FtsZ is an essential bacterial guanosine triphosphatase and homolog of mammalian beta-tubulin that polymerizes and assembles into a ring to initiate cell division. We have created a class of small synthetic antibacterials, exemplified by PC190723, which inhibits FtsZ and prevents cell division. PC190723 has potent and selective in vitro bactericidal activity against staphylococci, including methicillin- and multi-drug-resistant Staphylococcus aureus. The putative inhibitor-binding site of PC190723 was mapped to a region of FtsZ that is analogous to the Taxol-binding site of tubulin. PC190723 was efficacious in an in vivo model of infection, curing mice infected with a lethal dose of S. aureus. The data validate FtsZ as a target for antibacterial intervention and identify PC190723 as suitable for optimization into a new anti-staphylococcal therapy.

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Psychological stress has profound effects on gastrointestinal function, and investigations over the past few decades have examined the mechanisms by which neural and hormonal stress mediators act to modulate gut motility, epithelial barrier function and inflammatory states. With its cellular diversity and large commensal bacterial population, the intestinal mucosa and its overlying mucous environment constitute a highly interactive environment for eukaryotic host cells and prokaryotic bacteria. The elaboration of stress mediators, particularly norepinephrine, at this interface influences host cells engaged in mucosal protection and the bacteria which populate the mucosal surface and gut lumen. This review will address growing evidence that norepinephrine and, in some cases, other mediators of the adaptation to stress modulate mucosal interactions with enteric bacteria. Stress-mediated changes in this delicate interplay may shift the microbial colonization patterns on the mucosal surface and alter the susceptibility of the host to infection. Moreover, changes in host-microbe interactions in the digestive tract may also influence ongoing neural activity in stress-responsive brain areas.

Severe spinal cord injuries above mid-thoracic levels can lead to a potentially life-threatening hypertensive condition termed autonomic dysreflexia, which is often triggered by painful distension of pelvic viscera (bladder or bowel) and consequent sensory fiber activation, including nociceptive C-fibers. Interruption of tonically active medullo-spinal pathways after injury causes disinhibition of thoracolumbar sympathetic preganglionic neurons, and intraspinal sprouting of nerve growth factor (NGF)-responsive primary afferent fibers is thought to contribute to their hyperactivity. We investigated spinal levels that are critical for eliciting autonomic dysreflexia using a model of noxious colorectal distension (CRD) after complete spinal transection at the fourth thoracic segment in rats. Post-traumatic sprouting of calcitonin gene-related peptide (CGRP)-immunoreactive primary afferent fibers was selectively altered at specific spinal levels caudal to the injury with bilateral microinjections of adenovirus encoding the growth-promoting NGF or growth-inhibitory semaphorin 3A (Sema3a) compared with control green fluorescent protein (GFP). Two weeks later, cardio-physiological responses to CRD were assessed among treatment groups before histological analysis of afferent fiber density at the injection sites. Dysreflexic hypertension was significantly higher with NGF overexpression in lumbosacral segments compared with GFP, whereas similar overexpression of Sema3a significantly reduced noxious CRD-evoked hypertension. Quantitative analysis of CGRP immunostaining in the spinal dorsal horns showed a significant correlation between the extent of fiber sprouting into the spinal segments injected and the severity of autonomic dysreflexia. These results demonstrate that site-directed genetic manipulation of axon guidance molecules after complete spinal cord injury can alter endogenous circuitry to modulate plasticity-induced autonomic pathophysiology.

While thermoelectric materials can be used for solid state cooling, waste heat recovery, and solar electricity generation, low values of the thermoelectric figure of merit, zT, have led to an efficiency too low for widespread use. Thermoelectric effects are characterized by the Seebeck coefficient or thermopower, which is related to the entropy associated with charge transport. For example, coupling spin entropy with the presence of charge carriers has enabled the enhancement of zT in cobalt oxides. We demonstrate that the coupling of a continuous phase transition to carrier transport in Cu2Se over a broad (360–410 K) temperature range results in a dramatic peak in thermopower, an increase in phonon and electron scattering, and a corresponding doubling of zT (to 0.7 at 406 K), and a similar but larger increase over a wider temperature range in the zT of Cu1.97Ag.03Se (almost 1.0 at 400 K). The use of structural entropy for enhanced thermopower could lead to new engineering approaches for thermoelectric materials with high zT and new green applications for thermoelectrics.

IPEC-J2 cells are porcine intestinal columnar epithelial cells that were isolated from neonatal piglet mid-jejunum. This cell line forms polarized monolayers with high transepithelial electrical resistance when cultured on 0.4 μm pore-size filters. The cell line is unique in that it is derived from small intestinal tissue (compared to the common human colon-derived lines HT-29, T84, and Caco-2) and is not transformed (compared to the porcine small intestinal line, IPI-2I). Porcine intestinal epithelial cells more closely mimic human physiology than analogous rodent cell lines (e.g. IEC-6 or IEC-18), which is important in studies of zoonotic infections; in addition, they provide specificity to study porcine-derived infections. IPEC-J2 cells are increasingly being used in microbiological studies to examine the interactions of various animal and human pathogens, including Salmonella enterica and pathogenic Escherichia coli, with intestinal epithelial cells. The IPEC-J2 cell line has also been employed in some probiotic studies, in which the cells have been used as an initial screening tool for adhesiveness and anti-inflammatory properties of the potential probiotic microorganisms. The validity of these studies is not clear as follow-up studies to assess the efficacy of the probiotics in vivo have not been published to date. The aims of this review are to provide a comprehensive overview of the microbiological studies that have been conducted with IPEC-J2 cells and a reference guide of key cellular and immune markers that have been identified in this cell line that may prove to be useful in future studies.

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The porcine intestinal tract possesses functional and pathological similarities to the human digestive tract and the organization of the porcine enteric nervous system, like that of the human, appears to be more complex than that of commonly investigated guinea-pig intestine. Intrinsic primary afferent neurones appear to differ in the intestines of large and small animals in terms of their chemical coding, distribution over enteric neural networks, electrophysiological behaviour and synaptic properties. Opioid receptors on afferent and motor neurones in the porcine small intestine are predominately of the delta type, whereas those in guinea-pig ileum are mu. Moreover, delta-opioid receptors associated with the myenteric and submucosal plexuses of porcine ileum that, respectively, modulate neurogenic smooth muscle contractions and mucosal ion transport appear to differ in their pharmacological characteristics. These profound interspecies and interregional differences underscore the complexity of the enteric nervous system, and the development of new drugs designed to treat human neurogastrointestinal disorders should be based on the results of investigations in homologous animal models, such as the pig.