Lab-On-Chip Clinorotation System for Live-Cell Microscopy Under Simulated Microgravity

Cells in microgravity are subject to mechanical unloading and changes to the surrounding chemical environment. How these factors jointly influence cellular function is not well understood. We can investigate their role using ground-based analogues to spaceflight, where mechanical unloading is simulated through the time-averaged nullification of gravity. The prevailing method for cellular microgravity simulation is to use fluid-filled containers called clinostats. However, conventional clinostats are not designed for temporally tracking cell response, nor are they able to establish dynamic fluid environments. To address these needs, we developed a Clinorotation Time-lapse Microscopy (CTM) system that accommodates lab-on- chip cell culture devices for visualizing time-dependent alterations to cellular behavior. For the purpose of demonstrating CTM, we present preliminary results showing time-dependent differences in cell area between human mesenchymal stem cells (hMSCs) under modeled microgravity and normal gravity

The WiggleZ Dark Energy Survey: galaxy evolution at 0.25 ≤ z ≤ 0.75 using the second red-sequence cluster survey

We study the evolution of galaxy populations around the spectroscopic WiggleZ sample of star-forming galaxies at 0.2

The Burden of Trachoma in Ayod County of Southern Sudan

Trachoma, a neglected tropical disease, is the leading cause of infectious blindness and is targeted for global elimination by the year 2020. We conducted a survey in Ayod County of Jonglei State, Southern Sudan, to determine whether blinding trachoma was a public health problem and to plan interventions to control this disease. We found the burden of trachoma in Ayod to be one of the most severe ever documented. Not only were adults affected by the advanced manifestations of the disease as is typical for older age groups, but young children were also affected. At least one person with clinical signs of trachoma was found in nearly every household, and 1 in 3 households had a person with severe blinding trachoma. Characteristics previously identified as risk factors were ubiquitous among surveyed households, but we were unable to identify why trachoma is so severe in this location. Surgical interventions are needed urgently to improve vision and prevent irreversible blindness in children and adults. Mass antibiotic distribution may alleviate current infections and transmission of trachoma may be reduced if communities adopt the behavior of face washing and safe disposal of human waste. Increasing access to improved water sources may not only improve hygiene but also reduce the spread of guinea worm and other water-borne diseases

HoxA-11 and FOXO1A Cooperate to Regulate Decidual Prolactin Expression: Towards Inferring the Core Transcriptional Regulators of Decidual Genes

During the menstrual cycle, the ovarian steroid hormones estrogen and progesterone control a dramatic transcriptional reprogramming of endometrial stromal cells (ESCs) leading to a receptive state for blastocyst implantation and the establishment of pregnancy. A key marker gene of this decidualization process is the prolactin gene. Several transcriptional regulators have been identified that are essential for decidualization of ESCs, including the Hox genes HoxA-10 and HoxA-11, and the forkhead box gene FOXO1A. While previous studies have identified downstream target genes for HoxA-10 and FOXO1A, the role of HoxA-11 in decidualization has not been investigated. Here, we show that HoxA-11 is required for prolactin expression in decidualized ESC. While HoxA-11 alone is a repressor on the decidual prolactin promoter, it turns into an activator when combined with FOXO1A. Conversely, HoxA-10, which has been previously shown to associate with FOXO1A to upregulate decidual IGFBP-1 expression, is unable to upregulate PRL expression when co-expressed with FOXO1A. By co-immunoprecipitation and chromatin immunoprecipitation, we demonstrate physical association of HoxA-11 and FOXO1A, and binding of both factors to an enhancer region (−395 to −148 relative to the PRL transcriptional start site) of the decidual prolactin promoter. Because FOXO1A is induced upon decidualization, it serves to assemble a decidual-specific transcriptional complex including HoxA-11. These data highlight cooperativity between numerous transcription factors to upregulate PRL in differentiating ESC, and suggest that this core set of transcription factors physically and functionally interact to drive the expression of a gene battery upregulated in differentiated ESC. In addition, the functional non-equivalence of HoxA-11 and HoxA-10 with respect to PRL regulation suggests that these transcription factors regulate distinct sets of target genes during decidualization

Functions of Some Capsular Polysaccharide Biosynthetic Genes in Klebsiella pneumoniae NTUH K-2044

The growing number of Klebsiella pneumoniae infections, commonly acquired in hospitals, has drawn great concern. It has been shown that the K1 and K2 capsular serotypes are the most detrimental strains, particularly to those with diabetes. The K1 cps (capsular polysaccharide) locus in the NTUH-2044 strain of the pyogenic liver abscess (PLA) K. pneumoniae has been identified recently, but little is known about the functions of the genes therein. Here we report characterization of a group of cps genes and their roles in the pathogenesis of K1 K. pneumoniae. By sequential gene deletion, the cps gene cluster was first re-delimited between genes galF and ugd, which serve as up- and down-stream ends, respectively. Eight gene products were characterized in vitro and in vivo to be involved in the syntheses of UDP-glucose, UDP-glucuronic acid and GDP-fucose building units. Twelve genes were identified as virulence factors based on the observation that their deletion mutants became avirulent or lost K1 antigenicity. Furthermore, deletion of kp3706, kp3709 or kp3712 (ΔwcaI, ΔwcaG or Δatf, respectively), which are all involved in fucose biosynthesis, led to a broad range of transcriptional suppression for 52 upstream genes. The genes suppressed include those coding for unknown regulatory membrane proteins and six multidrug efflux system proteins, as well as proteins required for the K1 CPS biosynthesis. In support of the suppression of multidrug efflux genes, we showed that these three mutants became more sensitive to antibiotics. Taken together, the results suggest that kp3706, kp3709 or kp3712 genes are strongly related to the pathogenesis of K. pneumoniae K1

Multianalyte Sensing Of Addictive Over-the-counter (otc) Drugs

A supramolecular sensor array composed of two fluorescent cucurbit[n]uril-type receptors (probe 1 and probe 2) displaying complementary selectivities was tested for its ability to detect and quantify drug-related amines. The fluorimetric titration of the individual probes showed highly variable and cross-reactive analyte-dependent changes in fluorescence. An excellent ability to recognize a variety of analytes was demonstrated in qualitative as well as quantitative assays. Importantly, a successful quantitative analysis of several analytes of interest was achieved in mixtures and in human urine. The throughput and sensitivity surpass those of the current state-of-the-art methods that usually require analyte solid-phase extraction (SPE). These results open up the opportunity for new applications of cucurbit[n]uril-type receptors in sensing and pave the way for the development of simple high-throughput assays for various drugs in the near future

Man Bites Mosquito: Understanding the Contribution of Human Movement to Vector-Borne Disease Dynamics

In metropolitan areas people travel frequently and extensively but often in highly structured commuting patterns. We investigate the role of this type of human movement in the epidemiology of vector-borne pathogens such as dengue. Analysis is based on a metapopulation model where mobile humans connect static mosquito subpopulations. We find that, due to frequency dependent biting, infection incidence in the human and mosquito populations is almost independent of the duration of contact. If the mosquito population is not uniformly distributed between patches the transmission potential of the pathogen at the metapopulation level, as summarized by the basic reproductive number, is determined by the size of the largest subpopulation and reduced by stronger connectivity. Global extinction of the pathogen is less likely when increased human movement enhances the rescue effect but, in contrast to classical theory, it is not minimized at an intermediate level of connectivity. We conclude that hubs and reservoirs of infection can be places people visit frequently but briefly and the relative importance of human and mosquito populations in maintaining the pathogen depends on the distribution of the mosquito population and the variability in human travel patterns. These results offer an insight in to the paradoxical observation of resurgent urban vector-borne disease despite increased investment in vector control and suggest that successful public health intervention may require a dual approach. Prospective studies can be used to identify areas with large mosquito populations that are also visited by a large fraction of the human population. Retrospective studies can be used to map recent movements of infected people, pinpointing the mosquito subpopulation from which they acquired the infection and others to which they may have transmitted it

Viral hepatitis-associated intrahepatic cholangiocarcinoma shares common disease processes with hepatocellular carcinoma

Bile duct cells and hepatocytes differentiate from the same hepatic progenitor cells. To investigate the possible association of viral hepatitis B and C with intrahepatic cholangiocarcinoma (ICC), we conducted a retrospective case–control study using univariate and multivariate logistic analyses to identify risk factors for ICC. Besides hepatic lithiasis (25.6%; P<0.001), seropositivity for hepatitis B surface antigen (37.5% of all ICC patients; odds ratio (OR) =4.985, P<0.001) and seropositivity for hepatitis C antibodies (13.1%; OR=2.709; P=0.021) are the primary independent risk factors for ICC. Cirrhosis exerted synergic effects on the development of ICC. We compared the age distributions of viral-hepatitis associated ICC to that of viral hepatitis-associated hepatocellular carcinoma (HCC). The mean age of ICC patients with viral hepatitis B (56.4±11.1 years) were 9 years younger than that of ICC patients with viral hepatitis C (65.6±9.17 years), similar to that observed in HCC. The incidence ratio of HCC : ICC : CHC (combined hepatocellular cholangiocarcinoma) in our population was 233 : 17 : 1 consistent with the theoretic ratio of hepatocyte number to cholangiocyte number in the liver. Our findings indicated that both viral hepatitis-associated ICC and HCC shared common disease process for carcinogenesis and, possibly, both arose from the hepatic progenitor cells

Genes, Education, and Labor Market Outcomes: Evidence from the Health and Retirement Study

Recent advances have led to the discovery of specific genetic variants that predict educational attainment. We study how these variants, summarized as a genetic score variable, are associated with human capital accumulation and labor market outcomes in the Health and Retirement Study (HRS). We demonstrate that the same genetic score that predicts education is also associated with higher wages, but only among individuals with a college education. Moreover, the genetic gradient in wages has grown in more recent birth cohorts, consistent with interactions between technological change and labor market ability. We also show that individuals who grew up in economically disadvantaged households are less likely to go to college when compared to individuals with the same genetic score, but from higher socioeconomic status households. Our findings provide support for the idea that childhood socioeconomic status is an important moderator of the economic returns to genetic endowments. Moreover, the finding that childhood poverty limits the educational attainment of high-ability individuals suggests the existence of unrealized human potential