Crossing the Border: From Keto- to Imine Reduction in Short-Chain Dehydrogenases/Reductases

The family of NAD(P)H-dependent short-chain dehydrogenases/reductases (SDRs) comprises numerous biocatalysts capable of C=O or C=C reduction. The highly homologous noroxomaritidine reductase (NR) from Narcissus sp. aff. pseudonarcissus and Zt_SDR from Zephyranthes treatiae, however, are SDRs with an extended imine substrate scope. Comparison with a similar SDR from Asparagus officinalis (Ao_SDR) exhibiting keto-reducing activity, yet negligible imine-reducing capability, and mining the Short-Chain Dehydrogenase/Reductase Engineering Database indicated that NR and Zt_SDR possess a unique active-site composition among SDRs. Adapting the active site of Ao_SDR accordingly improved its imine-reducing capability. By applying the same strategy, an unrelated SDR from Methylobacterium sp. 77 (M77_SDR) with distinct keto-reducing activity was engineered into a promiscuous enzyme with imine-reducing activity, thereby confirming that the ability to reduce imines can be rationally introduced into members of the “classical” SDR enzyme family. Thus, members of the SDR family could be a promising starting point for protein approaches to generate new imine-reducing enzymes.     

Using an integrated process of data and modeling in HRA

The paper describes an approach taken to estimate the probabilities of failure associated with various railroad tasks to prevent accidents (principally collisions and derailments). These probabilities were estimated using an expert elicitation process that used partially relevant data available from a variety of databases and that were filtered and scaled to make them more directly relevant to the analyses being performed. Extensive qualitative studies were performed prior to the elicitation process to identify relevant contexts under which the tasks can be performed.     

欧洲主要电信运营商专线资费的演变

欧洲主要电信运营商所处国度的经济和人口布局情况不同，竞争环境也有差别，在专线资费方面的做法也有许多不同之处。考虑到地区之间竞争的差异。目前多数国家都取消了地区交叉补贴的做法，但还有一部分国家仍然坚持统一费率。在资费方面的基本促销手段为接合同年限和用户的支出额打折。从2000年到2003年资费演变的基本情况是；接入费扣2Mbit／s以下较低速率的专线租费保持平稳略有下降，较高速率专线的租费则有较大的下调幅虚。     

Wavelength-tunable 40-GHz picosecond harmonically mode-locked fiber laser source

We demonstrate a novel 40-GHz mode-locked fiber laser that utilizes a single active device to provide both gain and mode-locking. The laser produces pulses as short as 2.2 ps, is tunable over a 27-nm band centered at 1553 nm, and exhibits long-term stability without cavity-length feedback control. The pulse train at 1556 nm was used in a 40-Gb/s transmission experiment over 45 km with a low 0.4-dB power penalty.     

Animal-induced injuries and disease, neonatal jaundice, immunizations, and viral infections

Highlights from the past years' literature on the topics of animal-induced injuries and diseases, neonatal jaundice, immunizations, and viral infections are discussed from the perspective of the general pediatrician. An effort is made to place recent advances in care or understanding of clinical problems into the context of the pediatric office practice. The current reality of health care-be it managed care, care for the underserved, or the recent pressures on academic and hospital-based medicine-does not alter the importance of the delivery of quality care at the office level. Although it is now popular to define quality of health care in cute advertising copy, as if we are selling durable goods, excellence in pediatric office-based practice continues to require broad strokes of medical knowledge coupled with a unswerving commitment to and advocacy for the needs and well-being of infants, children, and young adults.     

Peripheral nerve stimulation in a whole-body echo-planar imaging system

Echo-planar techniques in MRI use a rapidly oscillating frequency-encoding gradient with the potential to produce peripheral nerve stimulation. To evaluate the incidence, type, and location of stimulation in a commercial whole-body scanner, we studied two groups: (a) 173 consecutive individuals scanned by echo-planar imaging for other purposes and (b) seven subjects who were scanned with an extensive set of 36 echo-planar sequences (with prompting after each scan to report any peripheral nerve stimulation) to test the effects of various parameters. Although only 5% of group A reported symptoms of peripheral nerve stimulation, all in group B experienced some type of stimulation, dependent primarily on direction of the oscillating gradient and location of the body within the gradient coil. Maximum stimulation typically occurred 30 to 40 cm from isocenter in the region of maximum dB/dt. Generally, y gradients produced truncal stimulation, and x gradients produced stimulation in the head. When hands were clasped over the abdomen, a tingling in the hands occasionally was felt. Patients should be instructed to keep their hands apart.     

Chicken acidic leucine-rich EGF-like domain containing brain protein (CALEB), a neural member of the EGF family of differentiation factors, is implicated in neurite formation

Chicken acidic leucine-rich EGF-like domain containing brain protein (CALEB) was identified by combining binding assays with immunological screens in the chicken nervous system as a novel member of the EGF family of differentiation factors. cDNA cloning indicates that CALEB is a multidomain protein that consists of an NH2-terminal glycosylation region, a leucine-proline-rich segment, an acidic box, a single EGF-like domain, a transmembrane, and a short cytoplasmic stretch. In the developing nervous system, CALEB is associated with glial and neuronal surfaces. CALEB is composed of a 140/130-kD doublet, an 80-kD band, and a chondroitinsulfate-containing 200-kD component. The latter two components are expressed in the embryonic nervous system and are downregulated in the adult nervous system. CALEB binds to the extracellular matrix glycoproteins tenascin-C and -R. In vitro antibody perturbation experiments reveal a participation of CALEB in neurite formation in a permissive environment.     

Visual results after submacular surgery for neovascularization in age-related macular degeneration

Orthopedists being more engaged in surgery are often asked about problems concerning exercise science. This article will summarize the existing basic knowledge, very close to practice, and put down the leading steps of how to build up a (therapeutical) training programme. A lab block is recommended acting on a preventive as well as on a sportive medical base.     

Tyrosine-dependent basolateral sorting signals are distinct from tyrosine-dependent internalization signals

Converting cysteine 543 to tyrosine in the influenza virus hemagglutinin (HA) introduces both a basolateral sorting signal and an internalization signal into the HA cytoplasmic domain. Another HA mutant, HA+8, contains eight additional amino acids at the end of the cytoplasmic domain that include a powerful internalization signal. HA+8 was also sorted efficiently to the basolateral surface of Madin-Darby canine kidney cells. The simplest explanation for the observation that multiple sorting phenotypes depend upon the same small amino acid sequence is that certain tyrosine-based internalization signals might also function as basolateral sorting signals. To test this hypothesis, second-site mutations were introduced into HA C543Y or HA+8 to determine if the internalization and basolateral sorting functions can be separated. For HA C543Y, the same sequence positions were important for both basolateral sorting and internalization, but the two functions responded differently to individual amino acid replacements, indicating that they were distinct. For HA+8, the basolateral sorting signal required the same tyrosine as the internalization signal, but did not share any other characteristics. Thus, even when basolateral sorting signals that depend on tyrosine overlap or are co-linear with internalizations signals, the two sorting processes are sensitive to different characteristics of the sequence.