Principles and pitfalls in designing site-directed peptide ligands

An immunoglobulin light chain dimer with a large generic binding cavity was used as a host molecule for designing a series of peptide guest ligands. In a screening procedure peptides coupled to solid supports were systematically tested for binding activity by enzyme linked immunosorbent assays (ELISA). Key members of the binding series were synthesized in milligram quantities and diffused into crystals of the host molecule for X-ray analyses. These peptides were incrementally increased in size and affinity until they nearly filled the cavity. Progressive changes in binding patterns were mapped by comparisons of crystallo-graphically refined structures of 14 peptide–protein complexes at 2.7 Å resolution. These comparisons led to guidelines for ligand design and also suggested ways to modify previously established binding patterns. By manipulating equilibria involving histidine, for example, it was possible to abolish one important intramolecular interaction of the bound ligand and substitute another. These events triggered a change inconformation of the ligand from a compact to an extended form and a comprehensive change in the mode of binding to the protein. In dipeptides of histidine and proline, protonation of both imidazolium nitrogen atoms was used to program anend-to-end reversal of the direction in which the ligand was inserted into the binding cavity. Peptides cocrystallized with proteins produced complexes somewhat different in structure from those in which ligandswere diffused into preexisting crystals. In sucha large and malleable cavity, space utilization was thus different when a ligand was introduced before the imposition of crystal packing restraints. © 1993 Wiley-Liss, Inc.     

Temperature niche conservatism and strong genetic structure are involved in the trans-Panamanian colonization of Matudaea (Hamamelidaceae) to Andean forests

Matudaea is the only genus of the Hamamelidaceae found in South America. The genus is composed by two extant species, M. trinervia, from Mexico and Costa Rica, and Matudaea colombiana, from the Colombian Andes; additional fossil records are present in Central Europe. Population genetics, molecular phylogenetics and niche modelling approaches were applied to explain processes related with the trans-Panamanian M. trinervia/M. colombiana split and the putative colonization of the latter to the northern Andes. The split between the two Matudaea species was estimated during Middle Miocene. The colonization of Matudaea into South America could have been facilitated by the closure of the Isthmus of Panama and the global decreasing of temperature during Miocene. Five haplotypes of M. colombiana were identified, which show an eastwards decline of genetic diversity and suggest a founder effect in the colonization of Eastern cordillera of the Colombian Andes. We detected a niche conservatism signal between the two Matudaea species related with Temperature of Coldest Month and Mean Temperature of Driest Quarter bioclimatic variables; this signal might be related to the narrow altitudinal range occupied by the two species.     

Planktonic indices in the evaluation of the ecological status and the trophic state of the longest lake in Poland

Due to the intensive mixing polymictic lakes should be homogenous. However, morphometric diversity and high water dynamics contribute to the differentiation of many parameters in various areas of the lakes. This study analyzes both phytoplankton and zooplankton to assess differences in water quality along the north–south axis of the longest lake in Poland. New phytoplankton indicators were applied for determining the lake's ecological status: the Q index based on functional groups and the PMPL (Phytoplankton Metric for Polish Lakes) index based on phytoplankton biomass. TSI_ROT index (Rotifer Trophic State Index), which comprises the percentage of species indicating a high trophic state in the indicatory group and the percentage of bacteriovorus in the Rotifera population, was used for zooplankton analysis.TP content was different at different sites – we observed its gradual increase from the south to the north. Spatial variation of phosphorus did not considerably affect plankton diversity. The phytoplankton was dominated by Oscillatoriales, typical of shallow, well-mixed eutrophic lakes. The ecological status of the lake based on the EQR (Ecological Quality Ratio) was poor or moderate. The zooplankton was dominated by rotifers (at almost all sites), which indicates a eutrophic state of the lake. The values of phytoplankton indices at the studied sites did not differ considerably; the differences resulted more from local conditions such as the contaminant inflow and the macrophyte development than water dynamics.We have demonstrated that in the lake dominated by filamentous Cyanobacteria the ecological status should be determined according to the PMPL index or other indices dependent on the dominant Cyanobacteria species. Since the Q index does not include the functional group S1, the results can lead to the false conclusion that water quality improves with an increased amount of phytoplankton. The high abundance of Cyanobacteria in the lake may have contributed to the poor growth of rotifers.     

Evaluation method for coalmining-based cities ecosystem based on attribute mathematical model with Huainan City as an example

Attributive recognition model of coalmining-based cities ecosystem classification is developed in terms of attributive mathematical theory. Based on the analysis of main causes of coalmining-based cities ecosystem, the city vitality, city structure strength, city resilience ability, service functions and health status are chosen as the criterion indicators of coalmining-based cities ecosystem classification; the attributive measurement functions are constructed to compute the attributive measurement of single indicator and multi-indicator; and the synthetic attributive measurement is calculated by the AHP; the health classification of cities ecosystem are recognized by the confidence criterion. An empirical analysis is made by the proposed model and method, the synthetic evaluation results are better than fuzzy comprehensive evaluation method which validates the proposed model feasible, effective and reliable in coalmining-based cities ecosystem classification. As attributive recognition theory can success fully resolve certain issues with a number of fuzzy attribution in comprehensive evaluation, its confidence criterion is established on the basis of the ordered evaluation sets, consequently it will make the evaluation results more reliable.     

Inter-session reliability and sex-related differences in hamstrings total reaction time,pre-motor time and motor time during eccentric isokinetic contractions in recreational athlete

The purposes were twofold: (a) to ascertain the inter-session reliability of hamstrings total reaction time, pre-motor time and motor time; and (b) to examine sex-related differences in the hamstrings reaction times profile. Twenty-four men and 24 women completed the study. Biceps femoris and semitendinosus total reaction time, pre-motor time and motor time measured during eccentric isokinetic contractions were recorded on three different occasions. Inter-session reliability was examined through typical percentage error (CV_TE), percentage change in the mean (CM) and intraclass correlations (ICC). For both biceps femoris and semitendinosus, total reaction time, pre-motor time and motor time measures demonstrated moderate inter-session reliability (CV_TE < 10%; CM < 3%; ICC > 0.7). The results also indicated that, although not statistically significant, women reported consistently longer hamstrings total reaction time (23.5 ms), pre-motor time (12.7 ms) and motor time (7.5 ms) values than men. Therefore, an observed change larger than 5%, 9% and 8% for total reaction time, pre-motor time and motor time respectively from baseline scores after performing a training program would indicate that a real change was likely. Furthermore, while not statistically significant, sex differences were noted in the hamstrings reaction time profile which may play a role in the greater incidence of ACL injuries in women.     

Does transpiration have an essential function in long-distance ion transport in plants?

Abstract. Long-term effects of transpiration on growth and on long-distance ion transport were investigated in maize over a whole growth cycle. Maize plants were grown with nutrients supplied at adequate levels in hydroculture or in soil at 50–60% and at >95% relative humidity. Although the amount of water lost by the plants under these conditions differed by a factor 2 to 3, there was neither a decrease in growth (fresh weight and dry weight) nor in ash content of the 'humid'plants. This was also found when the upper part of the shoot (70–150 cm) was tested separately. It is suggested that transpiration is not essential for long-distance transport of mineral elements in plants. Alternatives are discussed.     

Honey: Single food stuff comprises many drugs

Honey is a natural food item produced by honey bees. Ancient civilizations considered honey as a God gifted prestigious product. Therefore, a huge literature is available regarding honey importance in almost all religions. Physically, honey is a viscous and jelly material having no specific color. Chemically, honey is a complex blend of many organic and inorganic compounds such as sugars, proteins, organic acids, pigments, minerals, and many other elements. Honey use as a therapeutic agent is as old as human civilization itself. Prior to the appearance of present day drugs, honey was conventionally used for treating many diseases. At this instant, the modern research has proven the medicinal importance of honey. It has broad spectrum anti-biotic, anti-viral and anti-fungal activities. Honey prevents and kills microbes through different mechanism such as elevated pH and enzyme activities. Till now, no synthetic compound that works as anti-bacterial, anti-viral and anti-fungal drugs has been reported in honey yet it works against bacteria, viruses and fungi while no anti-protozoal activity has been reported. Potent anti-oxidant, anti-inflammatory and anti-cancerous activities of honey have been reported. Honey is not only significant as anti-inflammatory drug that relieve inflammation but also protect liver by degenerative effects of synthetic anti-inflammatory drugs. This article reviews physico-chemical properties, traditional use of honey as medicine and mechanism of action of honey in the light of modern scientific medicinal knowledge.     

A novel potent metal-binding NDM-1 inhibitor was identified by fragment virtual,SPR and NMR screening

NDM-1 can hydrolyze nearly all available β-lactam antibiotics, including carbapenems. NDM-1 producing bacterial strains are worldwide threats. It is still very challenging to find a potent NDM-1 inhibitor for clinical use. In our study, we used a metal-binding pharmacophore (MBP) enriched virtual fragment library to screen NDM-1 hits. SPR screening helped to verify the MBP virtual hits and identified a new NDM-1 binder and weak inhibitor A1. A solution NMR study of ¹⁵N-labeled NDM-1 showed that A1 disturbed all three residues coordinating the second zinc ion (Zn2) in the active pocket of NDM-1. The perturbation only happened in the presence of zinc ion, indicating that A1 bound to Zn2. Based on the scaffold of A1, we designed and synthesized a series of NDM-1 inhibitors. Several compounds showed synergistic antibacterial activity with meropenem against NDM-1 producing K. pneumoniae.