been designed to accommodate multimodal devices. In the present study, a 16-channel array coil was constructed for brain imaging of macaques at 3 Tesla (3 T). To construct this coil, a close-fitting helmet-shaped form was designed to host 16 coil loops for whole-brain coverage. This assembly is mountable onto stereotaxic head frame bars, and the coil functions while the monkey is in the sphinx position with a clear line of vision of stimuli presented from outside of the MRI system. In addition, 4 openings were allocated in the coil housing, allowing multimodal devices to directly access visual cortical regions such as V1-V4 and MT. Coil performance was evaluated in an anesthetized macaque by quantifying and comparing signal-to-noise ratios (SNRs), noise correlations, and g-factor maps to a vendor-supplied human pediatric coil frequently used for NHP MRI. The result from in vivo experiments showed that the NHP coil was well-decoupled, had higher SNRs in cortical regions, and improved data acquisition acceleration capability compared with a vendor-supplied human pediatric coil that has been frequently used in macaque MRI studies. Furthermore, whole-brain anatomic imaging, diffusion tensor imaging and functional brain imaging have also been conducted: the details of brain anatomical structure, such as cerebellum and brainstem, can be clearly visualized in T2-SPACE images; b0 SNR calculated from b0 maps was higher than the human pediatric coil in all regions of interest (ROIs); the time-course SNR (tSNR) map calculated for GRE-EPI images demonstrates that the presented coil can be used for high-resolution functional imaging at 3 T., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Whereas antiretroviral therapy (ART) suppresses viral replication, ART discontinuation results in viral rebound, indicating the presence of viral reservoirs (VRs) established within lymphoid tissues. Herein, by sorting CD4 T-cell subsets from the spleen, mesenteric and peripheral lymph nodes (LNs) of SIVmac251-infected rhesus macaques (RMs), we demonstrate that effector memory (TEM) and follicular helper (TFH) CD4 + T cells harbor the highest frequency of viral DNA and RNA, as well of early R-U5 transcripts in ART-naïve RMs. Furthermore, our results highlight that these two CD4 T cells subsets harbor viral DNA and early R-U5 transcripts in the spleen and mesenteric LNs (but not in peripheral LN) of RMs treated with ART at day 4 post infection suggesting that these two anatomical sites are important for viral persistence. Finally, after ART interruption, we demonstrate the rapid and, compared to peripheral LNs, earlier seeding of SIV in spleen and mesenteric LNs, thereby emphasizing the importance of these two anatomical sites for viral replication dynamics. Altogether our results advance understanding of early viral seeding in which visceral lymphoid tissues are crucial in maintaining TEM and TFH VRs.

The successful development of the mammalian cerebral neocortex is linked to numerous cognitive functions such as language, voluntary movement, and episodic memory. Neocortex development occurs when neural progenitor cells divide and produce neurons. Critically, although the progenitor cells are able to self-renew they do not reproduce themselves endlessly. Hence, to fully understand the development of the neocortex we are faced with the challenge of understanding temporal changes in cell division strategy. Our approach to modelling neuronal production uses non-autonomous ordinary differential equations and allows us to use a ternary coordinate system in order to define a strategy space, through which we can visualise evolving cell division strategies. Using this strategy space, we fit the known data and use approximate Bayesian computation to predict the founding progenitor population sizes, currently unavailable in the experimental literature. Counter-intuitively, we show that humans can generate a larger number of neurons than a macaque's even when starting with a smaller number of progenitor cells. Accompanying the article is a self-contained piece of software, which provides the reader with immediate simulated results that will aid their intuition. The software can be found at www.dpag.ox.ac.uk/team/noemi-picco., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Comparative neuroanatomy studies improve understanding of brain structure and function and provide insight regarding brain development, evolution, and also what features of the brain are uniquely human. With modern methods such as diffusion MRI (dMRI) and quantitative MRI (qMRI), we are able to measure structural features of the brain with the same methods across human and non-human primates. In this review article, we discuss how recent dMRI measurements of vertical occipital connections in humans and macaques can be compared with previous findings from invasive anatomical studies that examined connectivity, including relatively forgotten classic strychnine neuronography studies. We then review recent progress in understanding the neuroanatomy of vertical connections within the occipitotemporal cortex by combining modern quantitative MRI and classical histological measurements in human and macaque. Finally, we a) discuss current limitations of dMRI and tractography and b) consider potential paths for future investigations using dMRI and tractography for comparative neuroanatomical studies of white matter tracts between species. While we focus on vertical association connections in visual cortex in the present paper, this same approach can be applied to other white matter tracts. Similar efforts are likely to continue to advance our understanding of the neuroanatomical features of the brain that are shared across species, as well as to distinguish the features that are uniquely human., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

The recent intentional use of nerve agents and pesticides in Europe and Afghanistan highlights the need for an effective countermeasure against organophosphates (OP) toxins. The most developed pretreatment candidate to date is plasma (native) human butyrylcholinesterase (HuBChE), which is limited in availability and because of its 1:1 stoichiometry with OPs, a large dose will present challenges when delivered parenterally both in terms of pharmacokinetics and manageability in the field. A tetrameric recombinant (r) form of human BChE produced in CHO-K1 cells with similar structure, in vivo stability and antidotal efficacy as the native form, has been developed to deliver rHuBChE as an aerosol (aer) to form a pulmonary bioshield capable of neutralizing inhaled OPs in situ and prevent AChE inhibition in the blood and in the brain; the latter associated with the symptoms of OP toxicity. Previous proof-of-concept macaque studies demonstrated that delivery of 9 mg/kg using a microsprayer inserted down the trachea, resulted in protection against an inhaled dose of 15ug/kg of aer-paraoxon (aer-Px) given 72 h later. In the present studies, pulmonary delivery of rHuBChE in macaques was achieved using Aerogen vibrating mesh nebulizers, similar to that used for human self-administration. The promising findings indicate that despite the poor lung deposition observed in macaques using nebulizers (13-20%), protective levels of RBC-AChE were still present in the blood even when exposure aer-Px (55 μg/kg) was delayed for five days. This long term retention of 5 mg/kg rHuBChE deposited in the lung bodes well for the use of an aer-rHuBChE pretreatment in humans where a user-friendly customized nebulizer with increased lung deposition up to 50% will provide even longer protection at a lower dose., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Serum from convalescent Lassa fever patients was previously shown to be ineffective as a source of protective antibodies in some early studies. Subsequently, monoclonal antibodies (MAbs) to the Lassa virus (LASV) glycoprotein produced by memory B cells of West African patients who survived Lassa fever were identified. Development of MAbs as potential Lassa immunotherapeutics was facilitated by structural studies and mutational analyses that identified protective epitopes on the prefusion form of the LASV glycoprotein. Human mAbs were screened for reactivity to different neutralizing epitopes, potency, and broad reactivity against multiple lineages of LASV. MAbs were downselected in a guinea pig model of Lassa fever. A cocktail of three human MAbs designated Arevirumab-3 rescued 100% of Cynomolgus macaques at advanced stages of disease more than a week post-infection. Antibody therapeutics may be further developed in clinical trials in endemic areas potentially offering a key treatment option for Lassa fever., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Lassa virus (LASV) is an emerging zoonotic virus endemic in West Africa that can cause severe haemorrhagic Lassa fever (LF) in humans. LF recently gained international attention as a prominent infectious disease, leading to increasingly severe outbreaks in Nigeria over the past three years. Morbidity and mortality associated with LF disease in Nigeria continue to rise with 106 deaths reported in 2016, 143 in 2017 and 562 in 2018. Despite the significant health impact LF imposes on West Africa there are currently no FDA-approved therapeutics or vaccines available for treatment and prevention. This review focuses on the assessment and current state of LF antiviral therapeutics in animal models and their potential role in reducing disease burden throughout West Africa., (Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate through differential diagnosis whether hypertrophic osteoarthropathy was present on an adult macaque skeleton., Materials: Skeletal remains of a well-preserved adult macaque (Macaca) of unknown species curated by the archaeology department at University College London., Methods: Macroscopic and radiographic evaluation of pathological lesions., Results: Widespread bilateral and symmetrical periosteal new bone growth primarily affecting the limbs was observed., Conclusion: A careful differential diagnosis of the lesions and comparison with previously published cases of hypertrophic osteoarthropathy among humans and non-humans suggests this animal displays a case of Hypertrophic osteoarthropathy., Significance: Only been three reported cases of HOA in non-human primates have been reported, and all were apes. This study serves as the first reported case of HOA among non-hominoid simians, providing a detailed description of the skeletal lesions to aid future with paleopathological analyses., Limitations: Small sample sizes for comparison and lack of context for this specimen limits discussion of the scope of this disease among non-human primates., Suggestions for Further Research: Re-evaluate skeletal collections which have not been subject to recent osteological and pathological analysis., (Copyright © 2019 Elsevier Inc. All rights reserved.)