The Development of Socially Directed Attention: An Functional Magnetic Resonance Imaging Study in Infant Monkeys.

Socially guided visual attention, such as gaze following and joint attention, represents the building block of higher-level social cognition in primates, although their neurodevelopmental processes are still poorly understood. Atypical development of these social skills has served as early marker of autism spectrum disorder and Williams syndrome. In this study, we trace the developmental trajectories of four neural networks underlying visual and attentional social engagement in the translational rhesus monkey model. Resting-state fMRI (rs-fMRI) data and gaze following skills were collected in infant rhesus macaques from birth through 6 months of age. Developmental trajectories from subjects with both resting-state fMRI and eye-tracking data were used to explore brain-behavior relationships. Our findings indicate robust increases in functional connectivity (FC) between primary visual areas (primary visual cortex [V1] - extrastriate area 3 [V3] and V3 - middle temporal area, ventral motion areas middle temporal area - AST, as well as between TE and amygdala (AMY) as infants mature. Significant FC decreases were found in more rostral areas of the pathways, such as areas temporal area occipital part - TE in the ventral object pathway, V3 - lateral intraparietal (LIP) of the dorsal visual attention pathway and V3 - temporo-parietal area of the ventral attention pathway. No changes in FC were found between cortical areas LIP-FEF and temporo-parietal area - Area 12 of the dorsal and ventral attention pathways or between AST-AMY and AMY-insula. Developmental trajectory of gaze following revealed a period of dynamic changes with gradual increases from 1 to 2 months, followed by slight decreases from 3 to 6 months. Exploratory association findings across the 6-month period showed that infants with higher gaze following had lower FC between primary visual areas V1-V3, but higher FC in the dorsal attention areas V3-LIP, both in the right hemisphere. Together, the first 6 months of life in rhesus macaques represent a critical period for the emergence of gaze following skills associated with maturational changes in FC of socially guided attention pathways.

Relationship Between Cognitive Functions and Agility Performance in Elite Young Male Soccer Players.

ABSTRACT: Matlák, J, Fridvalszki, M, Kóródi, V, Szamosszegi, G, Pólyán, E, Kovács, B, Kolozs, B, Langmár, G, and Rácz, L. Relationship between cognitive functions and agility performance in elite, young, male soccer players. J Strength Cond Res 38(1): 116-122, 2024-The aim of this study was to assess the relationship between agility performance and cognitive functions measured under laboratory conditions among elite young soccer players. Twenty-five, elite, young, male soccer players (12.3 ± 0.4 years, 155.4 ± 7.6 cm, 42.6 ± 6.9 kg) completed a battery of field tests, including 5-, 10-, 20-m sprints, change of direction speed (CODS), standing long jump, and an agility test based on a human stimulus. Subjects also completed choice reaction (RT, S3) and reactive stress tolerance (DT, S1) tests on the Vienna Test System. There was a moderate significant relationship (p < 0.05) found between mean reaction time and mean motor time during the choice reaction task and decision time in the agility test. Decision time also showed a large significant correlation (p < 0.05) with total time in the agility test. No significant correlation was found between total time in the agility test and variables measured during RT and DT tests. No significant correlations were found between agility test results and results from straight line sprints, CODS, and standing long jump tests. The results of this study suggest that choice reaction time is related to decision-making speed during the agility task used in this study and can have an indirect effect on agility performance in elite young soccer players. Further studies assessing the relationship between different cognitive functions and agility performance in different sports and age categories could help in the identification of determinant cognitive functions in perceptual and decision-making factors of agility.

Addressing image misalignments in multi-parametric prostate MRI for enhanced computer-aided diagnosis of prostate cancer.

Prostate cancer (PCa) diagnosis on multi-parametric magnetic resonance images (MRI) requires radiologists with a high level of expertise. Misalignments between the MRI sequences can be caused by patient movement, elastic soft-tissue deformations, and imaging artifacts. They further increase the complexity of the task prompting radiologists to interpret the images. Recently, computer-aided diagnosis (CAD) tools have demonstrated potential for PCa diagnosis typically relying on complex co-registration of the input modalities. However, there is no consensus among research groups on whether CAD systems profit from using registration. Furthermore, alternative strategies to handle multi-modal misalignments have not been explored so far. Our study introduces and compares different strategies to cope with image misalignments and evaluates them regarding to their direct effect on diagnostic accuracy of PCa. In addition to established registration algorithms, we propose 'misalignment augmentation' as a concept to increase CAD robustness. As the results demonstrate, misalignment augmentations can not only compensate for a complete lack of registration, but if used in conjunction with registration, also improve the overall performance on an independent test set.

A longer Achilles tendon moment arm length is not associated with superior hopping performance.

Variability in musculoskeletal and lower leg structure has the potential to influence hopping height. Achilles tendon moment arm length and plantarflexor muscle strength can influence ankle joint torque development and, consequently, hopping performance. While most studies have examined the connection of the Achilles tendon moment arm with hopping performance including the resting length, in this study we attempted to explore how the changes in Achilles tendon moment arm are related to hopping performance. Therefore, the purpose of this study was to test for correlations between foot and lower leg muscle structure parameters (i.e., muscle mass, volume, cross-sectional area and Achilles tendon moment arm length) and hopping height performance in relation to changes in Achilles tendon moment arm length. Eighteen participants (10 males 8 female) performed repetitive bilateral hopping on a force platform while sagittal plane kinematics of the lower leg were recorded. Additionally, maximal isometric plantarflexion was measured. To obtain structural parameters of the lower leg, the right lower leg of each participant was scanned with magnetic resonance imaging. The cross-sectional areas of the Achilles tendon, soleus, lateral and medial gastrocnemius were measured, while muscle volumes, muscle mass, and Achilles tendon moment arm length were calculated. Contrary to our initial assumption, longer Achilles tendon moment arm did not result in superior hopping performance. Interestingly, neither maximal isometric plantarflexion force nor muscle size correlated with repetitive bilateral hopping performance. We can assume that the mechanical characteristics of the tendon and the effective utilization of the stored strain energy in the tendon may play a more important role in repetitive hopping than the structural parameters of the lower leg.

The Effects of Fatigue on the Lower Limb Biomechanics of Amateur Athletes during a Y-Balance Test.

The Y-Balance Test (YBT) is a reliable tool for assessing the dynamic balance of athletes' lower limbs. This study aimed to compare the effects of the YBT on lower limb biomechanics before and after fatigue. Sixteen adult male recreational athletes were recruited for the study, and motion capture in combination with a force plate was used to collect kinematic, dynamics, and center of pressure (COP) data of the dominant leg during YBT testing before and after fatigue. Based on the research findings, there were significant statistical differences in the distances reached during the YBT in three directions before and after fatigue. After fatigue, there is a significant decrease in the ROM of the hip and knee joints in all three directions. Also, there is a significant increase in hip joint torque in the anterior- and posterior-lateral directions, while a significant decrease in hip and ankle joint torque is observed in the posterior-medial direction. Moreover, there is an increasing trend in positive and negative joint work for the hip, knee, and ankle joints in all three directions after fatigue. The range of COP displacement also increases following fatigue. The decline in YBT scores demonstrates the detrimental impact of fatigue on the dynamic balance of the lower limbs of adult male amateur athletes. We hope that these results can provide information for athletes and coaches to better understand the effects of fatigue on the dynamic balance of lower limbs, so as to carry out targeted lower limb balance training and prevent sports injuries.

An Acute Transition from Rearfoot to Forefoot Strike does not Induce Major Changes in Plantarflexor Muscles Activation for Habitual Rearfoot Strike Runners.

Footstrike pattern has received increased attention within the running community because there is a common belief that forefoot strike running (FFS) is more advantageous (i.e., improve performance and reduce running injuries) than rearfoot strike running (RFS) in distance running. Literature reports suggest greater knee joint flexion magnitude and initial knee angle during stance in FFS compared with RFS running We examined the EMG activation of the triceps surae muscles during an acute transition from RFS to FFS strike. We tested the hypothesis that due to larger knee flexion in FFS the gastrocnemius muscles possibly decrease their EMG activity because muscle fascicles operate under unfavorable conditions. Fourteen competitive healthy middle- and long-distance runners who were habitual RFS runners ran on a treadmill at three speeds: 12, 14, and 16 km·h-1. Each running speed was performed with both FFS and RFS patterns. Lower limb kinematics in the sagittal plane and normalized electromyography (EMG) activity of medial gastrocnemius proximal, middle and distal regions, lateral gastrocnemius and soleus muscles were compared between footstrike patterns and running speeds across the stride cycle. Contrary to our expectations, the knee joint range of motion was similar in FFS and RFS running. However, the sagittal plane ankle joint motion was greater (p < 0.01) while running with FFS, resulting in a significantly greater muscle-tendon unit lengthening (p < 0.01) in FFS compared with RFS running. In addition, medial and lateral gastrocnemius showed higher EMG activity in FFS compared with RFS running in the late swing and early stance but only for a small percentage of the stride cycle. However, strike patterns and running speed failed to induce region-specific activation differences within the medial gastrocnemius muscle. Overall, well-trained RFS runners are able to change to FFS running by altering only the ankle joint kinematics without remarkably changing the EMG activity pattern.

Case study: The influence of Achilles tendon rupture on knee joint stress during counter-movement jump - Combining musculoskeletal modeling and finite element analysis.

Background: Presently, the current research concerning Achilles tendon rupture repair (ATR) is predominantly centered on the ankle joint, with a paucity of evidence regarding its impact on the knee joint. ATR has the potential to significantly impede athletic performance and increase tibiofemoral contact forces in athletes. The purpose of this study was to prognosticate the distribution of stress within the knee joint during a countermovement jump through the use of a simulation method that amalgamated a musculoskeletal model of a patient who underwent Achilles tendon rupture repair with a finite element model of the knee joint. Methods: A male elite badminton player who had suffered an acute Achilles tendon rupture in his right leg one year prior was selected as our study subject. In order to analyze his biomechanical data, we employed both the OpenSim musculoskeletal model and finite element model to compute various parameters such as joint angles, joint moments, joint contact forces, and the distribution of knee joint stress. Results: During the jumping phase, a significantly lower knee extension angle (p < 0.001), ankle dorsiflexion angle (p = 0.002), peak vertical ground reaction force (p < 0.001), and peak tibiofemoral contact force (p = 0.009) were observed on the injured side than on the uninjured side. During the landing phase, the ankle range of motion (ROM) was significantly lower on the injured side than on the uninjured side (p = 0.009), and higher peak vertical ground reaction forces were observed (p = 0.012). Additionally, it is logical that an injured person will put higher load on the uninjured limb, but the finite element analysis indicated that the stresses on the injured side of medial meniscus and medial cartilage were significantly greater than the uninjured side. Conclusions: An Achilles tendon rupture can limit ankle range of motion and lead to greater joint stress on the affected area during countermovement jumps, especially during the landing phase. This increased joint stress may also transfer more stress to the soft tissues of the medial knee, thereby increasing the risk of knee injury. It is worth noting that this study only involves the average knee flexion angle and load after ATR in one athlete. Caution should be exercised when applying the conclusions, and in the future, more participants should be recruited to establish personalized knee finite element models to validate the results.

Treatment with sofosbuvir attenuates the adverse neurodevelopmental consequences of Zika virus infection in infant rhesus macaques.

Zika virus (ZIKV) infection during infancy in a rhesus macaque (RM) model negatively impacts brain development resulting in long-term behavioral alterations. The current study investigated whether postexposure prophylaxis could alleviate these negative neurodevelopmental consequences. Three RM infants received a 14-day course of sofosbuvir (SOF; 15 mg/kg p.o.) treatment starting at 3 days post-infection with a Puerto Rican strain of ZIKV (PRVABC59) and were then monitored longitudinally for one year. In contrast to ZIKV-infected infant RMs who did not receive SOF, postexposure SOF treatment mitigated the neurodevelopmental, behavioral and cognitive changes seen after postnatal ZIKV infection even while not accelerating viral clearance from the blood. These data suggest that antiviral treatment may help ameliorate some, but not all, of the neurodevelopmental abnormalities associated with early postnatal ZIKV infection.

Phase-separated ribosome-nascent chain complexes in genotoxic stress response.

Assemblysomes are EDTA- and RNase-resistant ribonucleoprotein (RNP) complexes of paused ribosomes with protruding nascent polypeptide chains. They have been described in yeast and human cells for the proteasome subunit Rpt1, and the disordered amino-terminal part of the nascent chain was found to be indispensable for the accumulation of the Rpt1-RNP into assemblysomes. Motivated by this, to find other assemblysome-associated RNPs we used bioinformatics to rank subunits of Saccharomyces cerevisiae protein complexes according to their amino-terminal disorder propensity. The results revealed that gene products involved in DNA repair are enriched among the top candidates. The Sgs1 DNA helicase was chosen for experimental validation. We found that indeed nascent chains of Sgs1 form EDTA-resistant RNP condensates, assemblysomes by definition. Moreover, upon exposure to UV, SGS1 mRNA shifted from assemblysomes to polysomes, suggesting that external stimuli are regulators of assemblysome dynamics. We extended our studies to human cell lines. The BLM helicase, ortholog of yeast Sgs1, was identified upon sequencing assemblysome-associated RNAs from the MCF7 human breast cancer cell line, and mRNAs encoding DNA repair proteins were overall enriched. Using the radiation-resistant A549 cell line, we observed by transmission electron microscopy that 1,6-hexanediol, an agent known to disrupt phase-separated condensates, depletes ring ribosome structures compatible with assemblysomes from the cytoplasm of cells and makes the cells more sensitive to X-ray treatment. Taken together, these findings suggest that assemblysomes may be a component of the DNA damage response from yeast to human.

The role of puberty on physical and brain development: A longitudinal study in male Rhesus Macaques.

This study examined the role of male pubertal maturation on physical growth and development of neurocircuits that regulate stress, emotional and cognitive control using a translational nonhuman primate model. We collected longitudinal data from male macaques between pre- and peri-puberty, including measures of physical growth, pubertal maturation (testicular volume, blood testosterone -T- concentrations) and brain structural and resting-state functional MRI scans to examine developmental changes in amygdala (AMY), hippocampus (HIPPO), prefrontal cortex (PFC), as well as functional connectivity (FC) between those regions. Physical growth and pubertal measures increased from pre- to peri-puberty. The indexes of pubertal maturation -testicular size and T- were correlated at peri-puberty, but not at pre-puberty (23 months). Our findings also showed ICV, AMY, HIPPO and total PFC volumetric growth, but with region-specific changes in PFC. Surprisingly, FC in these neural circuits only showed developmental changes from pre- to peri-puberty for HIPPO-orbitofrontal FC. Finally, testicular size was a better predictor of brain structural maturation than T levels -suggesting gonadal hormones-independent mechanisms-, whereas T was a strong predictor of functional connectivity development. We expect that these neural circuits will show more drastic pubertal-dependent maturation, including stronger associations with pubertal measures later, during and after male puberty.

HCN channels at the cell soma ensure the rapid electrical reactivity of fast-spiking interneurons in human neocortex.

Accumulating evidence indicates that there are substantial species differences in the properties of mammalian neurons, yet theories on circuit activity and information processing in the human brain are based heavily on results obtained from rodents and other experimental animals. This knowledge gap may be particularly important for understanding the neocortex, the brain area responsible for the most complex neuronal operations and showing the greatest evolutionary divergence. Here, we examined differences in the electrophysiological properties of human and mouse fast-spiking GABAergic basket cells, among the most abundant inhibitory interneurons in cortex. Analyses of membrane potential responses to current input, pharmacologically isolated somatic leak currents, isolated soma outside-out patch recordings, and immunohistochemical staining revealed that human neocortical basket cells abundantly express hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel isoforms HCN1 and HCN2 at the cell soma membrane, whereas these channels are sparse at the rodent basket cell soma membrane. Antagonist experiments showed that HCN channels in human neurons contribute to the resting membrane potential and cell excitability at the cell soma, accelerate somatic membrane potential kinetics, and shorten the lag between excitatory postsynaptic potentials and action potential generation. These effects are important because the soma of human fast-spiking neurons without HCN channels exhibit low persistent ion leak and slow membrane potential kinetics, compared with mouse fast-spiking neurons. HCN channels speed up human cell membrane potential kinetics and help attain an input-output rate close to that of rodent cells. Computational modeling demonstrated that HCN channel activity at the human fast-spiking cell soma membrane is sufficient to accelerate the input-output function as observed in cell recordings. Thus, human and mouse fast-spiking neurons exhibit functionally significant differences in ion channel composition at the cell soma membrane to set the speed and fidelity of their input-output function. These HCN channels ensure fast electrical reactivity of fast-spiking cells in human neocortex.

Functional maturation in visual pathways predicts attention to the eyes in infant rhesus macaques: Effects of social status.

Differences in looking at the eyes of others are one of the earliest behavioral markers for social difficulties in neurodevelopmental disabilities, including autism. However, it is unknown how early visuo-social experiences relate to the maturation of infant brain networks that process visual social stimuli. We investigated functional connectivity (FC) within the ventral visual object pathway as a contributing neural system. Densely sampled, longitudinal eye-tracking and resting state fMRI (rs-fMRI) data were collected from infant rhesus macaques, an important model of human social development, from birth through 6 months of age. Mean trajectories were fit for both datasets and individual trajectories from subjects with both eye-tracking and rs-fMRI data were used to test for brain-behavior relationships. Exploratory findings showed infants with greater increases in FC between left V1 to V3 visual areas have an earlier increase in eye-looking before 2 months. This relationship was moderated by social status such that infants with low social status had a stronger association between left V1 to V3 connectivity and eye-looking than high status infants. Results indicated that maturation of the visual object pathway may provide an important neural substrate supporting adaptive transitions in social visual attention during infancy.

Application of Lacunarity for Quantification of Single Molecule Localization Microscopy Images.

The quantitative analysis of datasets achieved by single molecule localization microscopy is vital for studying the structure of subcellular organizations. Cluster analysis has emerged as a multi-faceted tool in the structural analysis of localization datasets. However, the results it produces greatly depend on the set parameters, and the process can be computationally intensive. Here we present a new approach for structural analysis using lacunarity. Unlike cluster analysis, lacunarity can be calculated quickly while providing definitive information about the structure of the localizations. Using simulated data, we demonstrate how lacunarity results can be interpreted. We use these interpretations to compare our lacunarity analysis with our previous cluster analysis-based results in the field of DNA repair, showing the new algorithm's efficiency.

Reliability Study of a Functional Test for the Offensive Agility Performance in Water Polo.

The aim of the study was to develop and assess the reliability of a functional agility test containing offensive elements for water polo players. Eighteen young male (15.3 ± 0.5 years, 178.3 ± 4.7 cm, 69.4 ± 10.0 kg) water polo players with a minimum of 5 years of sport-specific experience participated in this study. The test contained reactive high-intensity short-term swimming with changes in direction and manoeuvres after perceiving unknown stimuli given by tester players, and also included a shooting task at a goal, first from 7 m and then from 5 m. Execution time and shooting efficiency were measured by two experienced water polo coaches (Evaluators A and B). All statistical analyses were calculated using SPSS. The intrarater reliability between attempts showed good reliability for both evaluators (Evaluator A: ICC: 0.87; 95% CI: 0.66-0.95 and Evaluator B: ICC: 0.88; 95% CI: 0.68-0.96). Interrater reliability between Evaluators A and B was excellent at both attempts (Attempt 1: ICC: 0.97; 95% CI: 0.93-0.99 and Attempt 2: ICC: 0.98; 95% CI: 0.91-0.99). A lack of correlation between shooting performance from 7 m and 5 m distances and execution time was observed in the protocol. The test we presented in this study was found to be a reliable measurement tool for testing offensive agility performance based on open skill nature among water polo players.

Heritability of social behavioral phenotypes and preliminary associations with autism spectrum disorder risk genes in rhesus macaques: A whole exome sequencing study.

Nonhuman primates and especially rhesus macaques (Macaca mulatta) have been indispensable animal models for studies of various aspects of neurobiology, developmental psychology, and other aspects of neuroscience. While remarkable progress has been made in our understanding of influences on atypical human social behavior, such as that observed in autism spectrum disorders (ASD), many significant questions remain. Improved understanding of the relationships among variation in specific genes and variation in expressed social behavior in a nonhuman primate would benefit efforts to investigate risk factors, developmental mechanisms, and potential therapies for behavioral disorders including ASD. To study genetic influences on key aspects of social behavior and interactions-individual competence and/or motivation for specific aspects of social behavior-we quantified individual variation in social interactions among juvenile rhesus macaques using both a standard macaque ethogram and a macaque-relevant modification of the human Social Responsiveness Scale. Our analyses demonstrate that various aspects of juvenile social behavior exhibit significant genetic heritability, with estimated quantitative genetic effects similar to that described for ASD in human children. We also performed exome sequencing and analyzed variants in 143 genes previously suggested to influence risk for human ASD. We find preliminary evidence for genetic association between specific variants and both individual behaviors and multi-behavioral factor scores. To our knowledge, this is the first demonstration that spontaneous social behaviors performed by free-ranging juvenile rhesus macaques display significant genetic heritability and then to use exome sequencing data to examine potential macaque genetic associations in genes associated with human ASD.

Near cut-off wavelength operation of resonant waveguide grating biosensors.

Numerical simulations and analytical calculations are performed to support the design of grating-coupled planar optical waveguides for biological sensing. Near cut-off and far from cut-off modes are investigated, and their characteristics and suitability for sensing are compared. The numerical simulations reveal the high sensitivity of the guided mode intensity near the cut-off wavelength for any refractive index change along the waveguide. Consequently, it is sufficient to monitor the intensity change of the near cut-off sensing mode, which leads to a simpler sensor design compared to those setups where the resonant wavelength shift of the guided mode is monitored with high precision. The operating wavelength and the sensitivity of the proposed device can be tuned by varying the geometrical parameters of the corrugated waveguide. These results may lead to the development of highly sensitive integrated sensors, which have a simple design and therefore are cost-effective for a wide range of applications. These numerical findings are supported with experimental results, where the cut-off sensing mode was identified.

Validation of the Social Responsiveness Scale (SRS) to screen for atypical social behaviors in juvenile macaques.

Primates form strong social bonds and depend on social relationships and networks that provide shared resources and protection critical for survival. Social deficits such as those present in autism spectrum disorder (ASD) and other psychiatric disorders hinder the individual's functioning in communities. Given that early diagnosis and intervention can improve outcomes and trajectories of ASD, there is a great need for tools to identify early markers for screening/diagnosis, and for translational animal models to uncover biological mechanisms and develop treatments. One of the most widely used screening tools for ASD in children is the Social Responsiveness Scale (SRS), a quantitative measure used to identify individuals with atypical social behaviors. The SRS has been adapted for use in adult rhesus monkeys (Macaca mulatta)-a species very close to humans in terms of social behavior, brain anatomy/connectivity and development-but has not yet been validated or adapted for a necessary downward extension to younger ages matching those for ASD diagnosis in children. The goal of the present study was to adapt and validate the adult macaque SRS (mSRS) in juvenile macaques with age equivalent to mid-childhood in humans. Expert primate coders modified the mSRS to adapt it to rate atypical social behaviors in juvenile macaques living in complex social groups at the Yerkes National Primate Research Center. Construct and face validity of this juvenile mSRS (jmSRS) was determined based on well-established and operationalized measures of social and non-social behaviors in this species using traditional behavioral observations. We found that the jmSRS identifies variability in social responsiveness of juvenile rhesus monkeys and shows strong construct/predictive validity, as well as sensitivity to detect atypical social behaviors in young male and female macaques across social status. Thus, the jmSRS provides a promising tool for translational research on macaque models of children social disorders.

Structural development of cortical lobes during the first 6 months of life in infant macaques.

This study mapped the developmental trajectories of cortical regions in comparison to overall brain growth in typically developing, socially-housed infant macaques. Volumetric changes of cortical brain regions were examined longitudinally between 2-24 weeks of age (equivalent to the first 2 years in humans) in 21 male rhesus macaques. Growth of the prefrontal, frontal, parietal, occipital, and temporal cortices (visual and auditory) was examined using MRI and age-specific infant macaque brain atlases developed by our group. Results indicate that cortical volumetric development follows a cubic growth curve, but maturational timelines and growth rates are region-specific. Total intracranial volume (ICV) increased significantly during the first 5 months of life, leveling off thereafter. Prefrontal and temporal visual cortices showed fast volume increases during the first 16 weeks, followed by a plateau, and significant growth again between 20-24 weeks. Volume of the frontal and temporal auditory cortices increased substantially between 2-24 weeks. The parietal cortex showed a significant volume increase during the first 4 months, whereas the volume of the occipital lobe increased between 2-12 weeks and plateaued thereafter. These developmental trajectories show similarities to cortical growth in human infants, providing foundational information necessary to build nonhuman primate (NHP) models of human neurodevelopmental disorders.

Sequence diversity analyses of an improved rhesus macaque genome enhance its biomedical utility.

The rhesus macaque (Macaca mulatta) is the most widely studied nonhuman primate (NHP) in biomedical research. We present an updated reference genome assembly (Mmul_10, contig N50 = 46 Mbp) that increases the sequence contiguity 120-fold and annotate it using 6.5 million full-length transcripts, thus improving our understanding of gene content, isoform diversity, and repeat organization. With the improved assembly of segmental duplications, we discovered new lineage-specific genes and expanded gene families that are potentially informative in studies of evolution and disease susceptibility. Whole-genome sequencing (WGS) data from 853 rhesus macaques identified 85.7 million single-nucleotide variants (SNVs) and 10.5 million indel variants, including potentially damaging variants in genes associated with human autism and developmental delay, providing a framework for developing noninvasive NHP models of human disease.