In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes

The reprogramming of adult cells into pluripotent cells or directly into alternative adult cell types holds great promise for regenerative medicine. We reported previously that cardiac fibroblasts,which represent 50%of the cells in the mammalian heart, can be directly reprogrammed to adult cardiomyocyte-like cells in vitro by the addition of Gata4, Mef2c and Tbx5 (GMT). Here we use genetic lineage tracing to show that resident non-myocytes in the murine heart can be reprogrammed into cardiomyocyte-like cells in vivo by local delivery of GMT after coronary ligation. Induced cardiomyocytes became binucleate, assembled sarcomeres and had cardiomyocyte-like gene expression. Analysis of single cells revealed ventricular cardiomyocyte-like action potentials, beating upon electrical stimulation, and evidence of electrical coupling. In vivo delivery of GMT decreased infarct size and modestly attenuated cardiac dysfunction up to 3 months after coronary ligation. Delivery of the pro-angiogenic and fibroblast-activating peptide, thymosin b4, along with GMT, resulted in further improvements in scar area and cardiac function. These findings demonstrate that cardiac fibroblasts can be reprogrammed into cardiomyocyte-like cells in their native environment for potential regenerative purposes.     

Biodiversity loss and its impact on humanity

The most unique feature of Earth is the existence of life, and the most extraordinary feature of life is its diversity. Approximately 9 million types of plants, animals, protists and fungi inhabit the Earth. So, too, do 7 billion people. Two decades ago, at the first Earth Summit, the vast majority of the world's nations declared that human actions were dismantling the Earth's ecosystems, eliminating genes, species and biological traits at an alarming rate. This observation led to the question of how such loss of biological diversity will alter the functioning of ecosystems and their ability to provide society with the goods and services needed to prosper.     

Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein

Macrophages and dendritic cells have key roles in viral infections, providing virus reservoirs that frequently resist antiviral therapies and linking innate virus detection to antiviral adaptive immune responses. Human immunodeficiency virus 1 (HIV-1) fails to transduce dendritic cells and has a reduced ability to transduce macrophages, due to an as yet uncharacterized mechanism that inhibits infection by interfering with efficient synthesis of viral complementary DNA. In contrast, HIV-2 and related simian immunodeficiency viruses (SIVsm/mac) transduce myeloid cells efficiently owing to their virion-associated Vpx accessory proteins, which counteract the restrictive mechanism. Here we show that the inhibition of HIV-1 infection in macrophages involves the cellular SAM domain HD domain-containing protein 1 (SAMHD1). Vpx relieves the inhibition of lentivirus infection in macrophages by loading SAMHD1 onto the CRL4(DCAF1) E3 ubiquitin ligase, leading to highly efficient proteasome-dependent degradation of the protein. Mutations in SAMHD1 cause Aicardi-Goutières syndrome, a disease that produces a phenotype that mimics the effects of a congenital viral infection. Failure to dispose of endogenous nucleic acid debris in Aicardi-Goutières syndrome results in inappropriate triggering of innate immune responses via cytosolic nucleic acids sensors. Thus, our findings show that macrophages are defended from HIV-1 infection by a mechanism that prevents an unwanted interferon response triggered by self nucleic acids, and uncover an intricate relationship between innate immune mechanisms that control response to self and to retroviral pathogens.     

Changes induced by manganese in fish testis

Summary Exposure ofColisa fasciatus, a freshwater teleost, to 2500 mg/l manganese sulphate for 90 h caused decreased spermatogenic activity and hemorrhage in the testes.     

Effect of mycotoxin (T-2 toxin) on catecholamine and Na+, K+-ATPase levels in rat epididymis

The effect of mycotoxin (T-2 toxin) on catecholamines and Na+, K+-ATPase activities in rat epididymis has been evaluated. Dopamine and norepinephrine levels were significantly elevated in the caput and corpus regions whereas their levels remained unchanged in the caudal part of the epididymis. Na+, K+-ATPase activity was significantly increased in all the three regions of rat epididymis as a result of the toxin treatment. These changes may suggest an adverse effect on epididymal functions in rats.     

Secretion of chitinase byAphanocladium album,a hyperparasite of wheat rust

Summary Aphanocladium album, a hyperparasite of wheat rust,Puccinia graminis vartritici, secretes chitinase when grown on a chitin-containing medium. This enzyme was purified and shown to attack the mycelium of the parasitized rust fungus.Supported, in part, by a grant from the Naef-Roth-Foundation.     

A new neurosecretory system in fish,located in the gill region

Summary A peculiar neurosecretory system is reported in 6 teleost species;Clarias batrachus, Heteropneustes fossilis, Mystus seenghala, Ompak pabda, Glassogobius giuris andNotopterus notopterus. It is located in the gill region close to the pseudobranch or to the carotid labyrinth. The neurosecretory cells have been identified using stains specific for neurosecretion. The results are discussed in the light of the association of the neurosecretory system with the pseudobranch or the carotid labyrinth, and the airbreathing habit of these fishes.We are grateful to Prof. U.S. Srivastava for providing laboratory facilities and for encouragement. The work was financially supported by U.G.C. Research Project grant awarded to C.B.L.S., which is thankfully acknowledged. Thanks are due to M. Seal and Amarlata for technical help rendered.     

A note on the relevancy of behaviour of solutions of theLane-Emden equation in the immediate neighbourhood of the origin

Zusammenfassung Untersuchungen über Lösungen derLane-Emden-Gleichung in der Nähe des kritischen Punktes.