Rearrangement of the Keratin Cytoskeleton after Combined Treatment with Microtubule and Microfilament Inhibitors

In addition to containing microtubule and microfilament systems, vertebrate epithelial cells contain an elaborate keratin intermediate-filament cytoskeleton. Little is known about its structural organization or function. Using indirect immunofluorescence microscopy with an antikeratin antiserum probe, we found that destabilization of microtubules and microfilaments with cytostatic drugs induces significant alterations in the cytoskeletal organizationof keratin filaments in HeLa and fetal mouse epidermal cells. Keratin filament organizationwas observed to undergo a rapid (1-2 h) transition from a uniform distribution to an open lattice of keratin fibers stabilized by membrane-associated focal centers . Since addition of any one drug alone did not elicit significant organizational change in the keratin cytoskeleton,we suggest that microfilaments and microtubules have a combined role in maintaining the arrangement of keratin in these cells. Vimentin filaments, the only other intermediate sized filaments found in HeLa cells, did not co-distribute with keratin in untreated or drug treated cells. These findings offer a new way to approach the study of the dynamics and functional roles of the keratin cytoskeleton in epithelial cells

Interactive effects of modified tall oil and fat source on growth performance and carcass characteristics of finishing barrows and gilts

A total of 144 pigs (initially 90 lb) was used to determine the interactive effects of fat source: none (NF), 6% choice white grease (CWG), or 6% poultry fat (PF); modified tall oil (MTO, 0 or .5%); and sex (barrows or gilts) on growth performance and carcass characteristics. Regardless of fat source, MTO improved belly firmness but did not influence growth performance. Gilts were leaner, had increased loin muscle area, and had softer bellies compared to barrows. Added fat decreased ADFI and improved F/G. Pigs fed PF had the best F/G, but the fattest carcasses and softest loins and bellies.; Swine Day, Manhattan, KS, November 18, 199

Eclipse-Ballooning 2017: The U of MN – Twin Cities Experience

The stratospheric ballooning team at the U of MN – Twin Cities started working on eclipse-ballooning in the fall of 2013, even before the Montana Space Grant announced their plan to organize a national Eclipse Ballooning Project. Our team promptly signed up to assist their effort, and have been heavily involved ever since. This presentation will discuss our eclipse-ballooning efforts and progress over the past 4 years. Our experiences include experimenting with a GoPro-based video-telemetry system (which ultimately was not as successful as Montana’s Raspberry-Pi-based system), adopting (then helping test, modify, and teach other teams to learn to use) the Montana telemetry system, practicing with up-range and down-range ground station placement, developing and testing passive anti-rotation devices and active camera-pointing devices to improve video quality, landing two eclipse-telemetry systems in Minnesota lakes one week before the eclipse (ouch!), flying five balloon stacks during the eclipse from near Grand Island, NE, and organizing/hosting AHAC 2017. We will also discuss ways in which we have already begun to use the telemetry equipment for non-eclipse balloon missions. The eclipse project has greatly expanded our HAB network and ballooning capabilities in multiple different directions, and will continue to strongly influence our stratospheric ballooning program for years to come

Effects of microbiota-directed foods in gnotobiotic animals and undernourished children

To examine the contributions of impaired gut microbial community development to childhood undernutrition, we combined metabolomic and proteomic analyses of plasma samples with metagenomic analyses of fecal samples to characterize the biological state of Bangladeshi children with severe acute malnutrition (SAM) as they transitioned, after standard treatment, to moderate acute malnutrition (MAM) with persistent microbiota immaturity. Host and microbial effects of microbiota-directed complementary food (MDCF) prototypes targeting weaning-phase bacterial taxa underrepresented in SAM and MAM microbiota were characterized in gnotobiotic mice and gnotobiotic piglets colonized with age- and growth-discriminatory bacteria. A randomized, double-blind controlled feeding study identified a lead MDCF that changes the abundances of targeted bacteria and increases plasma biomarkers and mediators of growth, bone formation, neurodevelopment, and immune function in children with MAM

Bloodlines: mammals, leeches, and conservation in southern Asia

Southern Asia is a biodiversity hotspot both for terrestrial mammals and for leeches. Many small-mammal groups are under-studied in this region, while other mammals are of known conservation concern. In addition to standard methods for surveying mammals, it has recently been demonstrated that residual bloodmeals within leeches can be sequenced to find mammals in a given area. While these invertebrate-parasite-derived DNA (iDNA) methods are promising, most of the leech species utilized for this type of survey remain unevaluated, notwithstanding that their diversity varies substantially. Here we examine approximately 750 individual leech specimens in the genus Haemadipsa across a large range in southern Asia (Bangladesh, Cambodia, and China), specifically reviewing the diversity of mammals they feed on and their own genetic structuring. Leeches were found to feed on a considerable variety of mammals, corroborating prior studies. Additionally, leeches were found to have fed both on bats and on birds, neither of which has previously been recorded with this method. The genetic structuring of the leeches themselves revealed 15 distinct clades of which only two precisely corresponded to previously characterized species, indicating that much work is needed to finalize classifications in this genus. Most importantly, with regards to mammal conservation, leeches in these clades appear to feed on a broad range of mammals

The complete genome sequence of a Neandertal from the Altai Mountains

We present a high-quality genome sequence of a Neandertal woman from Siberia. We show that her parents were related at the level of half siblings and that mating among close relatives was common among her recent ancestors. We also sequenced the genome of a Neandertal from the Caucasus to low coverage. An analysis of the relationships and population history of available archaic genomes and 25 present-day human genomes shows that several gene flow events occurred among Neandertals, Denisovans and early modern humans, possibly including gene flow into Denisovans from an unknown archaic group. Thus, interbreeding, albeit of low magnitude, occurred among many hominin groups in the Late Pleistocene. In addition, the high quality Neandertal genome allows us to establish a definitive list of substitutions that became fixed in modern humans after their separation from the ancestors of Neandertals and Denisovans

Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.

GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10(-43)) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology

MitoQ improves mitochondrial dysfunction in heart failure induced by pressure overload.

Heart failure remains a major public-health problem with an increase in the number of patients worsening from this disease. Despite current medical therapy, the condition still has a poor prognosis. Heart failure is complex but mitochondrial dysfunction seems to be an important target to improve cardiac function directly. Our goal was to analyze the effects of MitoQ (100 µM in drinking water) on the development and progression of heart failure induced by pressure overload after 14 weeks. The main findings are that pressure overload-induced heart failure in rats decreased cardiac function in vivo that was not altered by MitoQ. However, we observed a reduction in right ventricular hypertrophy and lung congestion in heart failure animals treated with MitoQ. Heart failure also decreased total mitochondrial protein content, mitochondrial membrane potential in the intermyofibrillar mitochondria. MitoQ restored membrane potential in IFM but did not restore mitochondrial protein content. These alterations are associated with the impairment of basal and stimulated mitochondrial respiration in IFM and SSM induced by heart failure. Moreover, MitoQ restored mitochondrial respiration in heart failure induced by pressure overload. We also detected higher levels of hydrogen peroxide production in heart failure and MitoQ restored the increase in ROS production. MitoQ was also able to improve mitochondrial calcium retention capacity, mainly in the SSM whereas in the IFM we observed a small alteration. In summary, MitoQ improves mitochondrial dysfunction in heart failure induced by pressure overload, by decreasing hydrogen peroxide formation, improving mitochondrial respiration and improving mPTP opening

The guinea pig ileum lacks the direct, high-potency, M2-muscarinic, contractile mechanism characteristic of the mouse ileum

We explored whether the M2 muscarinic receptor in the guinea pig ileum elicits a highly potent, direct-contractile response, like that from the M3 muscarinic receptor knockout mouse. First, we characterized the irreversible receptor-blocking activity of 4-DAMP mustard in ileum from muscarinic receptor knockout mice to verify its M3 selectivity. Then, we used 4-DAMP mustard to inactivate M3 responses in the guinea pig ileum to attempt to reveal direct, M2 receptor-mediated contractions. The muscarinic agonist, oxotremorine-M, elicited potent contractions in ileum from wild-type, M2 receptor knockout, and M3 receptor knockout mice characterized by negative log EC50 (pEC50) values ± SEM of 6.75 ± 0.03, 6.26 ± 0.05, and 6.99 ± 0.08, respectively. The corresponding Emax values in wild-type and M2 receptor knockout mice were approximately the same, but that in the M3 receptor knockout mouse was only 36% of wild type. Following 4-DAMP mustard treatment, the concentration–response curve of oxotremorine-M in wild-type ileum resembled that of the M3 knockout mouse in terms of its pEC50, Emax, and inhibition by selective muscarinic antagonists. Thus, 4-DAMP mustard treatment appears to inactivate M3 responses selectively and renders the muscarinic contractile behavior of the wild-type ileum similar to that of the M3 knockout mouse. Following 4-DAMP mustard treatment, the contractile response of the guinea pig ileum to oxotremorine-M exhibited low potency and a competitive-antagonism profile consistent with an M3 response. The guinea pig ileum, therefore, lacks a direct, highly potent, M2-contractile component but may have a direct, lower potency M2 component