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The application of alkane tricosane (n-C23) to non-nestmates decreases aggression towards them in ants, in line with its high level in infected workers, pointing at a pacifying signal in parasitic interferences in ant nestmate discrimination.

Barrier membranes are commonly used as part of the dental surgical technique guided bone regeneration (GBR) and are often made of resorbable collagen or non-resorbable materials such as PTFE. While collagen membranes do not provide sufficient mechanical protection of the covered bone defect, titanium reinforced membranes and non-resorbable membranes need to be removed in a second surgery. Thus, biodegradable GBR membranes made of pure magnesium might be an alternative. In this study a biodegradable pure magnesium (99.95%) membrane has been proven to have all of the necessary requirements for an optimal regenerative outcome from both a mechanical and biological perspective. After implantation, the magnesium membrane separates the regenerating bone from the overlying, faster proliferating soft tissue. During the initial healing period, the membrane maintained a barrier function and space provision, whilst retaining the positioning of the bone graft material within the defect space. As the magnesium metal corroded, it formed a salty corrosion layer and local gas cavities, both of which extended the functional lifespan of the membrane barrier capabilities. During the resorption of the magnesium metal and magnesium salts, it was observed that the membrane became surrounded and then replaced by new bone. After the membrane had completely resorbed, only healthy tissue remained. The in vivo performance study demonstrated that the magnesium membrane has a comparable healing response and tissue regeneration to that of a resorbable collagen membrane. Overall, the magnesium membrane demonstrated all of the ideal qualities for a barrier membrane used in GBR treatment.

An ideal fixation system for guided bone (GBR) regeneration in oral surgery must fulfil several criteria that includes the provision of adequate mechanical fixation, complete resorption when no longer needed, complete replacement by bone, as well as be biocompatible and have a good clinical manageability. For the first time, a biodegradable magnesium fixation screw made of the magnesium alloy WZM211 with a MgF2 coating has been designed and tested to fulfill these criteria. Adequate mechanical fixation was shown for the magnesium fixation screw in several benchtop tests that directly compared the magnesium fixation screw with an equivalent polymeric resorbable device. Results demonstrated slightly superior mechanical properties of the magnesium device in comparison to the polymeric device even after 4 weeks of degradation. Biocompatibility of the magnesium fixation screw was demonstrated in several in vitro and in vivo tests. Degradation of the magnesium screw was investigated in in vitro and in vivo tests, where it was found that the screw is resorbed slowly and completely after 52 weeks, providing adequate fixation in the early critical healing phase. Overall, the magnesium fixation screw demonstrates all of the key properties required for an ideal fixation screw of membranes used in guided bone regeneration (GBR) surgeries.

The recent classification of pediatric thrombotic microangiopathies (TMA) takes into consideration mechanisms of disease for guidance to targeted therapies. We present our experience with seven patients with antibody mediated atypical hemolytic uremic syndrome (aHUS) and thrombotic thrombocytopenic purpura (TTP). Five children had aHUS with antibodies against complement factor H (CFH-ab) and two with TTP with antibodies against metalloproteinase ADAMTS13. In the aHUS cases diagnosed and treated before the eculizumab era, CFH-ab was detected using the ELISA assay. Mutational analysis of selected complement genes was performed. TTP was diagnosed if, in addition to microangiopathic hemolytic anemia and thrombocytopenia, ischemic organ involvement and severe deficiency in ADAMTS13 activity were present. Treatment protocol consisted of plasma exchanges (PE) and steroid pulses, followed by the combination of cyclophosphamide and rituximab to achieve long-term immunosuppression. Four patients with CFH-ab and the TTP patients with ADAMTS13 antibodies came into sustained remission. After a median follow-up of 11.7 (range 7.7–12.9) years without maintenance therapy, no disease recurrence was observed; nevertheless, six patients, two had hypertension and two had proteinuria as a late consequence. One patient, with late diagnosis of CFH-ab and additional genetic risk factors who was treated only with PE and plasma substitution, reached end-stage renal disease and was later successfully transplanted using eculizumab prophylaxis. In the cases of antibody-mediated TMAs, PE and early immunosuppressive treatment may result in sustained remission with preserved kidney function. Further data are needed to establish optimal treatment of anti-FH antibody-associated HUS.

Intrinsically disordered proteins mediate crucial biological functions through their interactions with other proteins. Mutual synergistic folding (MSF) occurs when all interacting proteins are disordered, folding into a stable structure in the course of the complex formation. In these cases, the folding and binding processes occur in parallel, lending the resulting structures uniquely heterogeneous features. Currently there are no dedicated classification approaches that take into account the particular biological and biophysical properties of MSF complexes. Here, we present a scalable clustering-based classification scheme, built on redundancy-filtered features that describe the sequence and structure properties of the complexes and the role of the interaction, which is directly responsible for structure formation. Using this approach, we define six major types of MSF complexes, corresponding to biologically meaningful groups. Hence, the presented method also shows that differences in binding strength, subcellular localization, and regulation are encoded in the sequence and structural properties of proteins. While current protein structure classification methods can also handle complex structures, we show that the developed scheme is fundamentally different, and since it takes into account defining features of MSF complexes, it serves as a better representation of structures arising through this specific interaction mode.

The success of methods for predicting the redox state of cysteine residues from the sequence environment seemed to validate the basic assumption that this state is mainly determined locally. However, the accuracy of predictions on randomized sequences or of non-cysteine residues remained high, suggesting that these predictions rather capture global features of proteins such as subcellular localization, which depends on composition. This illustrates that even high prediction accuracy is insufficient to validate implicit assumptions about a biological phenomenon. Correctly identifying the relevant underlying biochemical reasons for the success of a method is essential to gain proper biological insights and develop more accurate and novel bioinformatics tools.

Lengthy co-evolution of Homo sapiens and Mycobacterium tuberculosis, the main causative agent of tuberculosis, resulted in a dramatically successful pathogen species that presents considerable challenge for modern medicine. The continuous and ever increasing appearance of multi-drug resistant mycobacteria necessitates the identification of novel drug targets and drugs with new mechanisms of action. However, further insights are needed to establish automated protocols for target selection based on the available complete genome sequences. In the present study, we perform complete proteome level comparisons between M. tuberculosis, mycobacteria, other prokaryotes and available eukaryotes based on protein domains, local sequence similarities and protein disorder. We show that the enrichment of certain domains in the genome can indicate an important function specific to M. tuberculosis. We identified two families, termed pkn and PE/PPE that stand out in this respect. The common property of these two protein families is a complex domain organization that combines species-specific regions, commonly occurring domains and disordered segments. Besides highlighting promising novel drug target candidates in M. tuberculosis, the presented analysis can also be viewed as a general protocol to identify proteins involved in species-specific functions in a given organism. We conclude that target selection protocols should be extended to include proteins with complex domain architectures instead of focusing on sequentially unique and essential proteins only.

Many disordered proteins function via binding to a structured partner and undergo a disorder-to-order transition. The coupled folding and binding can confer several functional advantages such as the precise control of binding specificity without increased affinity. Additionally, the inherent flexibility allows the binding site to adopt various conformations and to bind to multiple partners. These features explain the prevalence of such binding elements in signaling and regulatory processes. In this work, we report ANCHOR, a method for the prediction of disordered binding regions. ANCHOR relies on the pairwise energy estimation approach that is the basis of IUPred, a previous general disorder prediction method. In order to predict disordered binding regions, we seek to identify segments that are in disordered regions, cannot form enough favorable intrachain interactions to fold on their own, and are likely to gain stabilizing energy by interacting with a globular protein partner. The performance of ANCHOR was found to be largely independent from the amino acid composition and adopted secondary structure. Longer binding sites generally were predicted to be segmented, in agreement with available experimentally characterized examples. Scanning several hundred proteomes showed that the occurrence of disordered binding sites increased with the complexity of the organisms even compared to disordered regions in general. Furthermore, the length distribution of binding sites was different from disordered protein regions in general and was dominated by shorter segments. These results underline the importance of disordered proteins and protein segments in establishing new binding regions. Due to their specific biophysical properties, disordered binding sites generally carry a robust sequence signal, and this signal is efficiently captured by our method. Through its generality, ANCHOR opens new ways to study the essential functional sites of disordered proteins.