Site-Directed Immobilization of an Engineered Bone Morphogenetic Protein 2 (BMP2) Variant to Collagen-Based Microspheres Induces Bone Formation In Vivo

For the treatment of large bone defects, the commonly used technique of autologous bone grafting presents several drawbacks and limitations. With the discovery of the bone-inducing capabilities of bone morphogenetic protein 2 (BMP2), several delivery techniques were developed and translated to clinical applications. Implantation of scaffolds containing adsorbed BMP2 showed promising results. However, off-label use of this protein-scaffold combination caused severe complications due to an uncontrolled release of the growth factor, which has to be applied in supraphysiological doses in order to induce bone formation. Here, we propose an alternative strategy that focuses on the covalent immobilization of an engineered BMP2 variant to biocompatible scaffolds. The new BMP2 variant harbors an artificial amino acid with a specific functional group, allowing a site-directed covalent scaffold functionalization. The introduced artificial amino acid does not alter BMP2′s bioactivity in vitro. When applied in vivo, the covalently coupled BMP2 variant induces the formation of bone tissue characterized by a structurally different morphology compared to that induced by the same scaffold containing ab-/adsorbed wild-type BMP2. Our results clearly show that this innovative technique comprises translational potential for the development of novel osteoinductive materials, improving safety for patients and reducing costs.     

Obesity and Male Reproduction: Do Sirtuins Play a Role?

Obesity is a major current public health problem of global significance. A progressive sperm quality decline, and a decline in male fertility, have been reported in recent decades. Several studies have reported a strict relationship between obesity and male reproductive dysfunction. Among the many mechanisms by which obesity impairs male gonadal function, sirtuins (SIRTs) have an emerging role. SIRTs are highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases that play a role in gene regulation, metabolism, aging, and cancer. SIRTs regulate the energy balance, the lipid balance, glucose metabolism, and adipogenesis, but current evidence also indicates a role for SIRTs in male reproduction. However, the majority of the studies have been conducted in animal models and very few have been conducted with humans. This review shows that SIRTs play an important role among the molecular mechanisms by which obesity interferes with male fertility. This highlights the need to deepen this relationship. It will be of particular interest to evaluate whether synthetic and/or natural compounds capable of modifying the activity of SIRTs may also be useful for the treatment of obesity and its effects on gonadal function. Although few studies have explored the role of SIRT activators in obesity-induced male infertility, some molecules, such as resveratrol, appear to be effective in modulating SIRT activity, as well as counteracting the negative effects of obesity on male fertility. The search for strategies to improve male reproductive function in overweight/obese patients is a challenge and understanding the role of SIRTs and their activators may open new interesting scenarios in the coming years.     

Effect of Acid Hydrolysis and Ball Milling on Porous Corn Starch

Porous corn starch from glucoamylase hydrolysis of native corn starch was examined before and after cross-linking, acid hydrolysis and dry ball milling. Cross-linking does not significantly change the crystallinity, water absorption or gelatinisation properties but acid hydrolysis at 60°C increases, proportionately, crystallinity and water absorption capacity and decreases moisture adsorption at humidities less than 80%, in comparison to untreated porous corn starch. Highly crystalline porous starch has a fragile granule structure. Ball milling destroys crystallinity in both normal, porous, and cross-linked or partially hydrolyzed starches. Particle sizes of 1–2m are obtained by milling dry starches for 48 h. Water absorption for milled starches is more than 200% (weight water/weight starch d.b.). Viscosities of these products were significantly reduced at high temperatures. Products formed stable gels in 25–30% dispersions in cold water.     

Gaucher Disease Diagnosis Using Lyso-Gb1 on Dry Blood Spot Samples: Time to Change the Paradigm?

For years, the gold standard for diagnosing Gaucher disease (GD) has been detecting reduced β-glucocerebrosidase (GCase) activity in peripheral blood cells combined with GBA1 mutation analysis. The use of dried blood spot (DBS) specimens offers many advantages, including easy collection, the need for a small amount of blood, and simpler transportation. However, DBS has limitations for measuring GCase activity. In this paper, we recount our cross-sectional study and publish seven years of experience using DBS samples and levels of the deacylated form of glucocerebroside, glucosylsphingosine (lyso-Gb1), for GD diagnosis. Of 444 screened subjects, 99 (22.3%) were diagnosed with GD at a median (range) age of 21 (1–78) years. Lyso-Gb levels for genetically confirmed GD patients vs. subjects negative to GD diagnosis were 252 (9–1340) ng/mL and 5.4 (1.5–16) ng/mL, respectively. Patients diagnosed with GD1 and mild GBA1 variants had lower median (range) lyso-Gb1, 194 (9–1050), compared to GD1 and severe GBA1 variants, 447 (38–1340) ng/mL, and neuronopathic GD, 325 (116–1270) ng/mL (p = 0.001). Subjects with heterozygous GBA1 variants (carrier) had higher lyso-Gb1 levels, 5.8 (2.5–15.3) ng/mL, compared to wild-type GBA1, 4.9 (1.5–16), ng/mL (p = 0.001). Lyso-Gb1 levels, median (range), were 5 (2.7–10.7) in heterozygous GBA1 carriers with Parkinson’s disease (PD), similar to lyso-Gb1 levels in subjects without PD. We call for a paradigm change for the diagnosis of GD based on lyso-Gb1 measurements and confirmatory GBA1 mutation analyses in DBS. Lyso-Gb1 levels could not be used to differentiate between heterozygous GBA1 carriers and wild type.     

Cellular and Molecular Signatures of Oxidative Stress in Bronchial Epithelial Cell Models Injured by Cigarette Smoke Extract

Exposure of the airways epithelium to environmental insults, including cigarette smoke, results in increased oxidative stress due to unbalance between oxidants and antioxidants in favor of oxidants. Oxidative stress is a feature of inflammation and promotes the progression of chronic lung diseases, including Chronic Obstructive Pulmonary Disease (COPD). Increased oxidative stress leads to exhaustion of antioxidant defenses, alterations in autophagy/mitophagy and cell survival regulatory mechanisms, thus promoting cell senescence. All these events are amplified by the increase of inflammation driven by oxidative stress. Several models of bronchial epithelial cells are used to study the molecular mechanisms and the cellular functions altered by cigarette smoke extract (CSE) exposure, and to test the efficacy of molecules with antioxidant properties. This review offers a comprehensive synthesis of human in-vitro and ex-vivo studies published from 2011 to 2021 describing the molecular and cellular mechanisms evoked by CSE exposure in bronchial epithelial cells, the most used experimental models and the mechanisms of action of cellular antioxidants systems as well as natural and synthetic antioxidant compounds.     

PET Recycling – Contributions of Crystallization to Sustainability

Polyethylene terephthalate (PET) is one of the most common thermoplastic polymers and its durability has become a major environmental concern. The current public debate on plastic debris also triggered the revision of PET recycling technologies. This Research Article focuses on the chemical recycling of PET by means of methanolysis. The process degrades PET into two main reaction products, dimethyl terephthalate (DMT) and ethylene glycol (EG). Subsequent separation by distillation combined with crystallization removes critical impurities and non-PET components from co-polymers, providing monomers of high purity needed for re-polymerization purposes.     

Amine-impregnated natural zeolite as filler in mixed matrix membranes for CO2/CH4 separation

Flat mixed matrix membranes (MMMs) comprising polysulfone and clinoptilolite-type natural zeolite were prepared by casting. Zeolite was modified with three alkylamines: ethanolamine (EA), bis(2-hydroxypropyl)amine (BHPA), and polyethylenimine (PEI) by the impregnation method. Impregnated zeolite samples were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, and N₂ adsorption–desorption. The alkylamine loading extent determined by thermogravimetric analysis was 5.2, 4.8, and 8.5% for EA, BHPA, and PEI, respectively. Analyses of MMMs showed that the incorporation of impregnated zeolite affected the glass-transition temperature (T_g) and mixed-gas transport properties. In this regard, a decreasing trend of the T_g values from 185.5 °C for the polymeric membrane up to 176.6 °C for Clino-EA-based MMM was recorded. In addition, the gas separation performance was evaluated at two different feed pressures. At 50 psi, MMMs showed an enhancement up to 30% on the CO₂ permeability (22.79 Barrer) and 55% on the CO₂/CH₄ selectivity (45.78) in comparison with the polymeric membrane (CO₂ permeability 17.34 Barrer; CO₂/CH₄ selectivity 29.38). These values varied depending on the alkylamine, BHPA being the most selective. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48286.     

Development and characterization of inks for screen printing of glass solders for SOFCs

Glass ceramics are supposed to produce stable sealants between ceramic electrolyte and ferritic steel in planar SOFC stacks. The screen printing method is a suitable industrial process in order to produce layers with tailored height and width reproducibly. An appropriate suspension was developed for this application and improved by adjusting the additive composition. This study investigates the rheological behavior of screen printing inks and the corresponding topography of the printed layers. Rotary measurements were carried out to analyse the impact of shear rates on viscosity showing shear thinning behavior. In addition, oscillatory rheometry is performed to gain information about the viscoelastic properties of the slurries and to understand the internal structure of the developed inks. The viscoelasticity and the recovery behavior after shear loading are crucial for the topography of printed films. The principal investigations are executed on solvent-based suspensions, whereby the knowledge gained is used for a transfer to water-based systems allowing a more environmentally friendly handling.     

New WS9326A Derivatives and One New Annimycin Derivative with Antimalarial Activity are Produced by Streptomyces asterosporus DSM 41452 and Its Mutant

In this study, we report that Streptomyces asterosporus DSM 41452 is a producer of new molecules related to the nonribosomal cyclodepsipeptide WS9326A and the polyketide annimycin. S. asterosporus DSM 41452 is shown to produce six cyclodepsipeptides and peptides, WS9326A to G. Notably, the compounds WS9326F and WS9326G have not been described before. The genome of S. asterosporus DSM 41452 was sequenced, and a putative WS9326A gene cluster was identified. Gene‐deletion experiments confirmed that this cluster was responsible for the biosynthesis of WS9326A to G. Additionally, a gene‐deletion experiment demonstrated that sas16 encoding a cytochrome P450 monooxygenase was involved in the synthesis of the novel (E)‐2,3‐dehydrotyrosine residue found in WS9326A and its derivatives. An insertion mutation within the putative annimycin gene cluster led to the production of a new annimycin derivative, annimycin B, which exhibited modest inhibitory activity against Plasmodium falciparum.     

Cuticular Hydrocarbons as Sex Pheromone of the Bee <Emphasis Type="Italic">Colletes cunicularius</Emphasis> and the Key to its Mimicry by the Sexually Deceptive Orchid, <Emphasis Type="Italic">Ophrys exaltata</Emphasis>

Male Colletes cunicularius bees pollinate the orchid, Ophrys exaltata, after being sexually deceived by the orchid’s odor-mimicry of the female bee’s sex pheromone. We detected biologically active volatiles of C. cunicularius by using gas chromatographic–electroantennographic detection (GC-EAD) with simultaneous flame ionization detection. After identification of the target compounds by coupled gas chromatography–mass spectrometry (GC-MS), we performed behavioral tests using synthetic blends of the active components. We detected 22 EAD active compounds in cuticular extracts of C. cunicularius females. Blends of straight chain, odd-numbered alkanes and (Z)-7-alkenes with 21–29 carbon atoms constituted the major biologically active compounds. Alkenes were the key compounds releasing mating behavior, especially those with (Z)-7 unsaturation. Comparison of patterns of bee volatiles with those of O. exaltata subsp. archipelagi revealed that all EAD-active compounds were also found in extracts of orchid labella. Previous studies of the mating behavior in C. cunicularius showed linalool to be an important attractant for patrolling males. We confirmed this with synthetic linalool but found that it rarely elicited copulatory behavior, in accordance with previous studies. A blend of active cuticular compounds with linalool elicited both attraction and copulation behavior in patrolling males. Thus, linalool appears to function as a long-range attractant, whereas cuticular hydrocarbons are necessary for inducing short-range mating behavior.