Loss of spindle assembly checkpoint–mediated inhibition of Cdc20 promotes tumorigenesis in mice

Genomic instability is a hallmark of human cancers. Spindle assembly checkpoint (SAC) is a critical cellular mechanism that prevents chromosome missegregation and therefore aneuploidy by blocking premature separation of sister chromatids. Thus, SAC, much like the DNA damage checkpoint, is essential for genome stability. In this study, we report the generation and analysis of mice carrying a Cdc20 allele in which three residues critical for the interaction with Mad2 were mutated to alanine. The mutant Cdc20 protein (AAA-Cdc20) is no longer inhibited by Mad2 in response to SAC activation, leading to the dysfunction of SAC and aneuploidy. The dysfunction could not be rescued by the additional expression of another Cdc20 inhibitor, BubR1. Furthermore, we found that Cdc20AAA/AAA mice died at late gestation, but Cdc20+/AAA mice were viable. Importantly, Cdc20+/AAA mice developed spontaneous tumors at highly accelerated rates, indicating that the SAC-mediated inhibition of Cdc20 is an important tumor-suppressing mechanism

Nazi Mass Execution Trenches at Fort IX, Kaunas Lithuania

Color poster with text, images, and maps.Shortly after the Nazi occupation of Lithuania in June of 1941, they began to round up the country’s Jewish population as part of the Nazi’s “Final Solution”. At Fort IX as many as 45,000 Jews and Communists were killed in series of execution trenches. In 1944, the Nazis knew that they were going to lose the war and needed to eliminate the evidence of the murders. The bodies were then exhumed from the trenches, burned, and the remains were spread across the landscape, leaving very little evidence. In July of 2017, Ground penetrating radar (GPR) grids using 225 MHz and 450 MHz antenna with step sizes of .1 and .05 meters, respectively, were taken in the locations where the trenches were thought to be. GPR profiles were processed using both GFP_Edit and EKKO_Project. The profiles show the existence of horizontal subsurface disturbances at the 10, 20, 30, and 40 meter marks. These correspond to eye-witness and past archaeological accounts. The results collected from this ground penetrating radar project provide important evidence in verifying the horrendous mass murders conducted by the Nazi Regime during the Holocaust.University of Wisconsin--Eau Claire Office of Research and Sponsored Programs

Ground Penetrating Radar Investigation of a Mass Grave and Malina Entrance at the HKP Site, Vilnius, Lithuania

Color poster with text, images, and maps.Major Karl Plague was a German officer during World War Two responsible for saving 250 Jewish forced labor workers at HKP 562 in Vilnius, Lithuania. The 750 other workers were captured and killed by Nazi SS members on their retreat out of the country during Adolf Hitler’s “Final Solution", their bodies buried in an unmarked grave. In the summer of 2017, an international team of Jewish scholars, archaeologists and geophysicists were invited to HKP to investigate two possible locations in which the mass grave may exist using ground penetrating radar (GPR). GPR is a noninvasive technology that sends electromagnetic frequencies into the subsurface to examine its stratigraphy. Using 225 and 450 MHz antennae with a step size of 0.1m and 0.05m (respectively), GPR data was collected over 6 grids, varying in size. Grids were located over a monument to those slaughtered, along the back wall of one of the buildings, and in the basement of the same building. GPR data was then processed using EKKO_Project and Voxler to examine the subsurface. Results showed extensive stratigraphic dipping along the back side of the building along with an anomaly in the basement believed to be the entrance to a malina.University of Wisconsin--Eau Claire Office of Research and Sponsored Programs

An analysis of 5′-inosine and 5′-guanosine monophosphate taste in rats

Inosine monophosphate (IMP) and guanosine monophosphate (GMP) elicit an umami taste in humans and synergistically increase the intensity of the umami taste of monosodium glutamate (MSG). Conditioned taste aversion (CTA) studies in rodents indicate that these nucleotides and MSG elicit quite similar tastes, but recent physiological evidence suggests that these nucleotides and MSG may not activate the same population of taste receptors and therefore may not elicit identical taste qualities. This study reports the findings of several behavioral experiments with rats that compared the taste properties of IMP and GMP with each other and with those of MSG. Well-trained rats were able to detect both nucleotides at nanomolar concentrations, but they did not respond to either nucleotide in two-bottle preference tests or brief-access CTA tests at concentrations less than 0.5 mM. Discrimination experiments found that the tastes of these nucleotides could not be discriminated from each other, but both could be discriminated from MSG, even when the taste of Na+ was controlled. Overall, these experiments indicate the taste properties of the two 5′-ribonucleotides are quite similar to each other, and even though they may elicit an umami sensation, these sensations are not identical to the taste of MSG. © 2007 Oxford University Press

Comparing Antennae Frequencies (225, 450 and 900 MHz) of a Windblown Dune, Kuršių Nerija National Park, Lithuania

Color poster with text, images, charts, photographs, maps, and grids.The Kuršių Nerija National Park is one of five national parks in Lithuania. The Park was established in 1991 to protect the unique environments of the Curonian Spit and Curonian Lagoon and is also recognized by UNESCO as a World Heritage site. Within the Park, the natural landscapes are dominated by coastal and windblown geomorphic processes. To test the applicability of ground penetrating radar (GPR) to image windblown dunes on the Curonian Spit, a collaborative project with Vilnius University focused on comparing a variety of antennae frequencies to compare the “range vs. resolution” question within the dunes. GPR, a non-destructive geophysical imaging methodology, allows one to use lower antennae frequencies to provide deeper imaging into the subsurface versus higher antennae frequencies which allow greater resolution of the sedimentary patterns. Data was collected using a pulseEKKO 1000 GPR system with three antennae frequencies (antennae separation/step size): 225 MHz (0.5 m/0.1m), 450 MHz (0.25m/0.05m) and 900 MHz (0.17m/0.02/m). To geometrically correct the data, a topographic survey was conducted using along each transect using a TopCon RL-H3CL laser level. The results highlight the importance in understanding the “range vs resolution” question when investigating sedimentary environments.University of Wisconsin--Eau Claire Office of Research and Sponsored Program

Association of MSX1 and TGFB3 with nonsyndromic clefting in humans.

Nonsyndromic cleft lip with or without cleft palate (CL/P) and nonsyndromic cleft palate only (CPO) are common congenital anomalies with significant medical, psychological, social, and economic ramifications. Both CL/P and CPO are examples of complex genetic traits. There exists sufficient evidence to hypothesize that disease loci for CL/P and CPO can be identified by a candidate-gene linkage-disequilibrium (LD) strategy. Candidate genes for clefting, including TGFA, BCL3, DLX2, MSX1, and TGFB3, were screened for LD with either CL/P or CPO in a predominantly Caucasian population, with both case-control- and nuclear-family-based approaches. Previously reported LD for TGFA with both CL/P and CPO could not be confirmed, except in CL/P patients with a positive family history. Also, in contrast to previous studies, no LD was found between BCL3 and either CL/P or CPO. Significant LD was found between CL/P and both MSX1 and TGFB3 and between CPO and MSX1, suggesting that these genes are involved in the pathogenesis of clefting. In addition, a mutation search in the genes DLX2, MSX1, and TGFB3 was performed in 69 CPO patients and in a subset of the CL/P patients. No common mutations were found in the coding regions of these genes; however, several rare variants of MSX1 and TGFB3 were found that may alter the latters' normal function. These results form the basis for future research, including (a) mutation searches in the MSX1 and TGFB3 genes in Caucasian CL/P patients and (b) extension of the search for MSX1 mutations in CPO patients to the noncoding regions