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The 9.4T scanner in Maastricht is a whole-body magnet with head gradients and parallel RF transmit capability. At the time of the design, it was conceptualized to be one of the best fMRI scanners in the world, but it has also been used for anatomical and diffusion imaging. 9.4T offers increases in sensitivity and contrast, but the technical ultra-high field (UHF) challenges, such as field inhomogeneities and constraints set by RF power deposition, are exacerbated compared to 7T. This article reviews some of the 9.4T work done in Maastricht. Functional imaging experiments included blood oxygenation level-dependent (BOLD) and blood-volume weighted (VASO) fMRI using different readouts. BOLD benefits from shorter T2* at 9.4T while VASO from longer T1. We show examples of both ex vivo and in vivo anatomical imaging. For many applications, pTx and optimized coils are essential to harness the full potential of 9.4T. Our experience shows that, while considerable effort was required compared to our 7T scanner, we could obtain high-quality anatomical and functional data, which illustrates the potential of MR acquisitions at even higher field strengths. The practical challenges of working with a relatively unique system are also discussed.

Background: Despite increased awareness for promoting diversity, orthopaedics remains one of the least diverse specialties. Studying health care providers in women’s professional sports provides a unique opportunity to analyze gender and racial diversity. Hypotheses: There would be low female and minority representation across the various women’s professional sports leagues. There would be an increased number of female head certified athletic trainers (ATCs) when compared with head team physicians (HTPs). Study Design: Cross-sectional study. Methods: We evaluated the perceived race and sex of designated HTPs and ATCs in the Women’s National Basketball Association, National Women’s Soccer League, and National Women’s Hockey League. Type of doctorate degree, specialty, and years in practice were also collected. Kappa (κ) coefficient measurements were used to determine interobserver agreement on race. Categorical and continuous variables were analyzed using chi-square and t tests, respectively. Results: There were significantly more female ATCs than female HTPs (74.1% vs 37.5%; P = .01). Minority representation between HTPs and ATCs was not significantly different (20.8% vs 40.7%; P = .13). Black HTPs (12.5%) and Black ATCs (22.2%) composed the largest proportion among the minority groups. There was high interobserver agreement of perceived race across HTPs (κ = 1.0) and ATCs (κ = 0.95). Conclusion: Although there were more female ATCs than HTPs in women’s professional sports leagues, both cohorts lack perceived racial diversity. These data suggest an opportunity for diversification in medical and training staff of women’s professional sports.

Background: breast cancer has a significant heritable basis, of which ∼60% remains unexplained. Testing for BRCA1/BRCA2 offers useful discrimination of breast cancer risk within families, and identification of additional breast cancer susceptibility genes could offer clinical utility. Patients and methods: we included 2135 invasive breast cancer cases recruited via the Breast and Ovarian Cancer Susceptibility study, a retrospective UK study of familial breast cancer. Eligibility criteria: female, BRCA-negative, white European ethnicity, and one of: (i) breast cancer family history, (ii) bilateral disease, (iii) young age of onset (Results: 159/2135 (7.4%) cases had a qualifying variant in an established breast cancer susceptibility gene, with minimal evidence of signal in other cancer susceptibility genes. Known breast cancer susceptibility genes PALB2, CHEK2, and ATM were the only genes to retain statistical significance after correcting for multiple testing. Due to the enrichment of hereditary cases in the series, we had good power (>80%) to detect a gene of BRCA1-like risk [odds ratio (OR) = 10.6] down to a population minor allele frequency of 4.6 × 10 −5 (1 in 10 799, less than one-tenth that of BRCA1)and of PALB2-like risk (OR = 5.0) down to a population minor allele frequency of 2.8 × 10 −4 (1 in 1779, less than half that of PALB2). Power was lower for identification of novel moderate penetrance genes (OR = 2-3) like CHEK2 and ATM. Conclusions: this is the largest case-control whole-exome analysis of enriched breast cancer published to date. Whilst additional breast cancer susceptibility genes likely exist, those of high penetrance are likely to be of very low mutational frequency. Contention exists regarding the clinical utility of such genes.

We conducted a preregistered multilaboratory project ( k = 36; N = 3,531) to assess the size and robustness of ego-depletion effects using a novel replication method, termed the paradigmatic replication approach. Each laboratory implemented one of two procedures that was intended to manipulate self-control and tested performance on a subsequent measure of self-control. Confirmatory tests found a nonsignificant result ( d = 0.06). Confirmatory Bayesian meta-analyses using an informed-prior hypothesis (δ = 0.30, SD = 0.15) found that the data were 4 times more likely under the null than the alternative hypothesis. Hence, preregistered analyses did not find evidence for a depletion effect. Exploratory analyses on the full sample (i.e., ignoring exclusion criteria) found a statistically significant effect ( d = 0.08); Bayesian analyses showed that the data were about equally likely under the null and informed-prior hypotheses. Exploratory moderator tests suggested that the depletion effect was larger for participants who reported more fatigue but was not moderated by trait self-control, willpower beliefs, or action orientation.

BACKGROUND AND PURPOSE: Dynamic contrast-enhanced MRI (DCE-MRI) can be employed to assess the blood-brain barrier (BBB) integrity. Detection of BBB leakage at lower field strengths (≤3T) is cumbersome as the signal is noisy, while leakage can be subtle. Utilizing the increased signal-to-noise ratio at higher field strengths, we explored the application of 7T DCE-MRI for assessing BBB leakage.METHODS: A dual-time resolution DCE-MRI method was implemented at 7T and a slow injection rate (0.3 ml/s) and low dose (3 mmol) served to obtain signal changes linearly related to the gadolinium concentration, that is, minimized for T2 * degradation effects. With the Patlak graphical approach, the leakage rate (Ki ) and blood plasma volume fraction (vp ) were calculated. The method was evaluated in 10 controls, an ischemic stroke patient, and a patient with a transient ischemic attack.RESULTS: Ki and vp were significantly higher in gray matter compared to white matter of all participants. These Ki values were higher in both patients compared to the control subjects. Finally, for the lesion identified in the ischemic stroke patient, higher leakage values were observed compared to normal-appearing tissue.CONCLUSION: We demonstrate how a dual-time resolution DCE-MRI protocol at 7T, with administration of half the clinically used contrast agent dose, can be used for assessing subtle BBB leakage. Although the feasibility of DCE-MRI for assessing the BBB integrity at 3T is well known, we showed that a continuous sampling DCE-MRI method tailored for 7T is also capable of assessing leakage with a high sensitivity over a range of Ki values.

Acinetobacter baumannii causes multi-system diseases in both nosocomial settings and a pre-disposed general population. The bacterium is not only desiccation-resistant but also notoriously resistant to multiple antibiotics and drugs of last resort including carbapenem, colistin, and sulbactam. The World Health Organization has categorized carbapenem-resistant A. baumannii at the top of its critical pathogen list in a bid to direct urgent countermeasure development. Several early-stage vaccines have shown a range of efficacies in healthy mice, but no vaccine candidates have advanced into clinical trials. Herein, we report our findings that both an ionizing γ-radiation-inactivated and a non-ionizing ultraviolet C-inactivated whole-cell vaccine candidate protects neutropenic mice from pulmonary challenge with virulent AB5075, a particularly pathogenic isolate. In addition, we demonstrate that a humoral response is sufficient for this protection via the passive immunization of neutropenic mice.

The extent to which physical therapy (PT) is used after meniscectomy is unknown. The objective of this study was to estimate the extent to which PT is implemented after meniscectomy and to identify factors associated with its utilization.The Mariner PearlDiver database was queried to identify patients who underwent uncomplicated meniscectomy. The number of PT visits for each patient was tabulated. Logistic regressions were used to compare demographic factors associated with no use of PT and use of nine or more PT visits.In total, 92,291 patients met inclusion criteria. Of these patients, 72.21% did not use PT and 27.8% used 1 or more PT visits. Of the patients who used PT, 19.76% had 1 to 8 PT visits and 8.03% had 9 or more PT visits. Older age and noncommercial insurance types were associated with no PT use. Male sex, Medicaid, and Medicare were associated with markedly lower odds of increased PT utilization.PT is used in the minority of the time after meniscectomy. Among patients who do use PT, however, notable variation exists in the amount of PT visits used. Patient age, sex, insurance status, and geographic variables were independently associated with PT utilization.

Antibody-secreting cells (ASC) or plasma cells secrete antibodies and form a cornerstone of humoral immunity. B cells that receive activation signals in the presence or absence of T cells initiate a differentiation program that requires epigenetic and transcriptional reprogramming in order to ultimately form ASC. Reprogramming is accomplished through the interplay of transcription factors that initiate gene expression programs and epigenetic mechanisms that maintain these programs and cell fates. An important consideration is that all of these factors are operating in the context of cell division. Recent technical advances now allow mechanistic studies to move beyond genetic studies to identify the promoters and enhancer repertoires that are regulated by epigenetic mechanisms and transcription factors in rare cell types and differentiation stages in vivo. This review will detail efforts to integrate transcriptional and epigenetic changes during B cell differentiation with cell division in vivo. What has emerged is a multi-phased differentiation model that requires distinct transcription factors and epigenetic programs at each step. The identification of markers that define each phase will help facilitate the manipulation of B cell differentiation for vaccine development or to treat diseases where antibodies are a component.

Additional co-authors: Ivan Ropovik, Balazs Aczel, Lena F. Aeschbach, Luca Andrighetto, Jack D. Arnal, Holly Arrow, Peter Babincak, Bence E. Bakos, Gabriel Banik, Ernest Baskin, Radomir Belopavlovic, Michael H. Bernstein, Michal Bialek, Nicholas G. Bloxsom, Bojana Bodroža, Diane B. V. Bonfiglio, Leanne Boucher, Florian Bruhlmann, Claudia C. Brumbaugh, Erica Casini, Yiling Chen, Carlo Chiorri, William J. Chopik, Oliver Christ, Antonia M. Ciunci, Heather M. Claypool, Sean Coary, Marija V. Cˇolic, W. Matthew Collins, Paul G. Curran, Chris R. Day, Anna Dreber, John E. Edlund, Filipe Falcao, Anna Fedor, Lily Feinberg, Ian R. Ferguson, Maire Ford, Michael C. Frank, Emily Fryberger, Alexander Garinther, Katarzyna Gawryluk, Kayla Ashbaugh, Mauro Giacomantonio, Steffen R. Giessner, Jon E. Grahe, Rosanna E. Guadagno, Ewa Halasa, Rias A. Hilliard, Joachim Huffmeier, Sean Hughes, Katarzyna Idzikowska, Michael Inzlicht, Alan Jern, William Jimenez-Leal, Magnus Johannesson, Jennifer A. Joy-Gaba, Mathias Kauff, Danielle J. Kellier, Grecia Kessinger, Mallory C. Kidwell, Amanda M. Kimbrough, Josiah P. J. King, Vanessa S. Kolb, Sabina Kolodziej, Marton Kovacs, Karolina Krasuska, Sue Kraus, Lacy E. Krueger, Katarzyna Kuchno, Caio Ambrosio Lage, Eleanor V. Langford, Carmel A. Levitan, Tiago Jesse Souza de Lima, Hause Lin, Samuel Lins, Jia E. Loy, Dylan Manfredi, Łukasz Markiewicz, Madhavi Menon, Brett Mercier, Mitchell Metzger, Venus Meyet, Jeremy K. Miller, Andres Montealegre, Don A. Moore, Rafal Muda, Gideon Nave, Austin Lee Nichols, Sarah A. Novak, Christian Nunnally, Ana Orlic, Anna Palinkas, Angelo Panno, Kimberly P. Parks, Ivana Pedovic, Emilian Pekala, Matthew R. Penner, Sebastiaan Pessers, Boban Petrovic, Thomas Pfeiffer, Damian Pienkosz, Emanuele Preti, Danka Puric, Tiago Ramos, Jonathan Ravid, Timothy S. Razza, Katrin Rentzsch, Juliette Richetin, Sean C. Rife, Anna Dalla Rosa, Kaylis Hase Rudy, Janos Salamon, Blair Saunders, Przemyslaw Sawicki, Kathleen Schmidt, Kurt Schuepfer, Thomas Schultze, Stefan Schulz-Hardt, Astrid Schutz, Ani N. Shabazian, Rachel L. Shubella, Adam Siegel, Ruben Silva, Barbara Sioma, Lauren Skorb, Luana Elayne Cunha de Souza, Sara Steegen, L. A. R. Stein, R. Weylin Sternglanz, Darko Stojilovic, Daniel Storage, Gavin Brent Sullivan, Barnabas Szaszi, Peter Szecsi, Orsolya Szoke, Attila Szuts, Manuela Thomae, Natasha D. Tidwell, Carly Tocco, Ann-Kathrin Torka, Francis Tuerlinckx, Wolf Vanpaemel, Leigh Ann Vaughn, Michelangelo Vianello, Domenico Viganola, Maria Vlachou, Ryan J. Walker, Sophia C. Weissgerber, Aaron L. Wichman, Bradford J. Wiggins, Daniel Wolf, Michael J. Wood, David Zealley, Iris Žeželj, Mark Zrubka, and Brian A. Nosek

Albarracín et al. (2008, Experiment 7) tested whether priming action or inaction goals (vs. no goal) and then satisfying those goals (vs. not satisfying them) would be associated with subsequent cognitive responding. They hypothesized and found that priming action or inaction goals that were not satisfied resulted in greater or lesser responding, respectively, compared with not priming goals ( N = 98). Sonnleitner and Voracek (2015) attempted to directly replicate Albarracín et al.’s (2008) study with German participants ( N = 105). They did not find evidence for the 3 × 2 interaction or the expected main effect of task type. The current study attempted to directly replicate Albarracín et al. (2008), Experiment 7, with a larger sample of participants ( N = 1,690) from seven colleges and universities in the United States. We also extended the study design by using a scrambled-sentence task to prime goals instead of the original task of completing word fragments, allowing us to test whether study protocol moderated any effects of interest. We did not detect moderation by protocol in the full 3 × 2 × 2 design (pseudo- r2 = 0.05%). Results for both protocols were largely consistent with Sonnleitner and Voracek’s findings (pseudo- r2s = 0.14% and 0.50%). We consider these results in light of recent findings concerning priming methods and discuss the robustness of action-/inaction-goal priming to the implementation of different protocols in this particular context.

Plant chromatin dynamics are generally recognized as playing a role in the genomic response to environmental stress. Although stress‐induced transcriptional activities of LTR‐retrotransposons have been reported, whether the stress response can be detected at the level of chromatin structure for LTR‐retrotransposons is largely unknown. Using differential nuclease sensitivity profiling, we identified that two out of 29 maize LTR‐retrotransposon families change their chromatin structure in response to drought stress in leaf tissue. The two LTR‐retrotransposon families, uloh and vegu, are classified as nonautonomous LTR‐retrotransposons. Differently from other families, the chromatin structure of these two families shifted from more open in normal conditions to more closed following drought stress. Although uloh and vegu lack sequence similarity, most of them shared an intriguing feature of having a new and uncharacterized insertion of a DNA sequence near one side of an LTR. In the uloh family, nine members with a strong drought response also exhibited a drought‐induced reduction of published H3K4me3 histone modification in the inserted DNA region, implicating this modification in the chromatin structural changes. Our results provide new insight into how LTR‐retrotransposons can alter their chromatin structure following stress response in plants.

Background Memorial University Medical Center conducts opt-out HIV screening in the Emergency Department (ED) for patients aged ≥ 13. After gaining consent, an electronic algorithm automatically orders an HIV test with the diagnostic evaluation for patients who meet CDC guidelines for HIV screening. Unfortunately, no pediatric patient aged 13–18 received HIV screening despite our out-opt testing protocol being in place since 2016. Approach Through a systematic analysis, implicit bias to gain consent was repeatedly identified as the most common barrier to HIV screening in this population. Pediatric leadership developed strategies to improve HIV screening, including education of parents and staff, on-site support for staff and parents/guardians, pediatric patient counseling, and adding HIV screening to syphilis tests. Despite these interventions, HIV screening in the pediatric population only improved about 37% from January 2017 through November 2020. As a final strategy HIV screening was added to the sexually transmitted infection (STI) order set for patients who met CDC guidelines for STI. Pediatric ED HIV education to clinical staff continued, specifically emphasizing the high prevalence of HIV in our community. Outcomes Persistence to drive change increased HIV screening by 61% from July 2020 to December 2020. Strategies producing the greatest impact were the inclusion of HIV testing in the standard STI panel and focused pediatric ED nurse education/support. As a result, current HIV screening in our pediatric patients aged 13–18 is now 88% of those who meet CDC guidelines to be screened. Significance Up to 20% of HIV diagnoses occur during adolescence making screening in this age group imperative. Removing implicit bias from HIV screening is difficult. However, continued persistence and automated testing protocols can lead to increases in pediatric ED HIV screening. Because of our high HIV screening rate, many pediatric patients will have early identification of HIV and linkage to care.

Multispectral imaging is increasingly used in specialty crops, but its benefits in assessment of disease severity and improvements in conventional scouting practice are unknown. Multispectral imaging was conducted using an unmanned aerial vehicle (UAV), and data were analyzed for five flights from Florida and Georgia commercial watermelon fields in 2017. The fields were rated for disease incidence and severity by extension agents and plant pathologists at randomized locations (i.e., conventional scouting) followed by ratings at locations that were identified by differences in normalized difference vegetation index (NDVI) and stress index (i.e., UAV-assisted scouting). Diseases identified by the scouts included gummy stem blight, anthracnose, Fusarium wilt, Phytophthora fruit rot, Alternaria leaf spot, and cucurbit leaf crumple disease. Disease incidence and severity ratings were significantly different between conventional and UAV-assisted scouting (P < 0.01, Bhapkar/exact test). Higher severity ratings of 4 and 5 on a scale of 1 to 5 from no disease to complete loss of the canopy were more consistent after the scouts used the multispectral images in determining sampling locations. The UAV-assisted scouting locations had significantly lower green, red, and red edge NDVI values and higher stress index values than the conventional scouting areas (P < 0.05, ANOVA/Tukey), and this corresponded to areas with higher disease severity. Conventional scouting involving human evaluation remains necessary for disease validation. Multispectral imagery improved watermelon field scouting owing to increased ability to identify disease foci and areas of concern more rapidly than conventional scouting practices with early detection of diseases 20% more often using UAV-assisted scouting.

Background and purpose: In neuro-oncology, high spatial accuracy is needed for clinically acceptable high-precision radiation treatment planning (RTP). In this study, the clinical applicability of anatomically optimised 7-Tesla (7T) MR images for reliable RTP is assessed with respect to standard clinical imaging modalities. Materials and methods: System- and phantom-related geometrical distortion (GD) were quantified on clinically-relevant MR sequences at 7T and 3T, and on CT images using a dedicated anthropomorphic head phantom incorporating a 3D grid-structure, creating 436 points-of-interest. Global GD was assessed by mean absolute deviation (MADGlobal). Local GD relative to the magnetic isocentre was assessed by MADLocal. Using 3D displacement vectors of individual points-of-interest, GD maps were created. For clinically acceptable radiotherapy, 7T images need to meet the criteria for accurate dose delivery (GD

Background: Discrepancies in race, ethnicity, and sex among health care providers and their patients have been shown to affect the patient-provider relationship as well as the quality of care. Currently, minority and female representation among orthopaedic surgeons remains low. Given the large proportion of minority athletes and their degree of public visibility, professional sports serves as an important arena within which to analyze the diversity of health care providers. Purpose: To describe and evaluate the current level of diversity of head team physicians (HTPs) and head athletic trainers (ATCs), primarily in terms of race and sex, within men’s professional sports leagues in the United States. Study Design: Cross-sectional study. Methods: Five major US professional sports leagues were evaluated: National Basketball Association, National Football League, National Hockey League, Major League Soccer, and Major League Baseball. Publicly available data were collected to identify the HTPs and head ATCs for each team within these leagues. Two independent observers analyzed photographs and names of these individuals to determine his or her perceived race and sex, with disagreements being resolved by a third independent observer. Other physician data collected included graduate degree(s), specialty, and number of years in practice. Kappa coefficients (κ) were employed to evaluate interobserver reliability. Chi-square, Fisher exact, and t tests were used for statistical comparisons across leagues. Results: The κ values for perceived race were 0.85 for HTPs and 0.89 for head ATCs, representing near-perfect interobserver agreement. Minorities comprised 15.5% of HTPs and 20.7% of ATCs ( P = .24). Women comprised 3.9% of HTPs and 1.3% of head ATCs ( P = .017). The majority of HTPs were orthopaedic surgeons with medical doctorates. Female HTPs had significantly fewer years in practice compared with male HTPs (15.0 ± 4.9 vs 23.1 ± 9.6; P = .04). Conclusion: The lead physicians and athletic training providers for men’s professional sports teams demonstrated low rates of minority and female representation, denoting a highly visible area for discussing the role of increased diversity in health care.

Background In the past decade, the zebrafish community has widely embraced targeted mutagenesis technologies, resulting in an abundance of mutant lines. While many lines have proven to be useful for investigating gene function, many have also shown no apparent phenotype, or phenotypes not of interest to the originating lab. In order for labs to document and share information about these lines, we have created ZebraShare as a new resource offered within ZFIN. Methods ZebraShare involves a form-based submission process generated by ZFIN. The ZebraShare interface (https://zfin.org/action/zebrashare) can be accessed on ZFIN under “Submit Data”. Users download the Submission Workbook and complete the required fields, then submit the completed workbook with associated images and captions, generating a new ZFIN publication record. ZFIN curators add the submitted phenotype and mutant information to the ZFIN database, provide mapping information about mutations, and cross reference this information across the appropriate ZFIN databases. We present here examples of ZebraShare submissions, including phf21aa, kdm1a, ctnnd1, snu13a, and snu13b mutant lines. Results Users can find ZebraShare submissions by searching ZFIN for specific alleles or line designations, just as for alleles submitted through the normal process. We present several potential examples of submission types to ZebraShare including a phenotypic mutants, mildly phenotypic, and early lethal mutants. Mutants for kdm1a show no apparent skeletal phenotype, and phf21aa mutants show only a mild skeletal phenotype, yet these genes have specific human disease relevance and therefore may be useful for further studies. The p120-catenin encoding gene, ctnnd1, was knocked out to investigate a potential role in brain development or function. The homozygous ctnnd1 mutant disintegrates during early somitogenesis and the heterozygote has localized defects, revealing vital roles in early development. Two snu13 genes were knocked out to investigate a role in muscle formation. The snu13a;snu13b double mutant has an early embryonic lethal phenotype, potentially related to a proposed role in the core splicing complex. In each example, the mutants submitted to ZebraShare display phenotypes that are not ideally suited to their originating lab’s project directions but may be of great relevance to other researchers. Conclusion ZebraShare provides an opportunity for researchers to directly share information about mutant lines within ZFIN, which is widely used by the community as a central database of information about zebrafish lines. Submissions of alleles with a phenotypic or unexpected phenotypes is encouraged to promote collaborations, disseminate lines, reduce redundancy of effort and to promote efficient use of time and resources. We anticipate that as submissions to ZebraShare increase, they will help build an ultimately more complete picture of zebrafish genetics and development.

Development of novel anti-tuberculosis combination regimens that increase efficacy and reduce treatment timelines will improve patient compliance, limit side-effects, reduce costs, and enhance cure rates. Such advancements would significantly improve the global TB burden and reduce drug resistance acquisition. Bioenergetics has received considerable attention in recent years as a fertile area for anti-tuberculosis drug discovery. Targeting the electron transport chain (ETC) and oxidative phosphorylation machinery promises not only to kill growing cells but also metabolically dormant bacilli that are inherently more drug tolerant. Over the last two decades, a broad array of drugs targeting various ETC components have been developed. Here, we provide a focused review of the current state of art of bioenergetic inhibitors of Mtb with an in-depth analysis of the metabolic and bioenergetic disruptions caused by specific target inhibition as well as their synergistic and antagonistic interactions with other drugs. This foundation is then used to explore the reigning theories on the mechanisms of antibiotic-induced cell death and we discuss how bioenergetic inhibitors in particular fail to be adequately described by these models. These discussions lead us to develop a clear roadmap for new lines of investigation to better understand the mechanisms of action of these drugs with complex mechanisms as well as how to leverage that knowledge for the development of novel, rationally-designed combination therapies to cure TB.

Acinetobacter baumannii is a bacterial pathogen that is often multidrug-resistant (MDR) and causes a range of life-threatening illnesses, including pneumonia, septicemia, and wound infections. Some antibiotic treatments can reduce mortality if dosed early enough before an infection progresses, but there are few other treatment options when it comes to MDR-infection. Although several prophylactic strategies have been assessed, no vaccine candidates have advanced to clinical trials or have been approved. Herein, we rapidly produced protective whole-cell immunogens from planktonic and biofilm-like cultures of A. baumannii, strain AB5075 grown using a variety of methods. After selecting a panel of five cultures based on distinct protein profiles, replicative activity was extinguished by exposure to 10 kGy gamma radiation in the presence of a Deinococcus antioxidant complex composed of manganous (Mn2+) ions, a decapeptide, and orthophosphate. Mn2+ antioxidants prevent hydroxylation and carbonylation of irradiated proteins, but do not protect nucleic acids, yielding replication-deficient immunogenic A. baumannii vaccine candidates. Mice were immunized and boosted twice with 1.0 × 107 irradiated bacterial cells and then challenged intranasally with AB5075 using two mouse models. Planktonic cultures grown for 16 h in rich media and biofilm cultures grown in static cultures underneath minimal (M9) media stimulated immunity that led to 80–100% protection.

Background Epithelioid hemangioma is a rare, benign vascular lesion classically presenting with painless nodules in the head and neck region. Hemangioma lesions are typically small, located within the dermis and subcutaneous tissue, and rarely exceed 10 cm in size. Complete surgical excision, with negative margins, is the recommended treatment as local recurrence is common. We describe an unusual presentation of epithelioid hemangioma that, to our knowledge, has not been previously described in the literature, epithelioid. Case presentation We report an atypical case of a large epithelioid hemangioma lesion with deep intramuscular involvement in a 16-year-old male. Ultrasound and MRI showed a hypervascular mass on the patient’s left upper back, and biopsy confirmed the diagnosis. Treatment consisted of preoperative embolization followed by excision and local tissue rearrangement. Conclusions Epithelioid hemangiomas are considered uncommon in the pediatric population. Moreover, it is challenging to diagnose these lesions due to their similarities to other vascular anomalies. We aim to increase awareness of this condition and obtain more precision in diagnosis, thus standardizing the approach for those treating individuals with vascular anomalies.

About 70% of the world's main crops depend on insect pollination. Climate change is already affecting the abundance and distribution of insects, which could cause geographical mismatches between crops and their pollinators. Crops that rely primarily on wild pollinators (e.g., crops that cannot be effectively pollinated by commercial colonies of honey bees) could be particularly in jeopardy. However, limited information on plant-pollinator associations and pollinator distributions complicate the assessment of climate change impacts on specific crops. To study the potential impacts of climate change on pollination of a specific crop in North America, we use the case of open-field tomato crops, which rely on buzz pollinators (species that use vibration to release pollen, such as bumble bees) to increase their production. We aimed to (1) assess potential changes in buzz pollinator distribution and richness, and (2) evaluate the overlap between areas with high densities of tomato crops and high potential decrease in richness. We used baseline (1961-1990) climate and future (2050s and 2080s) climatic projections in ecological niche models fitted with occurrences of wild bees, documented in the literature as pollinators of tomatoes, to estimate the baseline and future potential distribution of suitable climatic conditions of targeted species and to create maps of richness change across North America. We obtained reliable models for 15 species and found important potential decreases in the distribution of some pollinators (e.g., Lasioglossum pectorale and Augochlorella aurata). We observed geographical discrepancies in the projected change in species richness across North America, detecting important declines in the eastern United States (up to 11 species decrease for 2050s). After overlapping the maps of species richness change with a tomato crop map for the United States, we found spatial correspondence between richness declines and areas with high concentration of tomato crops. Disparities in the effects of climate change on the potential future distribution of different wild pollinators and geographical variation in richness highlight the importance of crop-specific studies. Our study also emphasizes the challenges of compiling and modeling crop-specific pollinator data and the need to improve our understanding of current distribution of pollinators and their community dynamics under climate change.

Bacterial infections still present a significant concern in orthopedic and dental implant failure. Previous investigations have focused on modifying the surface texture, roughness, or coating implants with antibiotics to provide enhanced anti-bacterial properties. However, they have demonstrated limited success. In this study, we attempted to engineer the titanium (Ti) alloy surface biomimetically at the nano level using alkaline hydrothermal treatment (AHT) inspired by cicada's wing structure. Two modified surfaces of Ti plates were developed using 4 and 8-hr AHT at 230°C. We found that the control plates showed a relatively smooth surface, with little artifacts on the surface. In contrast, 4-hr AHT and 8-hr AHT plates showed nano-spikes of heights around 250-350 and 100-1,250 nm, respectively, that were distributed randomly all over the surface. We found a statistically significant (p < 0.05) number of non-viable cells for both S. aureus and P. aeruginosa bacterial strains when incubated for 1 hr in a dynamic environment when compared with the control group. The 8-hr AHT groups killed 38.97% more S. aureus in static culture and 11.27% in a dynamic environment than the 4-hr AHT. Overall, the findings indicate that the nanostructures generated on titanium by the AHT showed significant bactericidal properties. We, therefore, recommend conducting alkaline hydrothermal treatment on the surfaces for future orthopedic and dental metallic implants.

Immune checkpoint inhibitor (ICI) therapies activate the immune system to unmask cancer cells that the body might otherwise not detect. These cancer therapies alter the immune system at different "checkpoint" proteins such as PD-1, PD-L1, or CTLA-4 to better target tumor cells, but also have the potential to affect normal tissues. In patients receiving ICI therapy, cutaneous reactions have been frequently documented, ranging from mild urticarial rashes to widespread cutaneous necrosis. Proper identification and management of ICI therapy side effects is essential to the care of these patients. Here, we present an unusual granulomatous cutaneous reaction in a patient receiving anti-CTLA-4 therapy for chronic myelomonocytic leukemia.

Cancer immunotherapy has impacted the treatment of numerous tumor types, including skin, lung, and colon cancers. Immune checkpoint inhibitors (ICI) activate the immune system to attack cancer cells, but this mechanism can also impact healthy cells. Dermatomyositis, an autoimmune syndrome affecting multiple organ systems, is often associated with cancer as a paraneoplastic syndrome, but this syndrome can also be induced by ICI. Here, we describe a case of dermatomyositis in a patient receiving pembrolizumab for treatment of squamous cell carcinoma of the lung and discuss the importance of recognizing complications of ICI.

Adverse medication side effects are not uncommon in the inpatient setting, where polypharmacy is the norm. Linear IgA bullous dermatosis (LABD) can be a cutaneous side effect of commonly used inpatient medications, such as vancomycin. Symptoms of LABD can be severe, and proper recognition of this drug-induced disease is important to ensuring proper treatment, including the removal of the inciting agent. This report describes a case of vancomycin-associated LABD in a 66-year-old man and the proper management of drug-induced LABD.

As aberrant Notch signaling has been linked to cancerous growth, Notch inhibitors represent a novel category of targeted oncological therapy. Notch pathways in tumor cells may contribute to proliferation or limit apoptosis and differentiation. Healthy skin differentiation and homeostasis are reliant on normal Notch expression, and disruption of this signaling has been implicated in dermatological conditions such as hidradenitis suppurativa, psoriasis, atopic dermatitis, and lichen planus. Here, we describe two cases of patients with cutaneous side effects from Notch inhibitor treatment for adenoid cyst carcinoma (ACC) and review the role of Notch signaling in skin disease. By illuminating connections between medication side effects and disease pathogenesis, our goal is to increase awareness of the cutaneous side effects of Notch inhibitor treatment.

Estimating invasion dynamic is important to the management of invasive species, and geopolitical-unit level data are usually the most abundant and available records of invasive species. Here, for the first time we evaluated performances and similarities of eight common methods to estimate spread pattern and spread dynamic of invasive species with geopolitical-unit level data, and assessed impacts of variations in geopolitical-units on each method using simulated spread data. We also formulated a concave hull boundary displacement method (i.e., CEB) and an area-based regression method (i.e., AER) for estimating spread with geopolitical-unit data. Three regions with different sized counties in the United States (U.S.) were selected to conduct simulations and three spread scenarios were simulated. R2 and root mean square error were used to evaluate the abilities of all methods to estimate spread. Correlation coefficients were used to assess the similarity pattern of all methods. Finally, kudzu bug Megacopta cribraria, an invasive insect in the U.S., was used as a case study to test the generality of some results concluded from the simulated research. We found the CEB and two regression methods consistently estimated the right expansion patterns. Two boundary displacement and two area-based regression methods estimated highly correlated spread and were the best four methods, among which CEB had the best estimation. Distance-based regression methods are sensitive to irregularity and stochasticity in spread, and the minimum spread distance method had low ability to estimate spread. The case study showed consistent results with the simulated research. Both regression and boundary displacement methods can estimate spread patterns, overall rate, and spread dynamics of invasive species. Boundary displacement methods best estimate spread rates and dynamics; however, for spread without clear infestation outlines, area-based regression methods can be good alternatives.

A concerted action on the part of international agencies and national governments has resulted in the near-eradication of poliomyelitis. However, both the oral polio vaccine (OPV) and the inactivated polio vaccine (IPV) have deficiencies which make them suboptimal for use after global eradication. OPV is composed of attenuated Sabin strains and stimulates robust immunity, but may revert to neurovirulent forms in the intestine which can be shed and infect susceptible contacts. The majority of IPV products are manufactured using pathogenic strains inactivated with formalin. Upon eradication, the production of large quantities of pathogenic virus will present an increased biosecurity hazard. A logical ideal endgame vaccine would be an inactivated form of an attenuated strain that could afford protective immunity while safely producing larger numbers of doses per unit of virus stock than current vaccines. We report here the development of an ionizing radiation (IR)-inactivated Sabin-based vaccine using a reconstituted Mn-decapeptide (MDP) antioxidant complex derived from the radioresistant bacterium Deinococcus radiodurans. In bacteria, Mn2+-peptide antioxidants protect proteins from oxidative damage caused by extreme radiation exposure. Here we show for the first time, that MDP can protect immunogenic neutralizing epitopes in picornaviruses. MDP protects epitopes in Polio Virus 1 and 2 Sabin strains (PV1-S and PV2-S, respectively), but viral genomic RNA is not protected during supralethal irradiation. IR-inactivated Sabin viruses stimulated equivalent or improved neutralizing antibody responses in Wistar rats compared to the commercially used IPV products. Our approach reduces the biosecurity risk of the current PV vaccine production method by utilizing the Sabin strains instead of the wild type neurovirulent strains. Additionally, the IR-inactivation approach could provide a simpler, faster and less costly process for producing a more immunogenic IPV. Gamma-irradiation is a well-known method of virus inactivation and this vaccine approach could be adapted to any pathogen of interest.

Risen and Gilovich (2008) found that subjects believed that “tempting fate” would be punished with ironic bad outcomes (a main effect), and that this effect was magnified when subjects were under cognitive load (an interaction). A previous replication study (Frank & Mathur, 2016) that used an online implementation of the protocol on Amazon Mechanical Turk failed to replicate both the main effect and the interaction. Before this replication was run, the authors of the original study expressed concern that the cognitive-load manipulation may be less effective when implemented online than when implemented in the lab and that subjects recruited online may also respond differently to the specific experimental scenario chosen for the replication. A later, large replication project, Many Labs 2 (Klein et al. 2018), replicated the main effect (though the effect size was smaller than in the original study), but the interaction was not assessed. Attempting to replicate the interaction while addressing the original authors’ concerns regarding the protocol for the first replication study, we developed a new protocol in collaboration with the original authors. We used four university sites ( N = 754) chosen for similarity to the site of the original study to conduct a high-powered, preregistered replication focused primarily on the interaction effect. Results from these sites did not support the interaction or the main effect and were comparable to results obtained at six additional universities that were less similar to the original site. Post hoc analyses did not provide strong evidence for statistical inconsistency between the original study’s estimates and our estimates; that is, the original study’s results would not have been extremely unlikely in the estimated distribution of population effects in our sites. We also collected data from a new Mechanical Turk sample under the first replication study’s protocol, and results were not meaningfully different from those obtained with the new protocol at universities similar to the original site. Secondary analyses failed to support proposed substantive mechanisms for the failure to replicate.

Magnetic resonance imaging (MRI) is a cornerstone in multiple sclerosis (MS) diagnostics and monitoring. Ultra-high field (UHF) MRI is being increasingly used and becoming more accessible. Due to the small diameter and mobility of the spinal cord, imaging this structure at ultra-high fields poses additional challenges compared to brain imaging. Here we review the potential benefits for the MS field by providing a literature overview of the use UHF spinal cord MRI in MS research and we elaborate on the challenges that are faced. Benefits include increased signal- and contrast-to-noise, enabling for higher spatial resolutions, which can improve MS lesion sensitivity in both the spinal white matter as well as grey matter. Additionally, these benefits can aid imaging of microstructural abnormalities in the spinal cord in MS using advanced MRI techniques like functional imaging, MR spectroscopy and diffusion-based techniques. Technical challenges include increased magnetic field inhomogeneities, distortions from physiological motion and optimalisation of sequences. Approaches including parallel imaging techniques, real time shimming and retrospective compensation of physiological motion are making it increasingly possible to unravel the potential of spinal cord UHF MRI in the context of MS research.

Transferability of species distribution models (SDMs) is key to predicting invasion patterns and can be challenged if niche shift occurs in the invaded range. When using native occurrences to estimate potential invasions with presence-only modeling methods, it is important to constrain the pseudo-absence (PA) sampling to the species’ native range. However, some studies including highly cited ones, do not follow this approach to selecting PA samples. In this research, we addressed two questions using an invasive species in the United States (U.S.), kudzu bug (Megacopta cribraria): 1) is model transferability challenged by a non-adaptive niche shift? and 2) is model performance affected by use of PA samples from outside the native range of the species? Kudzu bug is native to Asia, with recently observed non-adaptive niche shift in the U.S. To answer the first question, we quantified the environmental space anisotropy and non-adaptive niche change, and then evaluated the performances of seven SDMs. To answer the second question, we further compared the interpolation and transferability of seven SDMs trained with PAs from the native range and from both native and invaded ranges. We confirmed that the environmental space anisotropy (P = 0.01) and non-adaptive niche change (P = 0.01) are both statistically significant. Of the seven SDMs used, four models had transferability indices higher than 0.9. Boosted regression tree and random forests both had good interpolation and transferability (AUC>0.80 and kappa>0.60), whereas three other models showed good interpolation and fair transferability (AUC>0.70 and kappa>0.40). Inclusion of pseudo-absences from the invaded range significantly increased the interpolation (P

Srull and Wyer (1979) demonstrated that exposing participants to more hostility-related stimuli caused them subsequently to interpret ambiguous behaviors as more hostile. In their Experiment 1, participants descrambled sets of words to form sentences. In one condition, 80% of the descrambled sentences described hostile behaviors, and in another condition, 20% described hostile behaviors. Following the descrambling task, all participants read a vignette about a man named Donald who behaved in an ambiguously hostile manner and then rated him on a set of personality traits. Next, participants rated the hostility of various ambiguously hostile behaviors (all ratings on scales from 0 to 10). Participants who descrambled mostly hostile sentences rated Donald and the ambiguous behaviors as approximately 3 scale points more hostile than did those who descrambled mostly neutral sentences. This Registered Replication Report describes the results of 26 independent replications ( N = 7,373 in the total sample; k = 22 labs and N = 5,610 in the primary analyses) of Srull and Wyer’s Experiment 1, each of which followed a preregistered and vetted protocol. A random-effects meta-analysis showed that the protagonist was seen as 0.08 scale points more hostile when participants were primed with 80% hostile sentences than when they were primed with 20% hostile sentences (95% confidence interval, CI = [0.004, 0.16]). The ambiguously hostile behaviors were seen as 0.08 points less hostile when participants were primed with 80% hostile sentences than when they were primed with 20% hostile sentences (95% CI = [−0.18, 0.01]). Although the confidence interval for one outcome excluded zero and the observed effect was in the predicted direction, these results suggest that the currently used methods do not produce an assimilative priming effect that is practically and routinely detectable.

Functional mapping of cerebral blood volume (CBV) changes has the potential to reveal brain activity with high localization specificity at the level of cortical layers and columns. Non-invasive CBV imaging using Vascular Space Occupancy (VASO) at ultra-high magnetic field strengths promises high spatial specificity but poses unique challenges in human applications. As such, 9.4 T B1+ and B0 inhomogeneities limit efficient blood tagging, while the specific absorption rate (SAR) constraints limit the application of VASO-specific RF pulses. Moreover, short T2* values at 9.4 T require short readout duration, and long T1 values at 9.4 T can cause blood-inflow contaminations. In this study, we investigated the applicability of layer-dependent CBV-fMRI at 9.4 T in humans. We addressed the aforementioned challenges by combining multiple technical advancements: temporally alternating pTx B1+ shimming parameters, advanced adiabatic RF-pulses, 3D-EPI signal readout, optimized GRAPPA acquisition and reconstruction, and stability-optimized RF channel combination. We found that a combination of suitable advanced methodology alleviates the challenges and potential artifacts, and that VASO fMRI provides reliable measures of CBV change across cortical layers in humans at 9.4 T. The localization specificity of CBV-fMRI, combined with the high sensitivity of 9.4 T, makes this method an important tool for future studies investigating cortical micro-circuitry in humans.

BACKGROUND: Medial epicondylitis (ME), or “golfer’s elbow,” is often treated initially by conservative means. Up to 15% of recalcitrant cases require surgical intervention, according to small sample populations, but no national study has determined the incidence of the diagnosis or corroborated the rate of surgical intervention. PURPOSE/QUESTION: We sought to review the annual incidence of ME, surgical rates, and health care costs in a population setting. METHODS: A national database was queried for ME from 2007 to 2014. Annual rates and the percentage of diagnosed cases subjected to surgical intervention were recorded. Epidemiologic data was reported with descriptive statistics, and the significant trends over time were analyzed using linear regression. RESULTS: We identified 19,856 cases of ME in the study period. There was a significant increase in the annual incidence and overall incidence per 10,000 patients. The proportion of diagnoses in patients under 65 years of age decreased significantly, while the proportion in those 65 years of age or older significantly increased. The annual number of surgical interventions significantly increased over the study period, although the annual proportion of diagnosed cases proceeding to surgery remained constant. The proportion of patients 65 years of age or older undergoing surgery significantly increased. Total reimbursement for the management of ME during the study period was $1,877,189. While there was a significant increase in the total annual reimbursement, annual per-patient reimbursement did not change significantly. CONCLUSIONS: While the annual incidence of ME and surgical treatment of ME increased significantly from 2007 to 2014, the proportion of cases treated surgically did not. Notably, the proportion of patients 65 years of age or older diagnosed with and being surgically treated for ME has increased in recent years. Total reimbursement for ME has steadily risen, although per-patient reimbursement rates have not significantly changed.

A 66-year-old man with a recent history of herpes zoster in the second division of the trigeminal nerve presented with hyperkeratotic plaques along his left cheek and temple. A shave biopsy was found to be consistent with postherpetic hyperkeratosis. This case represents a unique presentation of Wolf’s postherpetic isotopic response: a new skin disorder emerging at the site of a previously healed herpetic, predominantly zoster, infection. We aim to increase awareness of an unusual complication of herpes zoster and the importance of appropriate vaccination to help protect patients from these potential postinfection effects.

Purpose To eliminate a slice-position–dependent excitation error commonly observed in bipolar-gradient composite excitations such as spokes pulses in parallel transmission. Theory and Methods An undesired timing delay between subpulses in the composite pulse and their bipolar slice-selective gradient is hypothesized to cause the error. A mathematical model is presented here to relate this mismatch to an induced slice-position–dependent phase difference between the subpulses. A new navigator method is proposed to measure the timing mismatch and eliminate the error. This is demonstrated at 7 Tesla with flip-angle maps measured by a presaturation turbo-flash sequence and in vivo images acquired by a simultaneous multislice/echo-planar imaging (SMS-EPI) sequence. Results Error-free flip-angle maps were obtained in two ways: 1) by correcting the time delay directly and 2) by applying the corresponding slice-position–dependent phase differences to the subpulses. This confirms the validity of the mathematical description. The radiofrequency (RF)-gradient delay measured by the navigator method was of 6.3 μs, which agreed well with the estimate from flip-angle maps at different delay times. By applying the timing correction, accurately excited EPI images were acquired with bipolar dual-spokes SMS-2 excitations. Conclusion An effective correction is proposed to mitigate slice-position–dependent errors in bipolar composite excitations caused by undesired RF-gradient timing delays. Magn Reson Med, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

In the past decade, black walnut (Juglans nigra) trees throughout western North America have suffered from widespread branch dieback and canopy loss, causing substantial tree mortality (2,3). The fungus, Geosmithia morbida, vectored by the walnut twig beetle (WTB), Pityophthorus juglandis, has been associated with this devastating disease known as Thousand Cankers Disease (TCD) (2,3). In August of 2012, branch samples from TCD symptomatic black walnut trees (5 to 10 cm in diameter and 15 to 30 cm long) were collected on the North Carolina side of the Great Smoky Mountain National Park (GRSM) in Cataloochee Cove (35°37.023′ N, 83°07.351′ W) and near the Big Creek Campground (35°45.290′ N, 83°06.473′ W), in Haywood County. Five symptomatic trees near the Big Creek Campground and three from Cataloochee Cove displayed typical TCD signs including progressive crown thinning, branch flagging, and branch dieback; however, insect holes were not observed. Samples were double bagged in Ziploc plastic bags, sealed in a 19-liter plastic bucket, and transported to the University of Tennessee. Outer bark was removed from the samples and small, elliptical, necrotic cankers were observed. Wood chips (3 to 4 mm2) from cankers were excised and placed on 1/10 strength potato dextrose agar amended with 30 mg/liter streptomycin sulfate and 30 mg/liter chlortetracycline HCL and incubated on a 12-h dark/light cycle at 22°C for 5 to 7 days. Fungal isolates were tentatively identified as G. morbida by using culture morphology, and characteristics of conidiophores and conidia (2). The isolated fungus from the Cataloochee Cove location was grown in 1/10 strength potato dextrose broth at room temperature for 2 weeks. Isolates from Big Creek Campground were contaminated and were not analyzed further. Fungal colonies were tan to light yellow. Conidia were tan, subcylindrical, and catenulate. Conidiophores were multibranched, verticillate, and verrucose. To verify the morphological data, DNA was extracted from fungal mycelia using DNeasy Plant Mini Kit (Qiagen, Valencia, CA) according to the manufacturer's published protocol. Isolates from Cataloochee Cove were characterized using ITS1 and ITS4 universal primers (4). The putative G. morbida isolate (GenBank Accession No. KC461929) had ITS sequences that were 100% identical to the G. morbida type isolate CBS124663 (FN434082.1) (2). Additionally, fungal DNA from Cataloochee Cove was amplified using G. morbida-specific microsatellite loci (GS04, GS27, and GS36) (1). PCR products were analyzed with the QIAxcel Capillary Electrophoresis System (Qiagen) and were similar to those previously published (2). To date, all confirmed cases of TCD in the native range of black walnut have been in urban areas, along rural roadsides and/or fence rows. The report in North Carolina is the first finding of G. morbida, the causal agent of TCD, in a forest setting. References: (1) D. Hadziabdic et al. Conserv. Genet. Resources 4:287, 2012. (2) M. Kolarik et al. Mycologia 103:325, 2011. (3) N. Tisserat et al. Plant Health Progr. doi:10.1094/PHP-2011-0630-01-BR, 2011. (4) T. J. White et al. Page 315 in: PCR Protocols: A Guide to Methods and Applications. M. A. Innis et al., eds. Academic Press, San Diego, CA, 1990.

Background Histone deacetylases (HDACs) are epigenetic factors that function to repress gene transcription by removing acetyl groups from the N-terminal of histone lysines. Histone deacetylase 4 (HDAC4), a class IIa HDAC, has previously been shown to regulate the process of endochondral ossification in mice via repression of Myocyte enhancer factor 2c (MEF2C), a transcriptional activator of Runx2, which in turn promotes chondrocyte maturation and production of bone by osteoblasts. Methods & Materials In this study, we generated two zebrafish lines with mutations in hdac4 using CRISPR/Cas9 and analyzed mutants for skeletal phenotypes and expression of genes known to be affected by Hdac4 expression. Results Lines have insertions causing a frameshift in a proximal exon of hdac4 and a premature stop codon. Mutations are predicted to result in aberrant protein sequence and a truncated protein, eliminating the Mef2c binding domain and Hdac domain. Zygotic mutants from two separate lines show a significant increase in ossification of pharyngeal ceratohyal cartilages at 7 days post fertilization (dpf) (p p runx2a and runx2b in the ceratohyal cartilage (p p in situ hybridizations from zygotic stages to 75–90% epiboly indicates that hdac4 is highly expressed in early embryos, but diminishes by late epiboly, becoming expressed again in larval stages. Discussion Loss of function of hdac4 in zebrafish is associated with increased expression of runx2a and runx2b targets indicating that a role for hdac4 in zebrafish is to repress activation of ossification of cartilage. These findings are consistent with observations of precocious cartilage ossification in Hdac4 mutant mice, demonstrating that the function of Hdac4 in skeletal development is conserved among vertebrates. Expression of hdac4 mRNA in embryos younger than 256–512 cells indicates that there is a maternal contribution of hdac4 to the early embryo. The increase in ossification and profound loss of first pharyngeal arch elements and anterior neurocranium in a subset of maternal-zygotic mutant and heterozygote larvae suggests that maternal hdac4 functions in cartilage ossification and development of cranial neural crest-derived structures.

Acinetobacter baumannii is a bacterial pathogen that is often multidrug-resistant (MDR) and causes a range of life-threatening illnesses, including pneumonia, septicemia, and wound infections. Some antibiotic treatments can reduce mortality if dosed early enough before an infection progresses, but there are few other treatment options when it comes to MDR-infection. Although several prophylactic strategies have been assessed, no vaccine candidates have advanced to clinical trials or have been approved. Herein, we rapidly produced protective whole-cell immunogens from planktonic and biofilm-like cultures of A. baumannii, strain AB5075 grown using a variety of methods. After selecting a panel of five cultures based on distinct protein profiles, replicative activity was extinguished by exposure to 10 kGy gamma radiation in the presence of a Deinococcus antioxidant complex composed of manganous (Mn2+) ions, a decapeptide, and orthophosphate. Mn2+ antioxidants prevent hydroxylation and carbonylation of irradiated proteins, but do not protect nucleic acids, yielding replication-deficient immunogenic A. baumannii vaccine candidates. Mice were immunized and boosted twice with 1.0 × 107 irradiated bacterial cells and then challenged intranasally with AB5075 using two mouse models. Planktonic cultures grown for 16 h in rich media and biofilm cultures grown in static cultures underneath minimal (M9) media stimulated immunity that led to 80–100% protection.