The Hemagglutinin of Bat-Associated Influenza Viruses Is Activated by TMPRSS2 for pH-Dependent Entry into Bat but Not Human Cells

New World bats have recently been discovered to harbor influenza A virus (FLUAV)-related viruses, termed bat-associated influenza A-like viruses (batFLUAV). The internal proteins of batFLUAV are functional in mammalian cells. In contrast, no biological functionality could be demonstrated for the surface proteins, hemagglutinin (HA)-like (HAL) and neuraminidase (NA)-like (NAL), and these proteins need to be replaced by their human counterparts to allow spread of batFLUAV in human cells. Here, we employed rhabdoviral vectors to study the role of HAL and NAL in viral entry. Vectors pseudotyped with batFLUAV-HAL and -NAL were able to enter bat cells but not cells from other mammalian species. Host cell entry was mediated by HAL and was dependent on prior proteolytic activation of HAL and endosomal low pH. In contrast, sialic acids were dispensable for HAL-driven entry. Finally, the type II transmembrane serine protease TMPRSS2 was able to activate HAL for cell entry indicating that batFLUAV can utilize human proteases for HAL activation. Collectively, these results identify viral and cellular factors governing host cell entry driven by batFLUAV surface proteins. They suggest that the absence of a functional receptor precludes entry of batFLUAV into human cells while other prerequisites for entry, HAL activation and protonation, are met in target cells of human origin.     

The origin of ovarian neuropeptide Y (NPY)-immunoreactive nerve fibres from the inferior mesenteric ganglion in the pig

Summary Applying a double-immunofluorescence technique, the porcine ovary is demonstrated to receive two populations of NPY-immunoreactive nerve fibres originating from the inferior mesenteric ganglion: one with colocalized tyrosine hydroxylase and supplying predominantly the ovarian vasculature, and a second, solely NPY-immunoreactive and almost exclusively associated with growing follicles. A third group of tyrosine hydroxylase-and dopamine--hydroxylase-positive, but NPY-negative nerve fibres is associated with ovarian blood vessels and, to a minor extent, with ovarian follicles. As revealed by retrograde tracing, the vast majority of postganglionic neurons projecting to the ovary is located in a discrete area of the ganglion, suggesting a somatotopic organization of the porcine inferior mesenteric ganglion. Moreover, the finding indicate that three subpopulations of postganglionic sympathetic neurons with different chemical codes supply different target components of the porcine ovary. The physiological relevance of the described neurons in the nervous control of ovarian functions remains to be elucidated.A portion of these results has been presented in abstract form (Majewski et al. 1991)     

ADP-Ribosylation of Brain Neuronal Proteins Is Altered by In Vitro and In Vivo Exposure to Inorganic Mercury

Abstract: ADP-ribosylation is an essential process in the metabolism of brain neuronal proteins, including the regulation of assembly and disassembly of biological polymers. Here, we examine the effect of HgCl₂ exposure on the ADP-ribosylation of tubulin and actin, both cytoskeletal proteins also found in neurons, and B-50/43-kDa growth-associated protein (B-50/GAP-43), a neuronal tissue-specific phosphoprotein. In rats we demonstrate, with both in vitro and in vivo experiments, that HgCl₂ markedly inhibits the ADP-ribosylation of tubulin and actin. This is direct quantitative evidence that HgCl₂, a toxic xenobiotic, alters specific neurochemical reactions involved in maintaining brain neuron structure.     

The Ontogeny of Vocal Sequences: Insights from a Newborn Wild Chimpanzee (Pan troglodytes schweinfurthii)

International Journal of Primatology - Observations of early vocal behaviours in non-human primates (hereafter primates) are important for direct comparisons between human and primate vocal...     

Furrows and dermal ridges of the hand in patients with alcohol embryopathy

Summary Palmar creases and dermal ridge patterns of 34 patients with alcohol embryopathy are compared with 470 healthy individuals. In alcohol embryopathy several typical deviations were noted. Palmar Creases. The interdigital part of the distal palmar crease is generally sharply bent, the proximal transverse crease is hypoplastic or missing, the thenar crease is commonly well marked. Simian creases and bridged palmar creases are more common in patients with alcohol embryopathy than in healthy individuals. Ridge Patterns of the Palm. The main line D coming from triradius d in patients with alcohol embryopathy mostly shows a low type of ending in the fourth interdigital area; in this area loops are twice as common as in healthy individuals. Patterns of the Fingertips. No deviations were noted in the distribution of whorls and loops, but virtually no arches were observed in patients with alcohol embryopathy. These anomalies suggest embryonic damage in the twelvth week of gestation.     

Monocyte-produced prostaglandin induces Fcγ receptor expression on human T cells

Incubation of human T cells for 18 hr with prostaglandin E₂ (PGE₂ 3 × 10^?6M) causes a slight but significant increase in the percentage of Tγ cells and a reduction in Tμ cells. When PGE was added to “non-Tγ” cells, the increase in the percentage of Tγ cells was more marked (from 1.5% Tγ without PGE to 11% Tγ with PGE₂, P < 0.001). Supernates from cultures of human monocytes also caused an increase in Tγ cells (10% Tγ without supernate to 18% with supernate, P < 0.01), and this increase was blocked if the monocytes were cultured with indomethacin, a prostaglandin synthetase inhibitor (9% Tγ cells). Thus, monocytes may regulate Fcγ receptors on T cells via PGE₂ production.     

Chemostat-cultivated Escherichia coli at high dilution rate: multiple steady states and drift

The representation of metabolic network reaction kinetics in a scaled, polynomial form can allow for the prediction of multiple steady states. The polynomial formalism is used to study chemostat-cultured Escherichia coli which has been observed to exhibit two multiple steady states under ammonium ion-limited growth conditions: a high cell density-low ammonium ion concentration steady state and a low cell density-high ammonium ion concentration steady state. Additionally, the low-cell-density steady state has been observed to drift to the high-cell-density steady state. Inspection of the steady-state rate expressions for the ammonium ion transport/assimilation network (in polynomial form) suggests that at low ammonium ion concentrations, two steady states are possible. One corresponds to heavy use of the glutamine synthetase-glutamate synthase (GLNS-GS) branch and the second to heavy use of the glutamate dehydrogenase (GDH) branch. Realization of the predicted intracellular steady states is also found to be dependent on the parameters of the transport process. Moreover, the two steady states differ in where their energy intensity lies. To explain the drift, GLNS, which is inducible under low ammonium ion concentrations, is suggested to be a "memory element." A chemostat-based model is developed to illustrate that perturbations in dilution rate can lead to drift between the two steady states provided that the disturbance in dilution rate is sufficiently large and/or long in duration.