Plants have evolved a range of cellular responses to maintain developmental homeostasis and to survive over a range of temperatures. Here, we describe the in vivo and in vitro functions of BOBBER1 (BOB1), a NudC domain containing Arabidopsis (Arabidopsisthaliana) small heat shock protein. BOB1 is an essential gene required for the normal partitioning and patterning of the apical domain of the Arabidopsis embryo. Because BOB1 loss-of-function mutants are embryo lethal, we used a partial loss-of-function allele (bob1-3) to demonstrate that BOB1 is required for organismal thermotolerance and postembryonic development. Recombinant BOB1 protein functions as a molecular chaperone and prevents the aggregation of a model protein substrate in vitro. In plants, BOB1 is cytoplasmic at basal temperatures, but forms heat shock granules containing canonical small heat shock proteins at high temperatures. In addition to thermotolerance defects, bob1-3 exhibits pleiotropic development defects during all phases of development. bob1-3 phenotypes include decreased rates of shoot and root growth as well as patterning defects in leaves, flowers, and inflorescence meristems. Most eukaryotic chaperones play important roles in protein folding either during protein synthesis or during cellular responses to denaturing stress. Our results provide, to our knowledge, the first evidence of a plant small heat shock protein that has both developmental and thermotolerance functions and may play a role in both of these folding networks.

WHIM is an acronym for a rare immunodeficiency syndrome (OMIM #193670) caused by autosomal dominant mutations truncating the C‐terminus of the chemokine receptor CXC chemokine receptor 4 (CXCR4). WHIM mutations may potentiate CXCR4 signalling, suggesting that the United States Food and Drug Administration (FDA)‐approved CXCR4 antagonist AnorMED3100 (AMD3100) (also known as Plerixafor) may be beneficial in WHIM syndrome. We have tested this at the preclinical level by comparing Chinese hamster ovary (CHO) and K562 cell lines matched for expression of recombinant wild‐type CXCR4 (CXCR4^WT) and the most common WHIM variant of CXCR4 (CXCR4^R334X), as well as leucocytes from a WHIM patient with the CXCR4^R334X mutation versus healthy controls. We found that CXCR4^R334X mediated modestly increased signalling (∼2‐fold) in all functional assays tested, but strongly resisted ligand‐dependent down‐regulation. AMD3100 was equipotent and equieffective as an antagonist at CXCR4^R334X and CXCR4^WT. Together, our data provide further evidence that CXCR4^R334X is a gain‐of‐function mutation, and support clinical evaluation of AMD3100 as mechanism‐based treatment in patients with WHIM syndrome.

Although conflicts of interest in biomedical research have received significant attention, the impact of conflicts of interest on surgical outcomes has not been fully explored. A systematic electronic search of the literature was performed for studies that evaluated surgical outcomes in acellular dermal matrix and non-acellular dermal matrix implant-based breast reconstruction. Surgical complications, including infection, seroma, hematoma, necrosis, and explantation, were used as outcome metrics and extracted from studies. Surgical outcomes were then pooled and compared between studies that disclosed conflicts of interest and those that did not disclose conflicts of interest. A total of 776 abstracts were identified, of which only 35 fulfilled the authors' inclusion criteria. Conflicts of interest were reported in 14 of these abstracts (40 percent). The pooled data from studies that reported no conflicts of interest and studies that reported conflicts of interest included a total of 8241 and 5384 breasts and 2852 and 1864 patients, respectively. Considered collectively, surgical complications were less common in studies that reported a conflict of interest than in studies that reported no conflicts of interest. When surgical outcome data were further stratified by acellular dermal matrix use, surgical complications were less common in studies with conflicts of interest when acellular dermal matrix was used. However, when acellular dermal matrix was not used, surgical complications were similar between authors that reported a conflict of interest and those that did not report a conflict of interest. Self-reported conflicts of interest are common in implant-based breast reconstruction research. Studies authored by groups with conflicts of interest are significantly associated with reporting lower surgical complications and therefore describing positive research findings, especially when industry-marketed products are being used in the study. Therapeutic, III.

Vascularized composite allotransplantation may now be considered a viable treatment option in patients with complex craniofacial and limb defects. However, the field is still in its infancy, and challenges continue to exist. These challenges, most notably the adverse effects of lifelong immunosuppression, must be weighed against the benefits of the procedure. Improvements in this risk-benefit ratio can be achieved by achieving tolerance and preventing rejection. Five decades after Dr. Joseph E. Murray introduced the field of transplantation to the world, we now have a better understanding of the immunologic factors that may contribute to rejection and inhibit tolerance. In this article, we review emerging evidence that suggests that "danger signals" associated with ischemia-reperfusion injury contribute to innate immune activation, promoting rejection, and inhibiting tolerance. Based on this understanding, we also describe several strategies that may ameliorate the damaging effects of ischemia-reperfusion and the clinical implications of ischemia-reperfusion on the vascularized composite tissue allotransplantation outcome.

Background: The purpose of this study was to analyze the frequency and nature of self-reported conflict-of-interest disclosures in the plastic surgery literature and to compare these findings to the Physician Payments Sunshine Act database. Methods: All articles published from August of 2013 through December of 2013 in four major plastic surgery journals were analyzed. For every publication, the conflict-of-interest disclosure statement for each investigator was reviewed. These statements were then compared to transactions of value for each investigator as reported by biomedical companies in the Sunshine Act database. An analysis was performed to identify and characterize specific factors associated with conflict-of-interest disclosures. Results: A total of 1002 independent investigators/authors were identified. Of these, 90 investigators (9 percent) self-reported a conflict of interest. In contrast, a total of 428 authors (42.7 percent) were found to have received transactions of value from a biomedical company according to the Sunshine Act database. Conversely, a total of 22 authors (2.2 percent) self-reported a conflict of interest but were not found to have received transactions of value in the Sunshine Act database. Our analysis found that (1) academic investigators, (2) transactions of value in excess of $500, and (3) publishing articles related to the sponsoring biomedical company were all statistically associated with reporting conflicts of interest (p < 0.0001). Conclusions: Discordance exists between investigator/authors self-reporting in scientific journals and the government-mandated reporting of conflicts of interest by industry. Factors associated with conflict-of-interest disclosure include academic status, transaction amount, and article content related to the sponsoring biomedical company.

Background: The purpose of this study was to assess the efficacy of biodegradable, electrospun poly(ε-caprolactone) nanofiber nerve conduits in improving nerve regeneration. Methods: The authors used a rat forelimb chronic denervation model to assess the effects of poly(ε-caprolactone) conduits on improving nerve regeneration and upper extremity function. Three groups of rats were examined: (1) negative-control animals (n = 5), which underwent 8 weeks of median nerve chronic denervation injury followed by repair with no conduit; (2) experimental animals (n = 5), which underwent 8 weeks of median nerve chronic denervation followed by repair and poly(ε-caprolactone) nerve conduit wrapping of the nerve coaptation site; and (3) positive-control animals (n = 5), which were naive controls. All animals underwent compound muscle action potential and functional testing. At 14 weeks after repair, the median nerve and flexor muscles were harvested for histologic analysis. Results: Histomorphometric analysis of regenerating median nerves demonstrated augmented axonal regeneration in experimental versus negative control animals (total axon count, 1769 ± 672 versus 1072 ± 123.80; p = 0.0468). With regard to functional recovery, experimental and negative-control animals (1.67 ± 0.04 versus 0.97 ± 0.39; p = 0.036) had regained 34.9 percent and 25.4 percent, respectively, of baseline hand grip strength at 14 weeks after repair. Lastly, less collagen deposition at the nerve coaptation site of experimental animals was found when compared to control animals (p < 0.05). Conclusion: Biodegradable, poly(ε-caprolactone) nanofiber nerve conduits can improve nerve regeneration and subsequent physiologic extremity function in the setting of delayed nerve repair by decreasing the scar burden at nerve coaptation sites.