Metallothionein (MT) -I and MT-II Expression Are Induced and Cause Zinc Sequestration in the Liver after Brain Injury

Experiments with transgenic over-expressing, and null mutant mice have determined that metallothionein-I and -II (MT-I/II) are protective after brain injury. MT-I/II is primarily a zinc-binding protein and it is not known how it provides neuroprotection to the injured brain or where MT-I/II acts to have its effects. MT-I/II is often expressed in the liver under stressful conditions but to date, measurement of MT-I/II expression after brain injury has focused primarily on the injured brain itself. In the present study we measured MT-I/II expression in the liver of mice after cryolesion brain injury by quantitative reverse-transcriptase PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) with the UC1MT antibody. Displacement curves constructed using MT-I/II knockout (MT-I/II−/−) mouse tissues were used to validate the ELISA. Hepatic MT-I and MT-II mRNA levels were significantly increased within 24 hours of brain injury but hepatic MT-I/II protein levels were not significantly increased until 3 days post injury (DPI) and were maximal at the end of the experimental period, 7 DPI. Hepatic zinc content was measured by atomic absorption spectroscopy and was found to decrease at 1 and 3 DPI but returned to normal by 7DPI. Zinc in the livers of MT-I/II−/− mice did not show a return to normal at 7 DPI which suggests that after brain injury, MT-I/II is responsible for sequestering elevated levels of zinc to the liver. Conclusion: MT-I/II is up-regulated in the liver after brain injury and modulates the amount of zinc that is sequestered to the liver

Torsional Vibration Analysis And Testing Of Synchronous Motor-Driven Turbomachinery.

Tutorialpg. 153-176One of the foremost concerns facing turbomachinery users today is that of torsional vibration. In contrast to lateral rotordynamics problems, torsional failures are especially heinous since the first symptom of a problem is often a broken shaft, gear tooth, or coupling. The difficulty of detecting incipient failures in the field makes the performance of a thorough torsional vibration analysis an essential component of the turbomachinery design process. The primary objective of this tutorial is to provide such a procedure for the special case where the turbomachine is driven by a synchronous motor. Synchronous motors are one of the most notorious sources or torsional vibration problems because of the large pulsating torques they generate during startups. The torsional shaft stresses generated by these large pulsations are usually greater than the shaft material endurance limits, thereby, causing the lives of such machines to be limited. The determination of the number of startups that these machines can survive is, therefore, a critical portion of their design process. It is the authors’ experience that there is a great deal of confusion over the proper way to do this. The full impact of this confusion was seen on a recently designed compressor train where the use of one method showed the allowable number of starts to be zero while a second procedure predicted infinite life. In an attempt to alleviate this confusion, a logical, step-by-step procedure, based on the strain-life theory of failure, was generated and is presented herein. An example illustrating how the authors used this procedure to design a critical 66,000 hp air compressor is also presented. The authors believe that employment of this method may well save the user from the need to introduce an expensive and unwieldy Holsetstyle damping coupling into some future compressor train. Although the presented analytical procedure is quite rigorous, there are cases, especially on critical equipment, where it is wise to augment its predictions with torsional test data taken from the field. The best way to do this in synchronous mo*tor-driven equipment is to apply strain gauges to critical shafts in the drive train and measure the actual torques that are generated during startup. Accordingly, a general description of strain gauge testing fundamentals is provided to familiarize all users with it. Additionally, the use of this valuable testing procedure is illustrated via the same 66,000 hp air compressor that was used to illustrate the analytical procedure. The tutorial closes with a comparison of the obtained analytical and test results and an illustration of how the authors used the testing to “fine-tune” the analytical results

Extended-Spectrum β-Lactamases in Klebsiella pneumoniae Bloodstream Isolates from Seven Countries: Dominance and Widespread Prevalence of SHV- and CTX-M-Type β-Lactamases

A huge variety of extended-spectrum β-lactamases (ESBLs) have been detected during the last 20 years. The majority of these have been of the TEM or SHV lineage. We have assessed ESBLs occurring among a collection of 455 bloodstream isolates of Klebsiella pneumoniae, collected from 12 hospitals in seven countries. Multiple β-lactamases were produced by isolates with phenotypic evidence of ESBL production (mean of 2.7 β-lactamases per isolate; range, 1 to 5). SHV-type ESBLs were the most common ESBL, occurring in 67.1% (49 of 73) of isolates with phenotypic evidence of ESBL production. In contrast, TEM-type ESBLs (TEM-10 type, -12 type, -26 type, and -63 type) were found in just 16.4% (12 of 73) of isolates. The finding of TEM-10 type and TEM-12 type represents the first detection of a TEM-type ESBL in South America. PER (for Pseudomonas extended resistance)-type β-lactamases were detected in five of the nine isolates from Turkey and were found with SHV-2-type and SHV-5-type ESBLs in two of the isolates. CTX-M-type ESBLs (bla(CTX-M-2) type and bla(CTX-M-3) type) were found in 23.3% (17 of 73) of isolates and were found in all study countries except for the United States. We also detected CTX-M-type ESBLs in four countries where they have previously not been described—Australia, Belgium, Turkey, and South Africa. The widespread emergence and proliferation of CTX-M-type ESBLs is particularly noteworthy and may have important implications for clinical microbiology laboratories and for physicians treating patients with serious K. pneumoniae infections

HDAC-mediated deacetylation of NF-κB is critical for Schwann cell myelination

Schwann cell myelination is tightly regulated by timely expression of key transcriptional regulators that respond to specific environmental cues, but the molecular mechanisms underlying such a process are poorly understood. We found that the acetylation state of NF-κB, which is regulated by histone deacetylases (HDACs) 1 and 2, is critical for orchestrating the myelination program. Mice lacking both HDACs 1 and 2 (HDAC1/2) exhibited severe myelin deficiency with Schwann cell development arrested at the immature stage. NF-κB p65 became heavily acetylated in HDAC1/2 mutants, inhibiting the expression of positive regulators of myelination and inducing the expression of differentiation inhibitors. We observed that the NF-κB protein complex switched from associating with p300 to associating with HDAC1/2 as Schwann cells differentiated. NF-κB and HDAC1/2 acted in a coordinated fashion to regulate the transcriptionally linked chromatin state for Schwann cell myelination. Thus, our results reveal an HDAC-mediated developmental switch for controlling myelination in the peripheral nervous system

Analysis of the Complete Genomes of Acholeplasma brassicae, A. palmae and A. laidlawii and Their Comparison to the Obligate Parasites from 'Candidatus Phytoplasma'

Analysis of the completely determined genomes of the plant-derived Acholeplasma brassicae strain O502 and A. palmae strain J233 revealed that the circular chromosomes are 1,877,792 and 1,554,229 bp in size, have a G + C content of 36 and 29%, and encode 1,690 and 1,439 proteins, respectively. Comparative analysis of these sequences and previously published genomes of A. laidlawii strain PG-8, ‘Candidatus Phytoplasma asteris' strains, ‘Ca. P. australiense' and ‘Ca. P. mali' show a limited shared basic genetic repertoire. The acholeplasma genomes are characterized by a low number of rearrangements, duplication and integration events. Exceptions are the unusual duplication of rRNA operons in A. brassicae and an independently introduced second gene for a single-stranded binding protein in both genera. In contrast to phytoplasmas, the acholeplasma genomes differ by encoding the cell division protein FtsZ, a wide variety of ABC transporters, the F₀F1 ATP synthase, the Rnf-complex, SecG of the Sec-dependent secretion system, a richly equipped repertoire for carbohydrate metabolism, fatty acid, isoprenoid and partial amino acid metabolism. Conserved metabolic proteins encoded in phytoplasma genomes such as the malate dehydrogenase SfcA, several transporters and proteins involved in host-interaction, and virulence-associated effectors were not predicted for the acholeplasmas.Peer Reviewe