Nonetheless, the impaired activation of RhoA clearly resulted in a reduced activity of Rho- kinase, as shown by reduced phosphorylation of moesin, a member of the family of ezrin-radixin-moesin proteins, which is phosphorylated at Thr-558 by Rho-kinase. The inhibition of RhoA/Rho kinase signaling is clearly implicated in the GW4064-mediated inhibition of stellate cell contraction as the phosphorylation of the downstream MLC is significantly decreased. Many studies have shown that, similar to smooth muscle cells, contraction of stellate cells is powered by myosin II through its action on the actin cytoskeleton, a process that is activated by phosphorylation of its myosin regulatory light chain. It’s likely that inhibition of ET-1-induced MLC phosphorylation by GW4064 plays an important role in its inhibitory effect on stellate cell contraction. In summary,Lesinurad in addition to its known anti-fibrotic effect, our study suggests a novel function of FXR in regulating intrahepatic vascular resistance through its inhibitory effect on stellate cell contraction. Although more studies are required to better understand the underlying mechanism, inhibition of RhoA/Rho kinase is likely to play a role in the FXR-mediated negative regulation of stellate cell contraction. Seasonality, which is driven by variation in solar influx, is one of the most dramatic environmental variables that affects the physical and biological properties of life. The recognition that humans are subject to seasonal changes in mood and behavior may date back to ancient times,Indinavir sulfate when Hippocrates observed variations in seasonal incidences of melancholy and mania. Poets have often portrayed a sense of sadness that may accompany the shortening days of fall and winter. Biologically, seasonal rhythms have been identified in many human social behaviors and in functions including weight, appetite, sleep, birth, death, and mood. Studies of recurrent seasonal depression also have enhanced interest in the clinical relevance of such seasonal changes. Although it is com- monly believed that human beings are affected by seasonality, no study has investigated the seasonal patterns of depression on a global scale. The Internet has become an important information source in recent years. Keyword-driven Internet search engines allow billions of people worldwide to have easy, instant access to a vast and diverse amount of information online. These search records, when properly archived and de-identified, are the largest dataset ever seen in human history and are priceless to scientific researchers in many fields. For example, Internet search query data have been demonstrated to predict influenza epidemics, other infectious diseases, or unemployment rate. Only recently, these search query data were available to the public using programs such as Google Insights for Search, a free service provided by Google Incorporation that allows researchers to examine trends of certain search keywords. This web-based service provides de- identified, normalized weekly trend data of certain keyword’s search volumes and opens a unique window to investigate collective human behaviors on the Internet on a gigantic scale. Here, we present a study based on search trend data from Google Insights for Search. Search interests of certain keywords such as ‘‘shirt’’ and ‘‘sweater’’ are obviously seasonally-dependent. Search queries for other words, such as those that convey emotional sense or medical meanings, may also reflect seasonal patterns of human behavior or illness.