bluuebunny/crossref_metadata_2025 huggingface dataset:
Flexible mixture model approaches that accommodate footprint size variability for robust detection of balancing selection
Authors: Cheng Xiaoheng , DeGiorgio Michael
Published: May 2019

Long-term balancing selection typically leaves narrow footprints of increased genetic diversity, and therefore most detection approaches only achieve optimal performances when sufficiently small genomic regions (i.e., windows) are examined. Such methods are sensitive to window sizes and suffer substantial losses in power when windows are large. This issue creates a tradeoff between noise and power in empirical applications. Here, we employ mixture models to construct a set of five composite likelihood ratio test statistics, which we collectively termBstatistics. These statistics are agnostic to window sizes and can operate on diverse forms of input data. Through simulations, we show that they exhibit comparable power to the best-performing current methods, and retain substantially high power regardless of window sizes. They also display considerable robustness to high mutation rates and uneven recombination landscapes, as well as an array of other common confounding scenarios. Moreover, we applied a specific version of theBstatistics, termedB2, to a human population-genomic dataset and recovered many top candidates from prior studies, including the then-uncharacterizedSTPG2andCCDC169-SOHLH2, both of which are related to gamete functions. We further appliedB2on a bonobo population-genomic dataset. In addition to theMHC-DQgenes, we uncovered several novel candidate genes, such asKLRD1, involved in viral defense, andSCN9A, associated with pain perception. Finally, we show that our methods can be extended to account for multi-allelic balancing selection, and integrated the set of statistics into open-source software namedBalLeRMixfor future applications by the scientific community.
Close-Range Interactions Favor Growth in Random-Paired Extracted Soil Bacteria
Authors: Dubey Manupriyam , Hadadi Noushin , Pelet Serge , Johnson David R. , van der Meer Jan R.
Published: May 2019

Species interactions at the cellular level are thought to govern the formation and functioning of microbial communities, but direct measurements of species interactions are difficult to perform between the hundreds of different species that constitute most microbial ecosystems. We developed a methodology to examine interactive growth of random cell pairs encapsulated inside 40–70 µm diameter agarose beads. We focused on a sandy soil as a test microbial ecosystem. By using gentle washing procedures, we detached microbial cells from sand and encapsulated them either in the absence or presence of pure culture inoculants. We then tested whether inoculants had on average positive or negative effects on the growth of resident community members depending on the growth substrate. Surprisingly, all the tested inoculants (includingPseudomonas veronii1YdBTEX2,Pseudomonas putidaF1,Pseudomonas protegensCHA0 andEscherichia coliMG1655) stimulated the growth of 40-80 percent of sand-derived cells when grown pair-wise in close proximity (i.e., within the same bead). This was true essentially irrespective of the growth substrate. Beneficial inoculant-sand cell partnerships resulted in up to 100-fold increase in productivity of the sand cell partner and up to 100-fold decrease in that of the inoculant. However, the maximum productivity attained by inoculant-sand cell partners within beads did not surpass that of inoculants alone. Further surprisingly, random pairs of sand cells encapsulated within the same bead also benefited growth in comparison to individual sand cells in a mutualistic manner (i.e., productivity when grown together was greater than the sum of individual productivities), but less than productivities observed in partnerships with the tested inoculants. This suggests that partnerships between inoculants and sand cells are not so much characterized by competition for substrate as by carbon loss through metabolite provision of the inoculant to sand cells (competitive exploitation).
A Novel Type 2 Diabetes Locus in sub-Saharan Africans, ZRANB3, is Implicated in Beta Cell Proliferation
Authors: Adeyemo Adebowale A. , Chen Guanjie , Doumatey Ayo P. , Hostelley Timothy L. , Leitch Carmen C. , Zhou Jie , Bentley Amy R. , Shriner Daniel , Fasanmade Olufemi , Okafor Godfrey , Eghan Benjamin , Agyenim-Boateng Kofi , Chandrasekharappa Settara , Adeleye Jokotade , Balogun William , Owusu Samuel , Amoah Albert , Acheampong Joseph , Johnson Thomas , Oli Johnnie , Adebamowo Clement ,   South Africa Zulu Type 2 Diabetes Case-Control Study, Collins Francis , Dunston Georgia , Zaghloul Norann A. , Rotimi Charles N.
Published: May 2019

Genome analysis of diverse human populations has contributed to the identification of novel genomic loci for diseases of major clinical and public health impact. Here, we report the largest genome-wide analysis of type 2 diabetes (T2D) in sub-Saharan Africans, an understudied ancestral group. We analyzed ~18 million autosomal SNPs in 5,231 individuals from Nigeria, Ghana and Kenya. TCF7L2 rs7903156 was the most significant locus (p=7.288 × 10−13). We identified a novel genome wide significant locus: ZRANB3 (Zinc Finger RANBP2-Type Containing 3, lead SNP chr2:136064024, T allele frequency=0.034, p=2.831×10−9). Knockdown of the zebrafish ortholog resulted in reduction in pancreatic beta cell number in the developing organism, suggesting a potential mechanism for its effect on glucose hemostasis. We also showed transferability in our study of 32 established T2D loci. Our findings provide evidence of a novel candidate T2D locus and advance understanding of the genetics of T2D in non-European ancestry populations.
The genetic interaction between HIV and the antibody repertoire
Authors: Strauli Nicolas , Fryer Emily Kathleen , Pham Olivia , Abdel-Mohsen Mohamed , Facente Shelley N. , Pilcher Christopher , Pennings Pleuni , Pillai Satish , Hernandez Ryan D.
Published: May 2019

The interaction between human immunodeficiency virus (HIV) and the antibody repertoire (AbR) during chronic infection can provide important information for HIV vaccine research, yet has not been well-characterized on a systems level. We deeply sequenced the HIV population and the AbR of ten HIV-infected, antiretroviral (ART)-naïve individuals, each with 10-20 longitudinal samples spanning 4-14 years. Our unbiased sequencing approach identified partitions of AbRs showing evidence of interaction with autologous HIV populations. We show that these HIV-associated partitions are enriched for the V gene segments of known HIV broadly neutralizing antibodies (bnAbs), indicating that the HIV-responding component of the AbR can be identified via time-series genetic data. Despite this evidence for larger-scale AbR/HIV interactions at the sub-population level, we found little to no evidence for antagonistic coevolution (i.e. an arms race). This suggests that antagonistic coevolution is either rare, or hard to detect, which has important vaccine design implications.
X-ray phase contrast imaging ofVitisspp. buds shows freezing pattern and correlation between volume and cold hardiness
Authors: Kovaleski Alisson P. , Londo Jason P. , Finkelstein Kenneth D.
Published: May 2019

Grapevine (Vitisspp.) buds must survive winter temperatures in order to resume growth when suitable conditions return in spring. They do so by developing cold hardiness through deep supercooling, but the mechanistic process of supercooling in buds remains largely unknown. Here we use synchrotron X-ray phase contrast imaging to study cold hardiness-related characteristics ofV. amurensis, V. riparia, andV. viniferabuds: time-resolved 2D imaging was used to visualize freezing; and microtomography was used to evaluate morphological changes during deacclimation. Bud cold hardiness was determined (low temperature exotherms; LTEs) using needle thermocouples during 2D imaging as buds were cooled with a N2gas cryostream. Resolution in 2D imaging did not allow for ice crystal identification, but freezing was assessed due to movement of tissues coinciding with LTE values. Freezing was observed to propagate from the center of the bud toward the outer bud scales. The freezing events observed lasted several minutes. Additionally, loss of supercooling ability appears to be correlated with increases in bud tissue volume during the process of deacclimation, but major increases in volume occur after most of the supercooling ability is lost, suggesting growth resumption processes are limited by deacclimation state.

Highlight

X-ray phase contrast imaging shows freezing occurs over several minutes and propagates from center toward tip ofVitisspp. buds. Incremental increase in bud volume correlates with cold deacclimation
Adaptation to low parasite abundance affects immune investment strategy and immunopathological responses of cavefish
Authors: Peuß Robert , Box Andrew C. , Chen Shiyuan , Wang Yongfu , Tsuchiya Dai , Persons Jenna L. , Kenzior Alexander , Maldonado Ernesto , Krishnan Jaya , Scharsack Jörn P. , Slaughter Brian P. , Rohner Nicolas
Published: May 2019

Reduced parasite infection rates in the developed world are suspected to underlie the rising prevalence of autoimmune disorders. However, the long-term evolutionary consequences of decreased parasite exposure on an immune system are not well understood. We used the Mexican tetraAstyanax mexicanusto understand how loss of parasite diversity influences the evolutionary trajectory of the vertebrate immune system by comparing river with cave morphotypes. Here, we present field data that affirms a strong reduction in parasite diversity in the cave ecosystem and show that cavefish immune cells display a more sensitive proinflammatory response towards bacterial endotoxins. Surprisingly, other innate cellular immune responses, such as phagocytosis, are drastically decreased in cavefish. Using two independent single-cell approaches, we identified a shift in the overall immune cell composition in cavefish as the underlying cellular mechanism, indicating strong differences in the immune investment strategy. While surface fish invest evenly into the innate and adaptive immune system, cavefish shifted immune investment to the adaptive immune system, and here, mainly towards specific T-cell populations that promote homeostasis. Additionally, inflammatory responses and immunopathological phenotypes in visceral adipose tissue are drastically reduced in cavefish. Our data indicate that long term adaptation to low parasite diversity coincides with a more sensitive immune system in cavefish, which is accompanied by a reduction of the immune cells that play a role in mediating the proinflammatory response.
Proteostasis collapse halts G1 progression and delimits replicative lifespan
Authors: Moreno David F. , Jenkins Kirsten , Morlot Sandrine , Charvin Gilles , Csikász-Nagy Attila , Aldea Martí
Published: May 2019

Loss of proteostasis and cellular senescence are key hallmarks of cell aging, but whether they are subject to direct cause-effect relationships is not known. We show that most yeast cells arrest in G1 before death with low nuclear levels of cyclin Cln3, a key activator of Start extremely sensitive to chaperone status. Chaperone availability is seriously compromised in aged cells, and the G1 arrest coincides with massive aggregation of a metastable chaperone-activity reporter. A mathematical model integrating autocatalytic protein aggregation and a minimal Start network recapitulates empirical observations. As key predictions, G1-cyclin overexpression increases lifespan in a chaperone-dependent manner, and lifespan reduction by enforced protein aggregation is greatly alleviated by increased expression of specific chaperones or cyclin Cln3. Overall, our data indicate the crucial role of chaperone malfunction in setting lifespan in yeast cells, and configure a molecular pathway whereby proteostasis breakdown acts as a direct effector of cell senescence.
Computational design of a modular protein sense/response system
Authors: Glasgow Anum A. , Huang Yao-Ming , Mandell Daniel J. , Thompson Michael , Ritterson Ryan , Loshbaugh Amanda L. , Pellegrino Jenna , Krivacic Cody , Pache Roland A. , Barlow Kyle A. , Ollikainen Noah , Jeon Deborah , Kelly Mark J. S. , Fraser James S. , Kortemme Tanja
Published: May 2019

Sensing and responding to signals is a fundamental ability of living systems, but despite remarkable progress in computational design of new protein structures, there is no general approach for engineering arbitrary new protein sensors. Here we describe a generalizable computational strategy for designing sensor/actuator proteins by building binding sites de novo into heterodimeric protein-protein interfaces and coupling ligand sensing to modular actuation via split reporters. Using this approach, we designed protein sensors that respond to farnesyl pyrophosphate, a metabolic intermediate in the production of valuable compounds. The sensors are functional in vitro and in cells, and the crystal structure of the engineered binding site matches the design model with atomic accuracy. Our computational design strategy opens broad avenues to link biological outputs to new signals.

One Sentence Summary

An engineering strategy to design modular synthetic signaling systems that respond to new small molecule inputs.
Age dependence of modern clinical risk groups for localized prostate cancer – a population-based study
Authors: Huynh-Le Minh-Phuong , Myklebust Tor Åge , Feng Christine H. , Karunamuni Roshan , Johannesen Tom Børge , Dale Anders M. , Andreassen Ole A. , Seibert Tyler M.
Published: May 2019

Background

Optimal prostate cancer (PCa) screening strategies will focus on men most likely to have potentially-lethal, localized disease. Age-specific incidence rates (ASIRs) for clinical risk groups could guide risk-stratified screening.

Objective

Determine ASIRs and proportions of PCa diagnoses in Norway for modern risk-group and Gleason score categories.

Design, Setting, and Participants

All men diagnosed with PCa in Norway in 2014-2017 (n=20,356).

Outcome Measurements and Statistical Analysis

Patients were assigned to clinical risk groups: low, favorable-intermediate, unfavorable-intermediate, high, regional, and metastatic, using Gleason score and clinical stage. Associations were assessed between age and (1) Gleason score (including Gleason 3+4 and 4+3) and (2) PCa risk group. Risk-group ASIRs were calculated by multiplying the overall Norwegian ASIR by the proportions observed for each category.

Results

Older age was significantly associated with higher Gleason score and more advanced disease. For example, among men aged 55-59, 65-69, 75-79, and 85-89 years, the percentage with Gleason 8-10 disease was 16.5%, 23.4%, 37.2%, and 59.9%, respectively (p<0.001); the percentage with at least high-risk disease was 29.3%, 39.1%, 60.4%, and 90.6%, respectively. Corresponding percentages for low-risk PCa were 24.0%, 17.9%, 10.2%, and 4.1% (p<0.001). The respective maximum ASIRs (per 100,000 men) for low-risk, favorable-intermediate-risk, unfavorable-intermediate-risk, high-risk, regional, and metastatic disease were: 157.1, 183.8, 194.8, 408.3, 172.3, and 330.0; incidence for low-risk and favorable-intermediate-risk PCa peaked before age 70, while more advanced categories peaked after 70. At age 75-79 years, the ASIR of high-risk disease was approximately 6 times greater than at 55-59 years.

Conclusions

Risk of clinically-significant, localized PCa increases with age. Healthy older men may be among those most likely to benefit from PCa screening.
CImP: Cellular Imprinting Proteomics applied to ocular disorders elicited by Congenital Zika virus Syndrome
Authors: Rosa-Fernandes Livia , Barbosa Raquel Hora , dos Santos Maria Luiza B. , Angeli Claudia B. , Silva Thiago P. , Melo Rossana C. N. , de Oliveira Gilberto Santos , Lemos Bernardo , Larsen Martin R. , Cardoso Claudete Araujo , Palmisano Giuseppe
Published: May 2019

IMPORTANCE

Ocular complications in infants with Congenital Zika Syndrome (CZS) have been reported. However, the molecular mechanisms underlying of eye dysfunctions are presently unknown.

OBJECTIVE

A method (termed Cellular Imprinting Proteomics, CImP) for the identification and quantification of the ocular surface proteome using a minimally invasive membrane filter device is described. Moreover, The CImP method was applied to profile the molecular alterations in the eyes of infants exposed to Zika virus (ZIKV) infection during gestation.

DESIGN, SETTINGS AND PARTICIMPANTS

The CImP method was applied to a cohort divided into three conditions: 1) Ctrl (infants with no infectious diseases, n=5). 2) Zikv (infants exposed to ZIKV gestation, with no microcephaly, n=5). 3) ZikvCZS(infants exposed to ZIKV, with microcephaly, n=3). All conditions were age and sex-matched. An improved impression cytology method was used to capture the outermost ocular surface cells. The number of impression cytology membrane collected was: Ctrl (12), Zikv (14) and ZikvCZS(8). Proteins were extracted and analysed using mass spectrometry-based proteomics technology followed by statistical analysis. Parallel reaction monitoring was performed to validate the expression of specific protein markers.

RESULTS

Using the CImP method, 2209 proteins were identified on the membrane-captured conjunctiva epithelial cells. Modulation of neutrophil degranulation, cell death, ocular and neurodevelopment pathways are reported in infants with CZS compared to matched controls. Moreover, the molecular pattern of ocular surface cells retrieved from infants infected during the gestation but with no CZS was different from matched controls.

CONCLUSIONS AND PERSPECTIVES

Molecular alterations in the ocular cell surface associated to ZIKV infection with and without CZS complications are reported for the first time. We predict that this method will be introduced successfully in the study of several neurological diseases with the aim to identify novel diagnostic and therapeutic biomarkers.
Metabolic adjustment ofDrosophilahemocyte number and sessility by an adipokine
Authors: Ramond Elodie , Petrignani Bianca , Dudzic Jan Paul , Boquete Jean-Philippe , Poidevin Mickaël , Kondo Shu , Lemaitre Bruno
Published: May 2019

In animals, growth is regulated by the complex interplay between paracrine and endocrine signals. When food is scarce, tissues compete for nutrients, leading to critical resource allocation and prioritization. Little is known about how the immune system maturation is coordinated with the growth of other tissues. Here, we describe a signaling mechanism that regulates the number of hemocytes (blood cells) according to the nutritional state of theDrosophilalarva. Specifically, we found that the adipokine NimB5 is produced in the fat body upon nutrient scarcity downstream of metabolic sensors. NimB5 is then secreted and bind to hemocytes to down-regulate their proliferation and adhesion. Blocking this signaling loop results in conditional lethality when larvae are raised on a poor diet, due to excessive hemocyte numbers and insufficient energy storage. Similar regulatory mechanisms shaping the immune system in response to nutrient availability are likely to be widespread in animals.

Author summary

Drosophilalarval hemocytes (blood cells) are found in two compartments: the lymph gland considered as a reservoir, and the peripheral compartment. Peripheral hemocytes form sessile patches attached to the internal surface of the larval body wall or are found freely circulating in the hemolymph. Little is known about the signals that regulate hemocytes proliferation and localization in the peripheral compartment. In this study, we have identified a new gene,NimrodB5, coding for the NimB5 protein, which is secreted by the fat body and binds to hemocytes. NimB5 inhibits hemocyte proliferation while promoting sessility, leading to an increased number of circulating hemocytes and adhesion defects inNimB5mutant. We show thatnimrodB5expression by the fat body is controlled by metabolic cues to adjust hemocyte number to the physiological state of the larvae.

Interestingly, deregulation ofNimB5causes lethality when larvae are raised on a poor diet due to a defect in regulating hemocytes proliferation. In conclusion, we have identified a new adipokine that optimizes hemocytes number to the physiological state of larvae. Our study also reveals a major role of the fat body in peripheral hematopoiesis regulation and outline how it can be costly to maintain a basal immune defense.
Determinants of birth asphyxia among newborns in Amhara national regional state referral hospitals, Ethiopia
Authors: Meshesha Alemwork Desta , Azage Muluken , Worku Endalkachew , Bogale Getahun Gebre
Published: May 2019

Background

Globally, every year, 2.5 million infants die within their first month of life. Neonatal asphyxia is the leading specific cause of neonatal mortality in low- and middle-income countries, including Ethiopia. Therefore, the aim of this study was to identify the determinants of birth asphyxia among newborns admitted in Amhara region referral hospitals, Ethiopia.

Methods

Facility-based unmatched case-control study was employed among 193 cases and 193 controls of newborns. Newborns admitted to neonatal intensive care units with admission criteria of birth asphyxia and without birth asphyxia were considered as cases (Apgar score<7) and controls (Apgar score>=7) respectively. Data were collected using a structured questionnaire by systematic random sampling technique with proportional allocation, and entered in to Epi-Info version 7 and exported to SPSS version 20 for statistical analysis. Bivariate and multivariable logistic regression models were fitted to identify determinants of birth asphyxia.

Results

Newborns with low birth weight (<2.5kg) had 8.94 higher odds of birth asphyxia than those whose weight at birth was >=2.5kg at birth (AOR: 8.94, 95% CI: 4.08, 19.56). Newborns born at health centers were 7.36 times more likely to develop birth asphyxia than those born at hospitals (AOR: 7.36, 95% CI: 2.44, 22.13). Newborns born using instrumental delivery were 3.03 times more likely to develop birth asphyxia than those delivered by vaginally (AOR: 3.03, 95% CI: 1.41, 6.49). Newborns from mothers with prolonged labor were 2 times more likely to suffer from birth asphyxia as compared to their counterparts (AOR: 2.00, 95% CI: 1.20, 3.36).

Conclusion

This study identified prolonged labor, instrumental delivery, delivered at health centers, and low birth weight were identified as determinants of birth asphyxia. Thus, intervention planning towards the identified determinants may be needed to reduce neonatal birth asphyxia.
A further investigation of the complex M3 murataite structure using Hf substitution and STEM-EELS techniques
Authors: Maki Ryosuke S. S. , Morgan Peter E. D.
Published: May 2019

Many members of the complex crystalline fluorite supercell structures (e.g. zirconolite, pyrochlore and murataite polytypes) have been considered/studied for possible long-term radioactive-waste immobilization. The eight-coordinated sites in these crystals are of particular importance because they are preferred for the accommodation of trivalent rare earths and actinides present in radioactive waste from fuel element processing. The fluorite-type supercell structures include the murataites, M3, M5, M7, M8, having those numbers of repeating fluorite sub-cell units. One simple technique, as shown here, namely the substitution of Hf into the Zr site, is very helpful for structural analysis in these very complex cases in order to further illuminate the site preference of the Zr ion. Three M3 murataite samples, Ca-Mn-Ti-Zr-Al-Fe-O (regular M3), Ca-Ti-Zr-Al-Fe-O (Mn-free M3) and Ca-Mn-Ti-Hf-Al-Fe-O (Hf-substituted M3) are investigated and, through techniques described for larger cells, show that the Zr is very likely not to be hosted in the [6]
Ti site in the M3 murataite structure, as suggested by Pakhomova et al. [(2013), Z. Kristallogr. Cryst. Mater.
228, 151–156], but more likely replaces the [8]
Ca1 site and less likely the [8]
Ca2 site. This adjusted site preference for each cation from the powder X-ray diffraction (PXRD) and scanning transmission electron microscopy electron energy-loss spectroscopy (STEM-EELS) methods, agrees well with the high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) image.
Crystal structure of zymonic acid and a redetermination of its precursor, pyruvic acid
Authors: Heger Dominik , Eugene Alexis J. , Parkin Sean R. , Guzman Marcelo I.
Published: May 2019

The structure of zymonic acid (systematic name: 4-hydroxy-2-methyl-5-oxo-2,5-dihydrofuran-2-carboxylic acid), C6H6O5, which had previously eluded crystallographic determination, is presented here for the first time. It forms by intramolecular condensation of parapyruvic acid, which is the product of aldol condensation of pyruvic acid. A redetermination of the crystal structure of pyruvic acid (systematic name: 2-oxopropanoic acid), C3H4O3, at low temperature (90 K) and with increased precision, is also presented [for the previous structure, see: Harata et al. (1977). Acta Cryst. B33, 210–212]. In zymonic acid, the hydroxylactone ring is close to planar (r.m.s. deviation = 0.0108 Å) and the dihedral angle between the ring and the plane formed by the bonds of the methyl and carboxylic acid carbon atoms to the ring is 88.68 (7)°. The torsion angle of the carboxylic acid group relative to the ring is 12.04 (16)°. The pyruvic acid molecule is almost planar, having a dihedral angle between the carboxylic acid and methyl-ketone groups of 3.95 (6)°. Intermolecular interactions in both crystal structures are dominated by hydrogen bonding. The common R
2
2(8) hydrogen-bonding motif links carboxylic acid groups on adjacent molecules in both structures. In zymonic acid, this results in dimers about a crystallographic twofold of space group C2/c, which forces the carboxylic acid group to be disordered exactly 50:50, which scrambles the carbonyl and hydroxyl groups and gives an apparent equalization of the C—O bond lengths [1.2568 (16) and 1.2602 (16) Å]. The other hydrogen bonds in zymonic acid (O—H...O and weak C—H...O), link molecules across a 21-screw axis, and generate an R
2
2(9) motif. These hydrogen-bonding interactions propagate to form extended pleated sheets in the ab plane. Stacking of these zigzag sheets along c involves only van der Waals contacts. In pyruvic acid, inversion-related molecules are linked into R
2
2(8) dimers, with van der Waals interactions between dimers as the only other intermolecular contacts.
Crystal structure of butane-1,4-diyl bis(furan-2-carboxylate)
Authors: Hoshide Mitsutoshi , Masu Hyuma , Sasanuma Yuji
Published: May 2019

The asymmetric unit of the title compound, C14H14O6, a monomeric compound of poly(butylene 2,5-furandicarboxylate), consists of one half-molecule, the whole all-trans molecule being generated by an inversion centre. In the crystal, the molecules are interconnected via C—H...O interactions, forming a molecular sheet parallel to (10\overline{2}). The molecular sheets are further linked by C—H...π interactions.
Crystal structure of 5-(4-tert-butoxyphenyl)-3-(4-n-octyloxyphenyl)-4,5-dihydroisoxazole
Authors: Sales Eric S. , Bortoluzzi Adailton J. , Merlo Aloir A.
Published: May 2019

The molecule of the title compound, C27H37NO3, was prepared by [3 + 2] 1,3-dipolar cycloaddition of 4-n-octylphenylnitrile oxide and 4-tert-butoxystyrene, the latter compound being a very useful intermediate to the synthesis of liquid-crystalline materials. In the molecule, the benzene rings of the n-octyloxyphenyl and tert-butoxyphenyl groups form dihedral angles of 2.83 (7) and 85.49 (3)°, respectively, with the mean plane of the isoxazoline ring. In the crystal, molecules are linked by weak C—H...O hydrogen interactions into chains running parallel to the b axis.
In search of microbial indicator taxa: shifts in stream bacterial communities along an urbanization gradient
Authors: Simonin Marie , Voss Kristofor A. , Hassett Brooke A. , Rocca Jennifer D. , Wang Si‐Yi , Bier Raven L. , Violin Christy R. , Wright Justin P. , Bernhardt Emily S.
Published: May 2019

A majority of environmental studies describe microbiomes at coarse scales of taxonomic resolution (bacterial community, phylum), ignoring key ecological knowledge gained from finer‐scales and microbial indicator taxa. Here, we characterized the distribution of 940 bacterial taxa from 41 streams along an urbanization gradient (0%–83% developed watershed area) in the Raleigh‐Durham area of North Carolina (USA). Using statistical approaches derived from macro‐organismal ecology, we found that more bacterial taxa were classified as intolerant than as tolerant to increasing watershed urbanization (143 vs 48 OTUs), and we identified a threshold of 12.1% developed watershed area beyond which the majority of intolerant taxa were lost from streams. Two bacterial families strongly decreased with urbanization: Acidobacteriaceae (Acidobacteria) and Xanthobacteraceae (Alphaproteobacteria). Tolerant taxa were broadly distributed throughout the bacterial phylogeny, with members of the Comamonadaceae family (Betaproteobacteria) presenting the highest number of tolerant taxa. Shifts in microbial community structure were strongly correlated with a stream biotic index, based on macroinvertebrate composition, suggesting that microbial assemblages could be used to establish biotic criteria for monitoring aquatic ecosystems. In addition, our study shows that classic methods in community ecology can be applied to microbiome datasets to identify reliable microbial indicator taxa and determine the environmental constraints on individual taxa distributions along environmental gradients.
Winning at all costs: An exploration of bottom‐line mentality, Machiavellianism, and organisational citizenship behaviour
Authors: Eissa Gabi , Wyland Rebecca , Lester Scott W. , Gupta Ritu
Published: May 2019

This study seeks to advance the bottom‐line mentality literature by exploring an antecedent and outcome of employee bottom‐line mentality. We build and test a moderated‐mediation model by arguing that the personality trait of Machiavellianism promotes an employee's adoption of a bottom‐line mentality. Moreover, drawing on trait activation theory, we argue that this relationship is fully activated when the employee perceives that the organisation endorses a bottom‐line mentality. To expand our theoretical model, we also suggest that employee bottom‐line mentality inhibits organisational citizenship behaviour directed towards co‐workers. Lastly, we investigate whether an employee's perception of an organisation's bottom‐line mentality conditionally moderates the indirect effect of Machiavellianism on organisational citizenship behaviour directed towards co‐workers through the mediated mechanism of employee bottom‐line mentality. Our theoretical model is tested across two distinct studies. Study 1, a field study conducted within a variety of organisations, provides evidence for our initial predictions (Hypotheses 1 and 2). Study 2, a multisource field study conducted in multiple industries, replicates and extends the findings from Study 1 by providing evidence for the entire moderated‐mediation model. We find support for our hypothesised model across both studies. Implications for theory and practice are discussed, and suggestions for future research are identified.
Lobectomy versus stereotactic ablative radiotherapy for medically operable patients with stage IA non‐small cell lung cancer: A virtual randomized phase III trial stratified by age
Authors: Seo Young‐Seok , Kim Hak Jae , Wu Hong Gyun , Choi Sun Mi , Park Samina
Published: May 2019

Background

Although the choice between stereotactic ablative radiotherapy (SABR) and lobectomy for early‐stage non‐small cell lung cancer (NSCLC) has been debated for years, the two procedures have not yet been directly compared in a randomized trial. We conducted a virtual randomized phase III trial stratified by age to compare the effectiveness of lobectomy and SABR for medically operable patients with stage IA (AJCC eighth) NSCLC using the Markov model analysis.

Methods

A Markov model was developed to simulate a cohort of patients aged 45–85 years with stage IA NSCLC who had undergone either lobectomy or SABR and were followed up for their remaining lifetime. Each virtual patient was randomly assigned to undergo lobectomy or SABR, and 10 000 patients were allocated to each group. All estimates of the variables were obtained by a systematic review of published articles.

Results

The lobectomy group showed a better life expectancy than the SABR group, in patients under 75 years of age. However, no statistically significant difference was seen in patients 75 years or older. The predicted life expectancy was 9.43 and 8.70 years in 75‐year‐old patients in the lobectomy and SABR groups, respectively. However, the 95%CI for the difference in life expectancy between the two groups was ‐ 0.06–1.50 years (P = 0.0689).

Conclusions

The Markov model showed no statistically significant difference in the expected overall survival in stage IA NSCLC patients who were older than 75 years and had undergone SABR or lobectomy.
Association of glaucoma with risk of retinal vein occlusion: A meta‐analysis
Authors: Yin Xue , Li Jianqin , Zhang Bingyu , Lu Peirong
Published: May 2019

To summarize epidemiological evidences on the association between glaucoma and the risk of retinal vein occlusion (RVO). Relevant studies were identified by searching in PubMed, EMBASE and Cochrane until February 2018. Fifteen eligible observational studies were aggregated in this analysis. All results were analysed and pooled using random effects models with 95% confidence intervals (CI). In all studies, the odds ratio (OR) of glaucoma as a risk factor for RVO was 4.01 (95% CI: 3.28–4.91). In RVO subtype‐differentiated subgroup analyses (six studies), the pooled OR showed that glaucoma was associated with central retinal vein occlusion (CRVO) (OR: 6.21; 95% CI: 4.64–8.31), branch retinal vein occlusion (BRVO) (OR: 2.38; 95% CI: 1.77–3.19) and hemiretinal vein occlusion (HRVO) (OR: 4.60; 95% CI: 2.26–9.35). In glaucoma‐classified subgroup analyses (five studies), primary open‐angle glaucoma (POAG) (OR: 5.03; 95% CI: 3.97–6.37) and chronic open‐angle glaucoma (COAG) (OR: 2.36; 95% CI: 1.39–4.02) were significant risk factors for RVO development. There was a plausible relationship between primary angle closure glaucoma (PACG) and RVO risk (OR: 1.85; 95% CI: 0.41–8.35); to be precise, the OR was 5.3 in PACG and CRVO risk (95% CI: 1.04–26.95; p = 0.045), while the OR was 0.65 in PACG and BRVO risk (95% CI: 0.07–6.27; p = 0.707). To sum up, this meta‐analysis shows that glaucoma is associated with the risk of RVO. Glaucoma should be kept in mind when investigating patients with RVO in the clinic.
Scleral and conjunctival features in patients with rhegmatogenous retinal detachment undergoing scleral buckling: an anterior segment optical coherence tomography and in vivo confocal microscopy study
Authors: Carpineto Paolo , Agnifili Luca , Senatore Alfonso , Agbeanda Aharrh‐Gnama , Lappa Andrea , Borrelli Enrico , Di Martino Giuseppe , Oddone Francesco , Mastropasqua Rodolfo
Published: May 2019

Purpose

To investigate the scleral and conjunctival features in patients with rhegmatogenous retinal detachment (RRD) undergoing scleral buckling (SB), using anterior segment optical coherence tomography (AS‐OCT) and in vivo confocal microscopy (IVCM).

Methods

Twenty RRD eyes were consecutively enrolled. AS‐OCT was performed at RRD diagnosis (RRD‐D) and day 1, week 1, month 1 and month 6 after SB to evaluate the sclera, in the affected and unaffected quadrants (AQ, UQ). IVCM was performed at RRD‐D, and at month 1 and month 6, to evaluate the conjunctiva in AQ and UQ. The main outcomes were as follows: mean intra‐scleral hypo‐reflective spaces area (MIHSA) at AS‐OCT; mean density and area of microcysts (MMD, MMA) at IVCM; and intra‐ocular pressure (IOP). The relations between MIHSA, MMA, MMD and IOP were evaluated.

Results

Rhegmatogenous retinal detachment‐ diagnosis (RRD‐D) overall‐mean intra‐scleral hypo‐reflective spaces (MISHA), ‐MMD and ‐MMA were significantly higher in affected eye (AE) compared with UE (p < 0.05) and in AQ compared with UQ (p < 0.05). After SB, overall‐, AQ‐ and UQ‐MISHA further increased (p < 0.05), whereas overall‐MMD and ‐MMA did not change. At all follow‐up, AQ and UQ parameters did not show significant differences between them. RRD‐D IOP was 14.3 ± 2.8 and 15.5 ± 2.7 mmHg in the AE and UE, respectively (p < 0.05). After SB, week‐1, month‐1 and ‐6 IOP was significantly lower than RRD‐D (p < 0.05). Rhegmatogenous retinal detachment‐ diagnosis (RRD‐D), 1‐ and 6‐month overall and AQ‐MISHA and AQ‐MMD negatively correlated with IOP (p < 0.05).

Conclusion

Rhegmatogenous retinal detachment (RRD) and SB induced scleral and conjunctival changes that suggested an activation of fluid outflow through the entire unconventional aqueous humour pathway; these modifications may in part account for the relative hypotony after RRD and SB.
Prevention and treatment of infectious diseases by traditional Chinese medicine: a commentary
Authors: Ma Yuexia , Chen Ming , Guo Yali , Liu Jian , Chen Weitao , Guan Mengyue , Wang Yue , Zhao Xuehui , Wang Xu , Li Haoyuan , Meng Lingxin , Wen Yulong , Wang Yuguang
Published: May 2019

The present review aimed to summarize the effectiveness and features of traditional Chinese medicine (TCM) for the treatment of infectious diseases and to discuss the limitation of the development of TCM. The personalized medicine with TCM exerts a curative effect on viral and bacterial infectious diseases with unique advantages on the improvement of clinical manifestation, pathogen inhibition, and organ recovery during severe and drug‐resistant infection. The deficiency of personalized medicine with TCM lies in that the current research design of TCM primarily focuses on the study of the effective components and material basis of Chinese herbs at the cellular, molecular, and genetic level, while ignoring the guidance of the TCM syndrome differentiation theory, which is the core concept of individualized treatment. Personalized medicine with TCM has a broad prospective for infectious diseases due to the specific efficacy and advantages. While the curative effect of individualized treatment with TCM cannot be excluded from the TCM syndrome differentiation theory, the study of personalized medicine with TCM for infectious diseases urgently requires a unified standardization of the clinical syndrome differentiation and the evolution rule of infectious diseases by TCM theory.
Molecular determinants of chemical modulation of two‐pore domain potassium channels
Authors: Şterbuleac Daniel
Published: May 2019

The K+ ion channels comprising the two‐pore domain (K2P) family have specific biophysical roles in generating the critical regulatory K+ current. Ion flow through K2P channels and, implicitly, channel regulation is mediated by diverse metabolic and physical inputs such as mechanical stimulation, interaction with lipids or endogenous regulators, intra‐ or extracellular pH, and phosphorylation, while their function can be finely tuned by chemical compounds. In the latter category, some drug–channel interactions can lead to side effects or have clinical action, while identifying novel chemical modulators of K2Ps is an area of intense research. Due to their cellular and therapeutic importance, much attention was turned to these channels in recent years and several experimental approaches have pinpointed the molecular determinants of K2P chemical modulation. Given their unique structural features and properties, chemical modulators act on K2P channels in multiple and diverse ways. In this review, the particularities of K2P modulation by chemical compounds, such as binding modality, affinity, or position, are identified, synthesized, and linked to structural and functional properties in order to refer to how activators and blockers modify channel function and vice versa, focusing on specificity related to protein structure (and its modification) and cross‐linking information among different subfamilies.
Soft tissue response to dental implant closure caps made of either polyetheretherketone (PEEK) or titanium
Authors: Caballé‐Serrano Jordi , Chappuis Vivianne , Monje Alberto , Buser Daniel , Bosshardt Dieter D.
Published: May 2019

Objective

Polyetheretherketone (PEEK) is a popular synthetic thermoplastic polymer for medical applications, but its clinical use suffers from several limitations. Therefore, the aim was to compare the soft tissue response to dental implant closure caps made of PEEK or titanium as evaluated by the occurrence of multinucleated giant cells (MNGCs).

Material and methods

Forty‐two implants were placed in the maxilla of seven miniature pigs. While commercially pure titanium (Ti) implants had a Ti closure cap, ceramic implants made of either zirconia (Zr) or alumina‐toughened zirconia (Zr + Al) received a PEEK closure cap. Histomorphometry was performed to evaluate the number of small and large MNGCs being in contact with the PEEK or the Ti in different compartments of the implant systems.

Results

No histological signs of inflammation were noticed, and MNGCs were observed on both PEEK and Ti closure caps and on all three implant types. Significantly higher numbers of MNGCs were found on closure caps made of PEEK than on closure caps made of Ti on the external closure cap surface facing both soft (p = 0.0008 for PEEK on Zr and p = 0.0016 for PEEK on Zr + Al) and hard tissues (p = 0.016 for PEEK on Zr and p = 0.003 for PEEK on Zr + Al) as well as in the internal closure cap surface (p = 0.014 for PEEK on Zr and p = 0.0088 for PEEK on Zr + Al). No statistically significant differences in the number of MNGCs were observed on the three implant types.

Conclusions

Significantly more MNGCs were in contact with PEEK than with Ti closure caps.
Functional study and pathogenicity classification of PRRT2 missense variants in PRRT2‐related disorders
Authors: Zhao Shao‐Yun , Li Li‐Xi , Chen Yu‐Lan , Chen Yi‐Jun , Liu Gong‐Lu , Dong Hai‐Lin , Chen Dian‐Fu , Li Hong‐Fu , Wu Zhi‐Ying
Published: May 2019

Aims

PRRT2 variants are associated with various paroxysmal disorders. To date, more than 90 PRRT2 variants have been reported in PRRT2‐related disorders. Lack of functional study in majority of missense variants makes their pathogenicity uncertain. We aim to evaluate the clinical significance of PRRT2 missense variants by performing in vitro experiments.

Methods

We systematically reviewed PRRT2‐related disorders and summarized reported PRRT2 missense variants. Protein expression and subcellular localization of mutant PRRT2 were investigated in mammal cells. American College of Medical Genetics and Genomics (ACMG) guidelines were used to analyze the pathogenicity of PRRT2 missense variants.

Results

A total of 29 PRRT2 missense variants were identified in PRRT2‐related disorders. Ten variants were observed to affect both subcellular localization and protein level, three variants only affect membrane localization, and two variants only affect protein level. According to ACMG guidelines, 15 variants were finally classified as “likely pathogenic”, three as “benign”, three as “likely benign”, and eight as “uncertain significance” variants. The likely pathogenic variants were concentrated in the C‐terminal of PRRT2.

Conclusions

The pathogenicity of eight uncertain significance variants needs further investigation. C‐terminal of PRRT2 is crucial for its physiological function.
The presence of governance: A system assessment based on innovative core regulatory principles for Brazilian regulators
Authors: de Carvalho Bruno Eustaquio , Costa Ana Sara , Marques Rui Cunha , Netto Oscar Cordeiro
Published: May 2019

Regulatory governance is considered as a new era in the state's intervention, and it is vital to foster both qualitative and quantitative performances of regulators. In this paper, the authors argue that the absence of governance principles allows regulators to justify the adoption of instruments to improve it. Five core regulatory principles, particularly accountability, administrative capacity, open government, regulatory quality, and rule of law build the bridge between regulatory governance and regulatory substance. The authors propose the application of a multicriteria modelling method (ELECTRE TRI‐C) in order to conduct the assessment and categorization of Brazilian subnational regulators according to the presence of governance, encompassing the opinions of legitimate stakeholders. The levels of regulatory governance are calculated for the regulators in order to provide some determinants of good governance, which could be stimulated by regulatory impact assessment, as a policy tool that improves institutional environments.
Clergy in the early modern Caribbean (ca. 1650–1800)
Authors: Brennan Margaret L.
Published: May 2019

Recent historical studies of religious life in the early modern Atlantic world have increasingly taken into consideration the slave societies of the Caribbean, a region considered by an earlier generation of scholarship to be overwhelmingly irreligious. New methodological approaches to well‐perused documents have yielded significant insights into the everyday religious experiences of Caribbean inhabitants, notably communities that have often been overlooked for their apparent inability to leave archival traces. Such studies have made important contributions to a broader scholarly conversation about categories of difference in the early modern world, particularly in regard to the momentous change in the era that saw race rather than religion emerge as a primary marker of social identity. A significant portion of the primary source material that historians in this dynamic field have consulted was, unsurprisingly, produced by religious officials like Inquisition officers, episcopal authorities, missionaries (both Protestant and Catholic), ministers, and regular clergy, among others. Because they were historical actors who undoubtedly contributed to this shift and because they also produced documentation relating to it, a comprehensive account of the role of clergy in this era is needed. This article surveys this body of scholarship. It interrogates its approach to religious sources and individual religious leaders and assesses what they have revealed about the spiritual and cultural life of the early modern Caribbean.
Oxidatively stable curcumin‐loaded oleogels structured by β‐sitosterol and lecithin: physical characteristics and release behaviour in vitro
Authors: Li Linlin , Wan Wenbo , Cheng Weiwei , Liu Guoqin , Han Lipeng
Published: May 2019

In this study, oleogel structured by β‐sitosterol and lecithin was prepared as a carrier for poorly water‐soluble bioactive compounds, curcumin. The mechanical and microscopic properties of curcumin‐loaded oleogel were determined by texture analyser and polarised light microscopy. The oxidation stability of the delivery system was determined by accelerated oxidation test and the bioaccessibility of curcumin was studied in vitro. The results showed that the existence of curcumin did not affect the mechanical strength and crystalline network of oleogel. The oxidative stability of curcumin‐loaded oleogel was higher than that of curcumin‐free oleogel and corn oil‐curcumin mixtures. It might be attributed to not only the antioxidative property of curcumin but also crystalline network of oleogel which served as an obstructor for the development of oxidation products. Additionally, oleogel enhanced the bioaccessibility of curcumin in fasted state (up to 67.66%). These findings suggest that oleogels can be promising candidates to delivery drugs and nutrients.