Tenofovir disoproxil fumarate induces peripheral neuropathy and alters inflammation and mitochondrial biogenesis in the brains of mice.

Mounting evidence suggests that antiretroviral therapy (ART) drugs may contribute to the prevalence of HIV-associated neurological dysfunction. The HIV envelope glycoprotein (gp120) is neurotoxic and has been linked to alterations in mitochondrial function and increased inflammatory gene expression, which are common neuropathological findings in HIV+ cases on ART with neurological disorders. Tenofovir disproxil fumarate (TDF) has been shown to affect neurogenesis in brains of mice and mitochondria in neurons. In this study, we hypothesized that TDF contributes to neurotoxicity by modulating mitochondrial biogenesis and inflammatory pathways. TDF administered to wild-type (wt) and GFAP-gp120 transgenic (tg) mice caused peripheral neuropathy, as indicated by nerve conduction slowing and thermal hyperalgesia. Conversely TDF protected gp120-tg mice from cognitive dysfunction. In the brains of wt and gp120-tg mice, TDF decreased expression of mitochondrial transcription factor A (TFAM). However, double immunolabelling revealed that TFAM was reduced in neurons and increased in astroglia in the hippocampi of TDF-treated wt and gp120-tg mice. TDF also increased expression of GFAP and decreased expression of IBA1 in the wt and gp120-tg mice. TDF increased tumor necrosis factor (TNF) α in wt mice. However, TDF reduced interleukin (IL) 1β and TNFα mRNA in gp120-tg mouse brains. Primary human astroglia were exposed to increasing doses of TDF for 24 hours and then analyzed for mitochondrial alterations and inflammatory gene expression. In astroglia, TDF caused a dose-dependent increase in oxygen consumption rate, extracellular acidification rate and spare respiratory capacity, changes consistent with increased metabolism. TDF also reduced IL-1β-mediated increases in IL-1β and TNFα mRNA. These data demonstrate that TDF causes peripheral neuropathy in mice and alterations in inflammatory signaling and mitochondrial activity in the brain

An alarming deterioration of neurological status

This clinical case should make us reflect on the potential dangers of lithium, often too readily prescribed by non expert physicians to elderly, and often poorly compliant, patients. There also needs to be very close monitoring of plasma lithium levels, in addition to paying attention to clinical signs, such as a persistent polyuria or hyperosmolarity, because these could be important early warning signs. It is therefore useful to reiterate that, in case of lithium intoxication with altered neurological status despite improvement blood tests, it is necessary to consider pontine or extra-pontine myelinolysis as a rare but possible complicatio

Looking at the Global Transformations: Why an Integrated Perspective is Still Required

In this article, the authors offer an introduction to the Sophia Global Studies center, its methodology and framework, and offer some reflections on the ways in which this center can respond to the complex issues facing humanity in an increasingly globalized world. They argue that the recent appearance of isolationist trends in various parts of the world only confirms the relevance of this center of global studies

Preliminary study of kaonic deuterium X-rays by the SIDDHARTA experiment at DAFNE

The study of the KbarN system at very low energies plays a key role for the understanding of the strong interaction between hadrons in the strangeness sector. At the DAFNE electron-positron collider of Laboratori Nazionali di Frascati we studied kaonic atoms with Z=1 and Z=2, taking advantage of the low-energy charged kaons from Phi-mesons decaying nearly at rest. The SIDDHARTA experiment used X-ray spectroscopy of the kaonic atoms to determine the transition yields and the strong interaction induced shift and width of the lowest experimentally accessible level (1s for H and D and 2p for He). Shift and width are connected to the real and imaginary part of the scattering length. To disentangle the isospin dependent scattering lengths of the antikaon-nucleon interaction, measurements of Kp and of Kd are needed. We report here on an exploratory deuterium measurement, from which a limit for the yield of the K-series transitions was derived: Y(K_tot)<0.0143 and Y(K_alpha)<0.0039 (CL 90%). Also, the upcoming SIDDHARTA-2 kaonic deuterium experiment is introduced.Comment: Accepted by Nuclear Physics

Effect of Starvation on the Feeding Activity Toward Sugary Food in the Ant Tapinoma nigerrimum (Nylander, 1856)

In this study, we investigated the effect of starvation on the feeding behavior of the ant Tapinoma nigerrimum. In particular, we tested the response of ants that had experienced different levels of starvation, toward sucrose solutions of increasing concentration. As expected, starved ants promptly reacted to the sugary food sources with a higher rate of acceptance as compared to satiated ones. Acceptance increased both with sugar concentration and the length of the starvation period. However, a consistent fraction of the starved ants did not feed on the solutions, suggesting that starvation had different effects on different individuals, even though they all had food ad libitum before the beginning of the tests, had comparable body sizes, and were collected from the same trail. The different acceptance of sugary solutions may be, therefore, merely because ants fed on the experimental food at different times. Interestingly, in all the experimental groups, ants appeared to satiate quickly, irrespective of the solution tested and fasting duration. This would suggest that the rate of ingestion was independent of these factors, a result partially at odds with previous studies. This study is one of the few ones dealing with the behavioral response of an ant species to a famine event

Dialogare: compendio di biologia

The compendium collects the basic themes of biology in a very simplified form, ideally following the programmatic criteria of secondary school. The didactic program is articulated starting from the molecules that make up living organisms to end at the theoretical basis of ecology and environmental protection. All the main topics of life sciences such as genetics, anatomy and the evolution of organisms are addressed, always trying to convey the heart of the theoretical concept through a simple but adequate terminology. The goal is to offer a first look at the basis of biology to those who intend to carry out an in-depth study of this subject, which is extremely fascinating but also decidedly complex, vast and multifaceted

The Effect of the Introduced Red Wood Ant Formica paralugubris on the Frequency of Ant Nests and First Plesiobiotic Association between Myrmica ruginodis (Nylander, 1846) and Lasius flavus (Fabricius, 1782)

Red wood ants are ecologically dominant species that affect the composition of the invertebrate community. In the past century, one of these species, Formica paralugubris (Seifert 1996), was introduced outside its native area (the Alps), in the Apennines (Italy). Here we investigated the effect of the presence of an introduced population of F. paralugubris on the frequency of nests of other ant species in Abetone, Central Apennines. Ant nests were found only in the area unoccupied by F. paralugubris. In this area, we also found one pleometrotic association between queens of Lasius flavus (Fabricius, 1782) and two plesiobiotic associations, one between Formica fusca (Linnaeus, 1758) and L. flavus and the other one between Myrmica ruginodis (Nylander, 1846) and L. flavus. This latter is the first plesiobiotic relationship reported between these two species, the second reported for M. ruginodis and the 10th for L. flavus. Additionally, this is the first plesiobiotic association reported for the Mediterranean region and Southern Europe