bluuebunny/crossref_metadata_2025 huggingface dataset:
Palmitoylation of the K
ATP
channel Kir6.2 subunit promotes channel opening by regulating PIP
2
sensitivity
Authors: Yang Hua-Qian , Martinez-Ortiz Wilnelly , Hwang JongIn , Fan Xuexin , Cardozo Timothy J. , Coetzee William A.
Published: April 2020

Significance

Protein diversity is substantially increased by posttranslational modifications of amino acid residues. Lipidation is poorly characterized for ion channels. We found regulated S-palmitoylation to occur in certain K
+
channels (Kir3.4, Kir6.1, and Kir6.2). For Kir6.2, lipidation at Cys
166
(or gene variants associated with diabetes) increases the channel open state. Experimental and molecular modeling studies show this due mainly to an increased sensitivity to PIP
2
, which results in altered regulation of K
ATP
channels by α1-adrenoceptor signaling in cardiomyocytes. Our data demonstrate complexity in the regulation of K
ATP
channels by long-chain acyl-CoA esters, which can be both acute and direct, but also be mediated through regulated S-palmitoylation. Strategies aimed at regulating the palmitoylation state of K
ATP
channels may represent new therapeutic opportunities.
Sample multiplexing for targeted pathway proteomics in aging mice
Authors: Yu Qing , Xiao Haopeng , Jedrychowski Mark P. , Schweppe Devin K. , Navarrete-Perea Jose , Knott Jeffrey , Rogers John , Chouchani Edward T. , Gygi Steven P.
Published: April 2020

Pathway proteomics strategies measure protein expression changes in specific cellular processes that carry out related functions. Using targeted tandem mass tags-based sample multiplexing, hundreds of proteins can be quantified across 10 or more samples simultaneously. To facilitate these highly complex experiments, we introduce a strategy that provides complete control over targeted sample multiplexing experiments, termed Tomahto, and present its implementation on the Orbitrap Tribrid mass spectrometer platform. Importantly, this software monitors via the external desktop computer to the data stream and inserts optimized MS2 and MS3 scans in real time based on an application programming interface with the mass spectrometer. Hundreds of proteins of interest from diverse biological samples can be targeted and accurately quantified in a sensitive and high-throughput fashion. It achieves sensitivity comparable to, if not better than, deep fractionation and requires minimal total sample input (∼10 µg). As a proof-of-principle experiment, we selected four pathways important in metabolism- and inflammation-related processes (260 proteins/520 peptides) and measured their abundance across 90 samples (nine tissues from five old and five young mice) to explore effects of aging. Tissue-specific aging is presented here and we highlight the role of inflammation- and metabolism-related processes in white adipose tissue. We validated our approach through comparison with a global proteome survey across the tissues, work that we also provide as a general resource for the community.
Machine learning predicts the functional composition of the protein corona and the cellular recognition of nanoparticles
Authors: Ban Zhan , Yuan Peng , Yu Fubo , Peng Ting , Zhou Qixing , Hu Xiangang
Published: April 2020

Protein corona formation is critical for the design of ideal and safe nanoparticles (NPs) for nanomedicine, biosensing, organ targeting, and other applications, but methods to quantitatively predict the formation of the protein corona, especially for functional compositions, remain unavailable. The traditional linear regression model performs poorly for the protein corona, as measured by
R
2
(less than 0.40). Here, the performance with
R
2
over 0.75 in the prediction of the protein corona was achieved by integrating a machine learning model and meta-analysis. NPs without modification and surface modification were identified as the two most important factors determining protein corona formation. According to experimental verification, the functional protein compositions (e.g., immune proteins, complement proteins, and apolipoproteins) in complex coronas were precisely predicted with good
R
2
(most over 0.80). Moreover, the method successfully predicted the cellular recognition (e.g., cellular uptake by macrophages and cytokine release) mediated by functional corona proteins. This workflow provides a method to accurately and quantitatively predict the functional composition of the protein corona that determines cellular recognition and nanotoxicity to guide the synthesis and applications of a wide range of NPs by overcoming limitations and uncertainty.
Molecular dysregulation of ciliary polycystin-2 channels caused by variants in the TOP domain
Authors: Vien Thuy N. , Wang Jinliang , Ng Leo C. T. , Cao Erhu , DeCaen Paul G.
Published: April 2020

Genetic variants in
PKD2
which encodes for the polycystin-2 ion channel are responsible for many clinical cases of autosomal dominant polycystic kidney disease (ADPKD). Despite our strong understanding of the genetic basis of ADPKD, we do not know how most variants impact channel function. Polycystin-2 is found in organelle membranes, including the primary cilium—an antennae-like structure on the luminal side of the collecting duct. In this study, we focus on the structural and mechanistic regulation of polycystin-2 by its TOP domain—a site with unknown function that is commonly altered by missense variants. We use direct cilia electrophysiology, cryogenic electron microscopy, and superresolution imaging to determine that variants of the TOP domain finger 1 motif destabilizes the channel structure and impairs channel opening without altering cilia localization and channel assembly. Our findings support the channelopathy classification of
PKD2
variants associated with ADPKD, where polycystin-2 channel dysregulation in the primary cilia may contribute to cystogenesis.
Induction of recurrent break cluster genes in neural progenitor cells differentiated from embryonic stem cells in culture
Authors: Tena Aseda , Zhang Yuxiang , Kyritsis Nia , Devorak Anne , Zurita Jeffrey , Wei Pei-Chi , Alt Frederick W.
Published: April 2020

Mild replication stress enhances appearance of dozens of robust recurrent genomic break clusters, termed RDCs, in cultured primary mouse neural stem and progenitor cells (NSPCs). Robust RDCs occur within genes (“RDC-genes”) that are long and have roles in neural cell communications and/or have been implicated in neuropsychiatric diseases or cancer. We sought to develop an in vitro approach to determine whether specific RDC formation is associated with neural development. For this purpose, we adapted a system to induce neural progenitor cell (NPC) development from mouse embryonic stem cell (ESC) lines deficient for XRCC4 plus p53, a genotype that enhances DNA double-strand break (DSB) persistence to enhance detection. We tested for RDCs by our genome-wide DSB identification approach that captures DSBs via their ability to join to specific genomic Cas9/single-guide RNA–generated bait DSBs. In XRCC4/p53-deficient ESCs, we detected seven RDCs, all of which were in genes and two of which were robust. In contrast, in NPCs derived from these ESC lines we detected 29 RDCs, a large fraction of which were robust and associated with long, transcribed neural genes that were also robust RDC-genes in primary NSPCs. These studies suggest that many RDCs present in NSPCs are developmentally influenced to occur in this cell type and indicate that induced development of NPCs from ESCs provides an approach to rapidly elucidate mechanistic aspects of NPC RDC formation.
Pan-cancer analysis identifies mutations in
SUGP1
that recapitulate mutant SF3B1 splicing dysregulation
Authors: Liu Zhaoqi , Zhang Jian , Sun Yiwei , Perea-Chamblee Tomin E. , Manley James L. , Rabadan Raul
Published: April 2020

Significance

SF3B1 is the most commonly mutated splicing factor in cancers, and
SF3B1
mutations result in aberrant 3′ splice site usage during splicing of a subset of introns. Here, we utilized an unbiased computational biology approach to determine whether cancer-associated mutations in any other genes produce the same pattern of aberrant splicing as do
SF3B1
mutations. We found that, while rare, the most frequently mutated gene that causes such splicing defects is
SUGP1
. This is striking because previous biochemical studies indicated that loss of SF3B1 interaction with SUGP1 underlies the effects of
SF3B1
mutations on splicing. Our findings thus establish the cancer relevance of the biochemical link between SF3B1 and SUGP1 and also identify
SUGP1
as a cancer-associated gene.
NORs on human acrocentric chromosome p-arms are active by default and can associate with nucleoli independently of rDNA
Authors: van Sluis Marjolein , van Vuuren Chelly , Mangan Hazel , McStay Brian
Published: April 2020

Significance

A detailed description of how the genome is organized within the human nucleus is a major research goal. Nucleolar organizer regions (NORs) comprising ribosomal DNA (rDNA) arrays are located on the p-arms of the five human acrocentric chromosomes. Here we characterize the rules of engagement between NORs and nucleoli. We reveal variation in rDNA distribution, with some primary cell lines containing as many as four acrocentrics devoid of rDNA. We establish the default status of NORs as active and show that acrocentric p-arms devoid of rDNA retain nucleolar association potential. Based on our data, we propose that in diploid human cells, all 10 acrocentric chromosomes are nucleolar-associated, with involvement of non-rDNA sequences buffering against variable rDNA distribution.
Surtitles and the multi-semiotic balance
Authors: Palmer Judi
Published: April 2020

When surtitles were first introduced, in 1982, they were intended to make opera accessible to a
larger audience. They fulfilled the basic requirement of maximum comprehension, minimum distraction. In the
intervening years, however, there has been an increase in the quantity of displayed text so that the titles have
become distracting and intrusive. In my contribution, I explore the reasons for this and discuss why I believe there
is a need to put surtitles into their perspective, within the multi-semiotic balance of lyric theatre
performances.
Fluid borders: From Carmen to The Car Man. Bourne’s ballet in the light of
post-translation
Authors: Vidal Claramonte M. Carmen África
Published: April 2020

This paper takes Matthew Bourne’s The Car Man as an example of today’s
enlarged definition of translation, following Maria Tymoczko’s, Susan Bassnett’s, Edwin
Gentzler’s and other, new post-positivist approaches to contemporary translation. Bourne’s post-translation offers an
up-to-date version of Bizet’s world: he deconstructs genres and genders by subverting opera and dance, but also
straight and gay binary oppositions, thus creating richer and more ambiguous identities and characters. Bourne’s
translation in The Car Man wants his intersemiotic rewriting of the past to be more down to earth and
more real, taking ballet and opera closer to a new audience. The Car Man is a paradigm of crossroads
which breaks away from linear discourses and binary oppositions and which opts for less common lines and different
angles. In sum, a contemporary translation.
Translations, adaptations or rewritings?
Authors: Degott Pierre
Published: April 2020

This paper analyses the various English translations of Da Ponte and Mozart’s Don
Giovanni, with an aim at showing that each version tends to adapt the social, cultural and sexual
contexts of the opera. From Natalia Macfarren’s Victorian translation of the 1870s to Jeremy Sams’ modern version
currently in use at the English National Opera, via Edward Dent’s sprightly text written in the 1930s for the London
lower middle classes, Ruth and Thomas Martin’s version meant for a conservative American public and W. H. Auden’s most
poetical reinterpretation, all versions resort to strategies aimed at drawing on the new receiver’s culture. Whatever
their own specificities, all versions tend to reduce the strangeness and otherness of the original text, offering
their own interpretations of Mozart and Da Ponte’s universal masterpiece.
“Ordne die Reih’n”
Authors: Kaindl Klaus
Published: April 2020

The aim of this study is to investigate the translation politics in the field of opera in the Third
Reich with a special focus on the three Mozart-Da Ponte operas. Mozart was considered as a central part of the German
culture. His collaboration with the Jewish librettist Lorenzo Da Ponte and the fact that the most popular German
translation at the time came from the Jewish conductor Hermann Levi forced the Nazi authorities to create a new
translation. In the first section of the article I will analyse the various front lines in this translation war,
drawing on Bourdieu’s field theory. The second part of this paper investigates the strategies adopted by a committee
which Goebbels established in order to create a new translation of the Mozart operas. The last section of the article
is then dedicated to Georg Schünemann, the translator who was nominated by the committee, and his translatorial
habitus.
Two English translations of Jaroslav Kvapil’s Rusalka libretto
Authors: Corness Patrick John
Published: April 2020

This study investigates two translations into English of Jaroslav Kvapil’s
Rusalka libretto, set to music by Antonín Dvořák: the singing translation in verse by Daphne
Rusbridge (1954) and Paula Kennedy’s
(1998) prose translation. It identifies sources in mythologies and folk tales, and outlines notable
characteristics of language and composition in the Czech libretto. Semantic and stylistic shifts are discussed, with
the aim of highlighting the impact of constraints under which the translators had to work, rather than criticising
discovered shifts as avoidable errors. A summary of the translation shifts found, and their implications for the
reception in English of Kvapil’s libretto, includes both critical and favourable comments.
Weight Stigma and Weight-Related Health: Associations of Self-Report Measures Among Adults in Weight Management
Authors: Pearl Rebecca L , Puhl Rebecca M , Himmelstein Mary S , Pinto Angela M , Foster Gary D
Published: April 2020

Background

Weight stigma impairs health. Few studies have disentangled the associations of experienced versus internalized stigma with weight-related outcomes.

Purpose

To examine weight and health variables associated with weight stigma experiences and internalization in the largest-to-date sample of adults in weight management.

Methods

WW (formerly Weight Watchers) members (N = 18,769, 94.6% female, 91.1% white) completed an online survey from 2017 to 2018. Participants reported whether they had experienced weight stigma and, if so, the onset, past-year frequency and distress, and interpersonal sources of stigma. Participants completed the Modified Weight Bias Internalization Scale (WBIS-M) and self-reported: past-year weight and lifetime weight cycles; current self-monitoring behaviors; eating self-efficacy; physical activity; perceived stress; eating to cope; body image; and mental and physical health-related quality-of-life (HRQOL). Participants reported their demographic characteristics, including height and weight to compute body mass index.

Results

In logistic and linear regression analyses (controlling for participant characteristics), WBIS-M scores were negatively associated with weight loss, self-monitoring, eating self-efficacy, body image, and mental HRQOL and positively associated with weight gain, weight cycling, perceived stress, and eating to cope (p < .001). Experiencing weight stigma was associated with greater weight loss and less weight gain, although associations with other variables had small effect sizes (absolute β values < 0.10). WBIS-M scores remained significantly associated with all variables when including stigma onset, frequency/distress, and sources.

Conclusions

Internalized, but not experienced, weight stigma was consistently associated with adverse weight and health factors. Developing and testing interventions targeting internalized stigma in the context of weight management should be a research priority.
Establishment of variation source and age-related reference interval models for 22 common biochemical analytes in older people using real-world big data mining
Authors: Ma Chaochao , Xia Liangyu , Cheng Xinqi , Wu Jie , Yin Yicong , Hou Lian , Li Xiaoqi , Guo Xiuzhi , Lin Songbai , Qiu Ling
Published: April 2020

Background

the ageing population has increased in many countries, including China. However, reference intervals (RIs) for older people are rarely established because of difficulties in selecting reference individuals. Here, we aimed to analyse the factors affecting biochemical analytes and establish RI and age-related RI models for biochemical analytes through mining real-world big data.

Methods

data for 97,220 individuals downloaded from electronic health records were included. Three derived databases were established. The first database included 97,220 individuals and was used to build age-related RI models after identifying outliers by the Tukey method. The second database consisted of older people and was used to establish variation source models and RIs for biochemical analytes. Differences between older and younger people were compared using the third database.

Results

sex was the main source of variation of biochemical analytes for older people in the variation source models. The distributions of creatinine and uric acid were significantly different in the RIs of biochemical analytes for older people established according to sex. Age-related RI models for biochemical analytes that were most affected by age were built and visualized, revealing various patterns of changes from the younger to older people.

Conclusion

the study analysed the factors affecting biochemical analytes in older people. Moreover, RI and age-related RI models of biochemical analytes for older people were established to provide important insight into biological processes and to assist clinical use of various biochemical analytes to monitor the status of various diseases for older people.
Leave me alone: solitary females attract more mates in a nocturnal insect
Authors: Lehtonen Topi K , Kaitala Arja
Published: April 2020

Spatial distributions of sexual competitors and potential mating partners have a large impact on sexual selection and mating systems. Typically, such effects are investigated with regard to male aggregations. However, females may also need to compete for mating opportunities. Here, we investigated the consequences of clustering and rival attractiveness on female mate attraction success under field conditions in a nocturnal beetle, the common glowworm, Lampyrus noctiluca. We placed dummy females of two glow intensity (attractiveness) levels either alone or in clusters of varying attractiveness compositions. We found that, by displaying alone rather than in a cluster, females have a higher probability of mating and greater potential to exercise mate choice. Within clusters, females of both attractiveness levels had the highest probability of mating when having neighbors of only the less attractive type. These results show that both the presence and attractiveness of rivals can strongly influence females’ mate attraction. The findings also suggest that the typical distribution of glowing females in the wild is better explained by female than male benefits. Hence, the results highlight the important links between spatial distribution of females, male mate searching, and sexual selection.
Vocal recognition suggests premating isolation between lineages of a lekking hummingbird
Authors: Cruz-Yepez Nataly , González Clementina , Ornelas Juan Francisco
Published: April 2020

Species with genetically differentiated allopatric populations commonly differ in phenotypic traits due to drift and/or selection, which can be important drivers of reproductive isolation. Wedge-tailed sabrewing (Campylopterus curvipennis) is a species complex composed of three genetically and acoustically differentiated allopatric lineages that correspond to currently recognized subspecies in Mexico: C. c. curvipennis (Sierra Madre Oriental), C. c. pampa (Yucatán Peninsula), and C. c. excellens (Los Tuxtlas). Although excellens is taxonomically recognized as a distinct species, there is genetic evidence that lineages excellens and curvipennis have diverged from each other later than pampa. In this study, we experimentally tested C. c. curvipennis song recognition as a major factor in premating reproductive isolation for lineage recognition. To this end, we conducted a song playback experiment to test whether territorial males of one C. c. curvipennis lek discriminate among potential competitors based on male songs from the three lineages. Males of curvipennis responded more aggressively to songs of their own lineage and excellens, than to songs of the most divergent lineage pampa, as evidenced by significant differences in a variety of intensity and latency response variables. This indicate that the pampa male song does not represent a competitive threat as curvipennis and excellens songs, in which divergence and song recognition represent premating reproductive isolation between these isolated lineages. However, the acoustic limits between curvipennis and excellens might be attenuated by gene flow in case of secondary contact between them, despite the strong and relatively rapid divergence of their sexually selected song traits.
MicroRNA-21 as a regulator of human cumulus cell viability and its potential influence on the developmental potential of the oocyte
Authors: Bartolucci Alison F , Uliasz Tracy , Peluso John J
Published: April 2020

MicroRNA-21 is expressed in bovine, murine, and human cumulus cells with its expression in murine and bovine cumulus cells correlated with oocyte developmental potential. The aim of this study was to assess the relationship between cumulus cell MIR-21 and human oocyte developmental potential. These studies revealed that both the immature and mature forms of MicroRNA-21 (MIR-21-5p) were elevated in cumulus cells of oocytes that developed into blastocysts compared to cumulus cells of oocytes that arrested prior to blastocyst formation. This increase in MicroRNA-21 was observed regardless of whether the oocytes developed into euploid or aneuploid blastocysts. Moreover, MIR-21-5p levels in cumulus cells surrounding oocytes that either failed to mature or matured to metaphase II but failed to fertilize, were ≈50% less than the MIR-21-5p levels associated with oocytes that arrested prior to blastocyst formation. Why cumulus cells associated with oocytes of reduced developmental potential expressed less MIR-21-5p is unknown. It is unlikely due to reduced expression of either the receptors of growth differentiation factor 9 or rosha Ribonuclease III (DROSHA) and Dicer Ribonuclease III (DICER) which sequentially promote the conversion of immature forms of MicroRNA-21 to mature MicroRNA-21. Furthermore, cultured cumulus cells treated with a MIR-21-5p inhibitor had an increase in apoptosis and a corresponding increase in the expression of PTEN, a gene known to inhibit the AKT-dependent survival pathway in cumulus cells. These studies provide evidence for a role of MicroRNA-21 in human cumulus cells that influences the developmental potential of human oocytes.
CIB4 is essential for the haploid phase of spermatogenesis in mice†
Authors: Xu Zoulan , Miyata Haruhiko , Kaneda Yuki , Castaneda Julio M , Lu Yonggang , Morohoshi Akane , Yu Zhifeng , Matzuk Martin M , Ikawa Masahito
Published: April 2020

Spermatogenesis is a complex developmental process that involves the proliferation of diploid cells, meiotic division, and haploid differentiation. Many genes are shown to be essential for male fertility using knockout (KO) mice; however, there still remain genes to be analyzed to elucidate their molecular mechanism and their roles in spermatogenesis. Calcium- and integrin-binding protein 1 (CIB1) is a ubiquitously expressed protein that possesses three paralogs: CIB2, CIB3, and CIB4. It is reported that Cib1 KO male mice are sterile due to impaired haploid differentiation. In this study, we discovered that Cib4 is expressed strongly in mouse and human testis and begins expression during the haploid phase of spermatogenesis in mice. To analyze the function of CIB4 in vivo, we generated Cib4 KO mice using the CRISPR/Cas9 system. Cib4 KO male mice are sterile due to impaired haploid differentiation, phenocopying Cib1 KO male mice. Spermatogenic cells isolated from seminiferous tubules demonstrate an essential function of CIB4 in the formation of the apical region of the sperm head. Further analysis of CIB4 function may shed light on the etiology of male infertility caused by spermatogenesis defects, and CIB4 could be a target for male contraceptives because of its dominant expression in the testis.
Tmprss12 is required for sperm motility and uterotubal junction migration in mice†
Authors: Larasati Tamara , Noda Taichi , Fujihara Yoshitaka , Shimada Keisuke , Tobita Tomohiro , Yu Zhifeng , Matzuk Martin M , Ikawa Masahito
Published: April 2020

Spermatozoa are produced in the testis but gain their fertilizing ability during epididymal migration. This necessary step in sperm maturation includes posttranslational modification of sperm membrane proteins that includes protein processing by proteases. However, the molecular mechanism underpinning this epididymal sperm maturation remains unknown. In this study, we focused on transmembrane serine protease 12 (Tmprss12). Based on multi-tissue expression analysis by PCR, Tmprss12 was specifically expressed in the testis, and its expression started on day 10 postpartum, corresponding to the stage of zygotene spermatocytes. TMPRSS12 was detected in the acrosomal region of spermatozoa by immunostaining. To reveal the physiological function of TMPRSS12, we generated two knockout (KO) mouse lines using the CRISPR/Cas9 system. Both indel and large deletion lines were male sterile showing that TMPRSS12 is essential for male fertility. Although KO males exhibited normal spermatogenesis and sperm morphology, ejaculated spermatozoa failed to migrate from the uterus to the oviduct. Further analysis revealed that a disintegrin and metalloprotease 3 (ADAM3), an essential protein on the sperm membrane surface that is required for sperm migration, was disrupted in KO spermatozoa. Moreover, we found that KO spermatozoa showed reduced sperm motility via computer-assisted sperm analysis, resulting in a low fertilization rate in vitro. Taken together, these data indicate that TMPRSS12 has dual functions in regulating sperm motility and ADAM3-related sperm migration to the oviduct. Because Tmprss12 is conserved among mammals, including humans, our results may explain some genetic cases of idiopathic male infertility, and TMPRSS12 and its downstream cascade may be novel targets for contraception.
Developing a Poverty-Aware Pedagogy: From Paradigm to Reflexive Practice in Post-Academic Social Work Education
Authors: Roets Griet , Van Beveren Laura , Saar-Heiman Yuval , Degerickx Heidi , Vandekinderen Caroline , Krumer-Nevo Michal , Rutten Kris , Roose Rudi
Published: April 2020

Social work scholars have argued that poverty reminds us of the necessary commitment to educate professional social workers. Being inspired by a conceptual framework that captures how poverty-awareness can be the subject of teaching in social work programmes, this article offers a qualitative analysis of the reflections being made by a cohort of students about their learning process in a post-academic course. Five common themes are discussed: (i) from recognising micro-aggressions to tackling macro-aggressions; (ii) poverty is an instance of social injustice and requires collective indignation; (iii) notions of commitment and solidarity are ambiguous; (iv) poverty is an instance of social inequality rather than merely social exclusion; and (v) from being heroic agents to social change ‘from within’. Based on these findings, we raise the lessons learned for social work educators. First, they should invite students to reinvigorate the social justice aspirations of social work practices and take a stance in relation to their environment and the wider historical and socio-political circumstances. Secondly, a poverty-aware pedagogy requires collective and long-lasting supervision at the frontline individual, organisational and societal/social policy level. Collective critical reflection and supervision might open up avenues to collectively challenge and change socially unjust rhetoric and practice.
Expanded neuromuscular morbidity in Hodgkin lymphoma after radiotherapy
Authors: Oishi Tatsuya , Kogelschatz Cory J , Young Nathan P , Hoffmann Ernest M , Staff Nathan P , Visscher Sue L , Borah Bijan J , Krauss William E , Arumaithurai Kogulavadanan , Shelly Shahar , Ansell Stephen M , Klein Christopher J
Published: April 2020

Our study aims to quantitate neuromuscular morbidity from radiotherapy in Hodgkin lymphoma including: (i) frequency and (ii) time of onsets for neurological localizations; (iii) degree of disabilities and (iv) number of clinical visits compared to cardiopulmonary Hodgkin lymphoma-radiation complications. Medical records from Mayo Health systems were retrieved; identifying neuromuscular radiation treated Hodgkin lymphoma-complications from 1 January 1994 to 31 December 2016. Of an estimated 4100 post-radiotherapy Hodgkin lymphoma patients, 4.6% (189) were identified with complications. Mean latency to physician visit for symptoms was 23.7 years (range: 1–50). Most commonly identified complications included: head drop 10% (19) with or without myopathy, myopathy 39% (73), plexopathy 29% (54), myelopathy 27% (51) and polyradiculopathy 13% (24). Other findings included benign and malignant nerve sheath tumours 5% (9), phrenic and long thoracic mononeuropathies 7% (14) and compressive spinal meningioma 2% (4). Patients frequently had multiple coexisting complications (single = 76% [144], double = 17% [33], triple = 4% [8], quadruple = 2% [4]). Cardiac 28% (53) and pulmonary 15% (29) complications were also seen in these patients. History of Hodgkin lymphoma was initially overlooked by neurologists (14.3%, 48/336 clinical notes). Hospital and outpatient visits for complications were frequent: neuromuscular 19% (77/411) versus cardiopulmonary 30% (125/411). Testing was largely exclusionary, except when imaging identified secondary malignancy. Modified Rankin score at diagnosis varied: 0–1 (55.8%), 2–3 (5.8%) and 4–5 (38.3%). Neuromuscular complications among post-radiation Hodgkin lymphoma are diverse, occurring in ∼1 of 20 having markedly delayed onsets often eluding diagnosis. Frequent care visits and major morbidity are common. Survivorship recommendations should recognize the diverse neurological complications.
Comparative Analysis of the Chemical Consistency Between the Traditional and Mixed Decoction of Maimendong Decoction by Ultra-Performance Liquid Chromatography Coupled to Quadrupole with Time-of-Flight Mass Spectrometry (UPLC–QTOF-MS)-Based Chemical Profiling Approach
Authors: Yang Lan , Zhu Zhenhua , Qi Zhonghua , Fan Xinsheng , Qian Dawei , Zhang Jingjing , Duan JinAo
Published: April 2020

Take Maimendong Decoction (MMDD), one of the Chinese classic herbal formulas, as an object to evaluate the chemical consistency between traditional decoction and mixed decoction. The ultra-performance liquid chromatography coupled to quadrupole with time-of-flight mass spectrometry-based chemical profiling approach has been utilized. A total of 48 major peaks are detected from these two decoctions under the present chromatographic and mass spectrometry conditions. The results of negative ion mode show nine significant inconsistencies. Liquiritin, ginsenoside Ro and ginsenoside Rg5/Rk1 are detected with higher intensity in traditional preparation sample than the mixed decoction, while licoisoflavone A is higher in mixed decoction samples than the traditional one. The mechanisms involved in the chemical changes were assumed to be anti-inflammation, anti-oxidative stress and so on, suggesting these two different preparation approaches of MMDD may lead to a possibility of discrepant clinical outcomes.
Preferential Infection of α4β7+ Memory CD4+ T Cells During Early Acute Human Immunodeficiency Virus Type 1 Infection
Authors: Tokarev Andrey , McKinnon Lyle R , Pagliuzza Amélie , Sivro Aida , Omole Tosin E , Kroon Eugene , Chomchey Nitiya , Phanuphak Nittaya , Schuetz Alexandra , Robb Merlin L , Eller Michael A , Ananworanich Jintanat , Chomont Nicolas , Bolton Diane L
Published: April 2020

Background

Establishment of persistent human immunodeficiency virus type 1 (HIV-1) reservoirs occurs early in infection, and biomarkers of infected CD4+ T cells during acute infection are poorly defined. CD4+ T cells expressing the gut homing integrin complex α4β7 are associated with HIV-1 acquisition, and are rapidly depleted from the periphery and gastrointestinal mucosa during acute HIV-1 infection.

Methods

Integrated HIV-1 DNA was quantified in peripheral blood mononuclear cells obtained from acutely (Fiebig I–III) and chronically infected individuals by sorting memory CD4+ T-cell subsets lacking or expressing high levels of integrin β7 (β7negative and β7high, respectively). HIV-1 DNA was also assessed after 8 months of combination antiretroviral therapy (cART) initiated in Fiebig II/III individuals. Activation marker and chemokine receptor expression was determined for β7-defined subsets at acute infection and in uninfected controls.

Results

In Fiebig I, memory CD4+ T cells harboring integrated HIV-1 DNA were rare in both β7high and β7negative subsets, with no significant difference in HIV-1 DNA copies. In Fiebig stages II/III and in chronically infected individuals, β7high cells were enriched in integrated and total HIV-1 DNA compared to β7negative cells. During suppressive cART, integrated HIV-1 DNA copies decreased in both β7negative and β7high subsets, which did not differ in DNA copies. In Fiebig II/III, integrated HIV-1 DNA in β7high cells was correlated with their activation.

Conclusions

β7high memory CD4+ T cells are preferential targets during early HIV-1 infection, which may be due to the increased activation of these cells.
First assessment of hoary fox (Lycalopex vetulus) seasonal ovarian cyclicity by non-invasive hormonal monitoring technique
Authors: Candeias Ísis Zanini das , da Motta Lima Caio Filipe , Lemos Frederico Gemesio , Spercoski Katherinne Maria , de Oliveira Claudio Alvarenga , Songsasen Nucharin , de Barros Vaz Guimarães Marcelo Alcindo
Published: April 2020

Reproduction is key to species survival, and reproductive physiology represents a high priority investigative area for conservation biology, as it provides a basic understanding of critical life-history traits, information that is helpful for the establishment of management strategies. Here, we generated knowledge about the reproductive endocrinology of the hoary fox (Lycalopex vetulus), a small canid (2.5–4 kg) endemic to open areas of the Brazilian Cerrado and listed in the Brazilian National List of Endangered species. Specifically, we utilized non-invasive hormone monitoring methods to assess oestrogen and progestagen metabolites from eight female hoary foxes housed in five zoological institutions in the state of São Paulo—Brazil. We observed the elevations of oestrogen and progestagen metabolites between July and September in six of the eight females. No significant evidence of ovarian activity was observed during other months. Two females, who shared the same enclosure, did not show a pattern of reproductive cyclicity. Based on these characteristics, we concluded that captive hoary foxes are seasonal monoestric, with the beginning of the oestrus cycle occurring mainly in July followed by 2 months of the luteal phase when conception does not occur. We suggest the dosage of faecal metabolites of estradiol and progesterone could be used to differentiate the reproductive period from a non-reproductive period in Lycalopex vetulus females, providing relevant information about their reproductive biology that may contribute to species conservation and management strategies, such as increased ex situ reproductive success.
Regadenoson-induced T-wave heterogeneity complements coronary stenosis detection by myocardial perfusion imaging in men and women
Authors: Araujo Silva Bruna , Hauser Thomas H , Nearing Bruce D , Bortolotto Alexandre L , Marum Alexandre A , Tessarolo Silva Fernanda , Medeiros Sofia A , Pedreira Giovanna C , Gervino Ernest V , Verrier Richard L
Published: April 2020

Aims 

We analysed whether incorporating electrocardiographic interlead T-wave heterogeneity (TWH) with myocardial perfusion imaging (MPI) during pharmacologic stress improves detection of flow-limiting lesions (FLL).

Methods and results 

Medical records of all 103 patients at our institution who underwent stress testing with regadenoson (0.4 mg IV bolus) within 3 months of coronary angiography from September 2017 to March 2019 were studied. Cases (N = 59) had angiographically significant FLL (≥50% of left main or ≥70% of other epicardial coronary arteries ≥2 mm in diameter); controls (N = 44) were normal or had non-FLL. TWH, i.e., interlead splay of T waves, was assessed from precordial leads V4–6 by second central moment analysis. Maximum TWHV4–6 levels during regadenoson stress were 68% higher in cases than in controls (P < 0.0001). TWHV4–6 generated areas under the receiver-operating characteristic (ROC) curve of 0.79 in men (P < 0.0001) and 0.71 in women (P = 0.007). In men, the ROC-guided 54-µV TWHV4–6 cut-point for FLL produced adjusted odds of 7.3 [95% confidence interval (CI): 1.3–41.5, P = 0.03], 79% sensitivity, and 78% specificity. In women, the ROC-guided 35-µV TWHV4–6 cut-point produced adjusted odds of 4.5 (95% CI: 1.1–18.9, P = 0.04), 84% sensitivity, and 52% specificity. Adding TWHV4–6 to MPI determinations reduced false-positive results by 70%, more than doubled true-negative results, and improved adjusted odds ratio to 6.8 (95% CI: 2.2–21.4, P = 0.001) with specificity of 78% in men and 86% in women.

Conclusion 

This observational study is the first to demonstrate the benefit of combining TWHV4–6 with MPI to enhance FLL detection during MPI with regadenoson in both men and women.
The electrocardiographic ‘triangular QRS-ST-T waveform’ pattern: a marker of severe haemodynamic compromise in Takotsubo syndrome—a case report
Authors: Joki Tuukka , Nikus Kjell , Laukkanen Jari
Published: April 2020

Background

Takotsubo cardiomyopathy is characterized by transient regional systolic dysfunction of the left ventricle, mimicking myocardial infarction. Although systolic left ventricular (LV) function normalizes in most cases, the outcome is not always favourable. Recently, a rare electrocardiogram (ECG) finding, lambda wave ST elevation or ‘triangular QRS-ST-T waveform’, was suggested as a possible marker of poor outcome in Takotsubo patients

Case summary

After a brief episode of chest pain and shortness of breath, a 67-year-old woman developed cardiogenic shock. Her resting ECG showed widespread ST elevations, which soon evolved into a pattern of triangular QRS-ST-T waveforms in the inferior leads and V3–V6. Emergent coronary angiography was normal. The ejection fraction was 20% with apical ballooning and an LV thrombus. At 1-month follow-up, the patient was asymptomatic and the ECG showed only T-wave inversions.

Discussion

The triangular QRS-ST-T waveform ECG pattern has recently been introduced as a high-risk marker in the Takotsubo syndrome.
Measure what matters: Counts of hospitalized patients are a better metric for health system capacity planning for a reopening
Authors: Kashyap Sehj , Gombar Saurabh , Yadlowsky Steve , Callahan Alison , Fries Jason , Pinsky Benjamin A , Shah Nigam H
Published: April 2020

Objective

Responding to the COVID-19 pandemic requires accurate forecasting of health system capacity requirements using readily available inputs. We examined whether testing and hospitalization data could help quantify the anticipated burden on the health system given shelter-in-place (SIP) order.

Materials and Methods

16,103 SARS-CoV-2 RT-PCR tests were performed on 15,807 patients at Stanford facilities between March 2 and April 11, 2020. We analyzed the fraction of tested patients that were confirmed positive for COVID-19, the fraction of those needing hospitalization, and the fraction requiring ICU admission over the 40 days between March 2nd and April 11th 2020.

Results

We find a marked slowdown in the hospitalization rate within ten days of SIP even as cases continued to rise. We also find a shift towards younger patients in the age distribution of those testing positive for COVID-19 over the four weeks of SIP. The impact of this shift is a divergence between increasing positive case confirmations and slowing new hospitalizations, both of which affects the demand on health systems.

Conclusion

Without using local hospitalization rates and the age distribution of positive patients, current models are likely to overestimate the resource burden of COVID-19. It is imperative that health systems start using these data to quantify effects of SIP and aid reopening planning.
Solid-Phase Extraction Combined with Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry for the Determination of 5 Trace Nitro-Polycyclic Aromatic Hydrocarbons in Barbecued Foods
Authors: Qu Lingli , Yu Huan , Yin Shuo , Li Yongxin , Sun Chengjun
Published: April 2020

Background

Nitrated polycyclic aromatic hydrocarbons (nitro-PAHs) are the derivatives of polycyclic aromatic hydrocarbon which are direct mutagens and carcinogens to human. Nitro-PAHs can be produced in the process of food barbecuing/grilling. At present, there are few studies for the determination of nitro-PAHs in food.

Objective

To assess the effect of barbecued food to human health, we have established a method for the determination of 5 nitro-PAHs in barbecued foods.

Methods

The target nitro-PAHs were extracted with the mixture of methanol/acetone and then purified with an HLB SPE cartridge and finally analyzed by ultra-high-performance liquid chromatography-tandem mass spectrometry. Two pairs of target multiple reaction monitoring (MRM) ion pairs have been successfully identified for the target nitro-PAHs, and confirmed by high-resolution mass spectrometry to explore their formation mechanism.

Results

The method had linear ranges of 2.0–500 µg/L (except 1-nitronaphthalene 20–5000 µg/L) with the correlation coefficients greater than 0.995. The extraction recoveries were between 70.1% and 85.6% with the relative standard deviations less than 10.0%. The limits of detection of the method were less than 0.60 µg/L (except 1-nitronaphthalene 6.0 µg/L).

Conclusions

The method has been successfully applied to the analysis of 5 nitro-PAHs in barbecued foods. 1-nitronaphthalene, 1,8-dinitropyrene , 1-nitropyrene were detected in some charcoal grilled samples with the contents of 1.35–12.9 µg/kg. 1,8-Dinitropyrene was detected in some oil-fried samples with the contents of 2.12–5.12 µg/kg.

Highlights

This work presents an ultra-high-performance liquid chromatography-tandem mass spectrometry method for the determination of 5 nitro-PAHs in barbecued foods for the first time. The method has been successfully applied to the analysis of 5 nitro-PAHs in various barbecued foods and the nitro-PAHs were detected in some barbecued food samples. The mechanism of mass spectrometric decomposition of nitro-PAHs was investigated as well.
Dietary supplementation of artificial sweetener and capsicum oleoresin as a strategy to mitigate the negative consequences of heat stress on pig performance
Authors: Biggs Morgan E , Kroscher Kellie A , Zhao Lidan D , Zhang Zhenhe , Wall Emma H , Bravo David M , Rhoads Robert P
Published: April 2020

Pigs exposed to elevated ambient temperatures exhibit reduced daily gain, alterations in muscle and fat deposition, and decreased health. Negative aspects of gastrointestinal (GI) function, integrity, and permeability also occur. High-intensity sweeteners can ameliorate the negative effects of heat stress (HS) by increasing GI glucagon-like peptide-2 production while capsicum oleoresin has been shown to reduce inflammatory response. The effects of an artificial high-intensity sweetener and capsicum oleoresin (CAPS-SUC; TakTik X-Hit, Pancosma, Switzerland) on growth performance of pigs were examined. Forty-eight pigs (12 wk of age, 43.2 ± 4.3 kg) were assigned to six treatments: thermoneutral conditions (21 ± 1.1 °C; 40% to 70% relative humidity) fed ad libitum with (TN+) or without supplement (TN−), heat stress (35 ± 1 °C; 20% to 40% relative humidity) fed ad libitum with (HS+) or without supplement (HS−), and thermoneutral conditions pair-fed to HS intake with (PFTN+) or without supplement (PFTN−). Supplementation (0.1 g/kg feed) began 2 d prior to the 3-d environmental treatment period. Body weights (BWs) and blood samples were collected on days −1 and 3. Rectal temperature (RT) and respiration rate (RR) were measured thrice daily and the feed intake (FI) was recorded daily. Intestinal sections were collected for histology. Pigs in HS conditions exhibited increased RT (~1.2 °C) and RR (~2.7-fold) compared with TN and PFTN groups (P < 0.01). HS+ animals had increased RR when compared with HS− animals (P < 0.02). Heat stress decreased FI compared with TN. HS and PFTN decreased (P < 0.05) average daily gain compared with TN. Supplement did not alter the BW gain. HS and PFTN decreased (P < 0.05) Gain:Feed compared with TN during environmental treatment. Supplementation with CAPS–SUC increased Gain:Feed by 0.12 (P < 0.05). Circulating glucose concentrations tended to decrease in CAPS–SUC vs. non-supplemented HS and PFTN animals (P ≤ 0.1). Circulating insulin concentrations as well as monocyte count increased in HS compared with PFTN (P < 0.04) but did not differ from TN and likely linked to altered FI. CAPS–SUC increased basophil count (P < 0.02), irrespective of environment. Ileal villus height tended to decrease during HS and PFTN compared with TN (P < 0.08), indicating an effect of intake. Overall, CAPS–SUC supplementation increased pig feed efficiency and may improve immune response.
Liquidity Insurance with Market Information
Authors: Iovino Luigi
Published: April 2020

This paper studies how market signals—such as stock prices—can help alleviate the severity of the asymmetric information problem in credit and liquidity management. Asymmetric information hinders the ability of borrowers (firms, investment banks, etc.) to undertake profitable investment opportunities and to insure themselves against liquidity shocks. I show that on the equilibrium path creditors do not learn anything from market signals because they can use a menu of contracts to screen the different types of borrowers. However, by conditioning liquidity insurance on ex post price signals, creditors are able to provide the borrowers with better incentives for truth telling. At the same time, prices depend on the liquidity that creditors offer to the borrowers. This two-way feedback impacts the design of the optimal contract and potentially generates multiple equilibria in financial markets.
DNA Barcoding of Simulium asakoae (Diptera: Simuliidae) From Northern Thailand
Authors: Low Van Lun , Srisuka Wichai , Saeung Atiporn , Tan Tiong Kai , Ya’cob Zubaidah , Yeong Yze Shiuan , Takaoka Hiroyuki
Published: April 2020

Previous studies suggested the presence of species complex in the so-called Simulium asakoae Takaoka & Davies (Diptera: Simuliidae) in Thailand due to its high morphological variability and genetic divergence. To investigate whether the true S. asakoae is present in Thailand, we performed a detailed morphological identification of S. asakoae and compared its DNA barcodes with the morphospecies S. asakoae from Myanmar and the typical S. asakoae from Malaysia. Phylogenetic analysis revealed the Thai materials analyzed in this study were indeed genetically similar with those from Myanmar and Malaysia, though genetic distances 0–2.27% were observed. We tentatively regard this divergence as intraspecific variation, and the automatic barcode gap discovery analysis further supports them as a single species.