Neuronal NLRP1 inflammasome activation of Caspase-1 coordinately regulates inflammatory interleukin-1-beta production and axonal degeneration-associated Caspase-6 activation.

Neuronal active Caspase-6 (Casp6) is associated with Alzheimer disease (AD), cognitive impairment, and axonal degeneration. Caspase-1 (Casp1) can activate Casp6 but the expression and functionality of Casp1-activating inflammasomes has not been well-defined in human neurons. Here, we show that primary cultures of human CNS neurons expressed functional Nod-like receptor protein 1 (NLRP1), absent in melanoma 2, and ICE protease activating factor, but not the NLRP3, inflammasome receptor components. NLRP1 neutralizing antibodies in a cell-free system, and NLRP1 siRNAs in neurons hampered stress-induced Casp1 activation. NLRP1 and Casp1 siRNAs also abolished stress-induced Casp6 activation in neurons. The functionality of the NLRP1 inflammasome in serum-deprived neurons was also demonstrated by NLRP1 siRNA-mediated inhibition of speck formation of the apoptosis-associated speck-like protein containing a caspase recruitment domain conjugated to green fluorescent protein. These results indicated a novel stress-induced intraneuronal NLRP1/Casp1/Casp6 pathway. Lipopolysaccharide induced Casp1 and Casp6 activation in wild-type mice brain cortex, but not in that of Nlrp1(-/-) and Casp1(-/-) mice. NLRP1 immunopositive neurons were increased 25- to 30-fold in AD brains compared with non-AD brains. NLRP1 immunoreactivity in these neurons co-localized with Casp6 activity. Furthermore, the NLRP1/Casp1/Casp6 pathway increased amyloid beta peptide 42 ratio in serum-deprived neurons. Therefore, CNS human neurons express functional NLRP1 inflammasomes, which activate Casp1 and subsequently Casp6, thus revealing a fundamental mechanism linking intraneuronal inflammasome activation to Casp1-generated interleukin-1-ß-mediated neuroinflammation and Casp6-mediated axonal degeneration.

Interobserver variation in cell selection for DNA image cytometry.

AIMS: To describe a systematic investigation of interobserver differences in interpretation of nuclear morphology in preparations of small cell lung cancer (SCLC). METHODS: The screening/reviewing facility on the highly optimised microscope environment was used to individually tag 127 nuclei, chosen to reflect the spectrum of morphological appearances in nuclear preparations from three biopsy specimens of SCLC. Each nucleus was reviewed and labelled as control (lymphocyte), malignant or unsatisfactory by each of four observers. DNA histograms were plotted for each specimen using the nuclei identified as malignant by each participant. The histograms were compared in terms of identification of DNA stemlines and by calculation of a 5c exceeding rate (5cER). RESULTS: Interobserver variation in assessment of morphology was seen in 55.1% of nuclei. Disagreement occurred most frequently in the malignant/unsatisfactory category. Differences in morphological classification had little influence on histogram assessment by means of visual inspection but did show an effect on 5cER. CONCLUSIONS: There are significant interobserver differences in subjective assessment of nuclear morphology in cytometric preparations. This effect may seriously influence cytometric measurements.

A new approach to man-machine communication for computerized microscopy.

HOME is a new computerized microscope designed to assist pathologists and cytotechnicians in routine examinations. The HOME workstation is composed of a standard light microscope fitted with objective and stage encoders, and a built-in high resolution computer display which superimposes dialog, drawing, and messages onto the optical microscope image. The software runs under Windows 3.x and provides interactive facilities such as accurate localization and relocation of zones of interest, morphometric measurements, patient data access, and quality control processes.

Formation of pile networks by long carbon nanotubes from decomposition of CO on Co-Mo film.

We report the formation of pile networks by long carbon nanotubes grown at 700 degrees C from a Co-Mo film on a quartz plate. Carbon monoxide (CO) was used as the carbon source. The networks were formed because the density of catalyst particles on the substrate was low, which resulted in low carbon nanotube density that did not support vertical growth. At the same time, the low carbon nanotube density makes it possible for CO to reach the catalysts on the substrate for continuous growth. No obvious amorphous carbon chunks were observed, suggesting that the pile networks consisted of fairly high-quality, long carbon nanotubes.

The buzz on buzz.

Word-of-mouth promotion has become an increasingly potent force, capable of catapulting products from obscurity into runaway commercial successes. Harry Potter, collapsible scooters, the Chrysler PT Cruiser, and The Blair Witch Project are all recent examples of the considerable power of buzz. Yet many top executives and marketing managers are misinformed about the phenomenon and remain enslaved to some common myths. In her article, author Renée Dye explores the truth behind these myths. Myth 1: Only outrageous or edgy products are buzz-worthy. That's simply not true. The most unlikely products, like prescription drugs, can generate tremendous buzz. Myth 2: Buzz just happens. Not so, says Dye. Buzz is increasingly the result of shrewd marketing tactics in which companies seed a vanguard group, ration supplies, use celebrity endorsements, leverage the power of lists, and initiate grassroots marketing. Myth 3: The best buzz-starters are your best customers. Often, a counterculture has a greater ability to start buzz. Myth 4: To profit from buzz, you must act first and fast. In fact, copycat companies can reap substantial profits if they know when and when not to jump in. Myth 5: The media and advertising are needed to create buzz. When used either too early or too much, the media and advertising can squelch buzz before it ignites. As globalization and brand proliferation continue, writes Dye, buzz may come to dominate the shaping of markets. Indeed, companies that are unable to control buzz may soon find the phenomenon controlling them.

The competitive dynamics of network-based businesses.

Telecommunications carriers, transportation companies, and banks are among the many network-based businesses--companies that move people, goods, or information from various points to various other points. Managers have long assumed that customers valued all links in these networks equally. It was thought that banking customers, for example, sought access to all of the branches throughout the network or that shipping customers wanted to be able to send packages everywhere. Intuitively, managers thought that many of their customers' needs were, in reality, narrower, but they had no way of knowing which links were most important. New computing power and robust mapping software now make it possible to understand network customers better. In applying this technology, the authors, both consultants from McKinsey & Company, have uncovered three distinct usage patterns: one in which all links are, indeed, valued equally; another in which customers concentrate their use in particular zones; and a third in which customers value only individual links. Each of these patterns requires a different strategy to direct executives in making the decisions fundamental to managing any network-based business: whether to open or close outlets, whether to connect their network to others, and how to organize business units so that they reflect the network's structure. Those who don't spot the patterns or understand their strategic implications will find themselves on the losing end of the network battle.