The Transcriptional Regulatory Network of Mycobacterium tuberculosis

Under the perspectives of network science and systems biology, the characterization of transcriptional regulatory (TR) networks beyond the context of model organisms offers a versatile tool whose potential remains yet mainly unexplored. In this work, we present an updated version of the TR network of Mycobacterium tuberculosis (M.tb), which incorporates newly characterized transcriptional regulations coming from 31 recent, different experimental works available in the literature. As a result of the incorporation of these data, the new network doubles the size of previous data collections, incorporating more than a third of the entire genome of the bacterium. We also present an exhaustive topological analysis of the new assembled network, focusing on the statistical characterization of motifs significances and the comparison with other model organisms. The expanded M.tb transcriptional regulatory network, considering its volume and completeness, constitutes an important resource for diverse tasks such as dynamic modeling of gene expression and signaling processes, computational reliability determination or protein function prediction, being the latter of particular relevance, given that the function of only a small percent of the proteins of M.tb is known

New fossil remains of Homo naledi from the Lesedi Chamber, South Africa

The Rising Star cave system has produced abundant fossil hominin remains within the Dinaledi Chamber, representing a minimum of 15 individuals attributed to Homo naledi. Further exploration led to the discovery of hominin material, now comprising 131 hominin specimens, within a second chamber, the Lesedi Chamber. The Lesedi Chamber is far separated from the Dinaledi Chamber within the Rising Star cave system, and represents a second depositional context for hominin remains. In each of three collection areas within the Lesedi Chamber, diagnostic skeletal material allows a clear attribution to H. naledi. Both adult and immature material is present. The hominin remains represent at least three individuals based upon duplication of elements, but more individuals are likely present based upon the spatial context. The most significant specimen is the near-complete cranium of a large individual, designated LES1, with an endocranial volume of approximately 610 ml and associated postcranial remains. The Lesedi Chamber skeletal sample extends our knowledge of the morphology and variation of H. naledi, and evidence of H. naledi from both recovery localities shows a consistent pattern of differentiation from other hominin species

Upregulation of Cellular Bcl-2 by the KSHV Encoded RTA Promotes Virion Production

Apoptosis of virus infected cells can restrict or dampen full blown virus propagation and this can serve as a protective mechanism against virus infection. Consequently, viruses can also delay programmed cell death by enhancing the expression of anti-apoptotic proteins. Human Bcl-2 is expressed on the surface of the mitochondrial membrane and functions as the regulator of the delicate balance between cell survival and apoptosis. In this report, we showed that the replication and transcription activator (RTA) encoded by KSHV ORF 50, a key regulator for KSHV reactivation from latent to lytic infection, upregulates the mRNA and protein levels of Bcl-2 in 293 cells, and TPA-induced KSHV-infected cells. Further analysis revealed that upregulation of the cellular Bcl-2 promoter by RTA is dose-dependent and acts through targeting of the CCN9GG motifs within the Bcl-2 promoter. The Bcl-2 P2 but not the P1 promoter is primarily responsive to RTA. The results of ChIP confirmed the direct interaction of RTA protein with the CCN9GG motifs. Knockdown of cellular Bcl-2 by lentivirus-delivered small hairpin RNA (shRNA) resulted in increased cell apoptosis and decreased virion production in KSHV-infected cells. These findings provide an insight into another mechanism by which KSHV utilizes the intrinsic apoptosis signaling pathways for prolonging the survival of lytically infected host cells to allow for maximum production of virus progeny

Case studies of speleogenesis in the Cradle Of Humankind UNESCO world heritage site and the West Rand expanse, South Africa : tectonic controls and their palaeoproterozoic components

Abstract: This study concerns itself with a comparison of tectonic structural control components for speleogenic propagation in the Cradle of Humankind UNESCO world heritage site 40 km NW of Johannesburg, and in the Far West Rand. From the Cradle of Humankind area, the Rising Star system situated at S26o 00.951′ E27o 44.071′ and Bats cave at S26o 02.008′; E27o 44.089′ were selected as they show the typical collective morphology and structural overprint of the majority of caves found in the area-showing cave genesis within this region to have been predominantly influenced by lithological, layer parallel controls interacting with crosscutting fracture systems reflecting an NW to SE directed extensional far-field stress. Armageddon Pot situated at 26o 23.517′ E27o 43.562′ in the vicinity of Westonaria, taken as an example of speleogenesis in the Far West Rand, is a massively developed linear cavity measuring ±2600 m in explored length and ±257m in depth. Its cave entrance is located at the bottom of a 50 m deep sinkhole that formed in the 1990’s due to stoping, gradually weakening the roof until it was structurally compromised. Armageddon Pot is situated along the southern margins of the Panvlakte/Witpoortjie horst domain. Its chief initiating structural control is a normal fault striking east to west and dipping at ±75o north to south. This structure appears clearly linked with the broader structural characteristics of the Panvlakte/Witpoortjie horst block domain (a succession of elevated crustal blocks of Witwatersrand Supergroup units), that in turn has a direct causal relationship with deep-seated Witwatersrand tectonics. This normal fault, as Armageddon’s chief linear structural control, is transverse (crossed) by older Pre-genetic (sub-horizontal) offset shear zones and numerous interleaved micro-shears. Along these offset shear zones, massive cataclasite bodies occur that enclose compressional as well as extensional structures. This has not been observed before in caves within the CoH...M.Sc. (Geology