Effect of autovaccination on the course of urinary tract infection in animal experiment

Autovaccination of rats with chronic pyelonephritis carried out approximately two months after the onset of infection does not result in an improved histological picture in the infected but can prevent destructive processes in the controlateral kidney. Cyclophosphamide administered in three doses of 30 mg/kg simultaneously with autovaccination slightly modulates the immune response to the infectious strain. The temporal relationship between immunization and cyclophosphamide administration determines the mode of action of cyclophosphamide. In the present experiment, the concept of Miller has not proved to be applicable. Cyclophosphamide administration causes a distinct increase in inflammatory processes in the kidney. Should an enhancement phenomenon be involved in the bacterial infection of the kidney, of which we have found no proof, cyclophosphamide therapy as it was used in the present study would not result in its removal and thus in improved elimination of the infectious organism. Additional experiments are required to determine whether animals subjected to autovaccination are protected against a new episode of urinary tract infection.     

Records Needed for Orthodontic Diagnosis and Treatment Planning: A Systematic Review

Background

Traditionally, dental models, facial and intra-oral photographs and a set of two-dimensional radiographs are used for orthodontic diagnosis and treatment planning. As evidence is lacking, the discussion is ongoing which specific records are needed for the process of making an orthodontic treatment plan.

Objective

To estimate the contribution and importance of different diagnostic records for making an orthodontic diagnosis and treatment plan.

Data sources

An electronic search in PubMed (1948–July 2012), EMBASE Excerpta Medica (1980–July 2012), CINAHL (1982–July 2012), Web of Science (1945–July 2012), Scopus (1996–July 2012), and Cochrane Library (1993–July 2012) was performed. Additionally, a hand search of the reference lists of included studies was performed to identify potentially eligible studies. There was no language restriction.

Study selection

The patient, intervention, comparator, outcome (PICO) question formulated for this study was as follows: for patients who need orthodontic treatment (P), will the use of record set X (I) compared with record set Y (C) change the treatment plan (O)? Only primary publications were included.

Data extraction

Independent extraction of data and quality assessment was performed by two observers.

Results

Of the 1041 publications retrieved, 17 met the inclusion criteria. Of these, 4 studies were of high quality. Because of the limited number of high quality studies and the differences in study designs, patient characteristics, and reference standard or index test, a meta-analysis was not possible.

Conclusion

Cephalograms are not routinely needed for orthodontic treatment planning in Class II malocclusions, digital models can be used to replace plaster casts, and cone-beam computed tomography radiographs can be indicated for impacted canines. Based on the findings of this review, the minimum record set required for orthodontic diagnosis and treatment planning could not be defined.

Systematic review registration number

CRD42012002365     

In-depth qualitative and quantitative analysis of composite glycosylation profiles and other micro-heterogeneity on intact monoclonal antibodies by high-resolution native mass spectrometry using a modified Orbitrap

Here, we describe a fast, easy-to-use, and sensitive method to profile in-depth structural micro-heterogeneity, including intricate N-glycosylation profiles, of monoclonal antibodies at the native intact protein level by means of mass spectrometry using a recently introduced modified Orbitrap Exactive Plus mass spectrometer. We demonstrate the versatility of our method to probe structural micro-heterogeneity by describing the analysis of three types of molecules: (1) a non-covalently bound IgG4 hinge deleted full-antibody in equilibrium with its half-antibody, (2) IgG4 mutants exhibiting highly complex glycosylation profiles, and (3) antibody-drug conjugates. Using the modified instrument, we obtain baseline separation and accurate mass determination of all different proteoforms that may be induced, for example, by glycosylation, drug loading and partial peptide backbone-truncation. We show that our method can handle highly complex glycosylation profiles, identifying more than 20 different glycoforms per monoclonal antibody preparation and more than 30 proteoforms on a single highly purified antibody. In analyzing antibody-drug conjugates, our method also easily identifies and quantifies more than 15 structurally different proteoforms that may result from the collective differences in drug loading and glycosylation. The method presented here will aid in the comprehensive analytical and functional characterization of protein micro-heterogeneity, which is crucial for successful development and manufacturing of therapeutic antibodies     

Differences in early callose deposition during adapted and non-adapted powdery mildew infection of resistant Arabidopsis lines

The deposition of callose, a (1,3)-β-glucan cell wall polymer, can play an essential role in the defense response to invading pathogens. We could recently show that Arabidopsis thaliana lines with an overexpression of the callose synthase gene PMR4 gained complete penetration resistance to the adapted powdery mildew Golovinomyces cichoracearum and the non-adapted powdery mildew Blumeria graminis f. sp hordei. The penetration resistance is based on the transport of the callose synthase PMR4 to the site of attempted fungal penetration and the subsequent formation of enlarged callose deposits. The deposits differed in their total diameter comparing both types of powdery mildew infection. In this study, further characterization of these callose deposits revealed that size differences were especially pronounced in the core region of the deposits. This suggests that specific, pathogen-dependent factors exist, which might regulate callose synthase transport to the core region of forming deposits.     

Thymosin β4 and Tissue Transglutaminase. Molecular Characterization of Cyclic Thymosin β4

Thymosin β₄ is the prototype of β-thymosins and is present in almost every mammalian cell. It is regarded to be the main intracellular G-actin sequestering peptide. Thymosin β₄ serves as a specific glutaminyl substrate for guinea pig transglutaminase. In the absence of an appropriate additional aminyl donor an ε-amino group of thymosin β₄ serves also as an aminyl substrate and an intramolecular bond is formed concomitantly NH₃ (17 Da) is lost. The molecular mass of the product is 4,949.6 Da. This is 16.3 Da less than the molecular mass of thymosin β₄ (4,965.9 Da). Digestion with endopeptidases and Edman degradation of the fragments identified the exact position of the ring forming isopeptide bond. In spite of 3 glutaminyl and 9 lysyl residues of thymosin β₄ only one isopeptide bond between Lys16 and Gln36 was formed (cyclic thymosin β₄). These two amino acid residues are conserved in all β-thymosins. Cyclic thymosin β₄ still forms a complex with G-actin albeit the stability of the complex is about one fiftieth of the stability of the thymosin β₄ × G-actin complex.