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Condamine et al. (2019; 22: 1900–1912) fitted linear and exponential functions of time‐dependent, diversity‐dependent and temperature‐dependent diversification to investigate diversification dynamics of tetrapod families. Here I highlight potential misinterpretations when using linear diversification dependencies and provide some clarifications.

Processing predictive relationships in sequential auditory input is a core capacity allowing for the emergence of syntax., Rawski et al. revisit our recent findings suggesting the latent ability to process nonadjacent dependencies (“Non-ADs”) in monkeys and apes. Specifically, the authors question the relevance of our findings for the evolution of human syntax. We argue that (i) these conclusions hinge upon an assumption that language processing is necessarily hierarchical, which remains an open question, and (ii) our goal was to probe the foundational cognitive mechanisms facilitating the processing of syntactic Non-ADs—namely, the ability to recognize predictive relationships in the input.

Evidence shows that animals match humans when learning sound patterns but not sentence patterns., We comment on the technical interpretation of the study of Watson et al. and caution against their conclusion that the behavioral evidence in their experiments points to nonhuman animals’ ability to learn syntactic dependencies, because their results are also consistent with the learning of phonological dependencies in human languages.

The article by Fan et al. inaccurately states that ProPerDP is inadequate for protein persulfide detection., The recent report by Fan et al. alleged that the ProPerDP method is inadequate for the detection of protein persulfidation. Upon careful evaluation of their work, we conclude that the claim made by Fan et al. is not supported by their data, rather founded in methodological shortcomings. It is understood that the ProPerDP method generates a mixture of cysteine-containing and non–cysteine-containing peptides. Instead, Fan et al. suggested that the detection of non–cysteine-containing peptides indicates nonspecific alkylation at noncysteine residues. However, if true, then such peptides would not be released by reduction and therefore not appear as products in the reported workflow. Moreover, the authors’ biological assessment of ProPerDP using Escherichia coli mutants was based on assumptions that have not been confirmed by other methods. We conclude that Fan et al. did not rigorously assess the method and that ProPerDP remains a reliable approach for analyses of protein per/polysulfidation.

A Science Advances paper concluding that GREs do not predict who will get a physics Ph.D. has many statistical errors., A recent paper in Science Advances by Miller et al. concludes that Graduate Record Examinations (GREs) do not help predict whether physics graduate students will get Ph.D.’s. Here, I argue that the presented analyses reflect collider-like stratification bias, variance inflation by collinearity and range restriction, omission of parts of a needed correlation matrix, a peculiar choice of null hypothesis on subsamples, blurring the distinction between failure to reject a null and accepting a null, and an unusual procedure that inflates the confidence intervals in a figure. Release of results of a model that leaves out stratification by the rank of the graduate program would fix many of the problems.

Additional analysis confirms that GRE-Q and GRE-P scores have limited reliability in predicting Ph.D. completion in physics., We provide statistical measures and additional analyses showing that our original analyses were sound. We use a generalized linear mixed model to account for program-to-program differences with program as a random effect without stratifying with tier and found the GRE-P (Graduate Record Examination physics test) effect is not different from our previous findings, thereby alleviating concern of collider bias. Variance inflation factors for each variable were low, showing that multicollinearity was not a concern. We show that range restriction is not an issue for GRE-P or GRE-V (GRE verbal), and only a minor issue for GRE-Q (GRE quantitative). Last, we use statistical measures of model quality to show that our published models are better than or equivalent to several alternates.

6-N-hydroxylaminopurine produced by the commensal skin bacterium Staphylococcus epidermidis MO34 is strongly mutagenic., A recent article in Science Advances described the striking discovery that the commensal Staphylococcus epidermidis strain MO34 displays antimicrobial and antitumor activities by producing a small molecule, identified as the nucleobase analog 6-N-hydroxylaminopurine (6-HAP). However, in contradiction to the literature, the authors claimed that 6-HAP is nonmutagenic and proposed that the toxic effect of 6-HAP results from its ability to inhibit, in its base form, DNA synthesis. To resolve the discrepancy, we proved by genetic experiments with bacteria and yeast that extracts of MO34 do contain a mutagenic compound whose effects are identical to chemically synthesized 6-HAP. The MO34 extract induced the same mutation spectrum as authentic 6-HAP. Notably, the toxic and mutagenic effects of both synthetic and MO34-derived 6-HAP depended on conversion to the corresponding nucleotide. The nucleobase 6-HAP does not inhibit DNA synthesis in vitro, and we conclude that 6-HAP exerts its biological activity when incorporated into DNA.

Does a wet winter recharge deep aquifers in California?, In a study by Murray and Lohman (M&L), the authors suggest that remote sensing data are useful for monitoring land subsidence due to aquifer system compaction. We agree. To infer aquifer dynamics, we provide a more detailed and joint analysis of deformation and groundwater data. Investigating well data in the Tulare Basin, we find that groundwater levels stabilized before 2015 and show that M&L’s observed continued subsidence through July 2016 is likely caused by the delayed compaction of the aquitard. Our analysis suggests the observed 2017 transient uplift is not due to recharge of the aquifer system after heavy winter rainfall because it requires an unrealistic vertical hydraulic gradient nearly five orders of magnitude larger than that typical of Tulare Basin. We find that, regardless of the amount of rainfall, transient annual uplifts of ~3 cm occur in May to June. Using an elastic skeletal storage coefficient of 5 × 10−3, we link this ground uplift to annual groundwater level changes.

Failed attempts to reproduce measurements suffer from lower resolution not ghosts., Gehring et al. argue that a splitting observed by us in the transverse acoustic (TA) phonon in the relaxor ferroelectric Pb[(Mg1/3Nb2/3)1−xTix]O3 with x = 0.30 (PMN-30PT) is caused by a combination of inelastic-elastic multiple scattering processes called ghostons. Their argument is motivated by differences observed between their measurements made on a triple-axis spectrometer and our measurements on a time-of-flight spectrometer. We show that the differences can be explained by differences in the instrument resolution functions. We demonstrate that the multiple scattering conditions proposed by Gehring et al. do not work for our scattering geometry. We also show that, when a ghoston is present, it is too weak to detect and therefore cannot explain the splitting. Last, this phonon splitting is just one part of the argument, and the overall conclusion of the original paper is supported by other results.

Phantom indications of phonon anticrossing in relaxor ferroelectrics can arise via an inelastic double-scattering process., Manley et al. (Science Advances, 16 September 2016, p. e1501814) report the splitting of a transverse acoustic phonon branch below TC in the relaxor ferroelectric Pb[(Mg1/3Nb2/3)1−xTix]O3 with x = 0.30 using neutron scattering methods. Manley et al. argue that this splitting occurs because these phonons hybridize with local, harmonic lattice vibrations associated with polar nanoregions. We show that splitting is absent when the measurement is made using a different neutron wavelength, and we suggest an alternative interpretation.

Hette‐Tronquart (2019, Ecol. Lett.) raises three concerns about our interpretation of stable isotope data in Sheppard et al. (2018, Ecol. Lett., 21, 665). We feel that these concerns are based on comparisons that are unreasonable or ignore the ecological context from which the data were collected. Stable isotope ratios provide a quantitative indication of, rather than being exactly equivalent to, trophic niche.

Canadian and U.S. wildlife management needs an improved scientific basis and clearer definition of “science-based” expectations., Mawdsley et al. (2018) respond disapprovingly to our 2018 review of 667 wildlife management systems across Canada and the United States, which found that many of these systems lacked the scientific hallmarks of clear objectives, evidence, transparency, and independent review. Although we strongly agree with several of Mawdsley et al.’s points about the role of science in management, their response suggests confusion about three elements of our approach that we clarify herein: (i) the selection of hallmarks, (ii) the role of science in wildlife management, and (iii) our engagement with wildlife agencies. We contend that both critics and defenders of the current approach to wildlife management in Canada and the United States similarly desire rigorous management that achieves social and ecological benefits. Our original study—which used a clear approach to define hallmarks of science-based management, employed a reasonable set of indicator criteria to test for them, and was based on data available to the general public on whose behalf management is conducted—found evidence that the current approach falls short. However, it also provided a framework for addressing shortcomings moving forward. We suggest that advancing discussion on the operational role of science in management, including clarifying what “science-based management” actually means, could curtail practitioners and critics of the status quo talking over each other’s heads and encourage all parties to work constructively to improve the governance of wildlife at a continental scale.

Biogeochemical models are more capable of capturing statewide soil NOx emissions than emission factors., Maaz et al. argue that inconsistencies across scales of observation undermine our working hypothesis that soil NOx emissions have been substantially overlooked in California; however, the core issues they raise are already discussed in our manuscript. We agree that point measurements cannot be reliably used to estimate statewide soil NOx emissions—the principal motivation behind our new modeling/airplane approach. Maaz et al.’s presentation of fertilizer-based emission factors (a nonmechanistic scaling of point measures to regions based solely on estimated nitrogen fertilizer application rates) includes no data from California or other semiarid sites, and does not explicitly account for widely known controls of climate, soil, and moisture on soil NOx fluxes. In contrast, our model includes all of these factors. Finally, the fertilizer sales data that Maaz et al. highlight are known to suffer from serious errors and do not offer a logically more robust pathway for spatial analysis of NOx emissions from soil.

Several inconsistencies undermine the conclusion that agricultural soils are a dominant source of NOx pollution in California., Almaraz et al. reported that agricultural soils are a dominant source of NOx pollution in California (20 to 32% of total statewide NOx emissions). However, this conclusion may be undermined by the lack of agreement between their modeled estimates and previously reported empirical measurements, the extrapolation of NOx fluxes during hot moments to derive annual estimates, and the overestimation of nitrogen fertilizer consumption in California.

Kondash et al. incorrectly claim that water intensity has increased in all regions, and several data errors are apparent., Kondash et al. provide a valuable contribution to our understanding of water consumption and wastewater production from oil and gas production using hydraulic fracturing. Unfortunately, their claim that the water intensity of energy production using hydraulic fracturing has increased in all regions is incorrect. More comprehensive data show that, while the water intensity of production may have increased in regions such as the Permian basin, it has decreased by 74% in the Marcellus and by 19% in the Eagle Ford region. This error likely stems from an improper method for estimating energy production from wells: The authors use the median well to represent regional production, which systematically underestimates aggregate production volumes. Across all regions, aggregate data suggest that the water intensity of oil and natural gas production using hydraulic fracturing has increased by 19%. There also appears to be an error in estimates for water consumption in the Permian basin.

Estimates of seismic response to injection rate reduction in Oklahoma are model-dependent and remain uncertain in 2017 and beyond., The state of Oklahoma has experienced an unprecedented increase in earthquake activity since 2009, likely driven by large-scale wastewater injection operations. Statewide injection rates peaked in early 2015 and steadily decreased thereafter, approximately coinciding with collapsing oil prices and regulatory action. If seismic activity is primarily driven by fluid injection, a noticeable seismogenic response to the decrease in injection rates is expected. Langenbruch and Zoback suggest that “the probability of potentially damaging larger events, should significantly decrease by the end of 2016 and approach historic levels within a few years.” We agree that the rate of small earthquakes has decreased toward the second half of 2016. However, their specific predictions about seismic hazard require reexamination. We test the influence of the model parameters of Langenbruch and Zoback based on fits to observed seismicity distributions. The results suggest that a range of realistic aftershock decay rates and b values can lead to an increase in moderate earthquake probabilities from 37 to 80% in 2017 without any further alteration to the model. In addition, the observation that all four M ≥ 5 earthquakes to date occurred when injection rates were below the triggering threshold of Langenbruch and Zoback challenges the applicability of the model for the most societally significant events.

Fundamental components of science are often lacking in U.S. state and Canadian provincial hunt management systems., Resource management agencies commonly defend controversial policy by claiming adherence to science-based approaches. For example, proponents and practitioners of the “North American Model of Wildlife Conservation,” which guides hunting policy across much of the United States and Canada, assert that science plays a central role in shaping policy. However, what that means is rarely defined. We propose a framework that identifies four fundamental hallmarks of science relevant to natural resource management (measurable objectives, evidence, transparency, and independent review) and test for their presence in hunt management plans created by 62 U.S. state and Canadian provincial and territorial agencies across 667 management systems (species-jurisdictions). We found that most (60%) systems contained fewer than half of the indicator criteria assessed, with more criteria detected in systems that were peer-reviewed, that pertained to “big game,” and in jurisdictions at increasing latitudes. These results raise doubt about the purported scientific basis of hunt management across the United States and Canada. Our framework provides guidance for adopting a science-based approach to safeguard not only wildlife but also agencies from potential social, legal, and political conflict.

We discuss possible mechanisms to explain paleoclimate as a predictor of the current distribution of global soil C content., The technical comment from Sanderman provides a unique opportunity to deepen our understanding of the mechanisms explaining the role of paleoclimate in the contemporary distribution of global soil C content, as reported in our article. Sanderman argues that the role of paleoclimate in predicting soil C content might be accounted for by using slowly changing soil properties as predictors. This is a key point that we highlighted in the supplementary materials of our article, which demonstrated, to the degree possible given available data, that soil properties alone cannot account for the unique portion of the variation in soil C explained by paleoclimate. Sanderman also raised an interesting question about how paleoclimate might explain the contemporary amount of C in our soils if such a C is relatively new, particularly in the topsoil layer. There is one relatively simple, yet plausible, reason. A soil with a higher amount of C, a consequence of accumulation over millennia, might promote higher contemporary C fixation rates, leading to a higher amount of new C in our soils. Thus, paleoclimate can be a good predictor of the amount of soil C in soil, but not necessarily of its age. In summary, Sanderman did not question the validity of our results but rather provides an alternative potential mechanistic explanation for the conclusion of our original article, that is, that paleoclimate explains a unique portion of the global variation of soil C content that cannot be accounted for by current climate, vegetation attributes, or soil properties.

Genome sequence and ancestry analysis confirm only two canid species in North America., A response to Hohenlohe et al.

We thank P. Lieberman for his technical comment, and we are pleased that he accepts our data, methods, and results and agrees with our main conclusion: that a macaque’s vocal tract would be able to produce speech sounds if macaques had the required neural control. However, we cannot agree that our findings, which expand the phonetic potential of macaques eightfold relative to that reported in his seminal 1969 paper, in any sense constitute a “replication” of that study or demonstrate the correctness of his earlier conclusions. To recap, both studies used measurements of macaque monkey vocal tracts to create a computer model, which was then queried to determine what vocalizations it could potentially produce: a space representing the “phonetic potential” of that vocal tract. The key difference between the two studies is that our vocal tract measurements were derived from x-rays of living monkeys vocalizing and communicating ( 1 ), whereas the measurements of Lieberman et al . [( 2 ), p. 1186] were derived from a single cast of a dead monkey, with possible perturbations “estimated” by “manipulating … an anesthetized monkey.” We believe that this difference in the quality of the input data is responsible for the key difference in our results: an eightfold increase in the macaque phonetic potential as estimated by our model [see our Fig. 3 in ( 1 )]. Going beyond Lieberman’s original study, we also generated five “monkey vowels” that optimally partitioned this enlarged acoustic space. Perceptual experiments then showed that humans readily discriminate between these five vowels. Five vowels were chosen because that is the modal number of vowels in human languages around the world, although the specific vowels vary, of course, from language to language ( 3 , 4 ). Given that nonhuman primate formant perception is very similar to that of humans ( 5 , 6 ), this finding …

DMS odors on plastic debris may not explain plastic ingestion by seabirds., In their recent paper, Savoca and collaborators (2016) showed that plastic debris in the ocean may acquire a dimethyl sulfide (DMS) signature from biofouling developing on their surface. According to them, DMS emission may represent an olfactory trap for foraging seabirds, which explains patterns of plastic ingestion among procellariiform seabirds. This hypothesis is appealing, but some of the data that Savoca et al. used to support their claim are questionable, resulting in a misclassification of species, as well as other decisions regarding the variables to include in their models. Furthermore, with their focus on a single lifestyle trait (nesting habit) of dubious relevance for explaining plastic ingestion, Savoca et al. neglect the opportunity to explore other factors that might provide better ecological insight. Finally, we are deeply concerned by the conservation policy recommendation proposed by Savoca et al.—to increase antifouling properties of consumer plastics—which constitutes a substantial environmental risk and delivers the wrong message to decision-makers. The reduction of plastic consumption, waste prevention, and proactive reuse through a circular economy should be at the heart of policy recommendations for future mitigation efforts.

DC vaccines have been used to induce tumour-specific cytotoxic T cells . However, this approach to cancer immunotherapy has had limited success. To be successful, injected DCs need to migrate to the LNs where they can stimulate effector T cells . We and others have previously demonstrated by MRI that tumour antigen-pulsed-DCs labelled ex vivo with superparamagnetic iron oxide nanoparticles migrated to the draining LNs and are capable of activating antigen-specific T cells . The results from our study demonstrated that ex vivo superparamagnetic iron oxide nanoparticles-labelled and OVA-pulsed DCs prime cytotoxic CD8(+) T-cell responses to protect against a B16-OVA tumour challenge. In the clinic, a possible noninvasive surrogate marker for efficacy of DC vaccination is to image the specific migration and accumulation of T cells following DC vaccination.

X-ray analyses of macaque vocal tract movements show that monkeys’ inability to speak is not due to limitations of peripheral anatomy., For four decades, the inability of nonhuman primates to produce human speech sounds has been claimed to stem from limitations in their vocal tract anatomy, a conclusion based on plaster casts made from the vocal tract of a monkey cadaver. We used x-ray videos to quantify vocal tract dynamics in living macaques during vocalization, facial displays, and feeding. We demonstrate that the macaque vocal tract could easily produce an adequate range of speech sounds to support spoken language, showing that previous techniques based on postmortem samples drastically underestimated primate vocal capabilities. Our findings imply that the evolution of human speech capabilities required neural changes rather than modifications of vocal anatomy. Macaques have a speech-ready vocal tract but lack a speech-ready brain to control it.

Independent evidence from rocks, fossils, and genes converge on a cohesive narrative of isthmus formation in the Pliocene., The formation of the Isthmus of Panama stands as one of the greatest natural events of the Cenozoic, driving profound biotic transformations on land and in the oceans. Some recent studies suggest that the Isthmus formed many millions of years earlier than the widely recognized age of approximately 3 million years ago (Ma), a result that if true would revolutionize our understanding of environmental, ecological, and evolutionary change across the Americas. To bring clarity to the question of when the Isthmus of Panama formed, we provide an exhaustive review and reanalysis of geological, paleontological, and molecular records. These independent lines of evidence converge upon a cohesive narrative of gradually emerging land and constricting seaways, with formation of the Isthmus of Panama sensu stricto around 2.8 Ma. The evidence used to support an older isthmus is inconclusive, and we caution against the uncritical acceptance of an isthmus before the Pliocene.

Natural killer (NK) cells are key cellular components of the innate immune system that act at the interface between innate and adaptive immune responses 1. An increasing body of evidence shows that specific clones of NK cells may be expanded in vivo under the influence of viruses such as human cytomegalovirus (CMV) 2,3. These adaptive-like NK-cell responses have been proposed to represent a human counterpart to the NK-cell memory responses observed in mice 4, and seem to be driven by activating receptors, including NKG2C and activating killer cell immunoglobulin-like receptors (KIRs) 2,5,6. So far, clonal-like expansion of specific NK-cell subsets has been documented mostly in the context of primary CMV infection, or conditions that are linked to a clinical or subclinical reactivation of CMV 2,3,6–9. Even so, there is an increasing interest in mapping adaptive-like NK-cell responses in other acute or chronic infections as well as in cancer.

The cellular response to IFN is an essential part of immune reactions and has been subject to investigations for over 50 years 1. The analyses on IFN function frequently involve the use of neutralizing antibodies to block responses and to document the dependence on IFN signals. In this context, we have previously described an unusual “IFN-like” response initiated by blocking antibodies to type I IFN in primary human endothelial cells (EC) or mononuclear blood cells. In the absence of exogenously added recombinant IFN (rIFN), the exposure of EC to increasing concentrations of IFN-blocking mAb resulted in the dose-dependent induction of IFN response genes at the mRNA and protein level 2. The effect was observed for four different mAb directed against human IFN-α or -β and was dependent on the type I IFN receptor. We concluded that an intrinsic feature of the IFN-blocking antibodies was responsible for the observed “IFN-like” activation of EC; a model was proposed of antibody binding to surface Fc-receptors with sequestration of autocrine IFN and subsequent release to nearby IFN receptors, which would result in the observed “IFN-like” signal. We have now obtained evidence that refutes this hypothesis showing that the “IFN-like” activity associated with IFN-blocking mAb is indeed a discrete component that can be separated from the antibody moiety by sequential cycles of antibody immunoprecipitation (Supporting Information Fig. 1 and Supporting Information Methodology). Furthermore, when the standard two-step procedure for antibody purification as performed by the manufacturer (based on ammonium sulfate precipitation and ion exchange chromatography) was extended by a third step of hydrophobic interaction chromatography, the “IFN-like” activity was lost and the neutralizing capacity of the respective antibodies prevailed (Fig. 1A–C). Figure 1 The “IFN-like” activity in antibody preparations can be eliminated by additional antibody purification (three-step process) and is inhibited by polyclonal anti-IFN-α antiserum. The neutralizing anti-IFN-α mAb MMHA-2 and ... Having established that the “IFN-like” activity was attributable to a discrete contaminant of the applied anti-IFN antibody preparations, the possible contamination with microbial products was first examined. Since the majority of pathogen-associated signals leading to the IFN pathway are mediated by the TLR family 3, 4 we screened for hallmarks of TLR activity. However, we did not observe the induction of the transcription factor NF-κB or the pro-inflammatory activation of EC, strongly arguing against TLR involvement (Supporting Information Fig. 2). We then obtained an indication towards contamination with type I IFN from competition studies showing that the contaminant in mAb preparations was neutralized by rabbit (data not shown) or sheep polyclonal anti-human IFN-α antiserum (Fig. 1D). Polyclonal anti-IFN-β antiserum or control antiserum obtained prior to immunization did not affect the “IFN-like” activity (data not shown). The co-purification (and cross-reactivity) of mouse IFN upon mAb isolation from mouse ascites was a potential source of contamination, which was addressed by cytopathic effect inhibition assays on mouse versus human target cells. There was a significantly higher impact on the human target cells, thus arguing for the presence of human rather than mouse IFN-α (Supporting Information Fig. 3A). However, the question remained as to why the contaminating human IFN-α was not neutralized by the investigated anti-IFN-α-blocking mAb (e.g. MMHA-2). When comparing the neutralizing capacity towards various rIFN-α subtypes, the three-step purified mAb failed to inhibit individual family members (IFN-α subtypes 8, 14, and 16) while the sheep polyclonal antiserum potently repressed all IFN-α subtypes (Supporting Information Fig. 3C). This finding supported the notion that a distinct human IFN-α subtype not neutralized by the respective monoclonal was present in the antibody preparation. In accordance, we found that the purified mAb could not block the “IFN-like” activity present in the contaminated mAb preparation (Supporting Information Fig. 3B). Of note, rIFN-α8 and rIFN-α14 had been produced by PBL prior to the preparation of the contaminated antibody MMHA-2. By applying two anti-human IFN-α ELISA tests (not mouse cross-reactive) with distinct sensitivity towards rIFN-α8 and rIFN-α14 evidence was gained for a predominant antibody contamination by human rIFN-α14 (Supporting Information Table 1). However, a combination of contaminating IFN cannot be excluded. Table 1 Level of detectable contamination with rIFN-α in various antibody preparationsa) Thus, the source of contamination could be traced to the sequential production of rIFN and anti-IFN-blocking antibodies with common equipment. Despite a time window of several months between productions, despite the regular two-step purification procedure, and despite standard equipment cleansing, the contamination of antibody preparations with functional type I IFN was substantial. The importance of our observation was further demonstrated by the frequent occurrence of detectable IFN activity in a considerable number of tested antibodies (Table 1). Apart from various mouse monoclonals against human IFN-α and IFN-β (MMHA-2, MMHA-3, MMHA-9, MMHA-13, MMHB-3, MMHB-12), rat anti-mouse antibodies directed against IFN-α (RMMA-1) or IFN-γ (RMMG-1) also presented with significant amounts of human rIFN. While most of these monoclonals originated from PBL and were supplied by PBL or associated distributors in the contaminated form, further examples for contaminated antibodies were found for an alternative supplier. Two anti-pig IFN mAb (K9, F17) similarly showed contamination with rIFN-α (Table 1). Based on the diverse specificity of contaminated antibodies we propose that unspecific co-purification rather than specific antibody binding accounts for the presence of contaminants. While most of the affected antibodies showed IFN-α contamination, the subtype present may vary. The range of detectable IFN activity varied considerably (by a factor of 1000). The highest levels of anti-viral activity as recorded for the anti-IFN-α mAb clone MMHA-2 equalled a concentration of 800 U/mL of human rIFN-α when applying the antibody at a dilution of 50 μg/mL (common for in vitro experiments). For example, stimulation of target cells with 1000 U/mL of biological or rIFN-α2a in the presence of 50 μg/mL of contaminated blocking mAb MMHA-2 would be expected to result in the complete neutralization of the α2a subtype, while exposing the cells to 800 U/mL of non-neutralized rIFN-α14. The net inhibitory effect on the target cells would be minor leading to the false interpretation of results, especially for an experimental setup where the involvement and concentration of type I IFN is the unknown parameter under investigation. Thus, the information given in this report may be of help in interpreting previously conducted experiments with the listed antibodies. With respect to PBL products, all mAb preparations have been carefully evaluated, and contaminated antibodies were found to date back to the last 2–8 years. More stringent purification and equipment cleaning procedures as well as routine testing for contaminating activity have been put in place at PBL in part due to these experiments. With respect to K9, F17, the company producing these antibodies was informed and has, in the meantime, provided the respective clones to PBL for antibody production. Hence, all products identified in this report to have previously been affected by contamination are now being supplied to the research community in a purified form; however, it is easy to envision that reagent providers who prepare multiple cytokines and mAb could face similar issues as those noted here.