bluuebunny/crossref_metadata_2025 huggingface dataset:
Abyssal oceanic circulation and acidification during the Middle Eocene Climatic Optimum (MECO)
Authors: Cornaggia Flaminia , Bernardini Simone , Giorgioni Martino , Silva Gabriel L. X. , Nagy André Istvan M. , Jovane Luigi
Published: April 2020

The Middle Eocene Climatic Optimum (MECO) is a global warming event that occurred at around 40 Ma and lasted about 500 kyr. We study this event in an abyssal setting of the Tasman Sea, using the IODP Core U1511B-16R, collected during the expedition 371. We analyse magnetic, mineralogical, and chemical parameters to investigate the evolution of the sea bottom conditions at this site during the middle Eocene. We observe significant changes indicating the response to the MECO perturbation. Mn oxides, in which Mn occurs under an oxidation state around +4, indicate a high Eh water environment. A prominent Mn anomaly, occurring just above the MECO interval, indicates a shift toward higher pH conditions shortly after the end of this event. Our results suggest more acid bottom water over the Tasman abyssal plain during the MECO, and an abrupt end of these conditions. This work provides the first evidence of MECO at abyssal depths and shows that acidification affected the entire oceanic water column during this event.
Could Vegetation Index be Derive from Synthetic Aperture Radar? – The Linear Relationship between Interferometric Coherence and NDVI
Authors: Bai Zechao , Fang Shibo , Gao Jian , Zhang Yuan , Jin Guowang , Wang Shuqing , Zhu Yongchao , Xu Jiaxin
Published: April 2020

Due to many factors in the physical properties of the ground surface, the corresponding interferometric coherence values change dynamically over time. Among these factors, the roles of the vegetation and its temporal variation have not yet been revealed so far. In this paper, synthetic aperture radar (Sentinel-1) data and optical remote sensing (Landsat TM) images over four whole seasons are employed to reveal the relationship between the interferometric coherence and the normalized difference vegetation index (NDVI) at five sites that have ground deformation due to mining in Henan province, China. The result showed: (1) As for the village area with few vegetation cover, the related coherence values are significantly higher than that in the farm land area with high densities of vegetation in the spring and summer, which indicates that the subsidence by mining in few vegetation cover area is easier to be monitored; (2) Linear regression coefficients ($${{\bf{R}}}^{{\bf{2}}}$$R2) between the interfereometric coherence values and the NDVI values is 0.62, which indicate the interferometric coherence values and the NDVI values change reversely in both farm land and village areas over the year. It suggests months between November and March with lower NDVI value are more suitable for deformation detecting. Therefore, the interfereometric coherence values can be used to detect the density of vegetation, while NDVI values can be reference for elucidating when the traditional differential interferometric synthetic aperture radar (DInSAR) could be effectively used.
Effect of asymmetrical heat rise/fall on the film flow of magnetohydrodynamic hybrid ferrofluid
Authors: Tlili Iskander , Mustafa M. T. , Kumar K. Anantha , Sandeep N.
Published: April 2020

The movement of the ferrous nanoparticles is random in the base fluid, and it will be homogeneous under the enforced magnetic field. This phenomenon shows a significant impact on the energy transmission process. In view of this, we inspected the stream and energy transport in magnetohydrodynamic dissipative ferro and hybrid ferrofluids by considering an uneven heat rise/fall and radiation effects. We studied the Fe3O4 (magnetic oxide) and CoFe2O4 (cobalt iron oxide) ferrous particles embedded in H2O-EG (ethylene glycol) (50–50%) mixture. The flow model is converted as ODEs with suitable similarities and resolved them using the 4th order Runge-Kutta scheme. The influence of related constraints on transport phenomena examined through graphical illustrations. Simultaneous solutions explored for both ferro and hybrid ferrofluid cases. It is found that the magnetic oxide and cobalt iron oxide suspended in H2O-EG (ethylene glycol) (50–50%) mixture effectively reduces the heat transfer rate under specific conditions.
Astaxanthin from Haematococcus pluvialis ameliorates the chemotherapeutic drug (doxorubicin) induced liver injury through the Keap1/Nrf2/HO-1 pathway in mice
Authors: Ma Haotian , Chen Shuaihang , Xiong Huaye , Wang Meng , Hang Wei , Zhu Xiaoli , Zheng Yubin , Ge Baosheng , Li Runzhi , Cui Hongli
Published: April 2020

The aim of this study is to probe a new function of astaxanthin (AST) from Haematococcus pluvialis on chemotherapeutic drug (doxorubicin) induced liver injury in mice.
Un modèle mathématique des débuts de l’épidémie de coronavirus en France
Authors: Bacaër Nicolas
Published: April 2020

On étudie un modèle mathématique de type S-E-I-R à deux phases, inspiré de l’épidémie actuelle de coronavirus. Si les contacts sont réduits à zéro à partir d’une certaine date T proche du début de l’épidémie, la taille finale de l’épidémie est proche de celle que l’on obtient en multipliant le nombre cumulé de cas R(T) à cette date par la reproductivité ℛ0 de l’épidémie. Plus généralement, si les contacts sont divisés au temps T par q > 1 de sorte que ℛ0/q<1, alors la taille finale de l’épidémie est proche de R(T) ℛ0 (1−1/q)/(1−ℛ0/q). On ajuste approximativement les paramètres du modèle aux données relatives au coronavirus en France.
Update Reanimation – Reanimation 4.0
Authors: Seewald Stephan , Jakisch Barbara
Published: April 2020

Die Zukunft der Notfallmedizin wird wesentlich durch technische Innovationen bestimmt werden: Neben einer virtuellen Lernumgebung im Rahmen der Ausbildung wird vor allem die Erkennung des Herz-Kreislauf-Stillstandes in Zukunft zunehmend digitalisiert werden. Der größte Meilenstein aber wird die individualisierte Reanimation sein – möglicherweise bestimmt schon bald der Computer stärker den Ablauf der Reanimation als standardisierte Algorithmen.
Update Breast Cancer 2020 Part 2 – Advanced Breast Cancer: New Treatments and Implementation of Therapies with Companion Diagnostics
Authors: Lüftner Diana , Schneeweiss Andreas , Hartkopf Andreas D. , Müller Volkmar , Wöckel Achim , Janni Wolfgang , Ettl Johannes , Belleville Erik , Schütz Florian , Thill Marc , Huober Jens , Fasching Peter A. , Kolberg Hans-Christian , Pöschke Patrik , Welslau Manfred , Overkamp Friedrich , Tesch Hans , Fehm Tanja N. , Lux Michael P.
Published: April 2020

For patients with locally advanced or metastatic breast cancer, new and effective therapies such as CDK4/6 inhibitors, PARP inhibitors and a PD-L1 inhibitor have been introduced in recent years. This review presents an update on the available studies with their data. In addition, two innovative anti-HER2 therapies are presented (trastuzumab-deruxtecan and tucatinib) for which the results from new studies have been reported. Molecular tests offer the possibility of defining patient populations or also monitoring courses of therapy. This can help identify patients with specific characteristics in order to provide them with individually targeted therapy within the framework of studies. In a large study, the benefit of such a biomarker study was able to be described for the first time.
Deletion of dpy-19 like 2 (DPY19L2) gene is associated with total but not partial globozoospermia
Authors: Alimohammadi Fatemeh , Ebrahimi Nasab Mahya , Rafaee Alemeh , Hashemi Mehrdad , Totonchi Mehdi , Mohseni Meybodi Anahita , Sadighi Gilani Mohammad Ali , Sabbaghian Marjan
Published: April 2020

The dpy-19 like 2 (DPY19L2) gene is the most common genetic cause of globozoospermia characterised by the production of round-headed spermatozoa without an acrosome. The present study was performed on 63 men with globozoospermia and 41 normozoospermic individuals to evaluate the frequency of the DPY19L2 gene and exons; deletion and genetic changes in exons 1, 5, 7–11, 19, 21 and interval introns; and some epidemiological factors (e.g. varicocele, smoking, drug use, alcohol consumption and a family history of infertility). Homozygous deletion of DPY19L2 was identified in 35% of men with globozoospermia. Exon 7 was deleted in 4.8% of men with globozoospermia in which DPY19L2 was not deleted. No genetic variations were observed within the DPY19L2 exons examined, but five intronic polymorphisms were detected: 1054–77T>C in intron 9, 1131+65T>C and 1131+53A>G in intron 10 and 1218+22T>C and 1218+73T>C in intron 11. There were significant differences in the frequency of 1054–77T>C and 1218+22T>C polymorphisms between the globozoospermic and normozoospermic groups. In addition, there were significant differences between the two groups in sperm count, sperm motility, a history of infertility in the family and varicocele. Based on these findings, DPY19L2 deletion is the major cause of total globozoospermia and there is no association between exons 1, 5, 8–11, 19 and 21 polymorphisms of the DPY19L2 gene in the occurrence of this defect.
Extent of Fermi-surface reconstruction in the high-temperature superconductor HgBa
2
CuO

4+
δ
Authors: Chan Mun K. , McDonald Ross D. , Ramshaw B. J. , Betts Jon B. , Shekhter Arkady , Bauer Eric D. , Harrison Neil
Published: April 2020

High magnetic fields have revealed a surprisingly small Fermi surface in underdoped cuprates, possibly resulting from Fermi-surface reconstruction due to an order parameter that breaks translational symmetry of the crystal lattice. A crucial issue concerns the doping extent of such a state and its relationship to the principal pseudogap and superconducting phases. We employ pulsed magnetic-field measurements on the cuprate

H
g
B
a

2

Cu

O

4
+
δ

to identify signatures of Fermi-surface reconstruction from a sign change of the Hall effect and a peak in the temperature-dependent planar resistivity. We trace the termination of Fermi-surface reconstruction to two hole concentrations where the superconducting upper critical fields are found to be enhanced. One of these points is associated with the pseudogap endpoint near optimal doping. These results connect the Fermi-surface reconstruction to both superconductivity and the pseudogap phenomena.
Translation, rewriting and formation of Singapore’s bilingual education policy
Authors: Wenqi Toh , Feng Cui
Published: April 2020

Individuals inevitably have their own perception of Singapore’s bilingual education policy, especially those who experienced its formation and history from the pre-independence days of the 1950s to the 1980s. The book, My Lifelong Challenge: Singapore’s Bilingual Journey by Lee Kuan Yew, the founding Prime Minister of Singapore, provides much information and insights into this part of history. Through the comparison of the English and Chinese editions, this paper discusses the poetics, patronage and ideological differences related to the reasons for the translation and rewriting by Lee Kuan Yew of the Chinese edition. It suggests that Lee Kuan Yew had different intentions for the English and Chinese editions in relation to the respective readerships; as regards the English readership, the author intends the readers to gain knowledge of the historical background and to emphasize to them the importance of Mother Tongue; as regards the Chinese readership, he seeks to address any misunderstandings and misgivings towards the government that this group of readers may have and to gain their support for the bilingual policy.
English-dominated Chinatown
Authors: Zhang Hui , Tupas Ruanni , Norhaida Aman
Published: April 2020

The current study reports a quantitative investigation of the linguistic landscape (LL) in Singapore’s Chinatown. The database of the study comprises a total of 831 instances of signs in the form of photographs that were collected in Chinatown. The study finds that English dominates the LL while Mandarin Chinese is ranked as the second frequently used language. The study also identifies significant differences in LL features between top-down and bottom-up signs. Specifically, these differences include what languages are used; monolingual, bilingual and multilingual compositions; code preference; and forms of Chinese scripts. The present study suggests that English now dominates the linguistic landscape of Chinatown. Even though many scholars have described the sociolinguistic situation in Singapore as being ‘English-knowing’, the data shows a shift towards being ‘English-dominant’, suggesting a gradual but sustained dilution of its multilingual ethos. The study also complicates our understanding of the dominance of English in multilingual societies such as Singapore, where a competing dominant language (Mandarin Chinese) may be seen to continue to exert considerable influence on the dynamics of English-dominant language use but, at the same time, whose main function is shifting towards the symbolic rather than communicative.
Media reporting of cyberbullying
Authors: Yang Lai Fong
Published: April 2020

Cyberbullying refers to aggression that is intentionally and repeatedly carried out in an electronic context
(e.g., e-mail, blogs, social networking sites, instant messages, text messages, etc.) against a person who cannot easily defend
him- or herself. Cyberbullying is an important phenomenon to research for many reasons. First, although varying prevalence rates
have been reported, cyberbullying victimization has been found to occur at frequencies that are cause for concern. Second, many
victims of cyberbullying have been found to experience a range of negative outcomes as a consequence. Third, previous studies
found that increased Internet usage has led to increased involvement as perpetrators, victims or witness in cyberbullying. It is
alarming that a survey conducted by Anis, Rahim and Lim (2012) in Malaysia revealed
that 60% of the cases took place in social networking sites such as Facebook and MySpace. This study aims to examine the coverage
of cyberbullying by The Star, which is the English-language daily newspaper with the largest circulation in
Malaysia. Framing theory was employed as the theoretical framework, while content analysis was used as the research methods. This
study revealed that coverage on cyberbullying in The Star was dominated by the “prevention and intervention
strategies” frame. The social problem was also presented as an individual-level problem (episodic framing) as well as
societal-level issue (thematic framing). Implications of the findings to the understanding of cyberbullying and framing research
were discussed.
Improvement in Brazilian Butt Lift (BBL) Safety With the Current Recommendations from ASERF, ASAPS, and ISAPS
Authors: Rios Luis , Gupta Varun
Published: April 2020

Background

In 2017, the ASERF Gluteal Fat Grafting Task Force reported gluteal fat grafting to be a high-risk procedure and recommended specific surgical techniques to decrease the risk of pulmonary fat embolism (PFE).

Objectives

The aim of this study was to determine whether ASAPS and ISAPS members were aware of the 2017 recommendations, what their current surgical techniques were, whether they had changed their techniques based on the 2017 recommendations, and whether the incidence of PFEs had changed since the recommendations were published.

Methods

An anonymous web-based survey was conducted among members of ASAPS and ISAPS. It included the questions from the 2017 survey, as well as questions about awareness of the Task Force recommendations and subsequent change in surgical techniques.

Results

In the 2 years following the publication of the recommendations, the incidence of any PFE was 1 in 2492 compared with 1 in 1030 reported in 2017 (P = 0.02). Trends indicated a decreased mortality rate from 1 in 3448 in 2017 to 1 in 14,952 in 2019. Ninety-four percent of respondents were aware of the recommendations. Only 0.8% of surgeons in the current survey reported injecting in deep muscle, compared with 13.1% in 2017 (P < 0.01). Compared with 4.1% in 2017, 29.8% of respondents in our survey reported that they only injected with cannulas ≥4.1 mm (P < 0.01). Only 4% of respondents reported angling the cannula down in the current survey, compared with 27.2% in 2017 (P < 0.01).

Conclusions

It appears that members were aware of the 2017 recommendations. There was a significant decrease in recent PFE and trends showed a change to safer techniques and an improvement in safety of the procedure.
Male ultraviolet reflectance and female mating history influence female mate choice and male mating success in a polyandrous lizard
Authors: Badiane Arnaud , Martin Mélissa , Meylan Sandrine , Richard Murielle , Decencière Ferrandière Beatriz , Le Galliard Jean-François
Published: April 2020

Pre-copulatory female mate choice based on male ultraviolet (UV) coloration has been demonstrated in several vertebrate species; however, post-copulatory mechanisms have been largely overlooked. Here, we investigated female mate preference based on male UV coloration in the common lizard Zootoca vivipara, in which males display conspicuous UV coloration on their throat. During two successive years, we staged sequential mating trials between females and four different males with UV-reduced or control belly and throat coloration. We recorded pre-copulatory female behaviour, copulation behaviour and assigned paternity to all offspring. Females were more aggressive towards UV-reduced males and, during the second year, UV-reduced males had a lower probability of siring at least one egg (fertilization success) during the last mating trials. However, in the second year, copulation was shorter with control males. Altogether, our results suggest that females exert subtle pre-copulatory mate preference based on male UV ornaments and, conditional on the study year and female mating history, some degree of post-copulatory preference for UV-control males leading to differential male fertilization success. This study suggests that UV-based female mate choice may be more widespread than previously thought in vertebrates, and emphasizes the importance of using a study design well adapted to the species reproductive behaviour.
Margin of Appreciation in Pursuit of Pluralism? Critical Remarks on the Judgments of the European Court of Human Rights on the ‘Burqa Bans’
Authors: Hwang Shu-Perng
Published: April 2020

In 2014 and 2017, the European Court of Human Rights, respectively, upheld France’s and Belgium’s general bans on wearing face-covering veils in public. Whereas both the acceptance of ensuring the minimum conditions for ‘living together’ as a legitimate aim and the recognition of a wide margin of appreciation appear to demonstrate a pluralistic approach taken by the Court, this article examines the Court’s understanding and application of the principle of pluralism in its reasoning and, in this way, explores why and how the Court’s pluralistic view has led to an anti-pluralistic outcome. It purports to show that it was precisely a majoritarian conception of pluralism that has led the Court to make decisions to the disadvantage of minorities. Moreover, it illustrates how the European multilevel system of human rights protection should be developed in support of the realisation of pluralism.
Effect of Precipitation and Temperature on Larval Survival of Cephus cinctus (Hymenoptera: Cephidae) in Barley Cultivars
Authors: Achhami Buddhi B , Reddy Gadi V P , Sherman Jamie D , Peterson Robert K D , Weaver David K
Published: April 2020

Host plant traits strongly affect survivorship of insect herbivores, and host suitability is especially important for the wheat stem sawfly, Cephus cinctus Norton, which spends its entire egg, larval, and pupal periods in a single stem. Measuring larval survival inside stems from egg hatch through diapause-mediated dormancy is a potential measure of population size for the next year but is also useful in assessing effects of growing season precipitation and temperature. Larval growth is synchronized with host plant growth, and the larva cannot switch hosts. Thus, incorporating plant physiological time, as growing degree days (GDD), may yield a better prediction of larval survival. Therefore, we assessed wheat stem sawfly survival from early larval growth to the beginning of autumnal diapause in barley cultivars selected from across feed, forage, and two- or six-row malt groups. Field experiments were conducted in Gallatin and Chouteau counties, Montana, in 2016 and 2017. We used Kaplan-Meier estimation to assess larval survival among cultivars. We found that the survival of pre-diapause larvae was greatest in ‘Hockett’ (36.5%) and lowest in ‘Celebration’ (15.4%). Precipitation and temperature during the growing season affected temporal patterns for larval survival across study sites. Adjusting survivorship curves using site-specific GDD accumulation allowed cultivar-specific survivorship to be estimated more precisely for each site, despite differing environmental influences. Our findings suggest that measuring wheat stem sawfly survival across barley cultivars and standardizing by site-specific GDDs may provide better recommendations on barley cultivars that impede wheat stem sawfly population growth and reduce economic losses.
Characterization of a dual-beam, dual-camera optical imaging polarimeter
Authors: Shrestha Manisha , Steele Iain A , Piascik Andrzej S , Jermak Helen , Smith Robert J , Copperwheat Chris M
Published: April 2020

Polarization plays an important role in various time-domain astrophysics to understand the magnetic fields, geometry, and environments of spatially unresolved variable sources. In this paper we present the results of laboratory and on-sky testing of a novel dual-beam, dual-camera optical imaging polarimeter (MOPTOP) exploiting high sensitivity, low-noise CMOS technology, and designed to monitor variable and transient sources with low systematic errors and high sensitivity. We present a data reduction algorithm that corrects for sensitivity variations between the cameras on a source-by-source basis. Using our data reduction algorithm, we show that our dual-beam, dual-camera technique delivers the benefits of low and stable instrumental polarization (<0.05 per cent for lab data and <0.25 per cent for on sky data) and high throughput while avoiding the additional sky brightness and image overlap problems associated with dual-beam, single-camera polarimeters.
Evidence for variability time-scale-dependent UV/X-ray delay in Seyfert 1 AGN NGC 7469
Authors: Pahari Mayukh , McHardy I M , Vincentelli Federico , Cackett Edward , Peterson Bradley M , Goad Mike , Gültekin Kayhan , Horne Keith
Published: April 2020

Using a month-long X-ray light curve from RXTE/PCA and 1.5 month-long UV continuum light curves from IUE spectra in 1220–1970 Å, we performed a detailed time-lag study of the Seyfert 1 galaxy NGC 7469. Our cross-correlation analysis confirms previous results showing that the X-rays are delayed relative to the UV continuum at 1315 Å by 3.49 ± 0.22 d, which is possibly caused by either propagating fluctuation or variable Comptonization. However, if variations slower than 5 d are removed from the X-ray light curve, the UV variations then lag behind the X-ray variations by 0.37 ± 0.14 d, consistent with reprocessing of the X-rays by a surrounding accretion disc. A very similar reverberation delay is observed between Swift/XRT X-ray and Swift/UVOT UVW2, U light curves. Continuum light curves extracted from the Swift/GRISM spectra show delays with respect to X-rays consistent with reverberation. Separating the UV continuum variations faster and slower than 5 d, the slow variations at 1825 Å lag those at 1315 Å by 0.29 ± 0.06 d, while the fast variations are coincident (0.04 ± 0.12 d). The UV/optical continuum reverberation lag from IUE, Swift, and other optical telescopes at different wavelengths are consistent with the relationship: τ ∝ λ4/3, predicted for the standard accretion disc theory while the best-fitting X-ray delay from RXTE and Swift/XRT shows a negative X-ray offset of ∼0.38 d from the standard disc delay prediction.
In Hydronephrosis‐Rats, BPC 157 Exerts a Strong Anti‐Ulcer Effect in Both Stomach and Duodenum along with Marked Kidney Recovery
Authors: Vranes Hrvoje , Krezic Ivan , Gojkovic Slaven , Zizek Helena , Durasin Tajana , Petrovic Andrea , Pavlov Katarina Horvat , Batelja Lovorka , Blagaic Alenka Boban , Seiwerth Sven , Sikiric Predrag
Published: April 2020

Background/Hypothesis

We focused on the anti‐ulcerogenic potential of the stable gastric pentadecapeptide BPC 157 in rats used to have unilateral ureter obstruction. Prolonged unilateral ureter obstruction (UUO) after obstruction removal in addition to renal injury, may produce significant stomach and duodenal lesions in rats. Previously, BPC 157 markedly counteracted gastric lesions in nephrectomized rats (FASEB J 2016; 30: 1 Suppl:720.2; FASEB J 2015;29: 1:628.10).

Methods

Rats had ureteral ligation for 72 hours, and thereby, hydronephrosis, fibrosis development, tubular cell damage, and interstitial inflammation. Then, at 5 min after the ureter was obstruction was removed, we applied medication (stable gastric pentadecapeptide BPC 157 (10 μg/kg; 10 ng/kg) or saline) given as an intraperitoneal bath (1mL bath/rat). Assessment was at 24 h and 96 h after medication and included renal lesions (0‐ healthy kidney, 1‐ mild hydronephrosis, 2‐ moderate hydronephrosis, visible dilation of renal pelvis, few lesions on kidney surface, 3‐ severe hydronephrosis, dilatation of renal pelvis, thinning of the renal parenchyma and considerable number of lesions on the kidney surface), gastric and duodenal lesions (sum of the longest diameters, mm), urea, creatinine, AST, ALT, bilirubin, K, Na, Mg, Ca, inorganic phosphates in serum, as described (Sikiric et al, Curr Pharm Des. 2014;20(7):1126–35).

Results

BPC 157 medication results in marked and advanced improvement, seen at 24 h and 96 h thereafter. For illustration, regular severe hydronephrosis, dilatation of renal pelvis, thinning of the renal parenchyma was reversed to only mild or no hydronephrosis. Likewise, both gastric and duodenal lesions, that regularly appear as quite severe hemorrhagic lesions (gastric 12±1; duodenal 9±2 at 24h), were markedly reduced, or completely eliminated after BPC 157 medication, either 10 μg or 10 ng regimen (stomach 1±1; duodenal 1±1 at 24 h, 10 ng‐regimen).

Conclusions

In hydronephrosis‐rats, BPC 157 exerts a strong anti‐ulcer effect in both stomach and duodenum along with marked kidney recovery.

Support or Funding Information

This work was supported by the University of Zagreb, Zagreb, Croatia (Grant BM 099).

Figure 1
The chloride channel Bestrophin‐1 acts in the Malpighian tubule and hindgut of Drosophila melanogaster to maintain salt and water balance
Authors: Rodan Aylin , Pleinis John , Jonusaite Sima , Hudac Jacob , Goodwin Austin , Zhang Feng , Sosa-Pagan Jason , Streeter Forest , Rothenfluh Adrian
Published: April 2020

Objective

The Malpighian tubule and hindgut are iono‐ and osmoregulatory epithelia in insects. The tubule secretes KCl‐rich fluid, and ions and water are subsequently reabsorbed in the hindgut. We characterized the role of the chloride channel, Bestrophin‐1 (Best1), in the tubule and hindgut of Drosophila melanogaster.

Methods

We studied flies carrying a germline mutation in Best1, Best1c04106, as well as Best1c04106 flies with genomic rescue, and flies with tissue‐specific knockdown (quantified by qRT‐PCR) or rescue of Best1. Malpighian tubule ion flux was measured ex vivo, and immunostaining was performed using antibodies to HA‐tagged Bestrophin‐1. Flies were assayed for lethality on normal vs. 0.3 M‐supplemented NaCl (high‐salt) diet and after water restriction. Excretion was quantified by counting excretory drops. Hemolymph and excretory drop osmolality were measured using a vapor pressure osmometer. Water weight was determined by measuring flies’ weight before and after baking at 60 °C.

Results

Best1c04106 mutant Malpighian tubules had decreased fluid secretion and transepithelial ion flux that was rescued by expression of wild‐type Best1 in the K+‐secreting principal cell. Principal cell Best1 knockdown decreased transcript levels by 80% and decreased fluid secretion and ion flux. We previously showed that NKCC is required for principal cell K+ secretion. Here, we immunolocalized both Best1 and NKCC to the principal cell basolateral membrane. There was no further decrease in ion transport in Best1 knockdown tubules when NKCC was mutated, suggesting that Best1 allows Cl− entering through the NKCC to recycle across the basolateral membrane. Best1c04106 mutant flies also had increased lethality on high‐salt diet. Hemolymph osmolality increased in control flies fed high‐salt diet, but Best1c04106 mutants had decreased osmolality on both normal and high salt diet, and increased number and osmolality of excretory drops. As a consequence, Best1c04106 mutant flies were dehydrated and died when water restricted. The Best1c04106 mutant phenotypes were rescued by genomic rescue (which recapitulates normal Best1 expression throughout the body), or targeted rescue in the Malpighian tubule and hindgut.

Conclusion

Best1 is required for normal ion transport in the Drosophila Malpighian tubule, and in the tubule and hindgut for iono‐ and osmoregulation, where ion reabsorption through Best1 in high‐salt conditions allows an increase in hemolymph osmolality to prevent osmotic water loss and dehydration.

Support or Funding Information

NIH DK110358
A cadaveric study on the origins of the profunda brachii artery
Authors: May Brandon , Morton-Gonzaba Nicolas A , Makhani Ahmed , Mattathil Shawna , Markko Tiffany , Rahimi Omid B. , Sakaguchi Alan Y , Kar Rekha
Published: April 2020

The aim of this study is to document the incidence of variation in the origin of the profunda brachii (deep brachial) artery in the cadavers donated to the UT Health San Antonio, Texas. Knowledge of such arterial variation is important for proper pre‐procedural planning particularly in surgical subspecialties. The profunda brachii artery is typically the largest branch of the brachial artery in the arm and accompanies the radial nerve along the radial groove as it passes posteriorly around the shaft of the humerus. One hundred upper limbs (right and left) of fifty cadavers were surveyed after routine dissection of the axillary region by the undergraduate medical students. The profunda brachii artery was dissected proximally to its origin and distally in its course through the radial groove. The profunda brachii artery originated from the brachial artery in 95% (95% confidence interval: 88.5% to 98.13%) of upper limbs. In 4% (95% confidence interval: 1.24% to 10.2%) of upper limbs, this artery originated from the subscapular artery, which is a branch of the third part of the axillary artery. In 1% (95% confidence interval: 0.01% to 5.99%) of upper limbs, the profunda brachii artery originated from a common trunk from the axillary artery which also gave rise to the subscapular artery and the anterior and posterior circumflex humeral arteries. Interestingly, these anomalous origins of the profunda brachii artery either from the subscapular artery or from the axillary artery were observed only on the right side of the cadavers. This study emphasizes the need for clinicians to be aware of these anatomical variations when performing surgeries in the axilla and the arm to avoid surgical complications.
Effects of Lipid Oxidation Products Found in Used Restaurant Fryer Oils on Adipocyte Differentiation and Lipid Metabolism
Authors: Arowolo Folagbayi , Bengtson Marah E. , Andhole Neha G. , Firmino Sofia N. , Shanmuganayagam Dhanansayan
Published: April 2020

Incidence of chronic disease such as obesity, metabolic syndrome and diabetes are rapidly increasing globally, and disproportionately in Western countries. A common theme in the initiation and progression of many chronic diseases, is the exacerbating role of metabolic deregulation associated with observed in obesity and metabolic syndrome. Here, metabolic deregulation and inflammation driven by adipose tissue is a notable culprit. It is suspected that endogenous oxidation of stored and membrane lipids produce lipid oxidation products (LOPs) that alter cellular function and signaling. However, what is neglected is in Western countries, that large amount of LOPs, produced exogenously by Western cooking practoces (e.g., deep frying, microwave cooking), are consumed in large quantities and subsequently stored in adipose. The effects of these LOPs on adipose biology is has not been not well studied. In this study, we examined the effects of a number of LOPs, including 2,4‐decadienal (24DD), found in locally‐sourced used restaurant fryer oil on adipocyte differentiation and lipid metabolism. During induction and subsequent maturation of pre‐adipocytes (3T3‐L1), the cells were cultured in 0, 1, 10, 100, 500 and 1000μM 24DD. Eight days post‐induction, lipid accumulation in mature adipocytes was determined. Lipid accumulation was markedly reduced in cells treated with 100, 500 and 1000μM 24DD, in a dose‐dependent manner. This data suggests that 24DD inhibits adipogenesis. Analysis of changes in gene‐expression are underway to elucidate mechanisms of effect.

Support or Funding Information

The research was supported by the Biomedical & Genomic Research Group Discretionary Fund, University of Wisconsin‐Madison.
CRISPR Knockout of CUL5 increases cell growth and affects the expression of Estrogen Receptor‐α in T47D breast cancer cells
Authors: Bonema Sarah C.
Published: April 2020

The CUL5/VACM‐1 protein is a component of the CRL5 E3 ligase complex responsible for tagging proteins with ubiquitin for degradation in the proteasome. Previous work has shown CUL5/VACM‐1 dependent E3 ligase decreases cellular proliferation, and lack of regulation in this ubiquitin proteasome pathway can lead to uncontrolled cell growth and tumor formation. The CRISPR/Cas9 system, which is a bacterial immune system used to edit genomic DNA, was independently designed in the lab to target and knockout the function of CUL5/VACM‐1 in T47D breast cancer cells and human umbilical vein endothelial cells (HUVEC). AlamarBlue® growth assays and Matrigel® growth imaging demonstrate that in the absence of CUL5/VACM‐1 cellular proliferation significantly increases. Subsequent immunocytochemistry analysis of estrogen receptor‐α (ERα) expression in T47D cells showed that in the absence of CUL5/VACM‐1 ERα expression was increased. Finally, q‐PCR OpenArray targeted gene expression analysis of control and CRISPR treated cells showed changes in gene regulation across signal transduction pathways. These results make CUL5/VACM‐1 a potential potent target for drug design and development in breast cancer treatment.

Support or Funding Information

This work was supported by the A. Paul Schaap Fund, Hope College, Chemistry Department.
The effect of tetrahydrobiopterin on microvascular function with advancing age assessed by passive leg movement
Authors: Bisconti Angela Valentina , Broxterman Ryan M. , Jarrett Catherine L. , Shields Katherine L. , Park Soung Hun , Garten Ryan S. , Wray D. Walter , Richardson Russell S.
Published: April 2020

Tetrahydrobiopterin (BH4) is a cofactor which recouples eNOS, potentially increasing nitric oxide (NO)‐bioavailability. Previously, BH4 has been documented to restore conduit artery vascular dysfunction, assessed by flow mediated vasodilation (FMD) in sedentary old subjects. This study aimed to determine if BH4 can restore microvascular function in the old, assessed by the, highly NO‐dependent, passive leg movement (PLM) test. Two approaches were employed, with the first recapitulating the experimental design of the prior FMD study: 1) Using a double‐blind, placebo controlled, crossover design, eight old subjects (74±8 yrs) ingested BH4 (100mg/kg) or placebo on two different days at least one week apart, with PLM assessed (blood flow ΔPeak and AUC) after both conditions. 2) On a single experimental day, PLM was assessed in an additional thirteen old subjects (74±8 yrs) prior to and ~ 4.5 hours after ingesting BH4 (100 mg/kg). With the first experimental approach, BH4 increased PLM ΔPeak and AUC by ≈20% (271±94 vs 326±158) and ≈29% (60±40 vs 77±51), respectively, compared to placebo, but did not achieve statistical significance. With the second approach, BH4 increased PLM ΔPeak and AUC ≈30% (323±182 vs 421±192; p=0.01) and ≈38% (64±62 vs 89±56; p=0.06), respectively. When the two data sets were combined, BH4 significantly increased both PLM ΔPeak ≈28%(305±156 vs 388±183; p=0.01) and AUC ≈43%(63±54 vs 85±53; p=0.02). Thus, improving eNOS‐recoupling with acute BH4 supplementation can improve microvascular function with advancing age and this is likely a result of increased NO‐bioavailability.
Exploring the Effect of Growth Conditions on the Volatile Metabolome of Chromobacterium vaccinii using GC×GC‐TOF‐MS
Authors: Ramirez Diana , Higgins Keppler Emily A. , Bean Heather D.
Published: April 2020

Chromobacterium spp. have been found to grow in a variety of environments and have an extensive metabolic flexibility. Due to this flexibility, studies have shown that Chromobacterium spp. produce an array of properties that can positively impact medicine, industry, and agriculture. C. vaccinii, isolated from cranberry bog soil, has been found to inhibit the growth of multiple pathogenic plant fungi through the production of volatile compounds. Fungal inhibition has been observed when the fungi is co‐cultured with C. vaccinii in separate petri dishes but with shared gas exchange. The same fungal inhibition is not observed when the fungus is exposed to C. vaccinii metabolites produced in liquid media. Based on this observation, we hypothesize that the volatiles produced in liquid media are not the same as the volatiles produced in agar. Experiments are being conducted to study the influence of growth conditions on C. vaccinii volatile metabolites. C. vaccinii will be cultured in liquid and semi‐solid media, the volatiles will be collected using thin film solid phase microextraction (TF‐SPME) and analyzed with two‐dimensional gas chromatography – time‐of‐flight mass spectroscopy (GC×GC‐TOFMS). The goal is to determine the differences between the volatiles produced in the different types of media. These results will lead to a better understanding of this natural occurring soil bacteria.

Support or Funding Information

NSF LEAP Scholars Program
Sex differences in ET‐1 levels in primary human endothelial cells
Authors: Kuczmarski Andrew V. , Hobson Joshua C. , Patik Jordan C. , Edwards David G. , Wenner Megan M.
Published: April 2020

Endothelin‐1 (ET‐1) is produced and secreted primarily by endothelial cells and acts as a potent vasoconstrictor. Our laboratory has previously shown that ET‐1 contributes to impaired vascular endothelial function in postmenopausal women (PMW). However, compared to PMW, ET‐1 mediated vasoconstriction is greater in men of a similar age. Although sex differences in ET‐1 receptor expression and/or responses may partially explain these differences, it is unknown whether ET‐1 levels in endothelial cells differ between PMW and men of similar age. The purpose of this study was to test the hypothesis that PMW have lower endothelial cell ET‐1 levels compared to men of similar age. Endothelial cells were harvested from the antecubital vein of healthy PMW (n=9, 59±3 yrs) and age‐matched men (n=7, 58±6 yrs) by threading a guide wire through an 18g IV catheter. The guide wire was rinsed in dissociation buffer to remove endothelial cells, which were then fixed in 4% paraformaldehyde, washed in phosphate buffered saline, pipetted onto coverglass, dried at 60°C, and stored at −80°C until staining. Immunocytochemistry was used to stain for ET‐1 (Endothelin‐1 Monoclonal Antibody (TR.ET.48.5), Thermo Fisher Scientific, Cat# MA3‐005), vascular endothelial cadherin (VE‐Cadherin polyclonal antibody, Thermo Fisher Scientific, Cat# 36‐1900) to identify endothelial cells, and 4′,6‐diamidino‐2‐phenylindole (DAPI, nuclear stain). Fluorescence intensity was measured in 30 cells on a Zeiss Axio imager using consistent laser intensity and exposure times. ET‐1 intensity was normalized to human umbilical vein endothelial cells, consistent with published literature. Results are reported as mean ± standard deviation. PMW and men were well match based on BMI (PMW; 25±5 kg/m2 vs. Men; 25±3), mean arterial blood pressure (PMW; 88±8 vs. Men; 93±9 mmHg), total cholesterol (PMW; 193±45 vs. Men; 192±40 mg/dL), LDL cholesterol (PMW; 103±39 vs. Men; 111±34 mg/dL), and fasting plasma glucose (PMW; 88±4 vs. Men; 92±6 mg/dL) all P>0.05. ET‐1 intensity levels were significantly lower in PMW (0.57±0.12 a.u) compared to Men (0.98±0.27 a.u, P =0.001). These preliminary findings suggest differences in endothelial ET‐1 levels between PMW and age‐matched men. Moreover, these data provide further evidence of the sexual dimorphisms in the ET‐1 system, and add insight into mechanisms underlying sex differences in vascular function.

Support or Funding Information

NIH R01 HL 146558, HL‐113514, P20 GM 113125, AHA 16SDG30700015, and University of Delaware Research Foundation.
Characterization of Delta Opioid Receptor Activity of MMP2200, a Mixed Efficacy Mu and Delta Opioid Receptor Agonist
Authors: Burgess Gwendolyn Erin , Polt Robin , Rice Kenner C. , Jutkiewicz Emily M.
Published: April 2020

Pharmacological modulation of the delta opioid receptor (DOR) in conjunction with a mu‐opioid receptor (MOR) agonist produces antinociceptive effects with potentially a better side effect profile. MMP2200 (a.k.a.Lactomorphin) is a CNS permeable, glycosylated peptide and an agonist at both MORs and DORs. Previous reports characterized the MOR agonist effects of MMP2200; however, the DOR agonist effects of MMP2200in vivo have not been explored. DOR agonists, such as SNC80, have been shown to produce convulsions and discriminative stimulus effects in rodents. Therefore, based on the DOR agonist activity of MMP2200, we hypothesized that MMP2200 would produce DOR‐mediated convulsions in mice and SNC80‐like discriminative stimulus effects in rats. Convulsions were evaluated by continual observation for up to 60 min in an observation cage. For SNC80 discrimination experiments, rats were trained to discriminate an injection of 3.2 mg/kg SNC80 from saline under a fixed ratio 10 schedule of food reinforcement, and different doses of SNC80 or MMP2200 were substituted to evaluate percent generalization and response rates. MMP2200 produced brief, non‐lethal convulsions in C57BL/6N, but not ICR, mice that were blocked by the DOR antagonist naltrindole and by genetic deletion of DOR, indicating that MMP2200‐induced convulsions are DOR mediated. Following acute drug administration, mice were then given a second dose of the DOR agonist 24 h later. These mice were tolerant to convulsions induced by SNC80, but not to MMP2200‐induced convulsions. Tolerance to the convulsive effects of MMP2200 was apparent 8 h following the initial injection. SNC80 induced convulsions were enhanced in mice lacking arrestin 2 but were unaltered in mice lacking arrestin 3. However, MMP2200‐induced convulsions were attenuated in mice lacking either arrestin 2 or 3. In rats trained to discriminate SNC80, MMP2200 fully generalized to the discriminative stimulus effects of SNC80 and only slightly decreased rates of responding. Overall, these results demonstrate that the dual MOR/DOR agonist MMP2200 produces many behavioral effects that are similar to the prototypical DOR agonist SNC80. Interestingly, there are some distinct differences in these DOR agonist effects, which may be mediated by concurrent MOR agonist activity with MMP2200 or by activating differential intracellular signaling molecules downstream of DOR activation. Future studies will evaluate the effects of DOR agonists and signaling pathways mediating these effects.
The Sphenoidal Synchondroses: Implications for the Midfacial Growth of Anthropoid Primates
Authors: Wood Brody , Mano Nanami , Oladipupo Lanre , Corbin Hayley , Vinyard Christopher , DeLeon Valerie B. , Smith Timothy D.
Published: April 2020

The basicranium of anthropoid primates is more flexed than in lemurs and lorises (strepsirrhines), which has implications for orientation of facial growth. Differential growth among cranial synchondroses is one suggested mechanism for variation in basicranial development. In this study, we measured length of bony elements of the cranial base using Amira software in a cross‐sectional age sample (late prenatal to juvenile), which included three monkey species and four species of lemurs and bushbabies (n = 59). In addition, we made preliminary measurements of the anteroposterior length of the spheno‐occipital synchondrosis (SOS), intrasphenoidal synchondrosis (ISS), and prespheno‐septal synchondrosis (PSept) using newborn samples. In order to assess differences in growth potential among sync
hondroses, the diameter of the proliferating (PZ) or hypertrophic (HZ) zones were also measured. Our other work has indicated that measurements of ossified elements of the cranial base reveal disproportionately more growth of presphenoid (PS) relatively to basisphenoid (BS) in monkeys. But in strepsirrhines, these bones scale similarly to one another when plotted against increasing cranial or midfacial length. When expressed as a ratio of the length of the PZ or HZ to total anteroposterior diameter of the synchondrosis, growth is relatively similar in ISS and SOS among all species studied. However, in anthropoids the length of the PZ in PSept is notably (more than two‐fold) greater than in any other synchondrosis. In strepsirrhines, length of the PZ in PSept is relatively similar to the same zone of other synchondroses. This suggests that the rapid increase in length of the presphenoid in anthropoids is mostly occurring anteriorly, at the midfacial interface. These results, taken at face value, might suggest that anthropoids have a greater magnitude of growth in the septal cartilage compared to strepsirrhines. However, our previous work established that growth at PSept in more multidirectional (radial) than in most other mammals. Instead, our findings emphasize different patterns of sphenoid growth among primates, and offer a tissue‐level explanation for the relatively large PS segment in anthropoid primates. In addition, these findings indicate suggest that growth of the sphenoid is more highly integrated with PS than BS and more interdependent with facial growth in monkeys than in strepsirrhine primates.

Support or Funding Information

NSF grant # BCS‐1830894, BCS‐1830919, BCS‐0959438