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Antibody-Peptide Epitope Conjugates for Personalized Cancer Therapy

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Antibody-peptide epitope conjugates (APEC) are a new class of modified antibody-drug conjugates that redirect T cell viral immunity against tumor cells. Investigators developed an experimental pipeline to create patient-specific APECs and identified new preclinical therapies for ovarian carcinoma. Based on functional assessment of viral peptide antigen responses to common viruses like cytomegalovirus in ovarian cancer patients, a library of 192 APECs with distinct protease cleavage sequences was created using the anti-epithelial cell adhesion molecule (EpCAM) antibody.

Effect of Hormone Replacement Therapy on Amyloid Beta (Aβ) Plaque Density in the Rhesus Macaque Amygdala

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Amyloid beta plaque density is associated with Alzheimer’s disease. In this study, the authors examined its concentration in aged female nonhuman primates’ cerebrospinal fluid, as well as in the amygdala, an area of the brain involved with emotion and memory. They set out to test the hypothesis that estrogen hormone replacement therapy can beneficially affect amygdala Aβ plaque density in “surgically menopausal” females (i.e., aged rhesus macaques that had undergone ovariectomy).

Effects of Pulsatile Intravenous Follicle-Stimulating Hormone Treatment on Ovarian Function in Women With Obesity

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By performing intravenous (IV) administration of pulsatile recombinant follicle-stimulating hormone (FSH), researchers established conditions for effective hypothalamic suppression in women with normal and high body mass index (BMI). In women with obesity, the treatment resulted in E2 and inhibin B levels comparable to those in normal-weight women. This work offers a potential strategy to mitigate some of the adverse effects of high BMI on fertility, assisted reproduction, and pregnancy outcomes. Supported by ORIP (K01OD026526), NIA, and NICHD.

Large-Scale Production of Human Blastoids Amenable to Modeling Blastocyst Development and Maternal-Fetal Crosstalk

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Human blastoids provide a valuable model to study early human development and implantation with reduced genetic heterogeneity between samples. Investigators reported a protocol for efficient generation of high-fidelity human blastoids from naïve pluripotent stem cells. The similarities between blastoids and blastocysts in signaling activities—demonstrated using single-cell RNA sequencing—support the use of blastoids to model lineage differentiation and cavity formation.

p38MAPKα Stromal Reprogramming Sensitizes Metastatic Breast Cancer to Immunotherapy

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This study emphasizes the importance of the metastatic tumor microenvironment in metastatic breast cancer growth and the identification of effective antimetastatic therapies. Using a stromal labeling approach and single-cell RNA sequencing, the authors showed that a combination of p38MAPK inhibition (p38i) and anti-OX40 synergistically reduced metastatic tumor growth and increased overall survival. Further engagement of cytotoxic T cells cured all metastatic disease in mice and produced durable immunologic memory.

Infection of the Maternal–Fetal Interface and Vertical Transmission Following Low-Dose Inoculation of Pregnant Rhesus Macaques (Macaca mulatta) with an African-Lineage Zika Virus

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Researchers examined transmission of Zika virus to nonhuman primate fetuses during pregnancy. Even with a low dosage of inoculation of the dams, the investigators found that the Zika virus infected fetuses, despite the presence of a “placental fortress,” which normally protects fetuses during gestation. This transmission illustrates the high level of infectivity threat that Zika poses, which may increase if mosquitoes expand their global habitats.

Association of Age at Menopause and Hormone Therapy Use With Tau and β-Amyloid Positron Emission Tomography

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To understand the predominance (70%) of women among individuals with Alzheimer’s disease, the investigators studied regional tau and β-amyloid (Aβ) in relation to age at menopause and hormone therapy (HT) in postmenopausal women and age-matched men using positron emission tomography. The study demonstrated that females exhibited higher tau deposition compared with age-matched males, particularly in the setting of elevated Aβ; earlier age at menopause and late initiation of HT were associated with increased tau vulnerability.

Impaired Placental Hemodynamics and Function in a Non-Human Primate Model of Gestational Protein Restriction

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Maternal malnutrition is a global health epidemic that adversely affects fetal outcomes and results in long-term health complications in children. Investigators used a previously developed model in nonhuman primates for gestational protein restriction to study the impact of undernutrition, specifically protein deficiency, on placental function and pregnancy outcomes. The data demonstrate that a 50% protein-restricted diet reduces maternal placental perfusion, decreases fetal oxygen availability, and increases fetal mortality.

Profile of a Veterinary Anatomic Pathologist and Researcher: Heather Shive, D.V.M., Ph.D., DACVP

Since her childhood, Dr. Heather Shive (Figure 1) has been interested in working with animals. This interest, combined with a love of scientific inquiry, led her on the path to becoming a Doctor of Veterinary Medicine (D.V.M.) who specializes in anatomic pathology, as well as a cancer researcher.

ORIP Support for Small Businesses Leads to New Commercial Technology Outcomes That Benefit Community Resources and Advance Research Discoveries

ORIP participates in two federal grant programs that provide funding to small businesses: the Small Business Innovation Research (SBIR) program and the Small Business Technology Transfer (STTR) program. The primary goal of ORIP’s small business programs is to attract innovative SBIR/STTR projects that could benefit research resources and communities associated with ORIP’s mission.

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