Early Detection and Staging of Lung Fibrosis Enabled by Collagen-Targeted MRI Protein Contrast Agent.

Chronic lung diseases, such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD), are major leading causes of death worldwide and are generally associated with poor prognoses. The heterogeneous distribution of collagen, mainly type I collagen associated with excessive collagen deposition, plays a pivotal role in the progressive remodeling of the lung parenchyma to chronic exertional dyspnea for both IPF and COPD. To address the pressing need for noninvasive early diagnosis and drug treatment monitoring of pulmonary fibrosis, we report the development of human collagen-targeted protein MRI contrast agent (hProCA32.

The Neurobiology of Love and Pair Bonding from Human and Animal Perspectives.

Love is a powerful emotional experience that is rooted in ancient neurobiological processes shared with other species that pair bond. Considerable insights have been gained into the neural mechanisms driving the evolutionary antecedents of love by studies in animal models of pair bonding, particularly in monogamous species such as prairie voles (). Here, we provide an overview of the roles of oxytocin, dopamine, and vasopressin in regulating neural circuits responsible for generating bonds in animals and humans alike.

CEST 2022 - A special issue on CEST MRI from the 9th international chemical exchange saturation transfer workshop.

The CEST2022 workshop was held at the Emory Conference Center Hotel from August 7th to 10th, 2022, and attracted over a hundred international participants from North America, Europe, and Asia. The workshop consisted of four plenary talks, 10 scientific sessions, nine invited talks, and 40 talks selected from abstracts. Four discussion sessions were also conducted to build consensus on CEST imaging standardization and quantification.

Comparison of model-free Lorentzian and spinlock model-based fittings in quantitative CEST imaging of acute stroke.

Purpose: CEST MRI detects complex tissue changes following acute stroke. Our study aimed to test if spinlock model-based fitting of the quasi-steady-state (QUASS)-reconstructed equilibrium CEST MRI improves the determination of multi-pool signal changes over the commonly-used model-free Lorentzian fitting in acute stroke.

Theory And Methods: Multiple three-pool CEST Z-spectra were simulated using Bloch-McConnell equations for a range of T , relaxation delay, and saturation times.

DREADD-mediated amygdala activation is sufficient to induce anxiety-like responses in young nonhuman primates.

Anxiety disorders are among the most prevalent psychiatric disorders, with symptoms often beginning early in life. To model the pathophysiology of human pathological anxiety, we utilized Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) in a nonhuman primate model of anxious temperament to selectively increase neuronal activity of the amygdala. Subjects included 10 young rhesus macaques; 5 received bilateral infusions of AAV5-hSyn-HA-hM3Dq into the dorsal amygdala, and 5 served as controls.

Seizure onset and offset pattern determine the entrainment of the cortex and substantia nigra in the nonhuman primate model of focal temporal lobe seizures.

Temporal lobe (TL) epilepsy is the most common form of drug-resistant epilepsy. A major focus of human and animal studies on TLE network has been the limbic circuit and the structures composing the temporal lobe. However, there is also evidence suggesting an active role of the basal ganglia in the propagation and control of temporal lobe seizures.

Subunit-selective PI3-kinase control of action strategies in the medial prefrontal cortex.

PI3-kinase (PI3K) is an intracellular signaling complex that is stimulated upon cocaine exposure and linked with the behavioral consequences of cocaine. We recently genetically silenced the PI3K p110β subunit in the medial prefrontal cortex following repeated cocaine in mice, reinstating the capacity of these mice to engage in prospective goal-seeking behavior. In the present short report, we address two follow-up hypotheses: 1) The control of decision-making behavior by PI3K p110β is attributable to neuronal signaling, and 2) PI3K p110β in the healthy (i.

CEST2022 - mapping multi-pool CEST signal changes in an animal model of brain tumor with quasi-steady-state reconstruction-empowered CEST quantification.

Chemical exchange saturated transfer (CEST) MRI has biomarker potential to assess tissue microenvironment in brain tumors. Multi-pool Lorentzian or spinlock models provides useful insights into the CEST contrast mechanism. However, T contribution to the complex overlapping effects of brain tumors is difficult under the non-equilibrium state.

Immune resilience despite inflammatory stress promotes longevity and favorable health outcomes including resistance to infection.

Some people remain healthier throughout life than others but the underlying reasons are poorly understood. Here we hypothesize this advantage is attributable in part to optimal immune resilience (IR), defined as the capacity to preserve and/or rapidly restore immune functions that promote disease resistance (immunocompetence) and control inflammation in infectious diseases as well as other causes of inflammatory stress. We gauge IR levels with two distinct peripheral blood metrics that quantify the balance between (i) CD8 and CD4 T-cell levels and (ii) gene expression signatures tracking longevity-associated immunocompetence and mortality-associated inflammation.

An AAV-CRISPR/Cas9 strategy for gene editing across divergent rodent species: Targeting neural oxytocin receptors as a proof of concept.

A major issue in neuroscience is the poor translatability of research results from preclinical studies in animals to clinical outcomes. Comparative neuroscience can overcome this barrier by studying multiple species to differentiate between species-specific and general mechanisms of neural circuit functioning. Targeted manipulation of neural circuits often depends on genetic dissection, and use of this technique has been restricted to only a few model species, limiting its application in comparative research.

HIV, asymptomatic STI, and the rectal mucosal immune environment among young men who have sex with men.

Young men who have sex with men (YMSM) are disproportionately affected by HIV and bacterial sexually transmitted infections (STI) including gonorrhea, chlamydia, and syphilis; yet research into the immunologic effects of these infections is typically pursued in siloes. Here, we employed a syndemic approach to understand potential interactions of these infections on the rectal mucosal immune environment among YMSM. We enrolled YMSM aged 18-29 years with and without HIV and/or asymptomatic bacterial STI and collected blood, rectal secretions, and rectal tissue biopsies.

WHEN REPRODUCTION IS NO LONGER AUTONOMOUS: FEELING RESPECTED BY MATERNITY CARE PROVIDERS MODERATES THE ASSOCIATION BETWEEN AUTONOMY IN DECISION MAKING AND BIRTH-RELATED PTSD SYMPTOMS IN A COMMUNITY SAMPLE OF POSTPARTUM BLACK WOMEN.

Black individuals are at particularly high risk for birth-related posttraumatic stress disorder (PTSD) symptoms, in part due to a lack of opportunity to lead maternity care decisions. Maternal care providers need evidence-based ways to reduce pregnant persons' risk for birth-related PTSD symptoms despite reduced autonomy in decision making resulting from heightened restrictions on reproductive rights. We investigated whether a potential relation between autonomy in decision making and birth-related PTSD symptoms would be moderated by being mistreated or feeling respected by maternity care providers in a community sample of Black women (N = 52; M = 28.

Lymph-Node-Based CD3 CD20 Cells Emerge from Membrane Exchange between T Follicular Helper Cells and B Cells and Increase Their Frequency following Simian Immunodeficiency Virus Infection.

CD4 T follicular helper (T) cells are key targets for human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) replication and contribute to the virus reservoir under antiretroviral therapy (ART). Here, we describe a novel CD3 CD20 double-positive (DP) lymphocyte subset, resident in secondary lymphoid organs of humans and rhesus macaques (RMs), that appear predominantly after membrane exchange between T and B cells. DP lymphocytes are enriched in cells displaying a T phenotype (CD4 PD1 CXCR5), function (interleukin 21 positive [IL-21]), and gene expression profile.

Dual orexin/hypocretin receptor antagonism attenuates NMDA receptor hypofunction-induced attentional impairments in a rat model of schizophrenia.

Schizophrenia is a neuropsychiatric condition that is associated with impaired attentional processing and performance. Failure to support increasing attentional load may result, in part, from inhibitory failure in attention-relevant cortical regions, and available antipsychotics often fail to address this issue. Orexin/hypocretin receptors are found throughout the brain and are expressed on neurons relevant to both attention and schizophrenia, highlighting them as a potential target to treat schizophrenia-associated attentional dysfunction.

Efficacy of mRNA-1273 and Novavax ancestral or BA.1 spike booster vaccines against SARS-CoV-2 BA.5 infection in nonhuman primates.

Omicron SARS-CoV-2 variants escape vaccine-induced neutralizing antibodies and cause nearly all current COVID-19 cases. Here, we compared the efficacy of three booster vaccines against Omicron BA.5 challenge in rhesus macaques: mRNA-1273, the Novavax ancestral spike protein vaccine (NVX-CoV2373), or Omicron BA.

Soluble ORF2 protein enhances HEV replication and induces long-lasting antibody response and protective immunity in vivo.

Background And Aims: The HEV is a small positive-sense RNA virus that encodes a cytoplasmic form of the capsid protein (ORF2c), essential for virion structure, and a secreted glycosylated form (ORF2s) that accumulates at high titer in serum and can mask neutralizing epitopes. We explored the contribution of ORF2s to HEV replication and its role in generating antibodies against ORF2 in a nonhuman primate model.

Approach And Results: We used a recombinant HEV genotype 3 variant that does not express ORF2s due to the introduction of stop codons (ORF2s mut ).

Broadly neutralizing antibodies against sarbecoviruses generated by immunization of macaques with an AS03-adjuvanted COVID-19 vaccine.

The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has placed an imperative on the development of countermeasures that provide broad protection against SARS-CoV-2 and related sarbecoviruses. Here, we identified extremely potent monoclonal antibodies (mAbs) that neutralized multiple sarbecoviruses from macaques vaccinated with AS03-adjuvanted monovalent subunit vaccines. Longitudinal analysis revealed progressive accumulation of somatic mutation in the immunoglobulin genes of antigen-specific memory B cells (MBCs) for at least 1 year after primary vaccination.

Chronic viral infection compromises the quality of circulating mucosal-invariant T cells and follicular T helper cells via expression of both activating and inhibitory receptors.

Chronic viral infection results in impaired immune responses rendering viral persistence. Here, we investigated the role of immune activation and compared the quality of T-cell responses in chronic HBV, HCV, and HIV infections. Cytokines were measured using a commercial Bio-plex Pro Human Cytokine Grp I Panel 17-plex kit (BioRad, Hercules, CA, USA).

A strategy for high antibody expression with low anti-drug antibodies using AAV9 vectors.

Introduction: Use of adeno-associated virus (AAV) vectors is complicated by host immune responses that can limit transgene expression. Recent clinical trials using AAV vectors to deliver HIV broadly neutralizing antibodies (bNAbs) by intramuscular administration resulted in poor expression with anti-drug antibodies (ADA) responses against the bNAb.

Methods: Here we compared the expression of, and ADA responses against, an anti-SIV antibody ITS01 when delivered by five different AAV capsids.

Cocaine and habit training cause dendritic spine rearrangement in the prelimbic cortex.

Successfully navigating dynamic environments requires organisms to learn the consequences of their actions. The prelimbic prefrontal cortex (PL) formulates action-consequence memories and is modulated by addictive drugs like cocaine. We trained mice to obtain food rewards and then unexpectedly withheld reinforcement, triggering new action-consequence memory.

Developmental pyrethroid exposure causes a neurodevelopmental disorder phenotype in mice.

Neurodevelopmental disorders (NDDs) are a widespread and growing public health challenge, affecting as many as 17% of children in the United States. Recent epidemiological studies have implicated ambient exposure to pyrethroid pesticides during pregnancy in the risk for NDDs in the unborn child. Using a litter-based, independent discovery-replication cohort design, we exposed mouse dams orally during pregnancy and lactation to the Environmental Protection Agency's reference pyrethroid, deltamethrin, at 3 mg/kg, a concentration well below the benchmark dose used for regulatory guidance.

Quantitative Evaluation of Oxygen Extraction Fraction Changes in the Monkey Brain during Acute Stroke by Using Quantitative Susceptibility Mapping.

Background: The oxygen extraction fraction (OEF) indicates the brain's oxygen consumption and can be estimated by using the quantitative susceptibility mapping (QSM) MRI technique. Recent studies have suggested that OEF alteration following stroke is associated with the viability of at-risk tissue. In the present study, the temporal evolution of OEF in the monkey brain during acute stroke was investigated using QSM.