Antibody targeting of conserved sites of vulnerability on the SARS-CoV-2 spike receptor-binding domain.

Given the continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VoCs), immunotherapeutics that target conserved epitopes on the spike (S) glycoprotein have therapeutic advantages. Here, we report the crystal structure of the SARS-CoV-2 S receptor-binding domain (RBD) at 1.95 Å and describe flexibility and distinct conformations of the angiotensin-converting enzyme 2 (ACE2)-binding site.

SARS-CoV-2 spike-ferritin-nanoparticle adjuvanted with ALFQ induces long-lived plasma cells and cross-neutralizing antibodies.

This study demonstrates the impact of adjuvant on the development of T follicular helper (Tfh) and B cells, and their influence on antibody responses in mice vaccinated with SARS-CoV-2-spike-ferritin-nanoparticle (SpFN) adjuvanted with either Army Liposome Formulation containing QS-21 (SpFN + ALFQ) or Alhydrogel (SpFN + AH). SpFN + ALFQ increased the size and frequency of germinal center (GC) B cells in the vaccine-draining lymph nodes and increased the frequency of antigen-specific naive B cells. A single vaccination with SpFN + ALFQ resulted in a higher frequency of IL-21-producing-spike-specific Tfh and GC B cells in the draining lymph nodes and spleen, S-2P protein-specific IgM and IgG antibodies, and elicitation of robust cross-neutralizing antibodies against SARS-CoV-2 variants as early as day 7, which was enhanced by a second vaccination.

Shark nanobodies with potent SARS-CoV-2 neutralizing activity and broad sarbecovirus reactivity.

Despite rapid and ongoing vaccine and therapeutic development, SARS-CoV-2 continues to evolve and evade, presenting a need for next-generation diverse therapeutic modalities. Here we show that nurse sharks immunized with SARS-CoV-2 recombinant receptor binding domain (RBD), RBD-ferritin (RFN), or spike protein ferritin nanoparticle (SpFN) immunogens elicit a set of new antigen receptor antibody (IgNAR) molecules that target two non-overlapping conserved epitopes on the spike RBD. Representative shark antibody variable NAR-Fc chimeras (ShAbs) targeting either of the two epitopes mediate cell-effector functions, with high affinity to all SARS-CoV-2 viral variants of concern, including the divergent Omicron strains.

Protection against SARS-CoV-2 Omicron BA.1 variant challenge in macaques by prime-boost vaccination with Ad26.COV2.S and SpFN.

Emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and waning immunity call for next-generation vaccine strategies. Here, we assessed the immunogenicity and protective efficacy of two SARS-CoV-2 vaccines targeting the WA1/2020 spike protein, Ad26.COV2.

Coronavirus Antibody Responses before COVID-19 Pandemic, Africa and Thailand.

Prior immune responses to coronaviruses might affect human SARS-CoV-2 response. We screened 2,565 serum and plasma samples collected from 2013 through early 2020, before the COVID-19 pandemic began, from 2,250 persons in 4 countries in Africa (Kenya, Nigeria, Tanzania, and Uganda) and in Thailand, including persons living with HIV-1. We detected IgG responses to SARS-CoV-2 spike (S) subunit 2 protein in 1.

Application of Stem Cell Therapy for Infertility.

Infertility creates an immense impact on the psychosocial wellbeing of affected couples, leading to poor quality of life. Infertility is now considered to be a global health issue affecting approximately 15% of couples worldwide. It may arise from factors related to the male (30%), including varicocele, undescended testes, testicular cancer, and azoospermia; the female (30%), including premature ovarian failure and uterine disorders; or both partners (30%).

Central prolactin binding site densities change seasonally in an adult male passerine bird (Junco hyemalis).

Seasonal reproduction is common across temperate zone avian species. In these species, physiological and behavioral adaptations have evolved to change according to day length (i.e.

Changes in Sleep Characteristics and Breathing Parameters During Sleep in Early and Late Pregnancy.

Study Objectives: Few studies have objectively evaluated sleep characteristics during pregnancy or investigated the relationship between altered spectral electroencephalogram (EEG) bands and sleep-disordered breathing (SDB). The study aimed to describe changes in sleep as measured by polysomnography (PSG) and spectral EEG bands during pregnancy and to examine the relationship between delta power in non-rapid eye movement (NREM) sleep and SDB.

Methods: This is a secondary analysis of a prospective study.

Role of intraoperative ropivacaine in adult post-tonsillectomy pain control: A randomized controlled trial.

We sought to evaluate the efficacy of ropivacaine in post-tonsillectomy pain management in adults and evaluate the timing of intraoperative ropivacaine administration for this purpose. A prospective, double-blinded, randomized, controlled trial with a paired design was performed in 25 consecutive adults undergoing tonsillectomy. To date, no studies examining the efficacy of local anesthetics in post-tonsillectomy pain control have used a paired design to account for the variability in pain difference between individuals.

Next generation sequencing analysis of soy glyceollins and 17-β estradiol: Effects on transcript abundance in the female mouse brain.

Glyceollins (Glys) are produced by soy plants in response to stress and are known for their anti-estrogenic activity both in vivo and in vitro in cancer cell lines as well as peripheral tissues. Glys can also exhibit non-estrogen receptor (ER) mediated effects. The effects of Glys on gene expression in the brain are still unclear.

Where are the Behavioral Sleep Medicine Providers and Where are They Needed? A Geographic Assessment.

Although it is widely acknowledged that there are not enough clinicians trained in either Behavioral Sleep Medicine (BSM) in general or in Cognitive Behavioral Therapy for Insomnia (CBT-I) in specific, what is unclear is whether this problem is more acute in some regions relative to others. Accordingly, a geographic approach was taken to assess this issue. Using national directories as well as e-mail listservs (Behavioral Sleep Medicine group and Behavioral Treatment for Insomnia Roster), the present study evaluated geographic patterning of CBSM and BSM providers by city, state, and country.

Investigation of pre-pubertal sex differences in wheel running and social behavior in three mouse strains.

Sex differences in social behaviors exist in mammals during adulthood, and further evidence suggests that sex differences in behavior are present before sexual maturity. In order to model behavioral disorders in animals, it is important to assess baseline sex-related behavioral differences, especially when studying disorders for which sex-related behavioral effects are expected. We investigated the effect of sex on behavior in 3 strains of pre-pubertal mice (C57BL/6, CFW, and CF1) using a wheel-running assay.

Soy glyceollins regulate transcript abundance in the female mouse brain.

Glyceollins (Glys), produced by soy plants in response to stress, have anti-estrogenic activity in breast and ovarian cancer cell lines in vitro and in vivo. In addition to known anti-estrogenic effects, Gly exhibits mechanisms of action not involving estrogen receptor (ER) signaling. To date, effects of Gly on gene expression in the brain are unknown.

Success of sequential free flaps in head and neck reconstruction.

Background: The need for additional free flaps following an initial free flap reconstruction sometimes arises. However, there is understandable hesitation to perform subsequent free flaps due to concerns regarding recipient vessel availability, flap loss, and other complications.

Methods: An analysis of patients undergoing one or more sequential head and neck free flap reconstructions between 2000 and 2012 was performed.

A large-scale, rapid public health response to rabies in an organ recipient and the previously undiagnosed organ donor.

This article describes and contrasts the public health response to two human rabies cases: one organ recipient diagnosed within days of symptom onset and the transplant donor who was diagnosed 18 months post-symptom onset. In response to an organ-transplant-related rabies case diagnosed in 2013, organ donor and recipient investigations were conducted by multiple public health agencies. Persons with potential exposure to infectious patient materials were assessed for rabies virus exposure.

Free flap failure in head and neck reconstruction.

Background: The purpose of this study was to determine the causes of head and neck free flap loss and to evaluate outcomes after subsequent microvascular and non-microvascular reconstruction.

Methods: Patients who experienced free flap loss between 2000 and 2012 were reviewed.

Results: There were 40 flap losses out of 3090 free flaps (1.

Tonotopic relationships reveal the charge density varies along the lateral wall of outer hair cells.

Outer hair cells amplify and improve the frequency selectivity of sound within the mammalian cochlea through a sound-evoked receptor potential that induces an electromechanical response in their lateral wall membrane. We experimentally show that the membrane area and linear membrane capacitance of outer hair cells increases exponentially with the electrically evoked voltage-dependent charge movement (Q(T)) and peak membrane capacitance (C(peak)). We determine the size of the different functional regions (e.

Management of lateral cervical metastases in papillary thyroid cancer: patterns of lymph node distribution.

In this article we discuss the management of lateral cervical lymph node metastases in papillary thyroid cancer (PTC). We conducted a retrospective analysis of cases of PTC at our tertiary academic medical center involving 32 patients who underwent 39 neck dissections for the management of lateral cervical metastases from 2000 to 2007. Of these patients, 18 underwent primary neck dissections at the time of thyroidectomy after fine-needle aspiration biopsy confirmed the PTC.

Androgen receptor location in the dark-eyed junco using a probe for in situ hybridization histochemistry generated from zebra finch cDNA.

Due to the role of sex steroids, namely testosterone (T), in the development and production of song in songbirds, androgen receptor (AR) densities in the brain regions controlling this behavior (i.e., the song control system) have long been studied.

Opioid receptor densities analyzed across seasons in the POM and VTA of the dark-eyed junco, Junco hyemalis.

The motivation of songbirds to sing is influenced by two brain regions, the medial preoptic area (POM) and ventral tegmental area (VTA), which are located outside the song control system itself. These areas receive opioidergic innervation. Furthermore, the opioid enkephalin has been proposed to play a role in the reward for singing.

Glyceollin I, a novel antiestrogenic phytoalexin isolated from activated soy.

Glyceollins, a group of novel phytoalexins isolated from activated soy, have recently been demonstrated to be novel antiestrogens that bind to the estrogen receptor (ER) and inhibit estrogen-induced tumor progression. Our previous publications have focused specifically on inhibition of tumor formation and growth by the glyceollin mixture, which contains three glyceollin isomers (I, II, and III). Here, we show the glyceollin mixture is also effective as a potential antiestrogenic, therapeutic agent that prevents estrogen-stimulated tumorigenesis and displays a differential pattern of gene expression from tamoxifen.

Effects of vinclozolin, an anti-androgen, on affiliative behavior in the Dark-eyed Junco, Junco hyemalis.

Endocrine disrupting chemicals (EDCs) produce changes in physiology and behavior via diverse mechanisms including acting as hormone mimics or antagonists, affecting intracellular signaling pathways, and altering hormone production pathways. The fungicide vinclozolin acts as an anti-androgen and is known to affect affiliative behaviors in rodents, fish and amphibians. To investigate the possible effects of exposure to EDCs on reproductive behavior in a wild population of songbirds, we examined the effects of vinclozolin in wild-caught Dark-eyed Juncos (Junco hyemalis).

Mechanisms to inhibit matrix metalloproteinase activity: where are we in the development of clinically relevant inhibitors?

Matrix metalloproteinases (MMPs) are involved in numerous pathophysiological processes, including cancer and cardiovascular disease. MMPs proteolyze multiple targets, including extracellular matrix, cytokines, and growth factors. Due to a high clinical relevance, MMPs have long been a target for pharmaceutical intervention.

Dietary phytoestrogens and photoperiodic response in a male songbird, the Dark-eyed Junco (Junco hyemalis).

Many commercial bird diets are made with soy products that contain phytoestrogens (i.e., plant compounds that have weak agonist activity at estrogen receptors), but the effects of these compounds on bird physiology and behavior are largely unknown.