Synthetic beta-solenoid proteins with the fragment-free computational design of a beta-hairpin extension

The ability to design and construct structures with atomic level precision is one of the key goals of nanotechnology. Proteins offer an attractive target for atomic design, as they can be synthesized chemically or biologically, and can self-assemble. However the generalized protein folding and design problem is unsolved. One approach to simplifying the problem is to use a repetitive protein as a scaffold. Repeat proteins are intrinsically modular, and their folding and structures are better understood than large globular domains. Here, we have developed a new class of synthetic repeat protein, based on the pentapeptide repeat family of beta-solenoid proteins. We have constructed length variants of the basic scaffold, and computationally designed de novo loops projecting from the scaffold core. The experimentally solved 3.56 ˚A resolution crystal structure of one designed loop matches closely the designed hairpin structure, showing the computational design of a backbone extension onto a synthetic protein core without the use of backbone fragments from known structures. Two other loop designs were not clearly resolved in the crystal structures and one loop appeared to be in an incorrect conformation. We have also shown that the repeat unit can accommodate whole domain insertions by inserting a domain into one of the designed loops

Accelerated diabetic wound healing by topical application of combination oral antidiabetic agents-loaded nanofibrous scaffolds: An in vitro and in vivo evaluation study

The combination of oral antidiabetic drugs, pioglitazone, metformin, and glibenclamide, which also exhibit the strongest anti-inflammatory action among oral antidiabetic drugs, were loaded into chitosan/gelatin/polycaprolactone (PCL) by electrospinning and polyvinyl pyrrolidone (PVP)/PCL composite nanofibrous scaffolds by pressurized gyration to compare the diabetic wound healing effect. The combination therapies significantly accelerated diabetic wound healing in type-1 diabetic rats and organized densely packed collagen fibers in the dermis, it also showed better regeneration of the dermis and epidermis than single drug-loaded scaffolds with less inflammatory cell infiltration and edema. The formation of the hair follicles started in 14 days only in the combination therapy and lower proinflammatory cytokine levels were observed compared to single drug-loaded treatment groups. The combination therapy increased the wettability and hydrophilicity of scaffolds, demonstrated sustained drug release over 14 days, has high tensile strength and suitable cytocompatibility on L929 (mouse fibroblast) cell and created a suitable area for the proliferation of fibroblast cells. Consequently, the application of metformin and pioglitazone-loaded chitosan/gelatin/PCL nanofibrous scaffolds to a diabetic wound area offer high bioavailability, fewer systemic side effects, and reduced frequency of dosage and amount of drug

A novel treatment strategy for preterm birth: Intra-vaginal progesterone-loaded fibrous patches

Progesterone-loaded poly(lactic) acid fibrous polymeric patches were produced using electrospinning and pressurized gyration for intra-vaginal application to prevent preterm birth. The patches were intravaginally inserted into rats in the final week of their pregnancy, equivalent to the third trimester of human pregnancy. Maintenance tocolysis with progesterone-loaded patches was elucidated by recording the contractile response of uterine smooth muscle to noradrenaline in pregnant rats. Both progesterone-loaded patches indicated similar results from release and thermal studies, however, patches obtained by electrospinning had smaller average diameters and more uniform dispersion compared to pressurized gyration. Patches obtained by pressurized gyration had better results in production yield and tensile strength than electrospinning; thereby pressurized gyration is better suited for scaled-up production. The patches did not affect cell attachment, viability, and proliferation on Vero cells negatively. Consequently, progesterone-loaded patches are a novel and successful treatment strategy for preventing preterm birth

New Mediterranean Marine biodiversity records

Based on recent biodiversity studies carried out in different parts of the Mediterranean, the following 19 species are included as new records on the floral or faunal lists of the relevant ecosystems: the green algae Penicillus capitatus (Maltese waters); the nemertean Amphiporus allucens (Iberian Peninsula, Spain); the salp Salpa maxima (Syria); the opistobranchs Felimida britoi and Berghia coerulescens (Aegean Sea, Greece); the dusky shark Carcharhinus obscurus (central-west Mediterranean and Ionian Sea, Italy); Randall’s threadfin bream Nemipterus randalli, the broadbanded cardinalfish Apogon fasciatus and the goby Gobius kolombatovici (Aegean Sea, Turkey); the reticulated leatherjack Stephanolepis diaspros and the halacarid Agaue chevreuxi (Sea of Marmara, Turkey); the slimy liagora Ganonema farinosum, the yellowstripe barracuda Sphyraena chrysotaenia, the rayed pearl oyster Pinctada imbricata radiata and the Persian conch Conomurex persicus (south-eastern Kriti, Greece); the blenny Microlipophrys dalmatinus and the bastard grunt Pomadasys incisus (Ionian Sea, Italy); the brown shrimp Farfantepenaeus aztecus (north-eastern Levant, Turkey); the blue-crab Callinectes sapidus (Corfu, Ionian Sea, Greece). In addition, the findings of the following rare species improve currently available biogeographical knowledge: the oceanic pufferfish Lagocephalus lagocephalus (Malta); the yellow sea chub Kyphosus incisor (Almuñécar coast of Spain); the basking shark Cetorhinus maximus and the shortfin mako Isurus oxyrinchus (north-eastern Levant, Turkey)

Infliximab plus methotrexate is superior to methotrexate alone in the treatment of psoriatic arthritis in methotrexate-naive patients: the RESPOND study

Objective: To compare the efficacy and safety of treatment with infliximab plus methotrexate with methotrexate alone in methotrexate-naive patients with active psoriatic arthritis (PsA). Methods: In this open-label study, patients 18 years and older with active PsA who were naive to methotrexate and not receiving disease-modifying therapy (N=115) were randomly assigned (1:1) to receive either infliximab (5 mg/kg) at weeks 0, 2, 6 and 14 plus methotrexate (15 mg/week); or methotrexate (15 mg/week) alone. The primary assessment was American College of Rheumatology (ACR) 20 response at week 16. Secondary outcome measures included psoriasis area and severity index (PASI), disease activity score in 28 joints (DAS28) and dactylitis and enthesitis assessments. Results: At week 16, 86.3% of patients receiving infliximab plus methotrexate and 66.7% of those receiving methotrexate alone achieved an ACR20 response (p<0.02). Of patients whose baseline PASI was 2.5 or greater, 97.1% receiving infliximab plus methotrexate compared with 54.3% receiving methotrexate alone experienced a 75% or greater improvement in PASI (p<0.0001). Improvements in C-reactive protein levels, DAS28 response and remission rates, dactylitis, fatigue and morning stiffness duration were also significantly greater in the group receiving infliximab. In the infliximab plus methotrexate group, 46% (26/57) had treatment-related adverse events (AE) and two patients had serious AE, compared with 24% with AE (13/54) and no serious AE in the methotrexate-alone group. Conclusions: Treatment with infliximab plus methotrexate in methotrexate-naive patients with active PsA demonstrated significantly greater ACR20 response rates and PASI75 improvement compared with methotrexate alone and was generally well tolerated. This trial is registered in the US National Institutes of Health clinicaltrials.gov database, identifier NCT00367237

New Mediterranean marine biodiversity records (December, 2013)

Based on recent biodiversity studies carried out in different parts of the Mediterranean, the following 19 species are included as new records on the floral or faunal lists of the relevant ecosystems: the green algae Penicillus capitatus (Maltese waters); the nemertean Am- phiporus allucens (Iberian Peninsula, Spain); the salp Salpa maxima (Syria); the opistobranchs Felimida britoi and Berghia coerulescens (Aegean Sea, Greece); the dusky shark Carcharhinus obscurus (central-west Mediterranean and Ionian Sea, Italy); Randall’s threadfin bream Nemipterus randalli, the broadbanded cardinalfish Apogon fasciatus and the goby Gobius kolombatovici (Aegean Sea, Turkey); the reticulated leatherjack Stephanolepis diaspros and the halacarid Agaue chevreuxi (Sea of Marmara, Turkey); the slimy liagora Ganon- ema farinosum, the yellowstripe barracuda Sphyraena chrysotaenia, the rayed pearl oyster Pinctada imbricata radiata and the Persian conch Conomurex persicus (south-eastern Kriti, Greece); the blenny Microlipophrys dalmatinus and the bastard grunt Pomadasys incisus (Ionian Sea, Italy); the brown shrimp Farfantepenaeus aztecus (north-eastern Levant, Turkey); the blue-crab Callinectes sapidus (Corfu, Ionian Sea, Greece). In addition, the findings of the following rare species improve currently available biogeographical knowledge: the oceanic pufferfish Lagocephalus lagocephalus (Malta); the yellow sea chub Kyphosus incisor (Almuñécar coast of Spain); the basking shark Cetorhinus maximus and the shortfin mako Isurus oxyrinchus (north-eastern Levant, Turkey).peer-reviewe

MEDLEM database, a data collection on large elasmobranchs in the Mediterranean and Black Seas

The Mediterranean Large Elasmobranchs Monitoring (MEDLEM) database contains more than 3,000 records (with more than 4,000 individuals) of large elasmobranch species from 21 different countries around the Mediterranean and Black seas, observed from 1666 to 2017. The principal species included in the archive are the devil ray (1,868 individuals), the basking shark (935 individuals), the blue shark (622 individuals), and the great white shark (342 individuals). In the last decades, other species such as the thresher shark (187 individuals), the shortfin mako (180 individuals), and the spiny butterfly ray (138) were reported with increasing frequency. This was possibly due to increased public awareness on the conservation status of sharks, and the consequent development of new monitoring programs. MEDLEM does not have homogeneous reporting coverage throughout the Mediterranean and Black seas and it should be considered as a database of observed species presence. Scientific monitoring efforts in the south-eastern Mediterranean and Black seas are generally lower than in the northern sectors and the absence of some species in our database does not imply their actual absence in these regions. However, the available data allowed us to analyse the frequency and spatial distribution of records, the size frequencies for a few selected the available data allowed us to analyse the frequency and spatial distribution of records, the size frequencies for a few selected species, the overall area coverage, and which species are involved as bycatch by different fishing gears

Cultural and leadership predictors of corporate social responsibility values of top management: A GLOBE study of 15 countries.

This paper examines cultural and leadership variables associated with corporate social responsibility values that managers apply to their decision-making. In this longitudinal study, we analyze data from 561 firms located in 15 countries on five continents to illustrate how the cultural dimensions of institutional collectivism and power distance predict social responsibility values on the part of top management team members. CEO visionary leadership and integrity were also uniquely predictive of such values. Journal of International Business Studies (2006) 37, 823–837. doi:10.1057/palgrave.jibs.8400230