ERRATUM: Effects of Loading on the Biomechanical Behavior of Molars of Homo,Pan, and Pongo. Am J Phys Anthropol 109:211–227.

ERRATUM: Macho GA and Spears IR. 1999. Effects of Loading on the Biomechanical Behavior of Molars of Homo, Pan, and Pongo. Am J Phys Anthropol 109:211–227. The correct title of the article is given above. The word “biochemical” should be read as “biomechanical.”     

Specific Depletion of Ly6Chi Inflammatory Monocytes Prevents Immunopathology in Experimental Cerebral Malaria

Plasmodium berghei ANKA (PbA) infection of C57BL/6 mice leads to experimental cerebral malaria (ECM) that is commonly associated with serious T cell mediated damage. In other parasitic infection models, inflammatory monocytes have been shown to regulate Th1 responses but their role in ECM remains poorly defined, whereas neutrophils are reported to contribute to ECM immune pathology. Making use of the recent development of specific monoclonal antibodies (mAb), we depleted in vivo Ly6C^hi inflammatory monocytes (by anti-CCR2), Ly6G⁺ neutrophils (by anti-Ly6G) or both cell types (by anti-Gr1) during infection with Ovalbumin-transgenic PbA parasites (PbTg). Notably, the application of anti-Gr1 or anti-CCR2 but not anti-Ly6G antibodies into PbTg-infected mice prevented ECM development. In addition, depletion of Ly6C^hi inflammatory monocytes but not neutrophils led to decreased IFNγ levels and IFNγ⁺CD8⁺ T effector cells in the brain. Importantly, anti-CCR2 mAb injection did not prevent the generation of PbTg-specific T cell responses in the periphery, whereas anti-Gr1 mAb injection strongly diminished T cell frequencies and CTL responses. In conclusion, the specific depletion of Ly6C^hi inflammatory monocytes attenuated brain inflammation and immune cell recruitment to the CNS, which prevented ECM following Plasmodium infection, pointing out a substantial role of Ly6C⁺ monocytes in ECM inflammatory processes.     

Pathogen Transmission from Humans to Great Apes is a Growing Threat to Primate Conservation

All six great ape species are listed as endangered or critically endangered by the IUCN and experiencing decreasing population trends. One of the threats to these non-human primates is the transmission of pathogens from humans. We conducted a literature review on occurrences of pathogen transmission from humans to great apes to highlight this often underappreciated issue. In total, we found 33 individual occurrences of probable or confirmed pathogen transmission from humans to great apes: 23 involved both pathogen and disease transmission, 7 pathogen transmission only, 2 positive antibody titers to zoonotic pathogens, and 1 pathogen transmission with probable disease. Great ape populations were categorized into captive, semi-free-living, and free-living conditions. The majority of occurrences involved chimpanzees (Pan troglodytes) (n = 23) or mountain gorillas (Gorilla beringei beringei) (n = 8). These findings have implications for conservation efforts and management of endangered great ape populations. Future efforts should focus on monitoring and addressing zoonotic pathogen and disease transmission between humans, great ape species, and other taxa to ensure the health of humans, wild and domestic animals, and the ecosystems we share.     

An apolipoprotein E-derived peptide mediates uptake of sterically stabilized liposomes into brain capillary endothelial cells

A promising strategy to solve the problems of insufficient membrane penetration of drugs and low target specificity is the localization of targeting and uptake-facilitating ligands on the surface of drug-carrier systems. This study investigated the role of a peptide derived from the LDL receptor (LDLr)-binding domain of apolipoprotein E (apoE) in initiating endocytosis in brain capillary endothelial cells. The highly cationic tandem dimer of apoE residues (141-150) was coupled covalently onto poly(ethylene glycol)-derivatized liposomes. Membrane binding and cellular uptake was monitored qualitatively by confocal-laser-scanning microscopy as well as quantitatively using a fluorescence assay. The peptide mediated an efficient, energy-dependent translocation of liposomes across the membrane of brain capillary endothelial cells. Liposomes without surface-located peptides displayed neither membrane accumulation nor cellular uptake. Low peptide affinity to LDLr and internalization of the complex into fibroblasts with up- and down-regulated receptor expression levels, as well as complex translocation into cells incubated with an antibody against the LDLr, pointed to a dominating role of an LDLr-independent transport route. Enzymatic digestion of heparan sulfate proteoglycan (HSPG) with heparinase I and addition of heparin and poly-l-lysin as competitors of HSPG and HSPG ligands, respectively, resulted in a significant loss in liposome internalization. The results suggested that HSPG played a major role in the apoE-peptide-mediated uptake of liposomes into endothelial cells of brain microvessels.     

Spatial Distribution and Fruiting Phenology of Protium heptaphyllum (Burseraceae) Determine the Design of the Underground Foraging System of Atta sexdens L. (Hymenoptera: Formicidae)

Leaf-cutting ants have long been recognized to forage via complex trail systems but the nature and the ecological drivers of the different foraging strategies adopted remain a key topic. Here, we described the spatiotemporal use of belowground foraging galleries by Atta sexdens L. in the Brazilian Atlantic forest, and examined the adaptive advantages of this foraging strategy. Protium heptaphyllum adult trees (DBH?>?10?cm), seed/seedling clumps and ant gallery entrances were mapped across two 1-ha plots during two consecutive fruiting seasons (2002 and 2004). We recorded 75 ca. 40?cm deep gallery entrances beneath 26 P. heptaphyllum trees at nest distances ranging from 14 to 57?m. Furthermore, gallery abundance and galleries associated with seed/seedling clumps correlated positively with P. heptaphyllum density. Our results indicate that A. sexdens was able to set a permanent system of underground galleries targeting P. heptaphyllum trees and their seeds on the ground. Such network of galleries was spatially arranged according to both the spatial distribution and abundance of P. heptaphyllum trees in a way that most gallery entrances were disposed beneath or in close periphery of P. heptaphyllum crowns. Our findings suggest that underground trail systems shaped by fruit resources represent a foraging strategy clearly more common than existing literature on the subject would suggest. In addition, it reinforces the notion that the spatiotemporal availability of resources combined with predation risk largely influence trail configurations as well as overall foraging strategies adopted by leaf-cutting ants.     

Autophagosome-independent essential function for the autophagy protein Atg5 in cellular immunity to intracellular pathogens

The physiologic importance of autophagy proteins for control of mammalian bacterial and parasitic infection in vivo is unknown. Using mice with granulocyte- and macrophage-specific deletion of the essential autophagy protein Atg5, we show that Atg5 is required for in vivo resistance to the intracellular pathogens Listeria monocytogenes and Toxoplasma gondii. In primary macrophages, Atg5 was required for interferongamma (IFN-gamma)/LPS-induced damage to the T. gondii parasitophorous vacuole membrane and parasite clearance. While we did not detect classical hallmarks of autophagy, such as autophagosomes enveloping T. gondii, Atg5 was required for recruitment of IFN-gamma-inducible p47 GTPase IIGP1 (Irga6) to the vacuole membrane, an event that mediates IFN-gamma-mediated clearance of T. gondii. This work shows that Atg5 expression in phagocytic cells is essential for cellular immunity to intracellular pathogens in vivo, and that an autophagy protein can participate in immunity and intracellular killing of pathogens via autophagosome-independent processes such as GTPase trafficking.     

Viruses in sanctuary chimpanzees across Africa

Infectious disease is a major concern for both wild and captive primate populations. Primate sanctuaries in Africa provide critical protection to thousands of wild-born, orphan primates confiscated from the bushmeat and pet trades. However, uncertainty about the infectious agents these individuals potentially harbor has important implications for their individual care and long-term conservation strategies. We used metagenomic next-generation sequencing to identify viruses in blood samples from chimpanzees (Pan troglodytes) in three sanctuaries in West, Central, and East Africa. Our goal was to evaluate whether viruses of human origin or other “atypical” or unknown viruses might infect these chimpanzees. We identified viruses from eight families: Anelloviridae, Flaviviridae, Genomoviridae, Hepadnaviridae, Parvoviridae, Picobirnaviridae, Picornaviridae, and Rhabdoviridae. The majority (15/26) of viruses identified were members of the family Anelloviridae and represent the genera Alphatorquevirus (torque teno viruses) and Betatorquevirus (torque teno mini viruses), which are common in chimpanzees and apathogenic. Of the remaining 11 viruses, 9 were typical constituents of the chimpanzee virome that have been identified in previous studies and are also thought to be apathogenic. One virus, a novel tibrovirus (Rhabdoviridae: Tibrovirus) is related to Bas-Congo virus, which was originally thought to be a human pathogen but is currently thought to be apathogenic, incidental, and vector-borne. The only virus associated with disease was rhinovirus C (Picornaviridae: Enterovirus) infecting one chimpanzee subsequent to an outbreak of respiratory illness at that sanctuary. Our results suggest that the blood-borne virome of African sanctuary chimpanzees does not differ appreciably from that of their wild counterparts, and that persistent infection with exogenous viruses may be less common than often assumed.