Nanopipettes as Monitoring Probes for the Single Living Cell: State of the Art and Future Directions in Molecular Biology.

Examining the behavior of a single cell within its natural environment is valuable for understanding both the biological processes that control the function of cells and how injury or disease lead to pathological change of their function. Single-cell analysis can reveal information regarding the causes of genetic changes, and it can contribute to studies on the molecular basis of cell transformation and proliferation. By contrast, whole tissue biopsies can only yield information on a statistical average of several processes occurring in a population of different cells. Electrowetting within a nanopipette provides a nanobiopsy platform for the extraction of cellular material from single living cells. Additionally, functionalized nanopipette sensing probes can differentiate analytes based on their size, shape or charge density, making the technology uniquely suited to sensing changes in single-cell dynamics. In this review, we highlight the potential of nanopipette technology as a non-destructive analytical tool to monitor single living cells, with particular attention to integration into applications in molecular biology

Dirac electron behavior and NMR evidence for topological band inversion in ZrTe5

We report $^{125}$Te NMR measurements of the topological quantum material ZrTe$_5$. Spin-lattice relaxation results, well-explained by a theoretical model of Dirac electron systems, reveal that the topological characteristic of ZrTe$_5$ is $T$-dependent, changing from weak topological insulator to strong topological insulator as temperature increases. Electronic structure calculations confirm this ordering, the reverse of what has been proposed. NMR results demonstrate a gapless Dirac semimetal state occurring at a Lifshitz transition temperature, $T_c=85$ K in our crystals. We demonstrate that the changes in NMR shift at $T_c$ also provide direct evidence of band inversion when the topological phase transition occurs.Comment: 5 pages, 4 figure

Gap-opening transition in Dirac semimetal ZrTe5_5

We apply $^{125}$Te nuclear magnetic resonance (NMR) spectroscopy to investigate the Dirac semimetal ZrTe$_5$. With the NMR magnetic field parallel to the $b$-axis, we observe significant quantum magnetic effects. These include an abrupt drop at 150 K in spin-lattice relaxation rate. This corresponds to a gap-opening transition in the Dirac carriers, likely indicating the onset of excitonic pairing. Below 50 K, we see a more negative shift for the Te$_z$ bridging site indicating the repopulation of Dirac levels with spin polarized carriers at these temperatures. This is the previously reported 3D quantum Hall regime; however, we see no sign of a charge density wave as has been proposed.Comment: 5 pages, 4 figure

Topological nodal line in ZrTe2_2 demonstrated by nuclear magnetic resonance

In this work, we report nuclear magnetic resonance (NMR) combined with density functional theory (DFT) studies of the transition metal dichalcogenide ZrTe$_2$. The measured NMR shift anisotropy reveals a quasi-2D behavior connected to a topological nodal line close to the Fermi level. With the magnetic field perpendicular to the ZrTe$_2$ layers, the measured shift can be well-fitted by a combination of enhanced diamagnetism and spin shift due to high mobility Dirac electrons. The spin-lattice relaxation rates with external field both parallel and perpendicular to the layers at low temperatures match the expected behavior associated with extended orbital hyperfine interaction due to quasi-2D Dirac carriers. In addition, calculated band structures also show clear evidence for the existence of nodal line in ZrTe$_2$ between $\Gamma$ and A. For intermediate temperatures, there is a sharp reduction in spin-lattice relaxation rate which can be explained as due to a reduced lifetime for these carriers, which matches the reported large change in mobility in the same temperature range. Above 200 K, the local orbital contribution starts to dominate in an orbital relaxation mechanism revealing the mixture of atomic functions.Comment: 9 pages, 5 figure

Financing Intercollegiate Athletics in the Southeastern Conference 1970-1979.

Financing intercollegiate athletics has become an ever present issue with the colleges and universities of the National Collegiate Athletic Association. Inflation and other factors have driven the cost of running a college sports program to alarmingly high levels. The literature is full of expressions of concern about the financial future of intercollegiate athletic competition. This study investigated trends in financing intercollegiate athletics among the 10 Southeastern Conference Universities. A two-part survey questionnaire was completed, one part by the athletic director and one by the business manager at each of these institutions. Revenues and expenditures for the fiscal years 1969-1970 through 1978-1979 were recorded, projections for 1979-1980 through 1983-1984 were made utilizing regression analysis, and the opinions of the SEC Athletic Directors were registered concerning financial issues. Revenue and expenditure relationships were analyzed. The findings of this investigation reveal a substantial number of negatiive balances among the actual and projected revenues and expenditures. Only two of the SEC schools had revenues greater than expenditures in every year included in the investigation. Football was the sport which supplied the greatest amount of revenue. Among revenues listed by source ticket sales was the major producer of funds. A trend toward raising money through contributions and donations was indicated by the substantial increases in revenue derived from these sources. Salaries and wages constituted the greatest expenditure item at the end of the period of investigation. Additional major expense categories were: other expenses, grant costs, travel, equipment and maintenance. In the sports categories spending for football was the highest. Inflation and the cost of adding sports to the program were major concerns among Southeastern Conference Athletic Directors. The athletic administrators endorsed more plans to increase revenues than reduce expenditures. The majority of the directors favored abolishing scholarships in non-revenue sports while the major thrust for increased revenues was in the area of contributions and donations. Evidence from this investigation indicated the athletic directors of the Southeastern Conference planned to maintain their competitive positions, particularly in football and basketball, while attempting to generate greater revenues

Attenuation of Na/K-ATPase Mediated Oxidant Amplification with pNaKtide Ameliorates Experimental Uremic Cardiomyopathy

We have previously reported that the sodium potassium adenosine triphosphatase (Na/K-ATPase) can effect the amplification of reactive oxygen species. In this study, we examined whether attenuation of oxidant stress by antagonism of Na/K-ATPase oxidant amplification might ameliorate experimental uremic cardiomyopathy induced by partial nephrectomy (PNx). PNx induced the development of cardiac morphological and biochemical changes consistent with human uremic cardiomyopathy. Both inhibition of Na/K-ATPase oxidant amplification with pNaKtide and induction of heme oxygenase-1 (HO-1) with cobalt protoporphyrin (CoPP) markedly attenuated the development of phenotypical features of uremic cardiomyopathy. In a reversal study, administration of pNaKtide after the induction of uremic cardiomyopathy reversed many of the phenotypical features. Attenuation of Na/K-ATPase oxidant amplification may be a potential strategy for clinical therapy of this disorder

HO-1 Upregulation Attenuates Adipocyte Dysfunction, Obesity, and Isoprostane Levels in Mice Fed High Fructose Diets

Background. Fructose metabolism is an unregulated metabolic pathway and excessive fructose consumption is known to activate ROS.HO-1 is a potent antioxidant gene that plays a key role in decreasing ROS and isoprostanes.We examinedwhether the fructosemediated increase in adipocyte dysfunction involves an increase in isoprostanes and that pharmacological induction ofHO-1would decrease both isoprostane levels and adipogenesis. Methods and Results. We examined the effect of fructose, on adipogenesis in human MSCs in the presence and absence of CoPP, an inducer of HO-1. Fructose increased adipogenesis and the number of large lipid droplets while decreasing the number of small lipid droplets ( \u3c 0.05). Levels of heme and isoprostane in fructose treated MSC-derived adipocytes were increased. CoPP reversed these effects andmarkedly increasedHO-1 and theWnt signaling pathway. Thehigh fructose diet increased heme levels in adipose tissue and increased circulating isoprostane levels ( \u3c 0.05 versus control). Fructose diets decreasedHO-1 and adiponectin levels in adipose tissue. Induction ofHO-1 by CoPP decreased isoprostane synthesis ( \u3c 0.05 versus fructose). Conclusion. Fructose treatment resulted in increased isoprostane production and adipocyte dysfunction, which was reversed by the increased expression of HO-1

Development of NASH in Obese Mice is Confounded by Adipose Tissue Increase in Inflammatory NOV and Oxidative Stress

Aim. Nonalcoholic steatohepatitis (NASH) is the consequence of insulin resistance, fatty acid accumulation, oxidative stress, and lipotoxicity.We hypothesize that an increase in the inflammatory adipokine NOV decreases antioxidant Heme Oxygenase 1 (HO- 1) levels in adipose and hepatic tissue, resulting in the development of NASH in obese mice. Methods. Mice were fed a high fat diet (HFD) and obese animals were administered an HO-1 inducer with or without an inhibitor of HO activity to examine levels of adipose-derived NOV and possible links between increased synthesis of inflammatory adipokines and hepatic pathology. Results. NASH mice displayed decreased HO-1 levels and HO activity, increased levels of hepatic heme, NOV, MMP2, hepcidin, and increased NAS scores and hepatic fibrosis. IncreasedHO-1 levels are associated with a decrease in NOV, improved hepatic NAS score, ameliorated fibrosis, and increases in mitochondrial integrity and insulin receptor phosphorylation. Adipose tissue function is disrupted in obesity as evidenced by an increase in proinflammatory molecules such as NOV and a decrease in adiponectin. Importantly, increased HO-1 levels are associated with a decrease of NOV, increased adiponectin levels, and increased levels of thermogenic and mitochondrial signaling associated genes in adipose tissue. Conclusions.These results suggest that the metabolic abnormalities in NASH are driven by decreased levels of hepatic HO-1 that is associated with an increase in the adipose-derived proinflammatory adipokine NOV in our obese mouse model of NASH. Concurrently, induction of HO-1 provides protection against insulin resistance as seen by increased insulin receptor phosphorylation. Pharmacological increases in HO-1 associated with decreases in NOV may offer a potential therapeutic approach in preventing fibrosis, mitochondrial dysfunction, and the development of NASH

Charge-carrier behavior in Ba-, Sr- and Yb-filled CoSb3_3: NMR and transport studies

We report $^{59}$Co NMR and transport measurements on $n$-type filled skutterudites Ba$_x$Yb$_y$Co$_4$Sb$_{12}$ and $A$$_x$Co$_4$Sb$_{12}$ ($A$= Ba, Sr), promising thermoelectric materials. The results demonstrate consistently that a shallow defect level near the conduction band minimum dominates the electronic behavior, in contrast to the behavior of unfilled CoSb$_3$. To analyze the results, we modeled the defect as having a single peak in the density of states, occupied at low temperatures due to donated charges from filler atoms. We fitted the NMR shifts and spin-lattice relaxation rates allowing for arbitrary carrier densities and degeneracies. The results provide a consistent picture for the Hall data, explaining the temperature dependence of the carrier concentration. Furthermore, without adjusting model parameters, we calculated Seebeck coefficient curves, which also provide good consistency. In agreement with recently reported computational results, it appears that composite native defects induced by the presence of filler atoms can explain this behavior. These results provide a better understanding of the balance of charge carriers, of crucial importance for designing improved thermoelectric materials.Comment: 9 pages, 8 figure