Sex-Specific Distributed White Matter Microarchitectural Alterations in Preadolescent Youths With Anxiety Disorders: A Mega-Analytic Study.

OBJECTIVE: Anxiety disorders are among the most common psychiatric disorders in youths and emerge during childhood. This is also a period of rapid white matter (WM) development, which is critical for efficient neuronal communication. Previous work in preadolescent children with anxiety disorders demonstrated anxiety disorder-related reductions in WM microstructural integrity (fractional anisotropy [FA]) in the uncinate fasciculus (UF), the major WM tract facilitating prefrontal cortical-limbic structural connectivity. Importantly, this association was found only in boys with anxiety disorders. To confirm this finding and more comprehensively understand WM changes in childhood anxiety, this mega-analytic study characterizes WM alterations related to anxiety disorders and sex in the largest sample of preadolescent children to date. METHODS: Diffusion tensor imaging data from published studies of preadolescent children with anxiety disorders and healthy volunteers (ages 8-12) (N=198) were combined with a new data set (N=97) for a total sample of 165 children with anxiety disorders and 132 healthy volunteers. Children with anxiety disorders met DSM-5 criteria for current generalized, separation, and/or social anxiety disorder. Analyses of tractography and voxel-wise data assessed between-group differences (anxiety disorder vs. healthy volunteer), effects of sex, and their interaction. RESULTS: Tract-based and voxel-wise analyses confirmed a significant reduction in UF FA in boys but not girls with anxiety disorders. Results also demonstrated other significant widespread anxiety disorder-related WM alterations specifically in boys, including in multiple commissural, association, projection, and brainstem regions. CONCLUSIONS: In addition to confirming male-specific anxiety disorder-related reductions in UF FA, the results demonstrate that anxiety disorders in boys and not girls are associated with broadly distributed WM alterations across the brain. These findings support further studies focused on understanding the extent to which WM alterations in boys with anxiety disorders are involved in pathophysiological processes that mediate anxiety disorders. The findings also suggest the possibility that WM microarchitecture could serve as a novel treatment target for childhood anxiety disorders.

Early life adversity in primates: Behavioral, endocrine, and neural effects.

BACKGROUND: Evidence suggests that early life adversity is associated with maladaptive behaviors and is commonly an antecedent of stress-related psychopathology. This is particularly relevant to rearing in primate species as infant primates depend on prolonged, nurturant rearing by caregivers for normal development. To further understand the consequences of early life rearing adversity, and the relation among alterations in behavior, physiology and brain function, we assessed young monkeys that had experienced maternal separation followed by peer rearing with behavioral, endocrine and multimodal neuroimaging measures. METHODS: 50 young rhesus monkeys were studied, half of which were rejected by their mothers and peer reared, and the other half were reared by their mothers. Assessments were performed at approximately 1.8 years of age and included: threat related behavioral and cortisol responses, cerebrospinal fluid (CSF) measurements of oxytocin and corticotropin releasing hormone (CRH), and multimodal neuroimaging measures (anatomical scans, resting functional connectivity, diffusion tensor imaging, and threat-related regional glucose metabolism). RESULTS: The results demonstrated alterations across behavioral, endocrine, and neuroimaging measures in young monkeys that were reared without their mothers. At a behavioral level in response to a potential threat, peer reared animals engaged in significantly less freezing behavior (p = 0.022) along with increased self-directed behaviors (p < 0.012). Levels of oxytocin in the CSF, but not plasma, were significantly reduced in the peer reared animals (p = 0.019). No differences in plasma cortisol or CSF CRH were observed. Diffusion tensor imaging revealed significantly decreased white matter density across the brain. Exploratory correlational and permutation analyses suggest that the impact of peer rearing on behavior, endocrine and brain structural alterations are mediated by separate parallel mechanisms. CONCLUSIONS: Taken together, these results demonstrate in NHPs the importance of maternal rearing on the development of brain, behavior and hormonal systems that are linked to social functioning and adaptive responses. The findings suggest that the effects of maternal deprivation are mediated via multiple independent pathways which may account for the heterogeneity in behavioral and biological alterations observed in individuals that have experienced this early life adversity.

New insights on the optical properties and upconversion fluorescence of Er-doped CoAl2O4 nanocrystals.

In this study, Er-doped CoAl2O4 nanocrystals (NCs) were synthesized via co-precipitation. All the NCs were crystallized in the form of a single phase with a spinel structure and Er3+ ions replaced Al3+ ions in the formation of the CoAl2-xErxO4 alloy structure. The optical characteristics of the Er3+ ion-doped CoAl2O4 NCs were thoroughly investigated by analyzing both the UV-VIS and photoluminescence spectra, using the Judd-Ofelt theory. The effect of Er doping content on the luminescent properties of the CoAl2O4 pigment (using lasers emitting at wavelengths of 413 and 978 nm) has been studied. The values of Judd-Oflet intensity parameters (Ω2, Ω4, and Ω6) were determined from the absorption spectra using the least square fitting method. The J-O parameters were calculated and compared with those of other host materials; the values of the Ω2, Ω4, and Ω6 parameters decreased with an increase in Er concentration. This suggests that the rigidity and local symmetry of the host materials become weaker as the concentration of Er3+ ions increases. The highest value of the Ω2 parameter, when compared with Ω4 and Ω6, suggests that the vibrational frequencies in the given samples are relatively low. The upconversion fluorescence phenomenon was observed and explained in detail under an excitation wavelength of 978 nm when the excitation power was varied.

A preliminary study of the effects of an antimuscarinic agent on anxious behaviors and white matter microarchitecture in nonhuman primates.

Myelination subserves efficient neuronal communication, and alterations in white matter (WM) microstructure have been implicated in numerous psychiatric disorders, including pathological anxiety. Recent work in rodents suggests that muscarinic antagonists may enhance myelination with behavioral benefits; however, the neural and behavioral effects of muscarinic antagonists have yet to be explored in non-human primates (NHP). Here, as a potentially translatable therapeutic strategy for human pathological anxiety, we present data from a first-in-primate study exploring the effects of the muscarinic receptor antagonist solifenacin on anxious behaviors and WM microstructure. 12 preadolescent rhesus macaques (6 vehicle control, 6 experimental; 8F, 4M) were included in a pre-test/post-test between-group study design. The experimental group received solifenacin succinate for ~60 days. Subjects underwent pre- and post-assessments of: 1) anxious temperament (AT)-related behaviors in the potentially threatening no-eye-contact (NEC) paradigm (30-min); and 2) WM and regional brain metabolism imaging metrics, including diffusion tensor imaging (DTI), quantitative relaxometry (QR), and FDG-PET. In relation to anxiety-related behaviors expressed during the NEC, significant Group (vehicle control vs. solifenacin) by Session (pre vs. post) interactions were found for freezing, cooing, and locomotion. Compared to vehicle controls, solifenacin-treated subjects exhibited effects consistent with reduced anxiety, specifically decreased freezing duration, increased locomotion duration, and increased cooing frequency. Furthermore, the Group-by-Session-by-Sex interaction indicated that these effects occurred predominantly in the males. Exploratory whole-brain voxelwise analyses of post-minus-pre differences in DTI, QR, and FDG-PET metrics revealed some solifenacin-related changes in WM microstructure and brain metabolism. These findings in NHPs support the further investigation of the utility of antimuscarinic agents in targeting WM microstructure as a means to treat pathological anxiety.

Controlling the optical and magnetic properties of CdTeSe and Gd-doped CdTeSe alloy semiconductor nanocrystals.

In this study, CdTexSe1-x (0 ≤ x ≤ 1) and CdTeSe:Gd y% (y = 0-8.05) alloy semiconductor nanocrystals (NCs) were prepared by wet chemical method. The presence and composition of the elements in the sample were determined by energy dispersive X-ray (EDX) spectroscopy and X-ray photoelectron spectroscopy (XPS). Structural analysis of X-ray diffraction (XRD) patterns indicated that most NCs crystallized in the zinc blende (ZB) structure however some Gd-doped NCs (y = 4.52 and 8.05%) crystallized in the wurtzite (WZ) structure. The emission peak of CdTexSe1-x (0 ≤ x ≤ 1) NCs varied over a wide range when changing x while the particle size remained almost unchanged. The effect of Gd doping on the structure and optical and magnetic properties of CdTeSe NCs was studied in detail. When the Gd concentration increases from 0-8.05%: (i) the structure of CdTeSe NCs gradually changed from ZB to WZ, (ii) the emission efficiency of the material was significantly reduced, (iii) the PL lifetime of samples increased more than 10 times, and (iv) the ferromagnetic properties of the material were enhanced. The research findings demonstrated that it is possible to control the crystal structure, optical characteristics, and magnetic properties of Gd-doped CdTeSe nanocrystals by adjusting the dopant concentration and chemical composition of the host material.

New insights on the luminescence properties and Judd-Ofelt analysis of Er-doped ZnO semiconductor quantum dots.

In this study, Er3+ doped ZnO semiconductor quantum dots (QDs) were synthesized using a wet chemical method. The successful doping of Er3+ ions into the ZnO host lattice and the elemental composition was confirmed by X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). The ZnO and Er3+ doped ZnO QDs with a hexagonal structure, spherical shape, and particle size of approximately 5 nm were revealed by XRD and transmission electron microscopy (TEM). The absorption, luminescence properties, and fluorescence lifetimes of the samples were studied as the concentration of Er3+ ions varied. The intensity parameters, emission transition probabilities, branching ratios, and emission lifetimes of the excited levels of Er3+ ions in the ZnO host were determined using the Judd-Ofelt theory, which provided insight into the covalent relationship between the ions and ligands as well as the nature of the ZnO host lattice. Moreover, the energy transfer process from the ZnO host to Er3+ ions and the yield of this process are explained in detail along with specific calculations. The Er3+ doped ZnO QDs displayed a significantly longer lifetime than undoped ZnO, which opens up many potential applications in fields such as photocatalysis, optoelectronics, photovoltaics, and biosensing.

Prefrontal influences on the function of the neural circuitry underlying anxious temperament in primates.

Anxious temperament, characterized by heightened behavioral and physiological reactivity to potential threat, is an early childhood risk factor for the later development of stress-related psychopathology. Using a well-validated nonhuman primate model, we tested the hypothesis that the prefrontal cortex (PFC) is critical in regulating the expression of primate anxiety-like behavior, as well as the function of subcortical components of the anxiety-related neural circuit. We performed aspiration lesions of a narrow 'strip' of the posterior orbitofrontal cortex (OFC) intended to disrupt both cortex and axons entering, exiting and coursing through the pOFC, particularly those of the uncinate fasciculus (UF), a white matter tract that courses adjacent to and through this region. The OFC is of particular interest as a potential regulatory region because of its extensive reciprocal connections with amygdala, other subcortical structures and other frontal lobe regions. We validated this lesion method by demonstrating marked lesion-induced decreases in the microstructural integrity of the UF, which contains most of the fibers that connect the ventral PFC with temporal lobe structures as well as with other frontal regions. While the lesions resulted in modest decreases in threat-related behavior, they substantially decreased metabolism in components of the circuit underlying threat processing. These findings provide evidence for the importance of structural connectivity between the PFC and key subcortical structures in regulating the functions of brain regions known to be involved in the adaptive and maladaptive expression of anxiety.

Tracking the turnover of SARS-CoV-2 VOCs Gamma to Delta in a Brazilian state (Minas Gerais) with a high-vaccination status.

The emergence and global dissemination of Severe Acute Respiratory Syndrome virus 2 (SARS-CoV-2) variants of concern (VOCs) have been described as the main factor driving the Coronavirus Disease 2019 pandemic. In Brazil, the Gamma variant dominated the epidemiological scenario during the first period of 2021. Many Brazilian regions detected the Delta variant after its first description and documented its spread. To monitor the introduction and spread of VOC Delta, we performed Polymerase Chain Reaction (PCR) genotyping and genome sequencing in ten regional sentinel units from June to October 2021 in the State of Minas Gerais (MG). We documented the introduction and spread of Delta, comprising 70 per cent of the cases 8 weeks later. Comparing the viral loads of the Gamma and Delta dominance periods, we provide additional evidence that the latter is more transmissible. The spread and dominance of Delta did not culminate in the increase in cases and deaths, suggesting that the vaccination may have restrained the epidemic growth. Analysis of 224 novel Delta genomes revealed that Rio de Janeiro state was the primary source for disseminating this variant in the state of MG. We present the establishment of Delta, providing evidence of its enhanced transmissibility and showing that this variant shift did not aggravate the epidemiological scenario in a high immunity setting.

A dynamic relation between whole-brain white matter microstructural integrity and anxiety symptoms in preadolescent females with pathological anxiety.

Pathological anxiety typically emerges during preadolescence and has been linked to alterations in white matter (WM) pathways. Because myelination is critical for efficient neuronal communication, characterizing associations between WM microstructure and symptoms may provide insights into pathophysiological mechanisms associated with childhood pathological anxiety. This longitudinal study examined 182 girls enrolled between the ages of 9-11 that were treatment-naïve at study entry: healthy controls (n = 49), subthreshold-anxiety disorders (AD) (n = 82), or meeting DSM-5 criteria for generalized, social, and/or separation ADs (n = 51), as determined through structured clinical interview. Anxiety severity was assessed with the Clinical Global Impression Scale and Screen for Child Anxiety and Related Emotional Disorders (SCARED). Participants (n = 182) underwent clinical, behavioral, and diffusion tensor imaging (DTI) assessments at study entry, and those with pathological anxiety (subthreshold-AD and AD, n = 133) were followed longitudinally for up to 3 additional years. Cross-sectional ANCOVAs (182 scans) examining control, subthreshold-AD, and AD participants found no significant relations between anxiety and DTI measurements. However, in longitudinal analyses of girls with pathological anxiety (343 scans), linear mixed-effects models demonstrated that increases in anxiety symptoms (SCARED scores) were associated with reductions in whole-brain fractional anisotropy, independent of age (Std. ß (95% CI) = -0.06 (-0.09 to -0.03), F(1, 46.24) = 11.90, P = 0.001). Using a longitudinal approach, this study identified a dynamic, within-participant relation between whole-brain WM microstructural integrity and anxiety in girls with pathological anxiety. Given the importance of WM microstructure in modulating neural communication, this finding suggests the possibility that WM development could be a viable target in the treatment of anxiety-related psychopathology.

Reinfection by the SARS-CoV-2 Gamma variant in blood donors in Manaus, Brazil.

BACKGROUND: The city of Manaus, north Brazil, was stricken by a second epidemic wave of SARS-CoV-2 despite high seroprevalence estimates, coinciding with the emergence of the Gamma (P.1) variant. Reinfections were postulated as a partial explanation for the second surge. However, accurate calculation of reinfection rates is difficult when stringent criteria as two time-separated RT-PCR tests and/or genome sequencing are required. To estimate the proportion of reinfections caused by Gamma during the second wave in Manaus and the protection conferred by previous infection, we identified anti-SARS-CoV-2 antibody boosting in repeat blood donors as a mean to infer reinfection. METHODS: We tested serial blood samples from unvaccinated repeat blood donors in Manaus for the presence of anti-SARS-CoV-2 IgG antibodies using two assays that display waning in early convalescence, enabling the detection of reinfection-induced boosting. Donors were required to have three or more donations, being at least one during each epidemic wave. We propose a strict serological definition of reinfection (reactivity boosting following waning like a V-shaped curve in both assays or three spaced boostings), probable (two separate boosting events) and possible (reinfection detected by only one assay) reinfections. The serial samples were used to divide donors into six groups defined based on the inferred sequence of infection and reinfection with non-Gamma and Gamma variants. RESULTS: From 3655 repeat blood donors, 238 met all inclusion criteria, and 223 had enough residual sample volume to perform both serological assays. We found 13.6% (95% CI 7.0-24.5%) of all presumed Gamma infections that were observed in 2021 were reinfections. If we also include cases of probable or possible reinfections, these percentages increase respectively to 22.7% (95% CI 14.3-34.2%) and 39.3% (95% CI 29.5-50.0%). Previous infection conferred a protection against reinfection of 85.3% (95% CI 71.3-92.7%), decreasing to respectively 72.5% (95% CI 54.7-83.6%) and 39.5% (95% CI 14.1-57.8%) if probable and possible reinfections are included. CONCLUSIONS: Reinfection by Gamma is common and may play a significant role in epidemics where Gamma is prevalent, highlighting the continued threat variants of concern pose even to settings previously hit by substantial epidemics.

Longitudinal assessment of early-life white matter development with quantitative relaxometry in nonhuman primates.

Alterations in white matter (WM) development are associated with many neuropsychiatric and neurodevelopmental disorders. Most MRI studies examining WM development employ diffusion tensor imaging (DTI), which relies on estimating diffusion patterns of water molecules as a reflection of WM microstructure. Quantitative relaxometry, an alternative method for characterizing WM microstructural changes, is based on molecular interactions associated with the magnetic relaxation of protons. In a longitudinal study of 34 infant non-human primates (NHP) (Macaca mulatta) across the first year of life, we implement a novel, high-resolution, T1-weighted MPnRAGE sequence to examine WM trajectories of the longitudinal relaxation rate (qR1) in relation to DTI metrics and gestational age at scan. To the best of our knowledge, this is the first study to assess developmental WM trajectories in NHPs using quantitative relaxometry and the first to directly compare DTI and relaxometry metrics during infancy. We demonstrate that qR1 exhibits robust logarithmic growth, unfolding in a posterior-anterior and medial-lateral fashion, similar to DTI metrics. On a within-subject level, DTI metrics and qR1 are highly correlated, but are largely unrelated on a between-subject level. Unlike DTI metrics, gestational age at birth (time in utero) is a strong predictor of early postnatal qR1 levels. Whereas individual differences in DTI metrics are maintained across the first year of life, this is not the case for qR1. These results point to the similarities and differences in using quantitative relaxometry and DTI in developmental studies, providing a basis for future studies to characterize the unique processes that these measures reflect at the cellular and molecular level.

miR-520a-5p regulates Frizzled 9 expression and mediates effects of cigarette smoke and iloprost chemoprevention.

Expression of Frizzled 9 (FZD9) is critical to the activity of the lung cancer chemoprevention agent and prostacyclin analogue, iloprost. FZD9 is required in lung epithelial cells for iloprost to activate peroxisome proliferator activated receptor gamma (PPARG) and related anti-tumor signaling. We aimed to investigate which miRNA regulate FZD9 in the context of cigarette smoke exposure and iloprost treatment. We found that miR-520a-5p binds the FZD9 3'UTR in lung cell lines and alters activity and expression of FZD9 downstream targets. Cigarette smoke condensate (CSC) increases expression of miR-520a-5p, while iloprost decreases expression. Cancer promoting effects of a miR-520a-5p mimic were rescued with iloprost treatment, and effects of cigarette smoke were partially rescued with a miR-520a-5p inhibitor. Here we confirm miR-520a-5p as a regulator of FZD9 activity and a mediator of CSC and iloprost effects in the lung. Targeting miR-520a-5p could be an approach to restoring FZD9 expression and improving response to iloprost lung cancer chemoprevention.

One-carbon metabolism pathway genes and their non-association with the development of amyotrophic lateral sclerosis.

Although of unknown etiology, some mechanisms associated with the metabolic cycle of folate are speculated to be related to the genesis of amyotrophic lateral sclerosis (ALS). Thus, the aim of the study was to analyze the role of genetic polymorphisms rs1051266 in SLC19A1 gene and rs1805087 in MTR gene and their associations with ALS development. A case-control study was conducted with 101 individuals with ALS and 119 individuals without diagnosis of neurodegenerative diseases, from the Brazilian central population. The polymorphisms were determined using the polymerase chain reaction-restriction fragment length polymorphism technique. The results showed no statistically significant differences, even when genotypes were analyzed by the dominant, recessive, codominant, and overdominant inheritance models. It was observed a statistical significance relating alcohol consumption with individuals in the case group (p = 0.01). Therefore, the need for more studies to evaluate the influence of genetic variants is highlighted, seeking to provide information on the etiopathogenesis of ALS.

Optical properties and energy transfer processes in Tb3+-doped ZnSe quantum dots.

Tb3+-Doped ZnSe quantum dots (QDs) with a Tb content in the range of 0.5-7% were successfully synthesized by a wet chemical method. X-Ray diffraction (XRD) and transmission electron microscopy (TEM) analyses revealed that the as-synthesized QDs had a zinc blende (ZB) structure with a particle size of approximately 4 nm. The effect of Tb-doping on the structure and optical properties of the ZnSe QDs was studied. The emission spectra and photoluminescence (PL) decay kinetics data confirmed the successful incorporation of Tb3+ ions into the ZnSe host. The PL spectra also revealed that the intensity of dopant emission was significantly enhanced owing to the energy transfer (ET) from the host emission. The efficiency of the ET process from the ZnSe host to Tb3+ ions and between Tb3+ ions and the nature of these interaction mechanisms were determined by applying the Inokuti-Hirayama and Reisfeld models. The features of the ligand field and the optical properties of Tb3+ ions in the ZnSe QDs were studied using Judd-Ofelt theory. The dependence of the chromaticity features of ZnSe:Tb3+ QDs on the Tb concentration was estimated by the chromaticity coordinates and correlated color temperature (CCT). The Tb3+-doped ZnSe QDs with visible, tunable, and very long lifetime emission have potential for practical applications such as biological labeling, photocatalysis, and white-LED devices.

Reinfection by the SARS-CoV-2 P.1 variant in blood donors in Manaus, Brazil

BackgroundThe city of Manaus, north Brazil, was stricken by a second epidemic wave of SARS-CoV-2 despite high seroprevalence estimates, coinciding with the emergence of the Gamma (P.1) variant. Reinfections were postulated as a partial explanation for the second surge. However, accurate calculation of reinfection rates is difficult when stringent criteria as two time-separated RT-PCR tests and/or genome sequencing are required. To estimate the proportion of reinfections caused by the Gamma variant during the second wave in Manaus and the protection conferred by previous infection, we analyzed a cohort of repeat blood donors to identify anti-SARS-CoV-2 antibody boosting as a means to infer reinfection. MethodsWe tested serial blood samples from unvaccinated repeat blood donors in Manaus for the presence of anti-SARS-CoV-2 IgG antibody. Donors were required to have three or more donations and at least one donation during each epidemic wave. Donors were tested with two assays that display waning in early convalescence, enabling the detection of reinfection-induced boosting. The serial samples were used to divide donors into six groups defined based on the inferred sequence of infection and reinfection with non-Gamma and Gamma variants. ResultsFrom 3,655 repeat blood donors, 238 met all inclusion criteria, and 223 had enough residual sample volume to perform both serological assays. Using a strict serological definition of reinfection, we found 13.6% (95% CI 7.0% - 24.5%) of all presumed Gamma infections that were observed in 2021 were reinfections. If we also include cases of probable or possible reinfections, these percentages increase respectively to 22.7% (95% CI 14.3% - 34.2%) and 39.3% (95% CI 29.5% - 50.0%). Previous infection conferred a protection against reinfection of 85.3% (95% CI 71.3% - 92.7%), decreasing to respectively 72.5% (95% CI 54.7% - 83.6%) and 39.5% (95% CI 14.1% - 57.8%) if probable and possible reinfections are included. ConclusionsReinfection due to Gamma is common and may play a significant role in epidemics where Gamma is prevalent, highlighting the continued threat variants of concern pose even to settings previously hit by substantial epidemics.

Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil.

Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Manaus, Brazil, resurged in late 2020 despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1 acquired 17 mutations, including a trio in the spike protein (K417T, E484K, and N501Y) associated with increased binding to the human ACE2 (angiotensin-converting enzyme 2) receptor. Molecular clock analysis shows that P.1 emergence occurred around mid-November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.7- to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 79% of the protection against infection with P.1 that it provides against non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness.

Genomics and epidemiology of a novel SARS-CoV-2 lineage in Manaus, Brazil.

Cases of SARS-CoV-2 infection in Manaus, Brazil, resurged in late 2020, despite high levels of previous infection there. Through genome sequencing of viruses sampled in Manaus between November 2020 and January 2021, we identified the emergence and circulation of a novel SARS-CoV-2 variant of concern, lineage P.1, that acquired 17 mutations, including a trio in the spike protein (K417T, E484K and N501Y) associated with increased binding to the human ACE2 receptor. Molecular clock analysis shows that P.1 emergence occurred around early November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.4-2.2 times more transmissible and 25-61% more likely to evade protective immunity elicited by previous infection with non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness.

Genomics and epidemiology of a novel SARS-CoV-2 lineage in Manaus, Brazil

Cases of SARS-CoV-2 infection in Manaus, Brazil, resurged in late 2020, despite high levels of previous infection there. Through genome sequencing of viruses sampled in Manaus between November 2020 and January 2021, we identified the emergence and circulation of a novel SARS-CoV-2 variant of concern, lineage P.1, that acquired 17 mutations, including a trio in the spike protein (K417T, E484K and N501Y) associated with increased binding to the human ACE2 receptor. Molecular clock analysis shows that P.1 emergence occurred around early November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.4-2.2 times more transmissible and 25-61% more likely to evade protective immunity elicited by previous infection with non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness. One-Sentence SummaryWe report the evolution and emergence of a SARS-CoV-2 lineage of concern associated with rapid transmission in Manaus.

Spatiotemporal dynamics of nonhuman primate white matter development during the first year of life.

White matter (WM) development early in life is a critical component of brain development that facilitates the coordinated function of neuronal pathways. Additionally, alterations in WM have been implicated in various neurodevelopmental disorders, including psychiatric disorders. Because of the need to understand WM development in the weeks immediately following birth, we characterized changes in WM microstructure throughout the postnatal macaque brain during the first year of life. This is a period in primates during which genetic, developmental, and environmental factors may have long-lasting impacts on WM microstructure. Studies in nonhuman primates (NHPs) are particularly valuable as a model for understanding human brain development because of their evolutionary relatedness to humans. Here, 34 rhesus monkeys (23 females, 11 males) were imaged longitudinally at 3, 7, 13, 25, and 53 weeks of age with T1-weighted (MPnRAGE) and diffusion tensor imaging (DTI). With linear mixed-effects (LME) modeling, we demonstrated robust logarithmic growth in FA, MD, and RD trajectories extracted from 18 WM tracts across the brain. Estimated rate of change curves for FA, MD, and RD exhibited an initial 10-week period of exceedingly rapid WM development, followed by a precipitous decline in growth rates. K-means clustering of raw DTI trajectories and rank ordering of LME model parameters revealed distinct posterior-to-anterior and medial-to-lateral gradients in WM maturation. Finally, we found that individual differences in WM microstructure assessed at 3 weeks of age were significantly related to those at 1 year of age. This study provides a quantitative characterization of very early WM growth in NHPs and lays the foundation for future work focused on the impact of alterations in early WM developmental trajectories in relation to human psychopathology.

Effect of dopant concentration and the role of ZnS shell on optical properties of Sm3+ doped CdS quantum dots.

The role of samarium (Sm) dopant on the structural, morphological, and optical properties of CdS QDs and CdS/ZnS core/shell QDs was methodically reported. The synthesis of Sm-doped CdS QDs and CdS/ZnS QDs was carried out via a facile wet chemical method. The structure, chemical composition, and optical properties of the synthesized QDs were investigated by using X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy (RS), and photoluminescence (PL) spectroscopy. XRD analysis showed that the synthesized CdS QDs exhibited zinc blende structure which was not affected by doping Sm3+ ions. The particle size of the CdS:Sm and CdS:Sm (2%)/ZnS QDs was estimated to be ∼4 nm and ∼7 nm, respectively. Transmission electron microscopy (TEM) images revealed that the incorporation of Sm dopant did not significantly affect the size and morphology of CdS QDs, while the formation of the ZnS shell increased the particle size. XPS and XRD results confirmed the successful incorporation of Sm3+ ions into the CdS QDs. The effect of dopant concentration on the structural and luminescent properties was studied. The emission and excitation spectra of Sm3+-doped CdS QDs and CdS/ZnS QDs consisted of the characteristic lines corresponding to the intra-configurational f-f transitions. The energy transfer (ET) mechanism from the host to Sm3+ ions and the ET process through cross-relaxation between Sm3+ ions have been elucidated. The effect of the ZnS shell on the optical stability of the Sm3+-doped CdS QDs was studied in detail and the results showed that the CdS:Sm (2%)/ZnS QDs retained their good emission characteristics after 376 days of fabrication. The luminescent properties of Sm-doped QDs ranging from violet to red and PL lifetime extending to milliseconds demonstrated that these QDs are the potential materials for applications in white LEDs, biomarkers, and photocatalysis.