Pest population dynamics are related to a continental overwintering gradient.

Overwintering success is an important determinant of arthropod populations that must be considered as climate change continues to influence the spatiotemporal population dynamics of agricultural pests. Using a long-term monitoring database and biologically relevant overwintering zones, we modeled the annual and seasonal population dynamics of a common pest, Helicoverpa zea (Boddie), based on three overwintering suitability zones throughout North America using four decades of soil temperatures: the southern range (able to persist through winter), transitional zone (uncertain overwintering survivorship), and northern limits (unable to survive winter). Our model indicates H. zea population dynamics are hierarchically structured with continental-level effects that are partitioned into three geographic zones. Seasonal populations were initially detected in the southern range, where they experienced multiple large population peaks. All three zones experienced a final peak between late July (southern range) and mid-August to mid-September (transitional zone and northern limits). The southern range expanded by 3% since 1981 and is projected to increase by twofold by 2099 but the areas of other zones are expected to decrease in the future. These changes suggest larger populations may persist at higher latitudes in the future due to reduced low-temperature lethal events during winter. Because H. zea is a highly migratory pest, predicting when populations accumulate in one region can inform synchronous or lagged population development in other regions. We show the value of combining long-term datasets, remotely sensed data, and laboratory findings to inform forecasting of insect pests.

Insulin-like growth factor receptor / mTOR signaling elevates global translation to accelerate zebrafish fin regenerative outgrowth.

Zebrafish robustly regenerate fins, including their characteristic bony ray skeleton. Amputation activates intra-ray fibroblasts and dedifferentiates osteoblasts that migrate under a wound epidermis to establish an organized blastema. Coordinated proliferation and re-differentiation across lineages then sustains progressive outgrowth. We generate a single cell transcriptome dataset to characterize regenerative outgrowth and explore coordinated cell behaviors. We computationally identify sub-clusters representing most regenerative fin cell lineages, and define markers of osteoblasts, intra- and inter-ray fibroblasts and growth-promoting distal blastema cells. A pseudotemporal trajectory and in vivo photoconvertible lineage tracing indicate distal blastemal mesenchyme restores both intra- and inter-ray fibroblasts. Gene expression profiles across this trajectory suggest elevated protein production in the blastemal mesenchyme state. O-propargyl-puromycin incorporation and small molecule inhibition identify insulin growth factor receptor (IGFR)/mechanistic target of rapamycin kinase (mTOR)-dependent elevated bulk translation in blastemal mesenchyme and differentiating osteoblasts. We test candidate cooperating differentiation factors identified from the osteoblast trajectory, finding IGFR/mTOR signaling expedites glucocorticoid-promoted osteoblast differentiation in vitro. Concordantly, mTOR inhibition slows but does not prevent fin regenerative outgrowth in vivo. IGFR/mTOR may elevate translation in both fibroblast- and osteoblast-lineage cells during the outgrowth phase as a tempo-coordinating rheostat.

longfin causes cis-ectopic expression of the kcnh2a ether-a-go-go K+ channel to autonomously prolong fin outgrowth.

Organs stop growing to achieve a characteristic size and shape in scale with the body of an animal. Likewise, regenerating organs sense injury extents to instruct appropriate replacement growth. Fish fins exemplify both phenomena through their tremendous diversity of form and remarkably robust regeneration. The classic zebrafish mutant longfint2 develops and regenerates dramatically elongated fins and underlying ray skeleton. We show longfint2 chromosome 2 overexpresses the ether-a-go-go-related voltage-gated potassium channel kcnh2a. Genetic disruption of kcnh2a in cis rescues longfint2, indicating longfint2 is a regulatory kcnh2a allele. We find longfint2 fin overgrowth originates from prolonged outgrowth periods by showing Kcnh2a chemical inhibition during late stage regeneration fully suppresses overgrowth. Cell transplantations demonstrate longfint2-ectopic kcnh2a acts tissue autonomously within the fin intra-ray mesenchymal lineage. Temporal inhibition of the Ca2+-dependent phosphatase calcineurin indicates it likewise entirely acts late in regeneration to attenuate fin outgrowth. Epistasis experiments suggest longfint2-expressed Kcnh2a inhibits calcineurin output to supersede growth cessation signals. We conclude ion signaling within the growth-determining mesenchyme lineage controls fin size by tuning outgrowth periods rather than altering positional information or cell-level growth potency.

Reduced toxin binding associated with resistance to Vip3Aa in the corn earworm (Helicoverpa zea).

IMPORTANCE: Helicoverpa zea is a major crop pest in the United States that is managed with transgenic corn and cotton that produce insecticidal proteins from the bacterium, Bacillus thuringiensis (Bt). However, H. zea has evolved widespread resistance to the Cry proteins produced in Bt corn and cotton, leaving Vip3Aa as the only plant-incorporated protectant in Bt crops that consistently provides excellent control of H. zea. The benefits provided by Bt crops will be substantially reduced if widespread Vip3Aa resistance develops in H. zea field populations. Therefore, it is important to identify resistance alleles and mechanisms that contribute to Vip3Aa resistance to ensure that informed resistance management strategies are implemented. This study is the first report of reduced binding of Vip3Aa to midgut receptors associated with resistance.

Nickel Phosphite-Catalyzed Tetradehydro-Diels-Alder Reactions of (E)-3-ene-1,8-diynes.

A nickel-catalyzed tetradehydro-Diels-Alder reaction of (E)-3-ene-1,8-diynes for the preparation of isoindolines, dihydroisobenzofurans, and tetrahydroisoquinolines has been developed. A series of air-stable nickel catalysts were used in this study, including the novel nickel(0)-phosphite catalysts, Ni[P(O-3,5-Me-Ph)3]4, Ni[P(O-1-naphthyl)3]4, and Ni[P(O-2-naphthyl)3]4. To help understand the type of intermediate in the initial cycloisomerization process, the trapping of nickellacycle intermediates with pinacolborane to yield vinyl boronates is also discussed.

Dirhodium-Catalyzed Transannulation of N-Sulfonyl-1,2,3-triazoles to 2,3-Dehydropiperazines.

The dirhodium(II)-catalyzed synthesis of a range of C2-substituted 2,3-dehydropiperazines using 1-mesyl-1,2,3-triazoles and ß-haloalkylcarbamates is reported. The reaction is proposed to proceed through an α-imino rhodium carbene 1,3-insertion into N-H followed by a base-mediated cyclization. C-Substituted dehydropiperazines can also be conducted directly from terminal alkynes in a three-step, one-pot operation, forming the triazole in situ. This methodology has also been expanded to afford several 2,5-disubstituted 2,3-dehydropiperazines as well as a larger 4,5,6,7-tetrahydro-1H-1,4-diazepine derivative.

Demographics and perceptions of diversity in dermatopathology workforce and training environments in the United States.

OBJECTIVES: The aim of this study was to determine the demographics and perceptions of diversity, equity, and inclusion (DEI) in the field of dermatopathology to provide a measurable baseline for future efforts to enhance equity measures within our subspecialty. METHODS: A questionnaire based on a previously validated instrument by Association of American Medical Colleges (AAMC) was sent to American Society of Dermatopathology (ASDP) members to collect the demographic information (gender, race, sexual orientation, disability, experience and practice setting, etc.) and evaluate eight diversity, engagement, and inclusivity statements on a 1-5 Likert scale. RESULTS: The demographics of 207 of 1331 (15%) respondents showed slight male predominance. Eleven percent of respondents identified as LGBTQI. The major racial distribution was comprised of 62% White, 18% Asian (including Middle Eastern/Indian), 10% Hispanic, and 4% Black respondents. New-in-practice respondents (those in practice-5 years or less) were more likely to have a pathology background (71% vs. 56%, p = 0.047) than their more-established peers with more than 5 years of service. This trend also contributed to increased diversity in terms of gender (66% females) and race (48% non-White) among the newer generation. Dermatology-trained dermatopathologists were mostly White (70%) and male (53%). Analysis of respondent demographics with perception statements showed that White and US graduate respondents (compared to other groups) were more likely to have a positive perception about DEI within the field of dermatopathology. CONCLUSIONS: The results provide a snapshot of the current state of diversity within the field of dermatopathology. Moreover, these results highlight opportunities for further increasing diversity in general and leadership in particular within dermatopathology.

Implementing a Produce Prescription Program in Partnership With a Community Coalition.

Healthy eating reduces risk for chronic disease, but can be out of reach for many Americans experiencing food insecurity. Produce Prescription Programs (PPPs) have emerged as an intervention to address barriers related to fruit and vegetable consumption. Using a social prescribing model, PPPs connect patients with referrals to community resources to reduce barriers to healthy eating. There is evidence of success of PPPs at improving dietary intake, yet little discussion within the literature of practical aspects of implementation. As interest grows around establishing PPPs within communities, increased attention to strategic planning and implementation remains necessary to develop robust and effective programming. We describe implementing the Pontiac Prescription for Health pilot program, highlighting the participatory planning process with partners. Development and implementation included a program model, recruitment methods and materials, a voucher contract and tracking system with produce vendors, physical activity opportunities, culturally competent health education sessions, and evaluation tools. We offer insight into lessons learned and practical implications for future "on-the-ground" planning and implementation. Engaging in a rigorous participatory planning process with all community partners, allowing adequate time to establish service agreements and a voucher system with vendors, and engaging program participants in different ways and spaces throughout the community can enhance program success.

Basal epidermis collective migration and local Sonic hedgehog signaling promote skeletal branching morphogenesis in zebrafish fins.

Teleost fish fins, like all vertebrate limbs, comprise a series of bones laid out in characteristic pattern. Each fin's distal bony rays typically branch to elaborate skeletal networks providing form and function. Zebrafish caudal fin regeneration studies suggest basal epidermal-expressed Sonic hedgehog (Shh) promotes ray branching by partitioning pools of adjacent pre-osteoblasts. This Shh role is distinct from its well-studied Zone of Polarizing Activity role establishing paired limb positional information. Therefore, we investigated if and how Shh signaling similarly functions during developmental ray branching of both paired and unpaired fins while resolving cellular dynamics of branching by live imaging. We found shha is expressed uniquely by basal epidermal cells overlying pre-osteoblast pools at the distal aspect of outgrowing juvenile fins. Lateral splitting of each shha-expressing epidermal domain followed by the pre-osteoblast pools precedes overt ray branching. We use ptch2:Kaede fish and Kaede photoconversion to identify short stretches of shha+basal epidermis and juxtaposed pre-osteoblasts as the Shh/Smoothened (Smo) active zone. Basal epidermal distal collective movements continuously replenish each shha+domain with individual cells transiently expressing and responding to Shh. In contrast, pre-osteoblasts maintain Shh/Smo activity until differentiating. The Smo inhibitor BMS-833923 prevents branching in all fins, paired and unpaired, with surprisingly minimal effects on caudal fin initial skeletal patterning, ray outgrowth or bone differentiation. Staggered BMS-833923 addition indicates Shh/Smo signaling acts throughout the branching process. We use live cell tracking to find Shh/Smo restrains the distal movement of basal epidermal cells by apparent 'tethering' to pre-osteoblasts. We propose short-range Shh/Smo signaling promotes these heterotypic associations to couple instructive basal epidermal collective movements to pre-osteoblast repositioning as a unique mode of branching morphogenesis.

Similarities and Differences between Crystal and Enzyme Environmental Effects on the Electron Density of Drug Molecules.

The crystal interaction density is generally assumed to be a suitable measure of the polarization of a low-molecular weight ligand inside an enzyme, but this approximation has seldomly been tested and has never been quantified before. In this study, we compare the crystal interaction density and the interaction electrostatic potential for a model compound of loxistatin acid (E64c) with those inside cathepsin B, in solution, and in vacuum. We apply QM/MM calculations and experimental quantum crystallography to show that the crystal interaction density is indeed very similar to the enzyme interaction density. Less than 0.1 e are shifted between these two environments in total. However, this difference has non-negligible consequences for derived properties.

Sucrose fatty acid esters: synthesis, emulsifying capacities, biological activities and structure-property profiles.

The notable physical and chemical properties of sucrose fatty acid esters have prompted their use in the chemical industry, especially as surfactants, since 1939. Recently, their now well-recognized value as nutraceuticals and as additives in cosmetics has significantly increased demand for ready access to them. As such a review of current methods for the preparation of sucrose fatty acid esters by both chemical and enzymatic means is warranted and is presented here together with an account of the historical development of these compounds as surfactants (emulsifiers). The somewhat belated recognition of the antimicrobial, anticancer and insecticidal activities of sucrose esters is also discussed along with a commentary on their structure-property profiles.

Factors associated with phosphatidylethanol (PEth) sensitivity for detecting unhealthy alcohol use: An individual patient data meta-analysis.

BACKGROUND: Objective measurement of alcohol consumption is important for clinical care and research. Adjusting for self-reported alcohol use, we conducted an individual participant data (IPD) meta-analysis to examine factors associated with the sensitivity of phosphatidylethanol (PEth), an alcohol metabolite, among persons self-reporting unhealthy alcohol consumption. METHODS: We identified 21 eligible studies and obtained 4073 observations from 3085 participants with Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) positive scores (≥3 for women and ≥4 for men) and PEth measurements. We conducted 1-step IPD meta-analysis using mixed effects models with random intercepts for study site. We examined the associations between demographic (sex, race/ethnicity, and age) and biologic (body mass index-BMI, hemoglobin, HIV status, liver fibrosis, and venous versus finger-prick blood collection) variables with PEth sensitivity (PEth≥8 ng/ml), adjusting for the level of self-reported alcohol use using the AUDIT-C score. RESULTS: One third (31%) of participants were women, 32% were African, 28% African American, 28% White, and 12% other race/ethnicity. PEth sensitivity (i.e., ≥8 ng/ml) was 81.8%. After adjusting for AUDIT-C, we found no associations of sex, age, race/ethnicity, or method of blood collection with PEth sensitivity. In models that additionally included biologic variables, those with higher hemoglobin and indeterminate and advanced liver fibrosis had significantly higher odds of PEth sensitivity; those with higher BMI and those living with HIV had significantly lower odds of PEth sensitivity. African Americans and Africans had higher odds of PEth sensitivity than whites in models that included biologic variables. CONCLUSIONS: Among people reporting unhealthy alcohol use, several biological factors (hemoglobin, BMI, liver fibrosis, and HIV status) were associated with PEth sensitivity. Race/ethnicity was associated with PEth sensitivity in some models but age, sex, and method of blood collection were not. Clinicians should be aware of these factors, and researchers should consider adjusting analyses for these characteristics where possible.

Shh promotes direct interactions between epidermal cells and osteoblast progenitors to shape regenerated zebrafish bone.

Zebrafish innately regenerate amputated fins by mechanisms that expand and precisely position injury-induced progenitor cells to re-form tissue of the original size and pattern. For example, cell signaling networks direct osteoblast progenitors (pObs) to rebuild thin cylindrical bony rays with a stereotypical branched morphology. Hedgehog/Smoothened (Hh/Smo) signaling has been variably proposed to stimulate overall fin regenerative outgrowth or promote ray branching. Using a photoconvertible patched2 reporter, we resolve active Hh/Smo output to a narrow distal regenerate zone comprising pObs and adjacent motile basal epidermal cells. This Hh/Smo activity is driven by epidermal Sonic hedgehog a (Shha) rather than Ob-derived Indian hedgehog a (Ihha), which nevertheless functions atypically to support bone maturation. Using BMS-833923, a uniquely effective Smo inhibitor, and high-resolution imaging, we show that Shha/Smo is functionally dedicated to ray branching during fin regeneration. Hh/Smo activation enables transiently divided clusters of Shha-expressing epidermis to escort pObs into similarly split groups. This co-movement likely depends on epidermal cellular protrusions that directly contact pObs only where an otherwise occluding basement membrane remains incompletely assembled. Progressively separated pObs pools then continue regenerating independently to collectively re-form a now branched skeletal structure.

High-Pressure-Promoted and Facially Selective Diels-Alder Reactions of Enzymatically Derived cis-1,2-Dihydrocatechols and Their Acetonide Derivatives: Enantiodivergent Routes to Homochiral and Polyfunctionalized Bicyclo[2.2.2]octenes.

cis-1,2-Dihydrocatechols 5 (X = Me and Cl), which are available in the homochiral form through the whole-cell biotransformation of toluene and chlorobenzene, respectively, undergo Diels-Alder cycloaddition reactions with a range of electron-deficient dienophiles at 19 kbar (1.9 GPa). The favored products of such reactions are adducts of the general form 7 and that arise through the operation of a contrasteric or syn-addition pathway. In contrast, the acetonide derivatives of metabolites 5 undergo anti-selective addition reactions under the same conditions and so producing adducts of the general form 11. Bicyclo[2.2.2]octenes 7 and 11, which embody carbocyclic frameworks of opposite enantiomeric form, are useful scaffolds for chemical synthesis. Computational studies reveal that syn-adduct formation is kinetically and normally thermodynamically favored over anti-adduct formation when the free diols 5 are involved, but the reverse is so when the corresponding acetonides participate as the 4π-addend. Furthermore, the reactions become more exothermic as pressure increases while, concurrently, the activation barrier diminishes and at 6 GPa (60 kbar) almost vanishes.

Asymmetric Synthesis and Stereochemical Assignment of 12C/13C Isotopomers.

A synthesis of chiral hydrocarbons having C1 axis and C3 symmetry, which owe their chirality due to asymmetrical distribution of 12C/13C isotopes, is reported. Their absolute configurations assigned using the vibrational circular dichroism technique conform with those deduced from the absolute configurations of the parent α-formyl cyclopropanes.

RNA-seq reveals disruption of gene regulation when honey bees are caged and deprived of hive conditions.

In this study, we present phenotypic and genetic data characterizing the impact of imidacloprid and caging stress on honey bee Apis mellifera physiological responses and regulation of 45 genes using targeted-RNA seq. The term 'caging stress' characterizes the effects of depriving honey bees of all hive aspects and conditions. Two cohorts of 1 day old sister bees were subjected to different conditions. One cohort was caged and fed different imidacloprid-tainted sugar solutions and the second was marked and introduced back to its natal hive. Physiological bee parameters and diet behavior were monitored daily for caged bees over several weeks. Bee samples from both cohorts were sampled weekly for RNA sequencing and oxidative stress analyses. Imidacloprid induced significant protein damage and post-ingestive aversion responses in caged bees, leading to lower tainted syrup consumption and higher water intake compared with the controls. No differentially expressed genes were observed among caged bees in regards to imidacloprid treatment. However, significant upregulation in antioxidant genes was recorded in caged bees as compared with hive bees, with overwhelming downregulation in all gene categories in caged bees at week 4. We identified two sets of genes that were constantly regulated in caged bees, including Rsod with unknown function in insects that could potentially characterize caging stress in honey bees.

Histone demethylases Kdm6ba and Kdm6bb redundantly promote cardiomyocyte proliferation during zebrafish heart ventricle maturation.

Trimethylation of lysine 27 on histone 3 (H3K27me3) by the Polycomb repressive complex 2 (PRC2) contributes to localized and inherited transcriptional repression. Kdm6b (Jmjd3) is a H3K27me3 demethylase that can relieve repression-associated H3K27me3 marks, thereby supporting activation of previously silenced genes. Kdm6b is proposed to contribute to early developmental cell fate specification, cardiovascular differentiation, and/or later steps of organogenesis, including endochondral bone formation and lung development. We pursued loss-of-function studies in zebrafish to define the conserved developmental roles of Kdm6b. kdm6ba and kdm6bb homozygous deficient zebrafish are each viable and fertile. However, loss of both kdm6ba and kdm6bb shows Kdm6b proteins share redundant and pleiotropic roles in organogenesis without impacting initial cell fate specification. In the developing heart, co-expressed Kdm6b proteins promote cardiomyocyte proliferation coupled with the initial stages of cardiac trabeculation. While newly formed trabecular cardiomyocytes display a striking transient decrease in bulk cellular H3K27me3 levels, this demethylation is independent of collective Kdm6b. Our results indicate a restricted and likely locus-specific role for Kdm6b demethylases during heart ventricle maturation rather than initial cardiogenesis.

Predictors of Alcohol Withdrawal Readmissions.

AIMS: Hospital readmissions serve as a major benchmark for the quality of care and alcohol withdrawal (AW) may lead to multiple hospitalizations and readmissions. We sought to evaluate readmission rates and predictors of having AW-related readmissions in a nationally representative sample. SHORT SUMMARY: In a nationally representative sample, AW readmission within 30 days and multiple readmissions during the year were high and were particularly predicted by discharge against medical advice (AMA), comorbid psychosis, comorbid depression, poor socioeconomic status, comorbid drug abuse and alcohol-related medical disease. METHODS: Subjects from the 2013 Nationwide Readmissions Database (NRD) with AW as a primary or secondary diagnosis. Cross-sectional and retrospective analyses were performed using regression methods appropriate for the NRD complex sampling design. The outcome measures were AW-related readmission, 30-day readmission and multiple readmissions. RESULTS: In 2013, 393,118 discharges involved ICD-9 coding for AW and 41.5% of these included AW as the primary discharge diagnosis. The rate of AW-related readmission in 2013, as estimated from first-quarter index events, was 58.8% (95% confidence interval (CI) 57.5-60.1), with an average of 1.8 readmissions (95% CI 1.7-1.9). The 30-day readmission rate, estimated from January-November index events, was 19.7% (95% CI 19.0-20.4). The strongest independent predictors of yearly, 30-day and multiple readmission were discharged AMA and comorbid psychotic disorder. CONCLUSION: AW readmission within 30 days and multiple readmissions during the year were common and were particularly predicted by AMA discharge and comorbid psychotic disorder. While these and other factors can help identify high-risk patients, further study to determine causal mechanisms may aid efforts to improve both the outcomes and costs associated with acute AW treatment.

Enantioselective Synthesis of anti-1,2-Oxaborinan-3-enes from Aldehydes and 1,1-Di(boryl)alk-3-enes Using Ruthenium and Chiral Phosphoric Acid Catalysts.

A cationic ruthenium(II) complex catalyzes double-bond transposition of 1,1-di(boryl)alk-3-enes to generate in situ 1,1-di(boryl)alk-2-enes, which then undergo chiral phosphoric acid catalyzed allylation of aldehydes producing homoallylic alcohols with a (Z)-vinylboronate moiety. 1,2-Anti stereochemistry is installed in an enantioselective manner. The (Z)-geometry forged in the products allows their isolation in a form of 1,2-oxaborinan-3-enes, upon which further synthetic transformations are operated.

Aging is associated with impaired angiogenesis, but normal microvascular network structure, in the rat mesentery.

A big problem associated with aging is thought to be impaired microvascular growth or angiogenesis. However, to link the evidence for impaired angiogenesis to microvascular dysfunction in aged tissues, we must compare adult vs. aged microvascular networks in unstimulated scenarios. The objective of this study was to test the hypothesis that aged microvascular networks are characterized by both fewer vessels and the impaired ability to undergo angiogenesis. Mesentery tissues from adult (9-mo) and aged (24-mo) male Fischer 344 rats were harvested and immunolabeled for platelet/endothelial cell adhesion molecule (an endothelial cell marker) according to two scenarios: unstimulated and stimulated. For unstimulated groups, tissues harvested from adult and aged rats were compared. For stimulated groups, tissues were harvested 3 or 10 days after compound 48/80-induced mast cell degranulation stimulation. Unstimulated aged microvascular networks displayed larger mean vascular area per tissue area compared with the unstimulated adult networks. The lack of a decrease in vessel density was supported at the gene expression level with RNA-Seq analysis and with comparison of vessel densities in soleus muscle. Following stimulation, capillary sprouting and vessel density were impaired in aged networks at 3 and 10 days, respectively. Our results suggest that aging associated with impaired angiogenesis mechanisms might not influence normal microvascular function, since unstimulated aged microvascular networks can display a "normal adult-like" vessel density and architecture. NEW & NOTEWORTHY: Using a multidimensional approach, we present evidence supporting that aged microvascular networks display vessel density and patterning similar to adult networks despite also being characterized by a decreased capacity to undergo angiogenesis. Thus, vessel loss is not necessarily a characteristic of aging.