Cathepsin B inhibitors: Further exploration of the nitroxoline core

Human cathepsin B is a cysteine protease with many house-keeping functions, such as intracellular proteolysis within lysosomes. Its increased activity and expression have been strongly associated with many pathological processes, including cancers. We present here the design and synthesis of novel derivatives of nitroxoline as inhibitors of cathepsin B. These were prepared either by omitting the pyridine part, or by modifying positions 2, 7, and 8 of nitroxoline. All compounds were evaluated for their ability to inhibit endopeptidase and exopeptidase activities of cathepsin B. For the most promising inhibitors, the ability to reduce extracellular and intracellular collagen IV degradation was determined, followed by their evaluation in cell-based in vitro models of tumor invasion. The presented data show that we have further defined the structural requirements for cathepsin B inhibition by nitroxoline derivatives and provided additional knowledge that could lead to non-peptidic compounds with usefulness against tumor progression.     

Effect of fruit host on wing morphology in Drosophila suzukii (Diptera: Drosophilidae): A first view using geometric morphometrics

The invasive alien fruit pest Drosophila suzukii, (Matsumura 1931) causes economic loss in soft‐skinned fruit production across Europe. After its first detection in 2008, the species has successfully expanded to a wide geographic area and invaded new host plants in a relatively short period of time. The aim of the present study was to analyze the connection between food preferences as host specialization and the morphology of D. suzukii. Population morphological variation in wings was investigated in two different host fruits (grape and strawberry) in which economic damage has been recorded. The geometric morphometric results revealed two noticeable wing shape morphotypes in D. suzukii (i.e. vein configuration) between the grape and strawberry fruits. Flies reared in grapes had wider wings, whereas flies grown in strawberries had more narrow wings. These differences in morphotype could be explained by the effects of wing aerodynamics, which affect the strength of the wings in flight. This, in turn, can lead to better dispersion within the associated fruit host. These results confirm that this extremely invasive species, found worldwide, is successful at spreading in part because of its potential to adapt rapidly under different rearing conditions. Therefore, adaptive variations in the wing shape of D. suzukii can be used to differentiate populations based on food preference (e.g. soft fruits) and can serve as an additional tool for detecting different bioecological types of D. suzukii.     

Perinatal period cytokines related to increased risk of future allergy development

Testing of cytokine levels in colostrum, cord blood and amniotic fluid of healthy and allergic mothers and their newborns (using protein microarrays and quantitative analysis by ELISA) revealed differences in the levels of IL-5, IL-10, TGF-beta, TNF-alpha, EGF and eotaxin between healthy and allergic groups. Significantly higher concentration of IL-5 and IL-10 in the colostrum of allergic mothers and cord blood of their children and also tendency to a higher level of IL-4 found at allergic mothers and their children (but without statistical significance) indicate a bias to T(H)2 response in this group. The higher level of TGF-beta in the colostrum of healthy mothers should be involved in beneficial immunological tuning of their children including enhanced IgA formation and better intestine maturation. In amniotic fluid, concentration of TGF-beta was higher in children of allergic mothers. A significantly higher level of EGF was proved in the colostrum of healthy mothers and in cord blood of their children in comparison with allergic group. EGF deficiency in the allergic group could impair or delay intestine maturation and support thus allergy development.     

Jure Piskur (1960—2014)

<正>Following a short struggle against an aggressive cancer,Prof.Jure Piskur(Fig.1),a professor of molecular genetics at Lund University(LU),Sweden,and the University of Nova Gorica(UNG),Slovenia,died in his home in Lund on 18 May 2014.He leaves behind his lifelong partner and wife,Judita Gartner,and their sons,Jan and Jure.Jure Piskur was born in 1960 in Slovenia,at that time part of Yugoslavia.Even when Jure’s research led him to many countries and the last quarter of a century to Scandinavia,he always kept close contact with his home country.He was proud to have participated in the Slovenian independence movement,which led to its international recognition as a sovereign state in     

Laboratory-scale biosynthesis ofTrichoderma mycolytic enzymes for protoplast release fromCochliobolus lunatus

Summary Microorganism useful for the induction of enzymes lytic towards walls of filamentous fungusCochliobolus lunatus were studies. Production of specificTrichoderma viride mycolytic enzymes was studied in a laboratory fermentor. The product with high chitinase and relatively low protease activity gave better yields ofC. lunatus protoplasts than commercial Novozym 234.     

Discontinuities in the Temperature Function of Transmembrane Water Transport in Chara: Relation to Ion Transport

The NMR (nuclear magnetic resonance) method of Conlon and Outhred (1972) was used to measure diffusional water permeability of the nodal cells of the green alga Chara gymnophylla. Two local minima at 15 and 30°C of diffusional water permeability (P _d ) were observed delimiting a region of low activation energy (E _a around 20 kJ/mol) indicative of an optimal temperature region for membrane transport processes. Above and below this region water transport was of a different type with high E _a (about 70 kJ/mol). The triphasic temperature dependence of the water transport suggested a channel-mediated transport at 15–30°C and lipid matrix-mediated transport beyond this region. The K⁺ channel inhibitor, tetraethylammonium as well as the Cl⁻ channel inhibitor, ethacrynic acid, diminished P _d in the intermediate temperature region by 54 and 40%, respectively. The sulfhydryl agent p-(chloromercuri-benzensulfonate) the water transport inhibitor in erythrocytes also known to affect K⁺ transport in Chara, only increased P _d below 15°C. In high external potassium (`K-state') water transport minima were pronounced. The role of K⁺ channels as sensors of the optimal temperature limits was further emphasized by showing a similar triphasic temperature dependence of the conductance of a single K⁺ channel also known to cotransport water, which originated from cytoplasmic droplets (putatively tonoplast) of C. gymnophylla. The minimum of K⁺ single channel conductance at around 15°C, unlike the one at 30°C, was sensitive to changes of growth temperature underlining membrane lipid involvement. The additional role of intracellular (membrane?) water in the generation of discontinuities in the above thermal functions was suggested by an Arrhenius plot of the cellular water relaxation rate which showed breaks at 13 and 29°C. Received: 12 August 1998/Revised: 13 November 1998     

Human skeletons from the Newgate site in the City of London

The graveyard excavated at the Newgate (General Post Office) site in the City of London contained 436 badly damaged individual graves of a medieval Saxon population. Detailed studies of the individual skeletons showed that the population was fairly homogenous with very small range of individual variations. The people were short in stature and were muscular in build. Old individuals were uncommon. One third of women's graves also contained a child. Some congenital deformations, degenerative disease and injuries were noted on the excavated bones. Everyone suffered from severe dental caries, periondontal disease and subsequent loss of teeth. The skeletal features are described and inferences drawn concerning the biological status of the population. Paper presented at the 4^th European Congress of Anthropology (Florence, Sept. 1984).     

The susceptibility of the poultry red mite,Dermanyssus gallinae (De Geer, 1778), to some acaricides under laboratory conditions

Toxicity of 14 selected acaricides was tested for a laboratory strain of femaleD. gallinae. The most toxic were carbaryl (LC₅₀=5.0 g/m²), deltamethrin (LC₅₀=7.8 g/m²), bendiocarb (LC₅₀=11.1g/m²), and permethrin (LC₅₀=12.6 g/m²). High level resistance to DDT inD. gallinae was recorded, with factors of resistance at LC₅₀/ LC₉₀ reaching 57/73.