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Bauer Holck posted an update 1 year, 7 months ago
In summary, we found that LincQ specifically interacts with Sox2 and contributes to the maintenance of pluripotency, highlighting the critical role of lincRNA in the pluripotency regulatory network. © AlphaMed Press 2020 SIGNIFICANCE STATEMENT This study shows that the long intergenic noncoding RNA LincQ is critical for embryonic stem cell (ESC) pluripotency maintenance. LincQ is highly expressed in ESCs and is downregulated during differentiation. Further, its inhibition leads to ESC differentiation. LincQ binds to Sox2 to regulate the transcription of pluripotency genes. Esrrb and Tfcp2l1 are the main downstream targets of LincQ/Sox2 that are involved in ESC maintenance. © 2020 AlphaMed Press.In humans and rodents, the entorhinal cortical (EC) -hippocampal (HPC) circuit is crucial for the formation and recall of memory, preserving both spatial and temporal information about the occurrence of past events. Both modeling and experimental studies have revealed circuits within this network that play crucial roles in encoding space and context. However, our understanding about the time-related aspects of memory are just beginning to be understood. In this review, we first describe updates regarding recent anatomical discoveries for the EC-HPC network, as several important neural circuits critical for memory formation have been discovered by newly developed neural tracing technologies. Second, we examine the complementary roles of multiple medial entorhinal cortical inputs, including newly discovered circuits, into the hippocampus for the temporal and spatial aspects of memory. Finally, we will discuss how temporal and contextual memory information is integrated in hippocampal CA1 cells. We provide new insights into the neural circuit mechanisms for anatomical and functional segregation and integration of the temporal and spatial aspects of memory encoding in the EC-HPC networks. This article is protected by copyright. All rights reserved.Human mesenchymal stem cells (MSCs) are promising therapeutics for autoimmune diseases due to their immunomodulatory effects. In particular, human umbilical cord blood-derived MSCs (hUCB-MSCs) have a prominent therapeutic effect on atopic dermatitis (AD). However, the underlying mechanism is unclear. This study investigated the role of transforming growth factor-beta (TGF-β) in the therapeutic effect of hUCB-MSCs on AD. Small interfering RNA (siRNA)-mediated depletion of TGF-β disrupted the therapeutic effect of hUCB-MSCs in a mouse model of AD by attenuating the beneficial changes in histopathology, mast cell infiltration, tumor necrosis factor-alpha (TNF-α) expression, and the serum IgE level. To confirm that hUCB-MSCs regulate secretion of TNF-α, we investigated whether they inhibit TNF-α secretion by activated LAD2 cells. Coculture with hUCB-MSCs significantly inhibited secretion of TNF-α by LAD2 cells. However, this effect was abolished by siRNA-mediated depletion of TGF-β in hUCB-MSCs. STAT5-IN-1 TNF-α expression in activated LAD2 cells was regulated by the extracellular signal-related kinase signaling pathway and was suppressed by TGF-β secreted from hUCB-MSCs. In addition, TGF-β secreted by hUCB-MSCs inhibited maturation of B cells. Taken together, our findings suggest that TGF-β plays a key role in the therapeutic effect of hUCB-MSCs on AD by regulating TNF-α in mast cells and maturation of B cells. ©AlphaMed Press 2020.Subtle executive function deficits, particularly regarding inhibitory control, have been reported in patients with phenylketonuria (PKU) despite early dietary treatment. Purpose of this study was to assess, whether young female adults with PKU exhibit altered neural activity underlying such deficits, particularly in a fronto-parietal cognitive control network (CCN). Behavioral data and functional magnetic resonance imaging (fMRI) data were acquired during a Go-NoGo task in 16 young adult patients with PKU and 17 control subjects. Hypothesis-driven analyses of behavioral and fMRI data in the CCN were supplemented by exploratory whole brain activation analyses. PKU patients exhibited a trend towards higher errors of commission. Patients exhibited marginally increased activation associated with inhibitory control in only one CCN core region (right middle frontal gyrus, p = 0.043). Whole brain analyses revealed widespread relatively increased activation in adults with PKU in the main task contrast (NoGo > Go). This increased activation was mainly observed outside the CCN and largely overlapped with the default mode network (DMN). In conclusion only subtle inhibitory control deficits and associated brain activity differences were observed in young adults with PKU. Thus, this work adds to the notion that this particular population seems to be only slightly affected by such cognitive deficits. While there were also only minimal increases when compared to healthy subjects in brain activity in a cognitive control network, we observed more widespread activation increases outside this network. These results support the assumption of DMN dysfunction in PKU. This article is protected by copyright. All rights reserved.BACKGROUND Subclinical bacteriuria is defined as a positive bacterial urine culture in the absence of clinical evidence of urinary tract infection (UTI). Studies have reported that hyperthyroid cats have UTIs (mostly subclinical) with prevalence rates of 12%-22%. Consequently, clinicians consider hyperthyroidism a risk factor for development of subclinical bacteriuria, and many recommend urine culture when evaluating hyperthyroid cats. OBJECTIVES To compare the prevalence of subclinical bacteriuria (based on positive urine culture) in untreated hyperthyroid cats to that in euthyroid cats of similar age and sex. ANIMALS Three hundred and ninety-three hyperthyroid cats presented for radioiodine treatment and 131 euthyroid cats (≥7 years of age) presented for routine examination. Cats with signs of lower urinary tract disease were excluded. METHODS Prospective cohort study. Both hyperthyroid and euthyroid cats had urine collected by cystocentesis for complete urinalysis and culture. Data pertaining to age, sex, body condition, and serum thyroxine and creatinine concentrations also were acquired.

