RNAscope

YAP and TAZ couple osteoblast precursor mobilization to angiogenesis and mechanoregulated bone development

Endochondral ossification requires coordinated mobilization of osteoblast precursors with blood vessels. During adult bone homeostasis, vessel adjacent osteoblast precursors respond to and are maintained by mechanical stimuli; however, the mechanisms by which these cells mobilize and respond to mechanical cues during embryonic development are unknown. Previously, we found that deletion of the mechanoresponsive transcriptional regulators, YAP and TAZ, from Osterix-expressing osteoblast precursors and their progeny caused perinatal lethality.

Area postrema neurons mediate interleukin-6 function in cancer-associated cachexia

Interleukin-6 (IL-6) has been long considered a key player in cancer-associated cachexia 1-15 . It is believed that sustained elevation of IL-6 production during cancer progression causes brain dysfunctions, which ultimately result in cachexia 16-20 . However, how peripheral IL-6 influences the brain remains poorly understood. Here we show that neurons in the area postrema (AP), a circumventricular structure in the hindbrain, mediate the function of IL-6 in cancer-associated cachexia in mice. We found that circulating IL-6 can rapidly enter the AP and activate AP neurons.

Wnt signaling regulates ion channel expression to promote smooth muscle and cartilage formation in developing mouse trachea

Ion channels play critical roles in the physiology and function of the nervous system and contractile tissue; however, their role in non-contractile tissue and embryonic development is less understood. Tracheobronchomalacia (TBM) and complete tracheal rings (CTR) are disorders affecting the muscle and cartilage of the trachea and bronchi, whose etiology remains poorly understood. We demonstrated that trachealis muscle organization and polarity are disrupted after the deletion of Wls , an essential component of the Wnt signaling pathway, in tracheal epithelium during embryonic development.

Identification of HSPA8 as an interacting partner of MAB21L2 and an important factor in eye development

Pathogenic variants in human MAB21L2 result in microphthalmia, anophthalmia, and coloboma. The exact molecular function of MAB21L2 is currently unknown. We conducted a series of yeast two-hybrid (Y2H) experiments to determine protein interactomes of normal human and zebrafish MAB21L2/mab21l2 as well as human disease-associated variant MAB21L2-p.(Arg51Gly) using human adult retina and zebrafish embryo libraries.These screens identified klhl31, tnpo1, TNPO2/tnpo2, KLC2/klc2, and SPTBN1/sptbn1 as co-factors of MAB21L2/mab21l2.

Interferon-τ -induced ISG15-AS regulates endometrial receptivity during early goat pregnancy

Endometrial receptivity is a critical process for the successful establishment of pregnancy in ruminants. However, the biological role of long non-coding RNAs (lncRNAs) in the development of endometrial receptivity is poorly understood. In this study, we performed RNA-seq analysis of immortalised goat endometrial epithelial cells (gEECs) treated with interferon-τ (IFNT). Transcriptome profiles showed that 8069 high-confidence putative lncRNAs, including 6498 intronic lncRNA transcripts, 1078 lincRNAs and 493 antisense lncRNAs were identified in gEECs with or without IFNT treatment.

High expression of LGR6 is a poor prognostic factor in esophageal carcinoma

Leucine-rich repeat-containing G-protein-coupled receptor 6 (LGR6) promotes carcinogenesis and progression in some cancer types. However, there are few reports of LGR6 expression in esophageal squamous cell carcinoma (ESCC). LGR6 expression and clinicopathological features in ESCC were investigated by RNAscope, a highly sensitive RNA in situ hybridization method.Appropriate tumors were selected from 41 cases of ESCC from which tissue microarrays were generated, and LGR6 expression was identified by RNAscope.Thirty-seven patients had LGR6 expression.

Recent advances in cutaneous HPV infection

More than 200 types of human papillomavirus (HPV) have been reported to date and have been associated with various dermatological diseases. Among dermatological diseases, viral verrucae are the most commonly reported to be associated with HPV. Epidermodysplasia verruciformis (EV) consists of three types: typical EV is an autosomal recessive genetic disorder with TMC6/TMC8 gene mutations, atypical EV develops due to various gene mutations that cause immunodeficiency, and acquired EV develops due to acquired immunodeficiency.

Maternal immune activation alters social affective behavior and sensitivity to corticotropin releasing factor in male but not female rats

Prenatal infection increases risk for neurodevelopmental disorders such as autism in offspring. In rodents, prenatal administration of the viral mimic Polyinosinic: polycytidylic acid (Poly I: C) allows for investigation of developmental consequences of gestational sickness on offspring social behavior and neural circuit function. Because maternal immune activation (MIA) disrupts cortical development and sociability, we examined approach and avoidance in a rat social affective preference (SAP) task.

Secreted protease ADAMTS18 in development and disease

ADAMTS18 was identified in 2002 as a member of the ADAMTS family of 19 secreted Zinc-dependent metalloproteinases. Prior to 2016, ADAMTS18 was known as a candidate gene associated with a wide range of pathologies, particularly various malignancies and eye disorders. However, functions and substrates of ADAMTS18 in normal conditions were unknown. Since 2016, with the development of Adamts18 knockout models, many studies had been conducted on the Adamts18 gene in vivo.

A patient advocating for transparent science in rare disease research

300 million people live with at least one of 6,000 rare diseases worldwide. However, rare disease research is not always reviewed with scrutiny, making it susceptible to what the author refers to as nontransparent science. Nontransparent science can obscure animal model flaws, misguide medicine regulators and drug developers, delay or frustrate orphan drug development, or waste limited resources for rare disease research. Flawed animal models not only lack pharmacologic relevance, but also give rise to issue of clinical translatability.

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