Body size effects and rates of cytochrome b evolution in tube-nosed seabirds

Variation in rates of molecular evolution now appears to be widespread. The demonstration that body size is correlated with rates of molecular evolution suggests that physiological and ecological factors may be involved in molecular rate variation, but large-scale comparative studies are still lacking. Here, we use complete cytochrome b sequences from 85 species of tube-nosed seabirds (order Procellariiformes) and 5 outgroup species of penguins (order Sphenisciformes) to test for an association between body mass and rates of molecular evolution within the former avian order. Cladistic analysis of the 90 sequences estimates a phylogeny largely consistent with the traditional taxonomy of the Procellariiformes. The Diomedeidae, Procellariidae, and Pelecanoididae are monophyletic, while the Hydrobatidae are basal and paraphyletic. However, the two subfamilies within the Hydrobatidae (Hydrobatinae and Oceanitinae) are monophyletic. A likelihood ratio test detects significant deviation from clocklike evolution in our data. Using a sign test for an association between body mass and branch length in the seabird phylogeny, we find that larger taxa tend to have shorter terminal branch lengths than smaller taxa. This observation suggests that rates of mitochondrial DNA evolution are slower for larger taxa. Rate calibrations based on the fossil record reveal concordant body size effects. We interpret these results as evidence for a metabolic rate effect, as the species in this order exhibit large differences in metabolic rates, which are known to be highly correlated with body mass in this group. Our results support previous findings of body size effects and show that this effect can be significant even within a single avian order. This suggests that even lineage-specific molecular clocks may not be tenable if calibrations involve taxa with different metabolic rates.      

Erratum to: Seroprevalence of Borrelia burgdorferi sensu lato and Anaplasma phagocytophilum in Danish horses

Background  

Borrelia burgdorferi sensu lato and Anaplasma phagocytophilum are able to infect horses. However, the extend to which Danish horses are infected and seroconvert due to these two bacteria is unknown. The aim of the present study was to evaluate the seroprevalence of B. burgdorferi sensu lato and A. phagocytophilum in Danish horses.     

Tannic acid-stained microtubules with 12, 13, and 15 protofilaments

Subunit structure in the walls of sectioned microtubules was first noted by Ledbetter and Porter (6), who clearly showed that certain microtubules of plant meristematic cells have 13 wall protofilaments when seen in cross section. Earlier, protofilaments of microtubular elements had been described in negatively stained material, although exact counts of their number were difficult to obtain. In microtubular elements of axonemes, some success has been achieved in visualizing protofilaments in conventionally fixed and sectioned material (8, 10); much less success has been achieved in identifying and counting protofilaments of singlet cytoplasmic microtubules. By using glutaraldehyde-tannic acid fixation, as described by Misuhira and Futaesaku (7), Tilney et al. (12) studied microtubules from a number of sources and found that all have 13 protofilaments comprising their walls. These authors note that "...the number of subunits and their arrangement as protofilaments appear universal...". Preliminary studies of ventral nerve cord of crayfish fixed in glutaraldehyde-tannic acid indicated that axonal microtubules in this material possess only 12 protofilaments (4). On the basis of this observation, tannic acid preparations of several other neuronal and non-neuronal systems were examined. Protofilaments in microtubules from these several cell types are clearly demonstrated, and counts have been made which show that some kinds of microtubules have more or fewer protofilaments than the usual 13 and that at least one kind of microtubule has an even rather than an odd number.     

Successful catheter ablation of persistent electrical storm late post myocardial infarction by targeting purkinje arborization triggers

Drug refractory ventricular tachycardia (VT) occurring as a storm after acute myocardial infarction has grave prognosis. We report a case of a middle-aged lady who presented with drug refractory VT that lead to persistent electrical storm two weeks after an anterior wall myocardial infarction. She underwent a successful catheter ablation of VT followed a few days later by implantation of an AICD. Catheter ablation of the VT could control the persistent electrical storm and the patient was free from a recurrence of VT at three month follow up.     

Novel non-peptidic vinylsulfones targeting the S2 and S3 subsites of parasite cysteine proteases

We describe here the identification of non-peptidic vinylsulfones that inhibit parasite cysteine proteases in vitro and inhibit the growth of Trypanosoma brucei brucei parasites in culture. A high resolution (1.75 Å) co-crystal structure of 8a bound to cruzain reveals how the non-peptidic P2/P3 moiety in such analogs bind the S2 and S3 subsites of the protease, effectively recapitulating important binding interactions present in more traditional peptide-based protease inhibitors and natural substrates.     

The structural basis of molecular adaptation

The study of molecular adaptation has long been fraught with difficulties, not the least of which is identifying out of hundreds of amino acid replacements those few directly responsible for major adaptations. Six studies are used to illustrate how phylogenies, site- directed mutagenesis, and a knowledge of protein structure combine to provide much deeper insights into the adaptive process than has hitherto been possible. Ancient genes can be reconstructed, and the phenotypes can be compared to modern proteins. Out of hundreds of amino acid replacements accumulated over billions of years those few responsible for discriminating between alternative substrates are identified. An amino acid replacement of modest effect at the molecular level causes a dramatic expansion in an ecological niche. These and other topics are creating the emerging field of "paleomolecular biochemistry."      

Role of context in the relationship between form and function: structural plasticity of some PROSITE patterns

True positive hits of PROSITE sequence pattern are expected to have a characteristic three-dimensional structure. The combined sequence-structure attributes of PROSITE patterns can be used for function prediction of an uncharacterized protein with known primary and 3D structure, a situation that might arise in structural genomics projects. We have found specific examples of true hits of PROSITE patterns displaying structural plasticity by assuming significantly different local conformation, depending upon the context. Our work highlights the importance of taking into account all the known distinct conformations of PROSITE patterns, while creating a sensitive 3D template for the pattern, for use in functional annotation.     

HSP70iQ435A to subdue autoimmunity and support anti-tumor responses

Developing immunosuppressive therapies for autoimmune diseases comes with a caveat that immunosuppression may promote the risk of developing other conditions or diseases. We have previously shown that biolistic delivery of an expression construct encoding inducible HSP70 (HSP70i) with one amino acid modification in the dendritic cell (DC) activating moiety 435–445 (HSP70i_Q435A) to mouse skin resulted in significant immunosuppressive activity of autoimmune vitiligo, associated with fewer tissue infiltrating T cells. To prepare HSP70i_Q435A as a potential therapeutic for autoimmune vitiligo, in this study we evaluated whether and how biolistic delivery of HSP70i_Q435A in mice affects anti-tumor responses. We found that HSP70i_Q435A in fact supports anti-tumor responses in melanoma-challenged C57BL/6 mice. Biolistic delivery of the HSP70i_Q435A-encoding construct to mice elicited significant anti-HSP70 titers, and anti-HSP70 IgG and IgM antibodies recognize surface-expressed and cytoplasmic HSP70i in human and mouse melanoma cells. A peptide scan revealed that the anti-HSP70 antibodies recognize a specific C-terminal motif within the HSP70i protein. The antibodies elicited surface CD107A expression among mouse NK cells, representative of antibody-mediated cellular cytotoxicity (ADCC), supporting the concept, that HSP70i_Q435A-encoding DNA elicits a humoral response to the stress protein expressed selectively on the surface of melanoma cells. Thus, besides limiting autoimmunity and inflammation, HSP70i_Q435A elicits humoral responses that limit tumor growth and may be used in conjunction with immune checkpoint inhibitors to not only control tumor but to also limit adverse events following tumor immunotherapy.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12192-021-01229-x.     

Chronic granulomatous disease, the McLeod phenotype and the contiguous gene deletion syndrome-a review

Chronic Granulomatous Disease (CGD), a disorder of the NADPH oxidase system, results in phagocyte functional defects and subsequent infections with bacterial and fungal pathogens (such as Aspergillus species and Candida albicans). Deletions and missense, frameshift, or nonsense mutations in the gp91^phox gene (also termed CYBB), located in the Xp21.1 region of the X chromosome, are associated with the most common form of CGD. When larger X-chromosomal deletions occur, including the XK gene deletion, a so-called "Contiguous Gene Deletion Syndrome" may result. The contiguous gene deletion syndrome is known to associate the Kell phenotype/McLeod syndrome with diseases such as X-linked chronic granulomatous disease, Duchenne muscular dystrophy, and X-linked retinitis pigmentosa. These patients are often complicated and management requires special attention to the various facets of the syndrome.     

Computational Chemical Imaging for Cardiovascular Pathology: Chemical Microscopic Imaging Accurately Determines Cardiac Transplant Rejection

Rejection is a common problem after cardiac transplants leading to significant number of adverse events and deaths, particularly in the first year of transplantation. The gold standard to identify rejection is endomyocardial biopsy. This technique is complex, cumbersome and requires a lot of expertise in the correct interpretation of stained biopsy sections. Traditional histopathology cannot be used actively or quickly during cardiac interventions or surgery. Our objective was to develop a stain-less approach using an emerging technology, Fourier transform infrared (FT-IR) spectroscopic imaging to identify different components of cardiac tissue by their chemical and molecular basis aided by computer recognition, rather than by visual examination using optical microscopy. We studied this technique in assessment of cardiac transplant rejection to evaluate efficacy in an example of complex cardiovascular pathology. We recorded data from human cardiac transplant patients’ biopsies, used a Bayesian classification protocol and developed a visualization scheme to observe chemical differences without the need of stains or human supervision. Using receiver operating characteristic curves, we observed probabilities of detection greater than 95% for four out of five histological classes at 10% probability of false alarm at the cellular level while correctly identifying samples with the hallmarks of the immune response in all cases. The efficacy of manual examination can be significantly increased by observing the inherent biochemical changes in tissues, which enables us to achieve greater diagnostic confidence in an automated, label-free manner. We developed a computational pathology system that gives high contrast images and seems superior to traditional staining procedures. This study is a prelude to the development of real time in situ imaging systems, which can assist interventionists and surgeons actively during procedures.