Less Deformable Erythrocyte Subpopulations Biomechanically Induce Endothelial Inflammation in Sickle Cell Disease.

Sickle cell disease (SCD) is canonically characterized by reduced red blood cell (RBC) deformability leading to microvascular obstruction and inflammation. While the biophysical properties of sickle RBCs are known to influence SCD vasculopathy, the contribution of poor RBC deformability to endothelial dysfunction has yet to be fully explored. Leveraging interrelated in vitro and in silico approaches, we introduce a new paradigm of SCD vasculopathy in which poorly deformable sickle RBCs directly cause endothelial dysfunction via mechanotransduction, where endothelial cells sense and pathophysiologically respond to aberrant physical forces independently of microvascular obstruction, adhesion, or hemolysis. We demonstrate that perfusion of sickle RBCs or pharmacologically-dehydrated healthy RBCs into small venule-sized "endothelialized" microfluidics leads to pathologic physical interactions with endothelial cells that directly induce inflammatory pathways. Using a combination of computational simulations and large venule-sized endothelialized microfluidics, we observed that perfusion of heterogeneous sickle RBC subpopulations of varying deformability, as well as suspensions of dehydrated normal RBCs admixed with normal RBCs leads to aberrant margination of the less-deformable RBC subpopulations towards the vessel walls, causing localized, increased shear stress. Increased wall stress is dependent on the degree of subpopulation heterogeneity and oxygen tension and leads to inflammatory endothelial gene expression via mechanotransductive pathways. Our multifaceted approach demonstrates that the presence of sickle RBCs with reduced deformability leads directly to pathological physical (i.e., direct collisions and/or compressive forces) and shear-mediated interactions with endothelial cells and induces an inflammatory response, thereby elucidating the ubiquity of vascular dysfunction in SCD.

Discovering multiscale and self-similar structure with data-driven wavelets.

Many materials, processes, and structures in science and engineering have important features at multiple scales of time and/or space; examples include biological tissues, active matter, oceans, networks, and images. Explicitly extracting, describing, and defining such features are difficult tasks, at least in part because each system has a unique set of features. Here, we introduce an analysis method that, given a set of observations, discovers an energetic hierarchy of structures localized in scale and space. We call the resulting basis vectors a "data-driven wavelet decomposition." We show that this decomposition reflects the inherent structure of the dataset it acts on, whether it has no structure, structure dominated by a single scale, or structure on a hierarchy of scales. In particular, when applied to turbulence-a high-dimensional, nonlinear, multiscale process-the method reveals self-similar structure over a wide range of spatial scales, providing direct, model-free evidence for a century-old phenomenological picture of turbulence. This approach is a starting point for the characterization of localized hierarchical structures in multiscale systems, which we may think of as the building blocks of these systems.

Enhancing predictive capabilities in data-driven dynamical modeling with automatic differentiation: Koopman and neural ODE approaches.

Data-driven approximations of the Koopman operator are promising for predicting the time evolution of systems characterized by complex dynamics. Among these methods, the approach known as extended dynamic mode decomposition with dictionary learning (EDMD-DL) has garnered significant attention. Here, we present a modification of EDMD-DL that concurrently determines both the dictionary of observables and the corresponding approximation of the Koopman operator. This innovation leverages automatic differentiation to facilitate gradient descent computations through the pseudoinverse. We also address the performance of several alternative methodologies. We assess a "pure" Koopman approach, which involves the direct time-integration of a linear, high-dimensional system governing the dynamics within the space of observables. Additionally, we explore a modified approach where the system alternates between spaces of states and observables at each time step-this approach no longer satisfies the linearity of the true Koopman operator representation. For further comparisons, we also apply a state-space approach (neural ordinary differential equations). We consider systems encompassing two- and three-dimensional ordinary differential equation systems featuring steady, oscillatory, and chaotic attractors, as well as partial differential equations exhibiting increasingly complex and intricate behaviors. Our framework significantly outperforms EDMD-DL. Furthermore, the state-space approach offers superior performance compared to the "pure" Koopman approach where the entire time evolution occurs in the space of observables. When the temporal evolution of the Koopman approach alternates between states and observables at each time step, however, its predictions become comparable to those of the state-space approach.

The Relationship Between the Anaerobic Speed Reserve and Acute Responses to High-Intensity Interval Training in Female Soccer Players.

ABSTRACT: Aspin, GL, Graham, M, Franklin, J, Hicks, KM, and Taylor, JM. The relationship between the anaerobic speed reserve and acute responses to high-intensity interval training in female soccer players. J Strength Cond Res 38(11): 1911-1916, 2024-The anaerobic speed reserve (ASR) is a popular method of profiling soccer players, often used to individualize training prescription. This study explored the reliability of ASR profiling, and the relationship between the ASR and acute physiological responses to high-intensity interval training (HIIT). Acute physiological responses to different HIIT types were also compared. Thirteen subelite female soccer players aged 20.2 ± 4.6 years completed 6 exercise sessions. In sessions 1-2, players completed a 40-m sprint to assess maximal sprint speed (MSS) and 1600-m time-trial to estimate maximal aerobic speed (MAS), which were used to calculate ASR and assess test-retest reliability. In sessions 3-6, players completed 4 HIIT sessions (repeated-sprint training, sprint interval training, long intervals, and short intervals HIIT). Intensities for long and short intervals HIIT were individualized according to MAS. Ratings of perceived exertion (RPE), heart rate (HR), and postsession blood lactates were recorded throughout. Relationships between the ASR and acute responses to HIIT, and between HIIT session comparisons in outcome measures were assessed. Anaerobic speed reserve (coefficient of variation ± 95% confidence limits; 3.1 ± 1.5%), MAS (1.8 ± 1.3%), and MSS (0.8 ± 0.6%) indicated acceptable reliability. Moderate correlations between ASR and RPE ( r = 0.33), postsession blood lactate ( r = 0.34), and HR ( r = 0.37) were observed during long intervals HIIT. A strong correlation was observed between ASR and RPE during SIT ( r = 0.50). Sprint interval training elicited higher RPE's and postsession blood lactate's than other HIIT sessions. Anaerobic speed reserve has good reliability and may influence acute physiological responses to HIIT in female soccer players.

Data-driven reduced-order modeling of spatiotemporal chaos with neural ordinary differential equations.

Dissipative partial differential equations that exhibit chaotic dynamics tend to evolve to attractors that exist on finite-dimensional manifolds. We present a data-driven reduced-order modeling method that capitalizes on this fact by finding a coordinate representation for this manifold and then a system of ordinary differential equations (ODEs) describing the dynamics in this coordinate system. The manifold coordinates are discovered using an undercomplete autoencoder-a neural network (NN) that reduces and then expands dimension. Then, the ODE, in these coordinates, is determined by a NN using the neural ODE framework. Both of these steps only require snapshots of data to learn a model, and the data can be widely and/or unevenly spaced. Time-derivative information is not needed. We apply this framework to the Kuramoto-Sivashinsky equation for domain sizes that exhibit chaotic dynamics with again estimated manifold dimensions ranging from 8 to 28. With this system, we find that dimension reduction improves performance relative to predictions in the ambient space, where artifacts arise. Then, with the low-dimensional model, we vary the training data spacing and find excellent short- and long-time statistical recreation of the true dynamics for widely spaced data (spacing of ∼ 0.7 Lyapunov times). We end by comparing performance with various degrees of dimension reduction and find a "sweet spot" in terms of performance vs dimension.

Formation Mechanism of Multipurpose Silica Nanocapsules.

Core-shell structures containing active materials can be fabricated using almost infinite reactant combinations. A mechanism to describe their formation is therefore useful. In this work, nanoscale all-silica shell capsules with an aqueous core were fabricated by the HCl-catalyzed condensation of tetraethyl orthosilicate (TEOS), using Pickering emulsion templates. Pickering emulsions were fabricated using modified commercial silica (LUDOX TMA) nanoparticles as stabilizers. By following the reaction over a 24 h period, a general mechanism for their formation is suggested. The interfacial activity of the Pickering emulsifiers heavily influenced the final capsule products. Fully stable Pickering emulsion templates with interfacially active particles allowed a highly stable sub-micrometer (500-600 nm) core-shell structure to form. Unstable Pickering emulsions, i.e., where interfacially inactive silica nanoparticles do not adsorb effectively to the interface and produce only partially stable emulsion droplets, resulted in capsule diameter increasing markedly (1+ µm). Scanning electron microscope (SEM) and transmission electron microscope (TEM) measurements revealed the layered silica "colloidosome" structure: a thin yet robust inner silica shell with modified silica nanoparticles anchored to the outer interface. Varying the composition of emulsion phases also affected the size of capsule products, allowing size tuning of the capsules. Silica capsules are promising protective nanocarriers for hydrophilic active materials in applications such as heat storage, sensors, and drug delivery.

Coil-stretch-like transition of elastic sheets in extensional flows.

The conformation of a long linear polymer dissolved in fluid and exposed to an extensional flow is well-known to exhibit a "coil-stretch" transition, which for sufficiently long chains can lead to bistability. The present work reports computations indicating that an analogous "compact-stretched" transition arises in the dynamics of a thin elastic sheet. Sheets of nominally circular, square or rectangular shape are simulated in planar and biaxial flows using a finite element method for the sheet conformations and a regularized Stokeslet method for the fluid flow. If a neo-Hookean constitutive model is used for the sheet elasticity, the sheets will stretch without bound once a critical extension rate, as characterized nondimensionally by a capillary number, is exceeded. Nonlinear elasticity, represented with the Yeoh model, arrests the stretching, leading to a highly-stretched steady state once the critical capillary number is exceeded. For all shapes and in both planar and biaxial extension, a parameter regime exists in which both weakly stretched (compact) and strongly stretched states can be found, depending on initial conditions. I.e. this parameter regime displays bistability. As in the long-chain polymer case, the bistable behavior arises from the hydrodynamic interaction between distant elements of the sheet, and vanishes if these interactions are artificially screened by use of a Brinkman model for the fluid motion. While the sheets can transiently display wrinkled shapes, all final shapes in planar and biaxial extension are planar.

Characterization of Mauritian Cynomolgus Macaque FcγR Alleles Using Long-Read Sequencing.

The FcγRs are immune cell surface proteins that bind IgG and facilitate cytokine production, phagocytosis, and Ab-dependent, cell-mediated cytotoxicity. FcγRs play a critical role in immunity; variation in these genes is implicated in autoimmunity and other diseases. Cynomolgus macaques are an excellent animal model for many human diseases, and Mauritian cynomolgus macaques (MCMs) are particularly useful because of their restricted genetic diversity. Previous studies of MCM immune gene diversity have focused on the MHC and killer cell Ig-like receptor. In this study, we characterize FcγR diversity in 48 MCMs using PacBio long-read sequencing to identify novel alleles of each of the four expressed MCM FcγR genes. We also developed a high-throughput FcγR genotyping assay, which we used to determine allele frequencies and identify FcγR haplotypes in more than 500 additional MCMs. We found three alleles for FcγR1A, seven each for FcγR2A and FcγR2B, and four for FcγR3A; these segregate into eight haplotypes. We also assessed whether different FcγR alleles confer different Ab-binding affinities by surface plasmon resonance and found minimal difference in binding affinities across alleles for a panel of wild type and Fc-engineered human IgG. This work suggests that although MCMs may not fully represent the diversity of FcγR responses in humans, they may offer highly reproducible results for mAb therapy and toxicity studies.

The school playground environment as a driver of primary school children's physical activity behaviour: A direct observation case study.

The school playground can promote PA for large numbers of children. This study identifies areas of the playground that children visited at break-times, the decisions according to gender and the influence of contextual and environmental variables on PA levels. The playground of a culturally diverse primary school was observed during morning break-times and lunchtimes. Counts of sedentary, LPA, and MVPA episodes, and the contexts in which they occurred were recorded using the system for observing play and leisure in youth (SOPLAY). Ball sports areas had higher counts of boys (mean ± SD; 9.9 ± 4.8) compared to girls (2.0 ± 3.5); areas promoting climbing and social interaction had higher counts of girls (7.9 ± 7.2) compared to boys (3.5 ± 2.9). The proportion of MVPA episodes during break-times was 34% ± 26%. Areas of the playground with organised activities had 2.70 (95%CI: 1.87 to 3.91) times higher MVPA counts than areas "not organised". Areas with "supervision" were associated with higher MVPA counts (1.34; 1.18 to 1.53) compared with "not supervised" areas. Organisation and supervision might influence PA choices and PA levels of children in the primary school playground. Further investigation is required to explore different playgrounds settings, and context and gender preferences.

Low- and High-Drag Intermittencies in Turbulent Channel Flows.

Recent direct numerical simulations (DNS) and experiments in turbulent channel flow have found intermittent low- and high-drag events in Newtonian fluid flows, at Reτ=uτh/ν between 70 and 100, where uτ, h and ν are the friction velocity, channel half-height and kinematic viscosity, respectively. These intervals of low-drag and high-drag have been termed "hibernating" and "hyperactive", respectively, and in this paper, a further investigation of these intermittent events is conducted using experimental and numerical techniques. For experiments, simultaneous measurements of wall shear stress and velocity are carried out in a channel flow facility using hot-film anemometry (HFA) and laser Doppler velocimetry (LDV), respectively, for Reτ between 70 and 250. For numerical simulations, DNS of a channel flow is performed in an extended domain at Reτ = 70 and 85. These intermittent events are selected by carrying out conditional sampling of the wall shear stress data based on a combined threshold magnitude and time-duration criteria. The use of three different scalings (so-called outer, inner and mixed) for the time-duration criterion for the conditional events is explored. It is found that if the time-duration criterion is kept constant in inner units, the frequency of occurrence of these conditional events remain insensitive to Reynolds number. There exists an exponential distribution of frequency of occurrence of the conditional events with respect to their duration, implying a potentially memoryless process. An explanation for the presence of a spike (or dip) in the ensemble-averaged wall shear stress data before and after the low-drag (or high-drag) events is investigated. During the low-drag events, the conditionally-averaged streamwise velocities get closer to Virk's maximum drag reduction (MDR) asymptote, near the wall, for all Reynolds numbers studied. Reynolds shear stress (RSS) characteristics during these conditional events are investigated for Reτ = 70 and 85. Except very close to the wall, the conditionally-averaged RSS is higher than the time-averaged value during the low-drag events.

Highly efficient maternal-fetal Zika virus transmission in pregnant rhesus macaques.

Infection with Zika virus (ZIKV) is associated with human congenital fetal anomalies. To model fetal outcomes in nonhuman primates, we administered Asian-lineage ZIKV subcutaneously to four pregnant rhesus macaques. While non-pregnant animals in a previous study contemporary with the current report clear viremia within 10-12 days, maternal viremia was prolonged in 3 of 4 pregnancies. Fetal head growth velocity in the last month of gestation determined by ultrasound assessment of head circumference was decreased in comparison with biparietal diameter and femur length within each fetus, both within normal range. ZIKV RNA was detected in tissues from all four fetuses at term cesarean section. In all pregnancies, neutrophilic infiltration was present at the maternal-fetal interface (decidua, placenta, fetal membranes), in various fetal tissues, and in fetal retina, choroid, and optic nerve (first trimester infection only). Consistent vertical transmission in this primate model may provide a platform to assess risk factors and test therapeutic interventions for interruption of fetal infection. The results may also suggest that maternal-fetal ZIKV transmission in human pregnancy may be more frequent than currently appreciated.

Recruitment tolerance to increased temperature present across multiple kelp clades.

Kelp systems dominate nearshore marine environments in upwelling zones characterized by cold temperatures and high nutrients. Worldwide, kelp population persistence and recruitment success generally decreases with rising water temperatures coupled with low nutrients, making kelp populations vulnerable to impending warming of the oceans. This response to climate change at a global scale, however, may vary due to regional differences in temperature variability, acclimation, and differential responses of kelp species to changing conditions. Culture experiments were conducted on 12 eastern Pacific kelp taxa across geographic regions (British Columbia, central California, and southern California) under three nitrate levels (1, 5, and 10 µmol/L) and two temperatures (12°C and 18°C) to determine sporophyte production (i.e., recruitment success). For all taxa from all locations, sporophytes were always present in the 12°C treatment and when recruitment failure was observed, it always occurred at 18°C, regardless of nitrate level, indicating that temperature is the driving factor limiting recruitment, not nitrate. Rising ocean temperatures will undoubtedly cause recruitment failure for many kelp species; however, the ability of species to acclimatize or adapt to increased temperatures at the warmer edge of their species range may promote a resiliency of kelp systems to climate change at a global scale.

Critical-Layer Structures and Mechanisms in Elastoinertial Turbulence.

Simulations of elastoinertial turbulence (EIT) of a polymer solution at low Reynolds number are shown to display localized polymer stretch fluctuations. These are very similar to structures arising from linear stability (Tollmien-Schlichting modes) and resolvent analyses, i.e., critical-layer structures localized where the mean fluid velocity equals the wave speed. Computations of self-sustained nonlinear Tollmien-Schlichting waves reveal that the critical layer exhibits stagnation points that generate sheets of large polymer stretch. These kinematics may be the genesis of similar structures in EIT.

Cellular softening mediates leukocyte demargination and trafficking, thereby increasing clinical blood counts.

Leukocytes normally marginate toward the vascular wall in large vessels and within the microvasculature. Reversal of this process, leukocyte demargination, leads to substantial increases in the clinical white blood cell and granulocyte count and is a well-documented effect of glucocorticoid and catecholamine hormones, although the underlying mechanisms remain unclear. Here we show that alterations in granulocyte mechanical properties are the driving force behind glucocorticoid- and catecholamine-induced demargination. First, we found that the proportions of granulocytes from healthy human subjects that traversed and demarginated from microfluidic models of capillary beds and veins, respectively, increased after the subjects ingested glucocorticoids. Also, we show that glucocorticoid and catecholamine exposure reorganizes cellular cortical actin, significantly reducing granulocyte stiffness, as measured with atomic force microscopy. Furthermore, using simple kinetic theory computational modeling, we found that this reduction in stiffness alone is sufficient to cause granulocyte demargination. Taken together, our findings reveal a biomechanical answer to an old hematologic question regarding how glucocorticoids and catecholamines cause leukocyte demargination. In addition, in a broader sense, we have discovered a temporally and energetically efficient mechanism in which the innate immune system can simply alter leukocyte stiffness to fine tune margination/demargination and therefore leukocyte trafficking in general. These observations have broad clinically relevant implications for the inflammatory process overall as well as hematopoietic stem cell mobilization and homing.

Novel full-length major histocompatibility complex class I allele discovery and haplotype definition in pig-tailed macaques.

Pig-tailed macaques (Macaca nemestrina, Mane) are important models for human immunodeficiency virus (HIV) studies. Their infectability with minimally modified HIV makes them a uniquely valuable animal model to mimic human infection with HIV and progression to acquired immunodeficiency syndrome (AIDS). However, variation in the pig-tailed macaque major histocompatibility complex (MHC) and the impact of individual transcripts on the pathogenesis of HIV and other infectious diseases is understudied compared to that of rhesus and cynomolgus macaques. In this study, we used Pacific Biosciences single-molecule real-time circular consensus sequencing to describe full-length MHC class I (MHC-I) transcripts for 194 pig-tailed macaques from three breeding centers. We then used the full-length sequences to infer Mane-A and Mane-B haplotypes containing groups of MHC-I transcripts that co-segregate due to physical linkage. In total, we characterized full-length open reading frames (ORFs) for 313 Mane-A, Mane-B, and Mane-I sequences that defined 86 Mane-A and 106 Mane-B MHC-I haplotypes. Pacific Biosciences technology allows us to resolve these Mane-A and Mane-B haplotypes to the level of synonymous allelic variants. The newly defined haplotypes and transcript sequences containing full-length ORFs provide an important resource for infectious disease researchers as certain MHC haplotypes have been shown to provide exceptional control of simian immunodeficiency virus (SIV) replication and prevention of AIDS-like disease in nonhuman primates. The increased allelic resolution provided by Pacific Biosciences sequencing also benefits transplant research by allowing researchers to more specifically match haplotypes between donors and recipients to the level of nonsynonymous allelic variation, thus reducing the risk of graft-versus-host disease.

Buckling Instabilities and Complex Trajectories in a Simple Model of Uniflagellar Bacteria.

Observations of uniflagellar bacteria show that buckling instabilities of the hook protein connecting the cell body and flagellum play a role in locomotion. To understand this phenomenon, we develop models at varying levels of description with a particular focus on the parameter dependence of the buckling instability. A key dimensionless group called the flexibility number measures the hook flexibility relative to the thrust exerted by the flagellum; this parameter and the geometric parameters of the cell determine the stability of straight swimming. Two very simple models amenable to analytical treatment are developed to examine buckling in stationary (pinned) and moving swimmers. We then consider a more detailed model incorporating a helical flagellum and the rotational degrees of freedom of the cell body and flagellum, and we use numerical simulations to map out the parameter dependence of the buckling instability. In all models, a bifurcation occurs as the flexibility number increases, separating equilibrium configurations into straight or bent, and for the full model, separating trajectories into straight or helical. More specifically for the latter, the critical flexibility marks the transition from periodicity to quasi-periodicity in the behavior of variables determining configuration. We also find that for a given body geometry, there is a specific flagellar geometry that minimizes the critical flexibility number at which buckling occurs. These results highlight the role of flexibility in the biology of real organisms and the engineering of artificial microswimmers.

Synthetic Approach To Determine the Effect of Nuclear Spin Distance on Electronic Spin Decoherence.

Nuclear-electronic interactions are a fundamental phenomenon which impacts fields from magnetic resonance imaging to quantum information processing (QIP). The realization of QIP would transform diverse areas of research including accurate simulation of quantum dynamics and cryptography. One promising candidate for the smallest unit of QIP, a qubit, is electronic spin. Electronic spins in molecules offer significant advantages with regard to QIP, and for the emerging field of quantum sensing. Yet relative to other qubit candidates, they possess shorter superposition lifetimes, known as coherence times or T2, due to interactions with nuclear spins in the local environment. Designing complexes with sufficiently long values of T2 requires an understanding of precisely how the position of nuclear spins relative to the electronic spin center affects decoherence. Herein, we report the first synthetic study of the relationship between nuclear spin-electron spin distance and decoherence. Through the synthesis of four vanadyl complexes, (Ph4P)2[VO(C3H6S2)2] (1), (Ph4P)2[VO(C5H6S4)2] (2), (Ph4P)2[VO(C7H6S6)2] (3), and (Ph4P)2[VO(C9H6S8)2] (4), we are able to synthetically place a spin-laden propyl moiety at well-defined distances from an electronic spin center by employing a spin-free carbon-sulfur scaffold. We interrogate this series of molecules with pulsed electron paramagnetic resonance (EPR) spectroscopy to determine their coherence times. Our studies demonstrate a sharp jump in T2 when the average V-H distance is decreased from 6.6(6) to 4.0(4) Å, indicating that spin-active nuclei sufficiently close to the electronic spin center do not contribute to decoherence. These results illustrate the power of synthetic chemistry in elucidating the fundamental mechanisms underlying electronic polarization transfer and provide vital principles for the rational design of long-coherence electronic qubits.

Major histocompatibility complex haplotyping and long-amplicon allele discovery in cynomolgus macaques from Chinese breeding facilities.

Very little is currently known about the major histocompatibility complex (MHC) region of cynomolgus macaques (Macaca fascicularis; Mafa) from Chinese breeding centers. We performed comprehensive MHC class I haplotype analysis of 100 cynomolgus macaques from two different centers, with animals from different reported original geographic origins (Vietnamese, Cambodian, and Cambodian/Indonesian mixed-origin). Many of the samples were of known relation to each other (sire, dam, and progeny sets), making it possible to characterize lineage-level haplotypes in these animals. We identified 52 Mafa-A and 74 Mafa-B haplotypes in this cohort, many of which were restricted to specific sample origins. We also characterized full-length MHC class I transcripts using Pacific Biosciences (PacBio) RS II single-molecule real-time (SMRT) sequencing. This technology allows for complete read-through of unfragmented MHC class I transcripts (~1100 bp in length), so no assembly is required to unambiguously resolve novel full-length sequences. Overall, we identified 311 total full-length transcripts in a subset of 72 cynomolgus macaques from these Chinese breeding facilities; 130 of these sequences were novel and an additional 115 extended existing short database sequences to span the complete open reading frame. This significantly expands the number of Mafa-A, Mafa-B, and Mafa-I full-length alleles in the official cynomolgus macaque MHC class I database. The PacBio technique described here represents a general method for full-length allele discovery and genotyping that can be extended to other complex immune loci such as MHC class II, killer immunoglobulin-like receptors, and Fc gamma receptors.

Improved full-length killer cell immunoglobulin-like receptor transcript discovery in Mauritian cynomolgus macaques.

Killer cell immunoglobulin-like receptors (KIRs) modulate disease progression of pathogens including HIV, malaria, and hepatitis C. Cynomolgus and rhesus macaques are widely used as nonhuman primate models to study human pathogens, and so, considerable effort has been put into characterizing their KIR genetics. However, previous studies have relied on cDNA cloning and Sanger sequencing that lack the throughput of current sequencing platforms. In this study, we present a high throughput, full-length allele discovery method utilizing Pacific Biosciences circular consensus sequencing (CCS). We also describe a new approach to Macaque Exome Sequencing (MES) and the development of the Rhexome1.0, an adapted target capture reagent that includes macaque-specific capture probe sets. By using sequence reads generated by whole genome sequencing (WGS) and MES to inform primer design, we were able to increase the sensitivity of KIR allele discovery. We demonstrate this increased sensitivity by defining nine novel alleles within a cohort of Mauritian cynomolgus macaques (MCM), a geographically isolated population with restricted KIR genetics that was thought to be completely characterized. Finally, we describe an approach to genotyping KIRs directly from sequence reads generated using WGS/MES reads. The findings presented here expand our understanding of KIR genetics in MCM by associating new genes with all eight KIR haplotypes and demonstrating the existence of at least one KIR3DS gene associated with every haplotype.