bluuebunny/crossref_metadata_2025 huggingface dataset:
Persistent panmixia despite extreme habitat loss and population decline in the threatened tricolored blackbird (Agelaius tricolor)
Authors: Barr Kelly , Beichman Annabel C. , Kalhori Pooneh , Rajbhandary Jasmine , Bay Rachael A. , Ruegg Kristen , Smith Thomas B.
Published: October 2020

Habitat loss and alteration has driven many species into decline, often to the point of requiring protection and intervention to avert extinction. Genomic data provide the opportunity to inform conservation and recovery efforts with details about vital evolutionary processes with a resolution far beyond that of traditional genetic approaches. The tricolored blackbird (Agelaius tricolor) has suffered severe losses during the previous century largely due to anthropogenic impacts on their habitat. Using a dataset composed of a whole genome paired with reduced representation libraries (RAD‐Seq) from samples collected across the species’ range, we find evidence for panmixia using multiple methods, including PCA (no geographic clustering), admixture analyses (ADMIXTURE and TESS conclude K = 1), and comparisons of genetic differentiation (average FST = 0.029). Demographic modeling approaches recovered an ancient decline that had a strong impact on genetic diversity but did not detect any effect from the known recent decline. We also did not detect any evidence for selection, and hence adaptive variation, at any site, either geographic or genomic. These results indicate that species continues to have high vagility across its range despite population decline and habitat loss and should be managed as a single unit.
Negative Partner Attributions Moderate the Association between Heart Rate Reactivity During Relationship Conflict and Relationship Satisfaction
Authors: Adamo Colin , Leo Karena , Hogan Jasara N. , Crenshaw Alexander O. , Baucom Katherine J. W. , Baucom Brian R. W.
Published: October 2020

Numerous theoretical models of relationship distress suggest that strong, negative reactions to conflict are directly associated with lower levels of relationship satisfaction. Consistent with this supposition, substantial evidence links higher levels of subjective negative emotion, more pronounced and frequent expressions of negative affect, and higher levels of negative communication behaviors to lower levels of relationship satisfaction (e.g., Bradbury, Fincham, & Beach, 2000, Journal of Marriage and Family, 62(4), 964). However, the evidence linking stress‐related physiological responding during relationship conflict and relationship satisfaction is less compelling than would be anticipated based on theory. We propose that these theoretically unexpected but empirically well‐replicated findings may be the result of different patterns in association between physiological reactivity and relationship satisfaction for couples with varying styles in how they typically perceive unwanted behavior in one another. The present study tests negative attributions for undesirable partner behaviors as a moderator of the association between heart rate reactivity (HRR) during relationship conflict and relationship satisfaction in a sample of 60 married couples. A significant interaction emerged between HRR and negative attributions of partner behavior in predicting relationship satisfaction such that higher levels of HRR were associated with lower levels of relationship satisfaction for individuals who typically made more negative attributions for undesirable partner behaviors, but with higher levels of relationship satisfaction for individuals who typically made fewer negative attributions for undesirable partner behaviors. Implications for conceptualizing reactivity during relationship conflict and couple interventions are discussed.
From pools to flow: The PROMISE framework for new insights on soil carbon cycling in a changing world
Authors: Waring Bonnie G. , Sulman Benjamin N. , Reed Sasha , Smith A. Peyton , Averill Colin , Creamer Courtney A. , Cusack Daniela F. , Hall Steven J. , Jastrow Julie D. , Jilling Andrea , Kemner Kenneth M. , Kleber Markus , Liu Xiao‐Jun Allen , Pett‐Ridge Jennifer , Schulz Marjorie
Published: October 2020

Soils represent the largest terrestrial reservoir of organic carbon, and the balance between soil organic carbon (SOC) formation and loss will drive powerful carbon‐climate feedbacks over the coming century. To date, efforts to predict SOC dynamics have rested on pool‐based models, which assume classes of SOC with internally homogenous physicochemical properties. However, emerging evidence suggests that soil carbon turnover is not dominantly controlled by the chemistry of carbon inputs, but rather by restrictions on microbial access to organic matter in the spatially heterogeneous soil environment. The dynamic processes that control the physicochemical protection of carbon translate poorly to pool‐based SOC models; as a result, we are challenged to mechanistically predict how environmental change will impact movement of carbon between soils and the atmosphere. Here, we propose a novel conceptual framework to explore controls on belowground carbon cycling: Probabilistic Representation of Organic Matter Interactions within the Soil Environment (PROMISE). In contrast to traditional model frameworks, PROMISE does not attempt to define carbon pools united by common thermodynamic or functional attributes. Rather, the PROMISE concept considers how SOC cycling rates are governed by the stochastic processes that influence the proximity between microbial decomposers and organic matter, with emphasis on their physical location in the soil matrix. We illustrate the applications of this framework with a new biogeochemical simulation model that traces the fate of individual carbon atoms as they interact with their environment, undergoing biochemical transformations and moving through the soil pore space. We also discuss how the PROMISE framework reshapes dialogue around issues related to SOC management in a changing world. We intend the PROMISE framework to spur the development of new hypotheses, analytical tools, and model structures across disciplines that will illuminate mechanistic controls on the flow of carbon between plant, soil, and atmospheric pools.
Generation of metabolically functional hepatocyte‐like cells from dedifferentiated fat cells by Foxa2, Hnf4a and Sall1 transduction
Authors: Hagiwara Reiko , Oki Yoshinao , Matsumaru Takashi , Ibayashi Shiho , Kano Koichiro
Published: October 2020

Mature adipocyte‐derived dedifferentiated fat (DFAT) cells have been identified to possess similar multipotency to mesenchymal stem cells, but a method for converting DFAT cells into hepatocytes was previously unknown. Here, using comprehensive analysis of gene expression profiles, we have extracted three transcription factors, namely Foxa2, Hnf4a and Sall1 (FHS), that can convert DFAT cells into hepatocytes. Hepatogenic induction has converted FHS‐infected DFAT cells into an epithelial‐like morphological state and promoted the expression of hepatocyte‐specific features. Furthermore, the DFAT‐derived hepatocyte‐like (D‐Hep) cells catalyzed the detoxification of several compounds. These results indicate that the transduction of DFAT cells with three genes, which were extracted by comprehensive gene expression analysis, efficiently generated D‐Hep cells with detoxification abilities similar to those of primary hepatocytes. Thus, D‐Hep cells may be useful as a new cell source for surrogate hepatocytes and may be applied to drug discovery studies, such as hepatotoxicity screening and drug metabolism tests.
The interprovincial slave trade from Rio de Janeiro, 1809–1833: An analysis of the Brazilian Institute of Applied Economic Research database
Authors: Cosby Katherine , Domingues da Silva Daniel B.
Published: October 2020

In the 19th century, Rio de Janeiro emerged as the largest slaving port in the Americas. Every year, ships, mainly from Brazil and Portugal, poured thousands of enslaved Africans in that port. But what happened to them after they disembarked? This paper examines a database of passports and other sources compiled by the Brazilian Institute of Applied Economic Research to address that question. It also discusses the challenges and methods of adjusting the database to an ongoing project focused on the intracontinental slave trade in the Americas from the 16th to the 19th centuries. The paper shows that, although Rio de Janeiro was the final destination for many slaves disembarked there, a significant proportion of them was re‐exported into the interprovincial traffic, to regions as distant as Minas Gerais, São Paulo, and Rio Grande do Sul.
Clinicopathological, immunohistochemical and fluorescence in‐situ hybridisation features of early subungual melanoma: an analysis of 65 cases
Authors: Ren Min , Ren Jing , Cai Xu , Shen Xu‐Xia , Kong Jin‐Cheng , Dai Bo , Kong Yun‐Yi
Published: October 2020

Aims

Very limited data are available concerning the clinicopathological and molecular features of early subungual melanoma (SM), especially with regard to the Asian population. The aim of this study was to investigate the clinical, histological, immunohistochemical and chromosomal features of early SM.

Methods and results

Fifty‐two in‐situ and 13 thin (Breslow thickness ≤1.0 mm) SM cases were retrospectively reviewed. All patients presented with longitudinal melanonychia involving a single digit, and the thumb was the most affected digit (35 of 65, 53.8%). Microscopically, most cases showed small to medium nuclear enlargement (58 of 65) and mild to moderate nuclear atypia (57 of 65). Hyperchromatism and irregular contours of nuclei were persistent features in all cases. The variation of melanocyte count (the number of melanocytes per mm dermal‐epithelial junction) ranged from 31 to 255. Intra‐epithelial mitoses were identified in 34 cases (52.3%). Statistically, features of in‐situ lesions including higher melanocyte count (>70), presence of multinucleated melanocytes, inflammatory infiltrate and cutaneous adnexal extension, were associated with early invasion. Melan‐A, human melanoma B (HMB)45, mouse monoclonal melanoma antibody (PNL2) and SOX10 antibodies (>95.0%) showed superior diagnostic sensitivity to S‐100 protein (83.1%). Fluorescence in‐situ hybridisation (FISH) results were positive in 15 of 23 successfully analysed cases.

Conclusions

To the best of our knowledge, this is the largest single‐institution study of early SM in an Asian population, and the largest cohort tested by FISH. Early SM mainly showed small to medium nuclear enlargement and mild to moderate nuclear atypia. High melanocyte count, hyperchromatism and irregular contours of nuclei and intra‐epithelial mitoses are crucial diagnostic parameters. Immunohistochemistry, especially SOX10 staining, and FISH analysis are valuable in the diagnosis of SM.
Infants' discrimination of consonant contrasts in the presence and absence of talker variability
Authors: Quam Carolyn , Clough Lauren , Knight Sara , Gerken LouAnn
Published: October 2020

To learn speech‐sound categories, infants must identify the acoustic dimensions that differentiate categories and selectively attend to them as opposed to irrelevant dimensions. Variability on irrelevant acoustic dimensions can aid formation of robust categories in infants through adults in tasks such as word learning (e.g., Rost and McMurray, 2009) or speech‐sound learning (e.g., Lively et al., 1993). At the same time, variability sometimes overwhelms learners, interfering with learning and processing. Two prior studies (Kuhl & Miller, 1982; Jusczyk, Pisoni, & Mullennix, 1992) found that irrelevant variability sometimes impaired early sound discrimination. We asked whether variability would impair or facilitate discrimination for older infants, comparing 7.5‐month‐old infants' discrimination of an early acquired native contrast, /p/ vs. /b/ (in the word forms /pIm/ vs. /bIm/), in Experiment 1, with an acoustically subtle, non‐native contrast, /n/ vs. /ŋ/ (in /nIm/ vs. /ŋIm/), in Experiment 2. Words were spoken by one or four talkers. Infants discriminated the native but not the non‐native contrast, and there were no significant effects of talker condition. We discuss implications for theories of phonological learning and avenues for future research.
Growth of thin film ferroelectric PZT, PHT, and antiferroelectric PHO from atomic layer deposition precursors
Authors: Strnad Nicholas A. , Hanrahan Brendan M. , Potrepka Daniel M. , Pulskamp Jeffrey S. , Phaneuf Raymond J. , Polcawich Ronald G.
Published: October 2020

We present a conformal method of growing ferroelectric lead hafnate‐titanate (PbHfxTi1−xO3, PHT) and lead zirconate‐titanate (PbZrxTi1−xO3, PZT) using atomic layer deposition (ALD) precursors. The 4+ cation precursors consist of tetrakis dimethylamino titanium (TDMAT), tetrakis dimethylamino zirconium (TDMAZ) and tetrakis dimethyl amino hafnium (TDMAH) for Ti, Zr, and Hf, respectively. The Pb (2+) precursor was Lead bis(3‐N,N‐dimethyl‐2‐methyl‐2‐propanoxide) [Pb(DMAMP)2]. PZT was limited to lead titanate (PTO)‐rich compositions, where x <0.25 for PbZrxTi1−xO3, and exhibited a remnant polarization of 26‐27 µC/cm2 with a coercive field between 150 and 170 kV/cm. The 3D‐structure coating capability of PZT was demonstrated by deposition on micromachined trench sidewalls 45 µm deep. We fabricated Microelectromechanical systems (MEMS) cantilever arrays with PZT thin films grown using the present method and demonstrated piezoelectric actuation. Alternatively, PHT was deposited with Ti and Hf compositions within ±1 at.% of the morphotropic phase boundary (MPB). The PHT exhibited a remanent polarization of 7.0‐8.7 µC/cm2 with a coercive field between 84‐100 kV/cm. We applied the same Pb and Hf precursors from the PHT process to grow antiferroelectric lead‐hafnate (PHO), which showed the characteristic electric field‐induced ferroelectric phase transition at approximately ±280 kV/cm and a maximum polarization of approximately ±32.8 µC/cm2.
Zinc Finger Protein ZBTB20 protects against cardiac remodelling post‐myocardial infarction via ROS‐TNFα/ASK1/JNK pathway regulation
Authors: Li Fangfang , Yang Yiming , Xue Chuanyou , Tan Mengtong , Xu Lu , Gao Jianbo , Xu Luhong , Zong Jing , Qian Wenhao
Published: October 2020

This study aims to determine the efficacy of Zinc finger protein ZBTB20 in treatment of post‐infarction cardiac remodelling. For this purpose, left anterior descending (LAD) ligation was operated on mice to induce myocardial infarction (MI) with sham control group as contrast and adeno‐associated virus (AAV9) system was used to deliver ZBTB20 to mouse heart by myocardial injection with vehicle‐injected control group as contrast two weeks before MI surgery. Then four weeks after MI, vehicle‐treated mice with left ventricular (LV) remodelling underwent deterioration of cardiac function, with symptoms of hypertrophy, interstitial fibrosis, inflammation and apoptosis. The vehicle‐injected mice also showed increase of infarct size and decrease of survival rate. Meanwhile, the ZBTB20‐overexpressed mice displayed improvement after MI. Moreover, the anti‐apoptosis effect of ZBTB20 was further confirmed in H9c2 cells subjected to hypoxia in vitro. Further study suggested that ZBTB20 exerts cardioprotection by inhibiting tumour necrosis factor α/apoptosis signal‐regulating kinase 1 (ASK1)/c‐Jun N‐terminal kinase 1/2 (JNK1/2) signalling, which was confirmed by shRNA‐JNK adenoviruses transfection or a JNK activator in vitro as well as ASK1 overexpression in vivo. In summary, our data suggest that ZBTB20 could alleviate cardiac remodelling post‐MI. Thus, administration of ZBTB20 can be considered as a promising treatment strategy for heart failure post‐MI.

Significance Statement: ZBTB20 could alleviate cardiac remodelling post‐MI via inhibition of ASK1/JNK1/2 signalling.
Microeukaryotic Communities Associated With the Seagrass Zostera marina Are Spatially Structured
Authors: Trevizan Segovia Bianca , Sanders‐Smith Rhea , Adamczyk Emily M. , Forbes Coreen , Hessing‐Lewis Margot , O’Connor Mary I. , Parfrey Laura Wegener
Published: October 2020

Epibiotic microorganisms link seagrass productivity to higher trophic levels, but little is known about the processes structuring these communities, and which taxa consistently associate with seagrass. We investigated epibiotic microeukaryotes on seagrass (Zostera marina) leaves, substrates, and planktonic microeukaryotes in ten meadows in the Northeast Pacific. Seagrass epibiotic communities are distinct from planktonic and substrate communities. We found sixteen core microeukaryotes, including dinoflagellates, diatoms, and saprotrophic stramenopiles. Some likely use seagrass leaves as a substrate, others for grazing, or they may be saprotrophic organisms involved in seagrass decomposition or parasites; their relatives have been previously reported from marine sediments and in association with other hosts such as seaweeds. Core microeukaryotes were spatially structured, and none were ubiquitous across meadows. Seagrass epibiota were more spatially structured than planktonic communities, mostly due to spatial distance and changes in abiotic conditions across space. Seawater communities were relatively more similar in composition across sites and more influenced by the environmental component, but more variable over time. Core and transient taxa were both mostly structured by spatial distance and the abiotic environment, with little effect of host attributes, further indicating that those core taxa would not show a strong specific association with Z. marina.
Increased odds ratio for COVID‐19 in patients with recurrent aphthous stomatitis
Authors: Katz Joseph , Yue Sijia
Published: October 2020

The ACE2 receptor, the binding sites for the COVID‐19, is expressed abundantly in the oral cavity, raising the question of whether the mouth is a target for the virus in addition to organs such as kidneys and lungs. Recently, a flurry of individual case reports on oral manifestation of COVID‐19 including ulceration, blistering lesions, and stomatitis were published. However, it is not clear whether the oral presentations that are not unique to the virus are indeed related to the virus and appear at a higher prevalence than in the general population. We used the i2b2 platform of hospital patient's registry to determine the odds ratio for COVID‐19 in patients that were diagnosed with recurrent aphthous stomatitis, an entity restricted to the oral cavity. The overall odds ratio for COVID‐19 in patients with recurrent aphthous stomatitis before adjustments was 14 and after adjustment for gender, race, and age was 13.9, 6.5, and 2.93, respectively. The odds ratio remained increased after adjustments of the comorbidities such as respiratory disease, endocrine disease, obesity, diabetes, circulatory disease, and smoking and was 3.66, 7.46, 4.6, 10.54, 7.37, and 7.52, respectively. When adjusted for recurrent aphthous stomatitis, the respiratory disease had an odd ratio of 8.56 to be associated with COVID‐19. African American race and age‐group 18‐34 were additional significant risk factors. The present study has demonstrated a significant association between COVID‐19 and RAS; however, additional longitudinal and laboratory studies are necessary to establish a cause and effect relationship between these 2 conditions.
Lexicographic choice under variable capacity constraints
Authors: Doğan Battal , Doğan Serhat , Yıldız Kemal
Published: October 2020

In several matching markets, to achieve diversity, agents' priorities are allowed to vary across an institution's available seats, and the institution is let to choose agents in a lexicographic fashion based on a predetermined ordering of the seats, called a (capacity‐constrained) lexicographic choice rule. We provide a characterization of lexicographic choice rules and a characterization of deferred acceptance mechanisms that operate based on a lexicographic choice structure under variable capacity constraints. We discuss some implications for the Boston school choice system and show that our analysis can be helpful in applications to select among plausible choice rules.
Symptomatic partial anomalous pulmonary venous connection in a kitten
Authors: Hsueh Tung , Yang Chung‐Chun , Lin Shiun‐Long , Chan I‐Ping
Published: October 2020

A 3‐month‐old intact female American Shorthair cat, with syncope and tachypnea, underwent cardiac examination which identified no heart murmur or gallop. Thoracic radiography disclosed mild generalized enlargement of the cardiac silhouette and a bronchial and interstitial pattern throughout the lungs. Echocardiography identified tubular structures near the left atrium. After agitated saline contrast imaging, persistent left cranial vena cava with unroofed coronary sinus was suspected. Computed tomography angiography showed the right cranial, right caudal and left caudal pulmonary veins draining into the coronary sinus and flowing into the right atrium. The left cranial pulmonary vein drained normally into the left atrium. Partial anomalous pulmonary venous connection (PAPVC) was diagnosed. The kitten was treated with diuretics but died of heart failure 2 months later. Permission for necropsy was not granted. This case represents symptomatic PAPVC in a kitten. Most pulmonary veins were connected abnormally with the coronary sinus. The prognosis was grave because of refractory heart failure.
Clinico‐immunological outcomes of HCV‐cured cryoglobulinemia: Lower relapse rate with interferon‐based than interferon‐free therapy
Authors: Colantuono Stefania , Marrapodi Ramona , Del Padre Martina , Collalti Giulia , Garzi Giulia , De Santis Adriano , Fiorilli Massimo , Basili Stefania , Visentini Marcella , Casato Milvia
Published: October 2020

Sustained virological response (SVR) obtained with interferon (IFN) or with direct‐acting antivirals (DAAs) is commonly followed by response of hepatitis C virus (HCV)‐associated mixed cryoglobulinemia vasculitis (MCV), but relapse of MCV despite SVR has been reported in several patients after DAAs and rarely after IFN. Since relapses could have been overlooked in studies with IFN, we retrospectively compared the outcomes of MCV in SVR patients treated with DAAs (n = 70) or IFN (n = 39) followed‐up, respectively, for 30.5 (range 11‐51) or 48 months. Groups were comparable for demographics and clinics and response rates of MCV were similar (92% and 86%); however, DAA‐treated patients less efficiently reduced cryoglobulins (P = .006) and circulating B‐cell clones (P = .004), and had more frequently relapses of MCV (18% vs 3%, P = .028) and need for rituximab therapy (P = .01). Although largely inferior on an intention‐to‐treat basis, IFN may be superior to DAAs on clinico‐immunological outcomes possibly owing to its antiproliferative activity.
Threshold versus intensity functions in two‐colour automated perimetry
Authors: Simunovic Matthew P. , Hess Kristina , Avery Neil , Mammo Zaid
Published: October 2020

Purpose

Two‐colour computerised perimetry is a technique developed for assessing cone‐ and rod‐function at fixed background luminances in retinal disease. However, the state of adaptation during testing is unknown but crucial in the interpretation of results. We therefore aimed to determine the adaptational state of rod‐ and cone‐mechanisms in two‐colour perimetry.

Methods

Sensitivity to 480 nm (blue) and 640 nm (red) Goldmann size V targets was determined for 10 normal subjects aged 16 to 46 years at 17 locations in the central 60 degrees of the visual field under scotopic conditions and then from −1.5 log cd m−2 to 2 log cd m−2 (white background) in 0.5 log unit steps. Data were fitted with threshold versus intensity (tvi) functions of the form logT = logT0 + log ((A + A0)/A0)n.

Results

No clear rod‐cone break was observed for 640 nm stimuli. For 480 nm stimuli, transition from rod‐detection to cone‐detection occurred at mesopic illumination levels, where rod adaptation approached Weber behaviour. Cone detection mechanisms did not display Weber‐like adaptation until the background luminance approached 1 log cd.m−2. Diseases resulting in a “filter effect” ‐ including disorders of the photoreceptors ‐ are therefore predicted to affect sensitivity when rod function is probed with short‐wavelength targets under scotopic conditions, but less so under mesopic conditions. Filter effects are similarly anticipated to affect cone function measured using long‐wavelength targets under mesopic conditions (e.g., during microperimetry), but less so under photopic conditions.

Conclusions

Asymmetries in adaptation in automated two‐colour perimetry are predicted to artefactually favour the detection of losses in rod sensitivity under scotopic conditions and cones under mesopic conditions.
Diversity of banana diploid hybrids: An assessment based on a hydroponic system
Authors: Santos Adriadna S. , Amorim Edson P. , Almeida Alex‐Alan F. , Ferreira Claudia F. , Coelho Filho Mauricio Antonio , Pirovani Carlos P.
Published: October 2020

Bananas are typical to tropical and subtropical climate regions, where they have better conditions due to high air humidity and soil water availability. The production of drought‐tolerant varieties is an alternative to expand the cultivation sites to drier areas. In this work, we present a hydroponic system for the genotype selection of Musa sp. (AA) subjected to water stress. A total of 14 banana genotypes were tested; 12 diploids and two commercial varieties with a known response to drought tolerance. The results show that the improved diploids have different responses with respect to water deficit, with the PMGB043 and PMGB044 genotypes considered more susceptible and the PMGB075 and PMGB099 genotypes more tolerant. Under water deficit conditions, most banana diploids maintain a high relative water content, but there is a reduction in aerial part growth and an increase in root dry mass. The accumulation of alcohol dehydrogenase, especially in control treatment plants, indicate that the glycolytic pathway was used to supply energy demand, showing potential flood‐tolerant genotypes. The results are essential for the preimprovement of banana cultivars.
Recurrent co‐alteration of HDGF and SETDB1 on chromosome 1q drives cutaneous melanoma progression and poor prognosis
Authors: Fazio Maurizio , van Rooijen Ellen , Mito Jeffrey K. , Modhurima Rodsy , Weiskopf Erika , Yang Song , Zon Leonard I.
Published: October 2020

A progressive increase in copy number variation (CNV) characterizes the natural history of cutaneous melanoma progression toward later disease stages, but our understanding of genetic drivers underlying chromosomal arm‐level CNVs remains limited. To identify candidate progression drivers, we mined the TCGA SKCM dataset and identified HDGF as a recurrently amplified gene whose high mRNA expression correlates with poor patient survival. Using melanocyte‐specific overexpression in the zebrafish BRAFV600E‐driven MiniCoopR melanoma model, we show that HDGF accelerates melanoma development in vivo. Transcriptional analysis of HDGF compared to control EGFP tumors showed the activation of endothelial/angiogenic pathways. We validated this observation using an endothelial kdrl:mCherry reporter line which showed HDGF to increases tumor vasculature. HDGF is frequently co‐altered with the established melanoma driver SETDB1. Both genes are located on chromosome 1q, and their co‐amplification is observed in up to 13% of metastatic melanoma. TCGA patients with both genes amplified and/or overexpressed have a worse melanoma specific survival. We tested co‐expression of HDGF and SETDB1 in the MiniCoopR model, which resulted in faster and more aggressive melanoma development than either gene individually. Our work identifies the co‐amplification of HDGF and SETDB1 as a functional driver of melanoma progression and poor patient prognosis.
The Irrelevance of History: In Defense of a Pure Functionalist Theory of Territorial Jurisdiction
Authors: Koch Mikalsen Kjartan
Published: October 2020

This article defends a pure functionalist theory of territorial jurisdiction according to which a state’s moral right to rule over a territory rests on its present moral performance as a freedom‐enabling institutional structure. A common objection against functionalist theories is that they cannot explain why it matters that one particular state has exclusive jurisdiction over a certain territory. This deficiency is often associated with the annexation challenge, which is supposed to show that functionalist theories cannot deal adequately with cases of annexation. Against this line of criticism, I argue that the pure functionalist justification of the right to rule is capable of tackling challenges related to particularity and annexation. First, the pure functionalist theory explains why it is important that one particular state rules over a given territory. It also tells us what set of laws and what government we should comply with. Second, the pure functionalist justification of the right to rule entails sufficient conceptual resources to account for the wrongdoing involved in annexation. Although the theory deems past wrongs irrelevant for the justification of the right to exercise jurisdiction on a territory, it is adequately sensitive to historical injustice.
Why a Hedgehog Cannot Have Political Obligations
Authors: Faggion Andrea
Published: October 2020

According to Ronald Dworkin, political obligation is to be justified as an associative obligation through membership in certain political communities. In this regard, I first argue that the concept of an associative obligation cannot help us to account for precise moral obligations. Second, I analyze certain disanalogies between paradigmatic cases of associative obligation and political obligation in order to show the inability of the former to justify the enforcement of a comprehensive obligation such as the latter. Finally, I argue that Dworkin could not have provided a better argument: His theory of law makes him incapable of justifying political obligation.
Steroid‐responsive neutropenia in a cat with progressive feline leukemia virus infection
Authors: Stavroulaki Evangelia M. , Mylonakis Mathios E. , Papanikolaou Eleni , Hatzis Aristodimos , Xenoulis Panagiotis G.
Published: October 2020

An 8‐month‐old female domestic shorthair cat was presented to the Animal Medical Center with anorexia, lethargy, and mild gastrointestinal signs. A CBC revealed a profound neutropenia, and serologic testing with an in‐house test kit (SNAP FIV/FeLV Combo, IDEXX) was positive for feline leukemia virus (FeLV) antigen. Serial hematologic examinations during hospitalization showed a persistent neutropenia with occasionally severe anemia and thrombocytopenia. Prednisolone administration afforded complete hematologic remission within 3 days. Four weeks after the premature discontinuation of prednisolone, the patient relapsed; however, complete and prolonged hematologic remission was achieved after prednisolone was re‐induced. Bone marrow aspiration cytology was consistent with immune‐mediated destruction of the mature myeloid cells. steroid‐responsive (likely immune‐mediated) cytopenias rarely occur in cats with progressive FeLV infection. Although only a few cases of FeLV‐positive, severely neutropenic cats that responded to immunosuppressive therapy have been reported, this case highlights that a grave prognosis should not always be given to these FeLV‐positive cats.
Exploring a New Management Option for Patients With Refractory Ascites: The PeriLeve Device
Authors: Jain Aseem , Scavo Laura , Cross Damian , Marra Steven P. , Nimgaonkar Ashish
Published: October 2020

Cirrhosis of the liver is often accompanied by refractory ascites, a condition characterized by fluid buildup in the peritoneal cavity that does not respond to diuretics or recurs shortly after therapeutic paracentesis. There are several management strategies in practice including large-volume paracentesis, transjugular intrahepatic portosystemic shunts, peritoneovenous shunting, and liver transplant. However, each of these options come with limitations such as high cost, poor efficacy, and increased risk of complications. This article explores a new management strategy with a novel biopowered shunt, the PeriLeve device, that moves fluid from the peritoneal cavity to the urinary bladder using natural changes in intra-abdominal pressure (IAP). By doing so, PeriLeve shifts the current paradigm of care from the hospital to the home which reduces costs to healthcare providers and patients while improving quality of life. The basic design of the pump consists of two check (i.e., one-way) valves on either side of a fluid filled cavity which is separated from an air cavity by an elastomeric membrane. This article presents benchtop testing results of a prototype PeriLeve pump. The performance of the pump was analyzed along six parameters: change in intra-abdominal pressure, valve opening pressure, membrane thickness, membrane stiffness, membrane surface area, and air cavity volume. Initial results indicate that, with future optimizations, the pump can ultimately move a clinically significant volume of fluid.
Raman scattering study of nanoscale Mo/Si and Mo/Be periodic multilayer structures
Authors: Kumar Niranjan , Volodin Vladimir A. , Smertin Ruslan M. , Yunin Pavel A. , Polkovnoikov Vladimir N. , Panda Kalpataru , Nechay Andrey N. , Chkhalo Nikolay I.
Published: October 2020

Investigation of the microstructure and phase analysis of the periodic Mo/Si and Mo/Be multilayers are essential for depositing high reflective multilayers that operate at soft x-ray to extreme ultraviolet radiations. Raman spectroscopy revealed the presence of an amorphous phase of silicon (Si) in the Mo/Si multilayers. Furthermore, the disorder of the amorphous Si phase was increased with decreasing the periodic thickness of the Si layers in the nanoscale Mo/Si multilayers. The polycrystalline Mo periodic layers coexisted with the amorphous silicon layers in the Mo/Si multilayers. In contrast, both the Mo and Be layers in the Mo/Be periodic multilayers were condensed into the polycrystalline phases. At higher annealing temperatures, the polycrystalline and amorphous phases in both the Mo/Si and Mo/Be multilayers were destroyed due to the extensive interdiffusion process. However, the amorphous Si phase was partially preserved due to the formation of crystalline intermetallic h-MoSi2 and t-MoSi2 phases, for critically thicker Si layers in periodic Mo/Si multilayers.
In plasma OK, critics see politics, not science
Authors: Kupferschmidt Kai , Cohen Jon
Published: October 2020

FDA's emergency move raises fears of rushed approval for other experimental medicines.
How Italy's ‘father of the swabs’ fought the virus
Authors: Starr Douglas
Published: October 2020

Microbiologist Andrea Crisanti defied the authorities to launch his testing campaign.
New feedbacks speed up the demise of Arctic sea ice
Authors: Voosen Paul
Published: October 2020

Wave action and a growing underwater blob of heat add to impact of warming air.
Increases in U.S. federal R&D needed in a global crisis
Authors: Hoy Anne Q.
Published: October 2020

Support can boost the U.S. economy, innovation, and global standing
Clean 2D superconductivity in a bulk van der Waals superlattice
Authors: Devarakonda A. , Inoue H. , Fang S. , Ozsoy-Keskinbora C. , Suzuki T. , Kriener M. , Fu L. , Kaxiras E. , Bell D. C. , Checkelsky J. G.
Published: October 2020

Alternative route to a 2D superconductor

Single layers of transition metal dichalcogenides exhibit exotic properties, including superconductivity. The usual route to obtaining such samples is to exfoliate a three-dimensional (3D) crystal. Devarakonda
et al.
instead grew a superlattice comprising alternating layers of the transition metal dichalcogenide hexagonal NbS
2
and the material Ba
3
NbS
5
(see the Perspective by Schoop). The inert Ba
3
NbS
5
layers serve to dissociate the superconducting NbS
2
layers from one another, resulting in 2D superconductivity with high carrier mobility. The combination of high mobility and reduced dimensionality may give rise to exotic quantum phases.

Science
, this issue p.
231
see also p.
170
Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection
Authors: Habibi Maximillian S. , Thwaites Ryan S. , Chang Meiping , Jozwik Agnieszka , Paras Allan , Kirsebom Freja , Varese Augusto , Owen Amber , Cuthbertson Leah , James Phillip , Tunstall Tanushree , Nickle David , Hansel Trevor T. , Moffatt Miriam F. , Johansson Cecilia , Chiu Christopher , Openshaw Peter J. M.
Published: October 2020

ACHOO!-trophils?

Why some individuals come down with a cold in any given year, whereas others are spared, is poorly understood. Habibi
et al.
exposed volunteers to respiratory syncytial virus (RSV), one of the pathogens responsible for the common cold, and then followed them over the ensuing 2 weeks (see the Perspective by Mirchandani and Walmsley). The main factor distinguishing the infected from the noninfected was that the former showed signs of airway neutrophil activation before exposure to RSV. Conversely, protected individuals showed enhanced interleukin-17 signaling soon after virus inoculation. Similarly, mice pretreated with a neutrophil chemoattractant were more susceptible to RSV infection and CD8
+
T cell–driven disease. Neutrophil proteases, which can modulate cytokine activity, may explain the disparity and could provide therapeutic targets for RSV and other respiratory infections.

Science
, this issue p.
eaba9301
; see also p.
166
Neural mechanisms resolving exploitation-exploration dilemmas in the medial prefrontal cortex
Authors: Domenech Philippe , Rheims Sylvain , Koechlin Etienne
Published: October 2020

To continue or to switch strategy?

Successful behavior in an uncertain, changing, and open-ended environment critically relies on the ability to decide between continuing with the ongoing strategy or exploring new options. Neuroimaging studies have shown that the human medial prefrontal cortex (mPFC) is the part of the brain that primarily deals with this dilemma. However, the contribution of the different mPFC regions remains largely unknown. Domenech
et al.
recorded neuronal activity in six epileptic patients with depth electrodes in this brain area (see the Perspective by Steixner-Kumar and Gläscher). The ventral mPFC inferred the reliability of the ongoing action plan according to action outcomes. It proactively flagged outcomes either as learning signals to better exploit this plan or as potential triggers to explore new ones. The dorsal mPFC then evaluated action outcomes and generated an adaptive behavioral strategy.

Science
, this issue p.
eabb0184
; see also p.
1056
A heterogeneous microbial consortium producing short-chain fatty acids from lignocellulose
Authors: Shahab Robert L. , Brethauer Simone , Davey Matthew P. , Smith Alison G. , Vignolini Silvia , Luterbacher Jeremy S. , Studer Michael H.
Published: October 2020

Building niches for multiple microbes

Microbial conversion of heterogeneous feedstocks such as lignocellulose into one or more desired products requires assembly of pathways to both break down the inputs and produce the outputs. Shahab
et al.
assembled a collection of microbes that occupy different spatial niches within a bioreactor and have different metabolic capabilities. In the simplest version of their setup, an aerobic fungus adeptly breaks down cellulose into short sugar chains, an oxygen-tolerant bacterium converts these to lactic acid, and an anaerobic bacterium uses the lactic acid to synthesize the short-chain fatty acid butyric acid. Additional microbes handle limitations in the intermediate stream or divert lactic acid to longer-chain fatty acids, which are potentially more valuable. The integrated production and use of lactic acid for biosynthetic reactions could ideally serve as a platform for biosynthesis using robust, heterogeneous microbial consortia.

Science
, this issue p.
eabb1214
Mosquito cellular immunity at single-cell resolution
Authors: Raddi Gianmarco , Barletta Ana Beatriz F. , Efremova Mirjana , Ramirez Jose Luis , Cantera Rafael , Teichmann Sarah A. , Barillas-Mury Carolina , Billker Oliver
Published: October 2020

Teasing apart the mosquito immune system

Hemocytes are key immune cells of insects, playing a major role in how vector species transmit disease. Raddi
et al.
collected and sequenced the RNA of more than 8000 individual hemocytes from the disease-carrying mosquitoes
Anopheles gambiae
and
Aedes aegypti
. These data were then analyzed to determine hemocyte differentiation lineages and population changes in response to noninfected and
Plasmodium
-infected blood meals. From these data, the researchers identified a new hemocyte type, the megacyte, defined by the transcription of specific marker genes. Gene-silencing experiments implied that the megacyte functions in hemocyte differentiation during immune priming and thus may be involved in the immune response in mosquitoes.

Science
, this issue p.
1128
The origins of water
Authors: Peslier Anne H.
Published: October 2020

New measurements of Earth's building blocks point to a simpler water source
Strategies for navigating a dynamic world
Authors: Steixner-Kumar Saurabh , Gläscher Jan
Published: October 2020

A rich neural representation of its environment enables an adaptable organism to respond to changes
Mutant Strains of Escherichia coli and Methicillin-Resistant Staphylococcus aureus Obtained by Laboratory Selection To Survive on Metallic Copper Surfaces
Authors: Bleichert Pauline , Bütof Lucy , Rückert Christian , Herzberg Martin , Francisco Romeu , Morais Paula V. , Grass Gregor , Kalinowski Jörn , Nies Dietrich H.
Published: October 2020

Microbes are rapidly killed on solid copper surfaces by contact killing. Copper surfaces thus have an important role to play in preventing the spread of nosocomial infections. Bacteria adapt to challenging natural and clinical environments through evolutionary processes, for instance, by acquisition of beneficial spontaneous mutations. We wish to address the question of whether mutants can be selected that have evolved to survive contact killing on solid copper surfaces. We isolated such mutants from
Escherichia coli
and methicillin-resistant
Staphylococcus aureus
(MRSA) by artificial laboratory evolution. The ability to survive on solid copper surfaces was a stable phenotype of the mutant population and not restricted to a small subpopulation. As a consequence, standard operation procedures with strict hygienic measures are extremely important to prevent the emergence and spread of copper-surface-tolerant persister-like bacterial strains if copper surfaces are to be sustainably used to limit the spread of pathogenic bacteria, e.g., to curb nosocomial infections.
GigC, a LysR Family Transcription Regulator, Is Required for Cysteine Metabolism and Virulence in Acinetobacter baumannii
Authors: Gebhardt Michael J. , Czyz Daniel M. , Singh Shweta , Zurawski Daniel V. , Becker Lev , Shuman Howard A.
Published: October 2020

A critical facet of mammalian innate immunity involves the hosts’ attempts to sequester and/or limit the availability of key metabolic products from pathogens. For example, nutritional immunity encompasses host approaches to limit the availability of key heavy metal ions such as zinc and iron. Previously, we identified several hundred genes in a multidrug-resistant isolate of
Acinetobacter baumannii
that are required for growth and/or survival in the
Galleria mellonella
infection model.
Efficient 5-OP-RU-Induced Enrichment of Mucosa-Associated Invariant T Cells in the Murine Lung Does Not Enhance Control of Aerosol Mycobacterium tuberculosis Infection
Authors: Vorkas Charles Kyriakos , Levy Olivier , Skular Miroslav , Li Kelin , Aubé Jeffrey , Glickman Michael S.
Published: October 2020

Mucosa-associated invariant T (MAIT) cells are an innate-like T cell subset in mammals that recognize microbial vitamin B metabolites presented by the evolutionarily conserved major histocompatibility complex class I (MHC I)-related molecule, MR1. Emerging data suggest that MAIT cells may be an attractive target for vaccine-induced protection against bacterial infections because of their rapid cytotoxic responses at mucosal services to a widely conserved bacterial ligand. In this study, we tested whether a MAIT cell priming strategy could protect against aerosol
Mycobacterium tuberculosis
infection in mice.
Management of chronic headache with referral from primary care to direct access to MRI compared with Neurology services: an observational prospective study in London
Authors: Rua Tiago , Mazumder Asif , Akande Yvonne , Margariti Charikleia , Ochulor Juliana , Turville Joanna , Razavi Reza , Peacock Janet L , McCrone Paul , Goh Vicky , Shearer James , Afridi Shazia
Published: October 2020

Objectives

To evaluate the cost, accessibility and patient satisfaction implications of two clinical pathways used in the management of chronic headache.

Intervention

Management of chronic headache following referral from Primary Care that differed in the first appointment, either a Neurology appointment or an MRI brain scan.

Design and setting

A pragmatic, non-randomised, prospective, single-centre study at a Central Hospital in London.

Participants

Adult patients with chronic headache referred from primary to secondary care.

Primary and secondary outcome measures

Participants’ use of healthcare services and costs were estimated using primary and secondary care databases and questionnaires quarterly up to 12 months postrecruitment. Cost analyses were compared using generalised linear models. Secondary outcomes assessed: access to care, patient satisfaction, headache burden and self-perceived quality of life using headache-specific (Migraine Disability Assessment Scale and Headache Impact Test) and a generic questionnaire (5-level EQ-5D).

Results

Mean (SD) cost up to 6 months postrecruitment per participant was £578 (£420) for the Neurology group (n=128) and £245 (£172) for the MRI group (n=95), leading to an estimated mean cost difference of £333 (95% CI £253 to £413, p<0.001). The mean cost difference at 12 months increased to £518 (95% CI £401 to £637, p<0.001). When adjusted for baseline and follow-up imbalances between groups, this remained statistically significant. The utilisation of brain MRI improved access to care compared with the Neurology group (p<0.001). Participants in the Neurology group reported higher levels of satisfaction associated with the pathway and led to greater change in care management.

Conclusion

Direct referral to brain MRI from Primary Care led to cost-savings and quicker access to care but lower satisfaction levels when compared with referral to Neurology services. Further research into the use of brain MRI for a subset of patient population more likely to be reassured by a negative brain scan should be considered.

Trial registration number

NCT02753933.