Cv2, functioning as a pro-BMP factor via twisted gastrulation, is required for early development of nephron precursors

AbstractThe fine-tuning of BMP signals is critical for many aspects of complex organogenesis. In this report, we show that the augmentation of BMP signaling by a BMP-binding secreted factor, Crossveinless2 (Cv2), is essential for the early embryonic development of mammalian nephrons. In the Cv2-null mouse, the number of cap condensates (clusters of nephron progenitors, which normally express Cv2) was decreased, and the condensate cells exhibited a reduced level of aggregation. In these Cv2–/– condensates, the level of phosphorylated Smad1 (pSmad1) was substantially lowered. The loss of a Bmp7 allele in the Cv2–/– mouse enhanced the cap condensate defects and further decreased the level of pSmad1 in this tissue. These observations indicated that Cv2 has a pro-BMP function in early nephrogenesis. Interestingly, the renal defects of the Cv2–/– mutant were totally suppressed by a null mutation of Twisted gastrulation (Tsg), which encodes another BMP-binding factor, showing that Cv2 exerts its pro-BMP nephrogenic function Tsg-dependently. By using an embryonic kidney cell line, we presented experimental evidence showing that Cv2 enhances pro-BMP activity of Tsg. These findings revealed the molecular hierarchy between extracellular modifiers that orchestrate local BMP signal peaks in the organogenetic microenvironment

Analysing features of Japanese splogs and characteristics of keywords

This paper focuses on analyzing (Japanese) splogs based on various characteristics of keywords contained in them. We estimate the behavior of spammers when creating splogs from other sources by analyzing the characteristics of key-words contained in splogs. Since splogs often cause noises in word occurrence statistics in the blogosphere, we assume that we can efficiently (manually) collect splogs by sampling blog homepages containing keywords of a certain type on the date with its most frequent occurrence. We manually exam-ine various features of collected blog homepages regarding whether their text content is excerpt from other sources or not, as well as whether they display affiliate advertisement or out-going links to affiliated sites. Among various infor-mative results, it is important to note that more than half of the collected splogs are created by a very small number of spammers

Collecting and Analyzing Japanese Splogs based on Characteristics of Keywords

This paper focuses on analyzing (Japanese) splogs based on various characteristics of keywords contained in them. We estimate the behavior of spammers when creating splogs from other sources by analyzing the characteristics of keywords contained in splogs. Since splogs often cause noises in word occurrence statistics in the blogosphere, we assume that we can efficiently collect splogs by sampling blog homepages containing keywords of a certain type on the date with its most frequent occurrence. We manually examine various features of collected blog homepages regarding whether their text content is excerpt from other sources or not, as well as whether they display affiliate advertisement or out-going links to affiliated sites. Among various informative results, it is important to note that more than half of the collected splogs are created by a very small number of spammers

Frequent mutations that converge on the NFKBIZ pathway in ulcerative colitis

潰瘍性大腸炎による上皮再構築メカニズムと発がんとの関係を解明 --IL-17シグナル経路に変異を獲得した上皮細胞は発がん過程で陰性に選択される--. 京都大学プレスリリース. 2019-12-20.Chronic inflammation is accompanied by recurring cycles of tissue destruction and repair and is associated with an increased risk of cancer1, 2, 3. However, how such cycles affect the clonal composition of tissues, particularly in terms of cancer development, remains unknown. Here we show that in patients with ulcerative colitis, the inflamed intestine undergoes widespread remodelling by pervasive clones, many of which are positively selected by acquiring mutations that commonly involve the NFKBIZ, TRAF3IP2, ZC3H12A, PIGR and HNRNPF genes and are implicated in the downregulation of IL-17 and other pro-inflammatory signals. Mutational profiles vary substantially between colitis-associated cancer and non-dysplastic tissues in ulcerative colitis, which indicates that there are distinct mechanisms of positive selection in both tissues. In particular, mutations in NFKBIZ are highly prevalent in the epithelium of patients with ulcerative colitis but rarely found in both sporadic and colitis-associated cancer, indicating that NFKBIZ-mutant cells are selected against during colorectal carcinogenesis. In further support of this negative selection, we found that tumour formation was significantly attenuated in Nfkbiz-mutant mice and cell competition was compromised by disruption of NFKBIZ in human colorectal cancer cells. Our results highlight common and discrete mechanisms of clonal selection in inflammatory tissues, which reveal unexpected cancer vulnerabilities that could potentially be exploited for therapeutics in colorectal cancer

Analysis of Outcomes in Ischemic vs Nonischemic Cardiomyopathy in Patients With Atrial Fibrillation A Report From the GARFIELD-AF Registry

IMPORTANCE Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes