Transient lymphopenia and interstitial pneumonia with endotheliitis in SARS-CoV-2-infected macaques

Using a reliable primate model is critical for developing therapeutic advances to treat humans infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Here, we exposed macaques to high titers of SARS-CoV-2 via combined transmission routes. We observed acute interstitial pneumonia with endotheliitis in the lungs of all infected macaques. All macaques had a significant loss of total lymphocytes during infection, which were restored over time. These data show that SARS-CoV-2 causes a coronavirus disease 2019 (COVID-19)-like disease in macaques. This new model could investigate the interaction between SARS-CoV-2 and the immune system to test therapeutic strategies.Y

Identification of Alternative Variants and Insertion of the Novel Polymorphic AluYl17 in TSEN54 Gene during Primate Evolution

TSEN54 encodes a subunit of the tRNA-splicing endonuclease complex, which catalyzes the identification and cleavage of introns from precursor tRNAs. Previously, we identified an AluSx-derived alternative transcript in TSEN54 of cynomolgus monkey. Reverse transcription-polymerase chain reaction (RT-PCR) amplification and TSEN54 sequence analysis of primate and human samples identified five novel alternative transcripts, including the AluSx exonized transcript. Additionally, we performed comparative expression analysis via RT-qPCR in various cynomolgus, rhesus monkey, and human tissues. RT-qPCR amplification revealed differential expression patterns. Furthermore, genomic PCR amplification and sequencing of primate and human DNA samples revealed that AluSx elements were integrated in human and all of the primate samples tested. Intriguingly, in langur genomic DNA, an additional AluY element was inserted into AluSx of intron eight of TSEN54. The new AluY element showed polymorphic insertion. Using standardized nomenclature for Alu repeats, the polymorphic AluY of the langur TSEN54 was designated as being of the AluYl17 subfamily. Our results suggest that integration of the AluSx element in TSEN54 contributed to diversity in transcripts and induced lineage- or species-specific evolutionary events such as alternative splicing and polymorphic insertion during primate evolution

Impaired Hand Dexterity Function in a Non-human Primate Model with Chronic Parkinson's Disease

Symptoms of Parkinson's disease (PD) caused by loss of dopaminergic neurons are accompanied by movement disorders, including tremors, rigidity, bradykinesia, and akinesia. Non-human primate (NHP) models with PD play an essential role in the analysis of PD pathophysiology and behavior symptoms. As impairments of hand dexterity function can affect activities of daily living in patients with PD, research on hand dexterity function in NHP models with chronic PD is essential. Traditional rating scales previously used in the evaluation of animal spontaneous behavior were insufficient due to factors related to subjectivity and passivity. Thus, experimentally designed applications for an appropriate apparatus are necessary. In this study, we aimed to longitudinally assess hand dexterity function using hand dexterity task (HDT) in NHP-PD models. To validate this assessment, we analyzed the alteration in Parkinsonian tremor signs and the functionality of presynaptic dopaminergic neuron using positron emission tomography imaging of dopamine transporters in these models. In addition, a significant inverse correlation between HDT and DAT level was identified, but no local bias was found. The correlation with intention tremor signs was lower than the resting tremor. In conclusion, the evaluation of HDT may reflect behavioral symptoms of NHP-PD models. Furthermore, HDT was effectively used to experimentally distinguish intention tremors from other tremors. Copyright © Experimental Neurobiology 2020.1

Erratum: Correction to: Germinal Center-Induced Immunity Is Correlated With Protection Against SARS-CoV-2 Reinfection But Not Lung Damage (The Journal of infectious diseases (2021) 224 11 (1861-1872))

In the original publication of this article, [Green K, Kim DH, Bae S et al. Germinal Center-Induced Immunity Is Correlated With Protection Against SARS-CoV-2 Reinfection But Not Lung Damage. https://doi.org/10.1093/jid/jiab535], a statement of equal contribution was missing for the authors Sung-Han Kim and Jung Joo Hong. This is currently available in the version of the article online.Y

Prof. Tütengil'i Anlamak ve tamamlamak

Taha Toros Arşivi, Dosya No: 200-Cavit Orhan Tütengil. Not: Gazetenin "Düşünenlerin Düşünceleri" köşesinde yayımlanmıştır.Unutma İstanbul projesi İstanbul Kalkınma Ajansı'nın 2016 yılı "Yenilikçi ve Yaratıcı İstanbul Mali Destek Programı" kapsamında desteklenmiştir. Proje No: TR10/16/YNY/010

Dual effect of fetal bovine serum on early development depends on stage-specific reactive oxygen species demands in pigs

<div><p>Despite the application of numerous supplements to improve <i>in vitro</i> culture (IVC) conditions of mammalian cells, studies regarding the effect of fetal bovine serum (FBS) on mammalian early embryogenesis, particularly in relation to redox homeostasis, are lacking. Herein, we demonstrated that early development of <i>in vitro</i>-produced (IVP) porcine embryos highly depends on the combination of FBS supplementation timing and embryonic reactive oxygen species (ROS) requirements. Interestingly, FBS significantly reduced intracellular ROS levels in parthenogenetically activated (PA) embryos regardless of the developmental stage. However, the beneficial effect of FBS on early embryogenesis was found only during the late phase (IVC 4–6 days) treatment group. In particular, developmental competence parameters, such as blastocyst formation rate, cellular survival, total cell number and trophectoderm proportion, were markedly increased by FBS supplementation during the late IVC phase. In addition, treatment with FBS elevated antioxidant transcript levels during the late IVC phase. In contrast, supplementation with FBS during the entire period (1–6 days) or during the early IVC phase (1–2 days) greatly impaired the developmental parameters. Consistent with the results from PA embryos, the developmental competence of <i>in vitro</i> fertilization (IVF) or somatic cell nuclear transfer (SCNT) embryos were markedly improved by treatment with FBS during the late IVC phase. Moreover, the embryonic stage-specific effects of FBS were reversed by the addition of an oxidant and were mimicked by treatment with an antioxidant. These findings may increase our understanding of redox-dependent early embryogenesis and contribute to the large-scale production of high-quality IVP embryos.</p></div

Involvement of p-p38 MAPK and p-AKT cascades in FBS-associated phenotypes during late IVC phase.

<p>(A) Western blot analysis of p-p38 MAPK and p-AKT in control and FBS supplementation during late phase in porcine PA embryos. (B) Representative photographs of the developed blastocysts (white asterisks; left panel) and quantification of blastocyst developmental rate (right panel) in the indicated groups. Bar = 100 μm. The data are from three independent experiments, and values represent the means ± SE (*P < 0.05). (C) Immunocytochemical analysis of Cdx2/DAPI. Merged images (light green) between Cdx2 (green) and DAPI (blue) signals are shown (top panel) and quantification of the total cell number (bottom left panel) and ICM/TE proportion (bottom right panel) in the indicated groups. Bar = 50 μm. (D) Apoptosis detection analysis in blastocysts from the indicated groups. Merged images (light green) between TUNEL (green, white arrow) and DAPI (blue) signals are shown (top panel) and quantification of apoptotic cells (bottom panel). Bar = 50 μm. The data are from three independent experiments, and values represent the means ± SE (^*<i>P</i> < 0.05).</p