Why Has the Number of Scientific Retractions Increased?

Background

The number of retracted scientific publications has risen sharply, but it is unclear whether this reflects an increase in publication of flawed articles or an increase in the rate at which flawed articles are withdrawn.

Methods and Findings

We examined the interval between publication and retraction for 2,047 retracted articles indexed in PubMed. Time-to-retraction (from publication of article to publication of retraction) averaged 32.91 months. Among 714 retracted articles published in or before 2002, retraction required 49.82 months; among 1,333 retracted articles published after 2002, retraction required 23.82 months (p<0.0001). This suggests that journals are retracting papers more quickly than in the past, although recent articles requiring retraction may not have been recognized yet. To test the hypothesis that time-to-retraction is shorter for articles that receive careful scrutiny, time-to-retraction was correlated with journal impact factor (IF). Time-to-retraction was significantly shorter for high-IF journals, but only ∼1% of the variance in time-to-retraction was explained by increased scrutiny. The first article retracted for plagiarism was published in 1979 and the first for duplicate publication in 1990, showing that articles are now retracted for reasons not cited in the past. The proportional impact of authors with multiple retractions was greater in 1972–1992 than in the current era (p<0.001). From 1972–1992, 46.0% of retracted papers were written by authors with a single retraction; from 1993 to 2012, 63.1% of retracted papers were written by single-retraction authors (p<0.001).

Conclusions

The increase in retracted articles appears to reflect changes in the behavior of both authors and institutions. Lower barriers to publication of flawed articles are seen in the increase in number and proportion of retractions by authors with a single retraction. Lower barriers to retraction are apparent in an increase in retraction for “new” offenses such as plagiarism and a decrease in the time-to-retraction of flawed work.     

A disulfide-bonded short chain collagen synthesized by degenerative and calcifying zones of bovine growth plate cartilage

Studies of collagen synthesis by specific sections of individual fetal bovine costochondral junction growth plates were conducted and histologically related to the zones from which the sections were derived. Sections were metabolically labeled in organ culture to examine the synthesis of collagen and its precursors. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that Type II collagen was the major species synthesized in all tissue sections; 1 alpha, 2 alpha, 3 alpha collagen chains were synthesized in all growth plate sections and to a small extent in the fetal structural cartilage. A short chain collagen was synthesized predominantly in the zones of degeneration and provisional calcification and accounted for 8-12% of the radioactivity in this section. This short chain collagen has 63-kDa subunits which are converted to 46-kDa species by limited proteolysis with pepsin. Two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated that both the pepsin- and non-pepsin-treated forms of short chain collagen are disulfide-bonded. Digestion with bacterial collagenase showed that the 46-kDa and a major portion of the 63-kDa forms are collagenous. Pulse-chase studies in organ culture did not demonstrate an obvious precursor to the 63-kDa form, and there was no conversion to the 46-kDa after 20 h. Synthesis of short chain collagen appears to be specific to the process of endochondral ossification in the growth plate; its appearance may be critical to this transition process.     

A Comparison of the Iron Bonding in Anhydrohemoglobin and Anhydromyoglobin

Mössbauer effect measurements show that the ferrous ions in dehydrated deoxymyoglobin are in the high spin state while those in dehydrated deoxyhemoglobin (AHb) are equally distributed between high and low spin states. It is concluded that the two spin states present in AHb are associated with the iron site difference of the α- and β-chains.     

Beta2 Adrenergic Receptor (ADRβ2) Haplotype Pair (2/4) Is Associated with Severe Asthma

Background

β2 adrenergic receptor (ADRβ2) polymorphisms including ADRβ2+46G>A have been reported to cause adverse outcomes in mild asthmatics. The extent to which ADRβ2 polymorphisms and in particular their haplotypes contribute to severe asthma is unknown.

Objective

To determine the association of ADRβ2 polymorphisms and haplotypes with asthma severity.

Methods

Caucasians (n = 2979) were genotyped for 11 ADRβ2 polymorphisms. The cohort (mean age 39.6, 60% female) included 2296 non-asthmatics, 386 mild asthmatics, 172 moderate asthmatics and 125 severe asthmatics. Haplotype frequency and haplotype pair for each subject was determined using the PHASE algorithm.

Results

The three asthmatic cohorts were comparable in age and gender but were distinguishable from each other in terms of symptoms, spirometry, medication use and health care utilisation (p <0.001). None of the polymorphisms showed a genotypic or allelic association with asthma diagnosis or severity. Nine haplotypes were identified and no association was found with asthma diagnosis or severity per se. Haplotype pair 2/4 was associated with asthma severity (Trend Test, OR 1.42, p = 0.0008) but not with asthma per se. Prevalence of haplotype pair 2/2 appeared to decrease with asthma severity (Trend Test, OR 0.78, p = 0.067). Two new haplotypes were identified, occurring exclusively in asthmatics at a frequency of ≥ 1%. In addition, a positive association between carriage of ADRβ2 +523*C and increased risk of atopy was discovered.

Conclusions

ADRβ2 haplotype pair 2/4 is associated with severe asthma and is consistent with findings of poor bronchodilator response in mild asthmatics who are also haplotype 2/4.     

Seed banks of a southern Australian wetland: the influence of water regime on the final floristic composition

The sediments of a southern Australian wetland complex were investigated to determine the germinable seed bank. The number of seeds ranged from 22,000 to 78,000 m^–2. Non-metric multi dimensional scaling (NMS) ordination based upon species composition separated the four basins but each contained the representatives of the major functional groups: terrestrial, amphibious and submerged. To test the influence of water regime on the final floristic composition derived from these seed banks, sediments were positioned at three elevations (0, 30 and 80 cm) and subjected to three hydrologic regimes (static water level, and draw down rates of 2.5 and 7 cm week^–1). Species compositions were analysed after 98 days via ordination. Despite significant differences in the initial seed bank composition the final floristic compositions were correlated with the water regime and independent of the initial seed bank composition. Species groups were segregated on a basis of whether sediments were continuously exposed to the atmosphere, the rate of draw down and the water depth. Moist sediments were dominated by species belonging to all the main functional groups. Sediments subject to rapid drying were dominated by terrestrial species whereas sediments that were flooded for the majority of the time were dominated by submerged species.     

A deletion mutant of vitronectin lacking the somatomedin B domain exhibits residual plasminogen activator inhibitor-1-binding activity

Vitronectin and plasminogen activator inhibitor-1 (PAI-1) are important physiological binding partners that work in concert to regulate cellular adhesion, migration, and fibrinolysis. The high affinity binding site for PAI-1 is located within the N-terminal somatomedin B domain of vitronectin; however, several studies have suggested a second PAI-1-binding site within vitronectin. To investigate this secondary site, a vitronectin mutant lacking the somatomedin B domain (rDeltasBVN) was engineered. The short deletion had no effect on heparin-binding, integrin-binding, or cellular adhesion. Binding to the urokinase receptor was completely abolished while PAI-1 binding was still observed, albeit with a lower affinity. Analytical ultracentrifugation on the PAI-1-vitronectin complex demonstrated that increasing NaCl concentration favors 1:1 versus 2:1 PAI-1-vitronectin complexes and hampers formation of higher order complexes, pointing to the contribution of charge-charge interactions for PAI-1 binding to the second site. Furthermore, fluorescence resonance energy transfer between differentially labeled PAI-1 molecules confirmed that two independent molecules of PAI-1 are capable of binding to vitronectin. These results support a model for the assembly of higher order PAI-1-vitronectin complexes via two distinct binding sites in both proteins.     

Targeted expression of redesigned and codon optimised synthetic gene leads to recrystallisation inhibition and reduced electrolyte leakage in spring wheat at sub-zero temperatures

Antifreeze proteins (AFPs) adsorb to ice crystals and inhibit their growth, leading to non-colligative freezing point depression. Crops like spring wheat, that are highly susceptible to frost damage, can potentially be made frost tolerant by expressing AFPs in the cytoplasm and apoplast where ice recrystallisation leads to cellular damage. The protein sequence for HPLC-6 α-helical antifreeze protein from winter flounder was rationally redesigned after removing the prosequences in the native protein. Wheat nuclear gene preferred amino acid codons were used to synthesize a recombinant antifreeze gene, rAFPI. Antifreeze protein was targeted to the apoplast using a Murine leader peptide sequence from the mAb24 light chain or retained in the endoplasmic reticulum using C-terminus KDEL sequence. The coding sequences were placed downstream of the rice Actin promoter and Actin-1 intron and upstream of the nopaline synthase terminator in the plant expression vectors. Transgenic wheat lines were generated through micro projectile bombardment of immature embryos of spring wheat cultivar Seri 82. Levels of antifreeze protein in the transgenic lines without any targeting peptide were low (0.06–0.07%). The apoplast-targeted protein reached a level of 1.61% of total soluble protein, 90% of which was present in the apoplast. ER-retained protein accumulated in the cells at levels up to 0.65% of total soluble proteins. Transgenic wheat line T-8 with apoplast-targeted antifreeze protein exhibited the highest levels of antifreeze activity and provided significant freezing protection even at temperatures as low as −7°C.