bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of Feeding Shapes Swimming Kinematics of Barnacle Naupliar Larvae: A Comparison between Trophic Modes
Authors: Wong J Y , Chan B K K , Chan K Y K
Published: April 2020

Synopsis

A central goal in evolutionary biology is connecting morphological features with ecological functions. For marine invertebrate larvae, appendage movement determines locomotion, feeding, and predator avoidance ability. Barnacle larvae are morphologically diverse, and the morphology of non-feeding lecithotrophic nauplii are distinct from those that are planktotrophic. Lecithotrophic larvae have a more globular body shape and simplified appendages when compared with planktotrophs. However, little is known about whether and how such morphological changes affect kinematics, hydrodynamics, and ecological functions. Here, we compared the nauplii kinematics and hydrodynamics of a lecithotrophic Rhizocephalan species, Polyascus planus, against that of the planktotrophic nauplii of an intertidal barnacle, Tetraclita japonica. High-speed, micro-particle image velocimetry analysis showed that the Polyascus nauplii swam faster and had higher amplitude and more synchronous appendage beating than the Tetraclita nauplii. This fast swimming was accompanied by a faster attenuation of induced flow with distance, suggesting reduced predation risk. Tetraclita nauplii had more efficient per beat cycles with less backward displacement during the recovery stroke. This “anchoring effect” resulted from the anti-phase beating of appendages. This movement, together with a high-drag body form, likely helps direct the suction flow toward the ventral food capturing area. In sum, the tradeoff between swimming speed and predation risks may have been an important factor in the evolution of the observed larval forms.
Study on the correlation between BMPR1B protein in sheep blood and reproductive performance
Authors: Zhang Xiaoyan , Zhang Liping , Sun Weibo , Lang Xia , Wu Jianping , Zhu Caiye , Jia Jianlei , Jin Jinpen , La Younfu , Casper David P
Published: April 2020

Sheep reproductive performance is one of the important economic traits in sheep farming. The bone morphogenetic protein receptor 1B (BMPR1B) gene and protein may play an important role in sheep fertility. This study was to investigate the association of blood BMPR1B protein expression with reproductive performance in sheep. Mongolian sheep with single and twin births and polytocous Small Tail Han sheep were selected due to differences in birth numbers. The BMPR1B mRNA in sheep blood was measured by a reverse transcription-polymerase chain reaction as well as the BMPR1B protein was measured by enzyme-linked immunosorbent assay in blood samples of Mongolian and Small Tail Han sheep. The results demonstrated that blood BMPR1B concentration in Mongolian sheep with twin birth was higher (P < 0.05) than Small Tail Han sheep and Mongolian sheep with single birth. The protein concentration in the anestrus season was higher (P < 0.045) than those in the estrus season for both Mongolian and Small Tail Han sheep. Moreover, BMPR1B concentration in Mongolian sheep increased (P < 0.05) at the age of 6 to 12 mo and that in Small Tail Han sheep increased (P < 0.05) at the age of 3 to 6 mo. The result indicates that the increase in BMPR1B protein concentrations in the blood of Mongolian ewes and Small Tail Han ewes may be beneficial to follicular development, but too high or too low of this blood protein concentration in Mongolian and Small Tail Han sheep is not conducive to ovulation.
Mobility and Dispersal of Two Cosmopolitan Stored-Product Insects Are Adversely Affected by Long-Lasting Insecticide Netting in a Life Stage-Dependent Manner
Authors: Wilkins Rachel V , Zhu Kun Yan , Campbell James F , Morrison William R
Published: April 2020

Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae) and Trogoderma variabile Ballion (Coleoptera: Dermestidae) are two stored-product insects that cause extensive damage to a variety of postharvest commodities. Long-lasting insecticide-incorporated netting (LLIN), commonly used to control vector-borne diseases in tropical regions, has only been recently studied in an agricultural setting. While prior research showed that LLIN was successful against stored-product beetles, little is known about differential susceptibility among stored-product insect life stages. The aim of this study was to evaluate LLIN efficacy against immature T. castaneum and T. variabile compared with adults. Movement and dispersal ability were evaluated after exposure to LLIN or an untreated, control netting. For the movement assay, video-tracking software recorded the postexposure effects of LLIN on distance traveled and velocity of the insects in 2-h trials. For the dispersal assay, insects were exposed to the netting then released into one end of a PVC pipe and allowed 48 h to disperse to a novel food patch located at the opposite end of the pipe. Our study found that movement and dispersal ability of T. variabile and T. castaneum are significantly reduced, often by multiple-fold, after LLIN exposure, with the larval stage of each species more tolerant to the insecticide netting than adults. These results indicate that LLIN is a promising tool for use in intercepting immigrating insects of different life stages in food facilities to protect stored products.
Collecting and Monitoring for Northern Fowl Mite (Acari: Macronyssidae) and Poultry Red Mite (Acari: Dermanyssidae) in Poultry Systems
Authors: Murillo Amy C , Mullens Bradley A
Published: April 2020

The two most economically important poultry ectoparasites are the northern fowl mite, Ornithonyssus sylviarum (Canestrini and Fanzago), and the poultry red mite, Dermanyssus gallinae (De Geer). Both mites are obligate blood feeders but differ in where they reside. Sampling methods thus focus on-host, especially the vent feathers, for northern fowl mite and off-host, especially cracks and crevices near the nighttime roosting areas, for poultry red mite. Much remains unknown, however, about the basic biology and ecology of both mites. Here we discuss mite detection, quantification, and decision making and provide thoughts on future directions for research.
Real-world use of temsirolimus in Japanese patients with unresectable or metastatic renal cell carcinoma: recent consideration based on the results of a post-marketing, all-case surveillance study
Authors: Sugiyama Shigeru , Sato Kazuo , Shibasaki Yoshiyuki , Endo Yutaka , Uryu Taku , Toyoshima Yasuharu , Oya Mototsugu , Miyanaga Naoto , Saijo Nagahiro , Gemma Akihiko , Akaza Hideyuki
Published: April 2020

Objective

A prospective, observational, post-marketing surveillance was conducted to assess the safety and effectiveness of temsirolimus in patients with renal cell carcinoma in Japan.

Methods

Patients prescribed temsirolimus for advanced renal cell carcinoma were registered and received temsirolimus (25 mg weekly, intravenous infusion for 30–60 minutes) in routine clinical settings (observation period: 96 weeks).

Results

Among 1001 patients included in the safety analysis data set (median age, 65.0 years; men, 74.8%; Eastern Cooperative Oncology Group performance status 0 or 1, 69.6%), 778 (77.7%) reported adverse drug reactions. The most common (≥10%) all-grade adverse drug reactions were stomatitis (26.7%), interstitial lung disease (17.3%) and platelet count decreased (11.1%). The incidence rate of grade ≥3 interstitial lung disease was 4.5%. The onset of interstitial lung disease was more frequent after 4–8 weeks of treatment or in patients with lower Eastern Cooperative Oncology Group performance status (21.6% for score 0 vs 8.3% for score 4, P < 0.001). Among 654 patients in the effectiveness analysis data set, the response and clinical benefit rates were 6.7% (95% confidence interval 4.9–8.9) and 53.2% (95% confidence interval 49.3–57.1), respectively. The median progression-free survival was 18.3 weeks (95% confidence interval 16.9–21.1).

Conclusions

The safety and effectiveness profile of temsirolimus observed in this study was similar to that observed in the multinational phase 3 study. The results are generalizable to the real-world scenario at the time of this research, and safety and effectiveness of temsirolimus as a subsequent anticancer therapy for renal cell carcinoma warrants further investigation. (ClinicalTrials.gov identifier NCT01210482, NCT01420601).
The effects of COVID-19 pandemic on the provision of urgent surgery: a perspective from the USA
Authors: Cheeyandira Abhiman
Published: April 2020

Corona virus pandemic has affected all the 50 states in the USA. States such as NY, CA and WA being the most affected. According to the Centers for Disease Control and Prevention (CDC) website, as of 28 March 2020, the total number of cases in the USA is over 103 300 and number of deaths to 1668. In the coming weeks, COVID-19 rates are expected to begin skyrocketing and hit a peak in late April/May/June given lessons learned from China, Italy and others.

COVID-19 has been declared a pandemic by the World Health Organization (WHO) as confirmed cases approach 575 444 patients with 26 654 deaths across over 160 countries, as of 28 March 2020.

There is a lot of impact on management of the urgent and emergent cases. This article highlights the changes that are being made in delivering urgent and emergent surgical care during the pandemic.
Limiting the shock acceleration of cosmic ray protons in the ICM
Authors: Wittor D , Vazza F , Ryu D , Kang H
Published: April 2020

Observations of large-scale radio emissions prove the existence of shock accelerated cosmic ray electrons in galaxy clusters, while the lack of detected γ-rays limits the acceleration of cosmic ray protons in galaxy clusters. This challenges our understanding of how diffusive shock acceleration works. In this work, we couple the most updated recipes for shock acceleration in the intracluster medium to state-of-the-art magnetohydrodynamical simulations of massive galaxy clusters. Furthermore, we use passive tracer particles to follow the evolution of accelerated cosmic rays. We show that when the interplay between magnetic field topology and the feedback from accelerated cosmic rays is taken into account, the latest developments of particle acceleration theory give results that are compatible with observational constraints.
Evolution of Human Brain Size-Associated NOTCH2NL Genes Proceeds toward Reduced Protein Levels
Authors: Lodewijk Gerrald A , Fernandes Diana P , Vretzakis Iraklis , Savage Jeanne E , Jacobs Frank M J
Published: April 2020

Ever since the availability of genomes from Neanderthals, Denisovans, and ancient humans, the field of evolutionary genomics has been searching for protein-coding variants that may hold clues to how our species evolved over the last ∼600,000 years. In this study, we identify such variants in the human-specific NOTCH2NL gene family, which were recently identified as possible contributors to the evolutionary expansion of the human brain. We find evidence for the existence of unique protein-coding NOTCH2NL variants in Neanderthals and Denisovans which could affect their ability to activate Notch signaling. Furthermore, in the Neanderthal and Denisovan genomes, we find unusual NOTCH2NL configurations, not found in any of the modern human genomes analyzed. Finally, genetic analysis of archaic and modern humans reveals ongoing adaptive evolution of modern human NOTCH2NL genes, identifying three structural variants acting complementary to drive our genome to produce a lower dosage of NOTCH2NL protein. Because copy-number variations of the 1q21.1 locus, encompassing NOTCH2NL genes, are associated with severe neurological disorders, this seemingly contradicting drive toward low levels of NOTCH2NL protein indicates that the optimal dosage of NOTCH2NL may have not yet been settled in the human population.
Proteasome inhibition as a therapeutic approach in atypical teratoid/rhabdoid tumors
Authors: Morin Andrew , Soane Caroline , Pierce Angela , Sanford Bridget , Jones Kenneth L , Crespo Michele , Zahedi Shadi , Vibhakar Rajeev , Mulcahy Levy Jean M
Published: April 2020

Background

Atypical teratoid/thabdoid tumor (AT/RT) remains a difficult-to-treat tumor with a 5-year overall survival rate of 15%–45%. Proteasome inhibition has recently been opened as an avenue for cancer treatment with the FDA approval of bortezomib (BTZ) in 2003 and carfilzomib (CFZ) in 2012. The aim of this study was to identify and characterize a pre-approved targeted therapy with potential for clinical trials in AT/RT.

Methods

We performed a drug screen using a panel of 134 FDA-approved drugs in 3 AT/RT cell lines. Follow-on in vitro studies used 6 cell lines and patient-derived short-term cultures to characterize selected drug interactions with AT/RT. In vivo efficacy was evaluated using patient derived xenografts in an intracranial murine model.

Results

BTZ and CFZ are highly effective in vitro, producing some of the strongest growth-inhibition responses of the evaluated 134-drug panel. Marizomib (MRZ), a proteasome inhibitor known to pass the blood–brain barrier (BBB), also strongly inhibits AT/RT proteasomes and generates rapid cell death at clinically achievable doses in established cell lines and freshly patient-derived tumor lines. MRZ also significantly extends survival in an intracranial mouse model of AT/RT.

Conclusions

MRZ is a newer proteasome inhibitor that has been shown to cross the BBB and is already in phase II clinical trials for adult high-grade glioma (NCT NCT02330562 and NCT02903069). MRZ strongly inhibits AT/RT cell growth both in vitro and in vivo via a moderately well-characterized mechanism and has direct translational potential for patients with AT/RT.
Democracy and the Politics of Coronavirus: Trust, Blame and Understanding
Authors: Flinders Matthew
Published: April 2020

This article explores the relationship between crises and democracy through a focus on the unfolding coronavirus pandemic. Its central argument is that to interpret the current pandemic purely in terms of its epidemiology and public health implications risks overlooking its potentially more significant socio-political consequences. This is because the challenges posed by the coronavirus crisis have themselves become overlaid or layered-upon a pre-existing set of concerns regarding the performance, efficiency and capacity of democratic political structures. The aim of this article is to try and understand and warn against what might be termed a rather odd form of cross-contamination whereby the cynicism, negativity and frustration concerning politicians, political processes and political institutions that existed before the coronavirus outbreak is allowed to direct, define and automatically devalue how democratic structures are subsequently judged in terms of how they responded to the challenge. As such, this article focuses on the link between the Coronavirus crisis and the democratic crisis; or, more precisely, the risk that the Coronavirus crisis may mutate into and fuel a broader crisis of democracy.
Prediction of school-age IQ, academic achievement, and motor skills in children with positional plagiocephaly
Authors: Wallace Erin R , Ola Cindy , Leroux Brian G , Speltz Matthew L , Collett Brent R
Published: April 2020

Introduction

Children with positional plagiocephaly and/or brachycephaly (PPB) are at risk of early developmental delay, but little is known about early life factors associated with school-age neurodevelopment. This study examined associations of demographic characteristics, prenatal risk factors and early neurodevelopment assessment with school-age IQ, academic performance, and motor development in children with PPB.

Methods

The study sample consisted of 235 school-age children with PPB followed since infancy. Outcome measures included IQ using the Differential Ability Scales-Second Edition, academic achievement as measured by the Wechsler Individualized Achievement Tests-Third Edition), and motor function using the Bruininks-Oseretsky Test of Motor Proficiency, Second Edition. Linear regression was used to examine the incremental improvement of model fit of demographics, prenatal and early life characteristics, severity of PPB, and neurodevelopment at ages 7, 18, and 36 months as measured by the Bayley-3 on school-age scores.

Results

Mean age at school-age assessment was 9.0 years. Adjusted r2 for demographic, prenatal, and early life risk factors ranged from 0.10 to 0.22. Addition of PPB severity and Bayley-3 measures at ages 7 and 18 months did not meaningfully change model fit. Adjusted r2 after inclusion of Bayley-3 at 36 months ranged from 0.35 to 0.41.

Conclusion

This study suggests that PPB severity and very early life neurodevelopment have little association with school-age neurodevelopment above and beyond demographic and early life risk factors. However, preschool-age neurodevelopmental assessment may still be useful in identifying children with PPB at risk for delay and who may benefit from early intervention.
Double contrast-enhanced ultrasonography of a small intestinal neuroendocrine tumor: a case report of a recommendable imaging modality
Authors: Zhao Jie-ying , Zhuang Hua , Luo Yuan , Su Ming-gang , Xiong Mo-li , Wu Yu-ting
Published: April 2020

A 57-year-old male presenting with spontaneously relieved abdominal cramp and distension was admitted to the West China Hospital. The diagnosis remained unclear after colonoscopy and computed tomography. Double contrast-enhanced ultrasonography was then performed and a neoplasm in the small intestine was suspected, supported by a thin-section computed tomography and positron emission tomography/computed tomography. This was confirmed pathologically after surgery to be a small intestinal G1 neuroendocrine tumor. Surgery was performed to remove approximately 25 cm of small bowel and a 3-cm solid mass located in the mesentery. The patient had a complete recovery and was tumor-free at the final follow-up. Small intestinal tumors including neuroendocrine tumors have always posed a diagnostic challenge. This case indicated that double contrast-enhanced ultrasonography is feasible in detection of small intestinal neuroendocrine tumors, and it may be an advisable approach assisting diagnosis of small intestinal tumors.
The Skewness of the Stock Market over Long Horizons
Authors: Neuberger Anthony , Payne Richard
Published: April 2020

Higher moments of long-horizon returns are important for asset pricing but are hard to measure accurately using standard techniques. We provide theory showing that short-horizon (e.g., daily) returns can be used to construct precise estimates of long-horizon (e.g., annual) moments without making strong assumptions about the data-generating process. Skewness comprises two components: skewness of short-horizon returns and a leverage effect, that is, covariance between variance and lagged returns. We provide similar results for kurtosis. An application to U.S. stock index returns shows that skew is large and negative and attenuates only slowly as one moves from monthly to multiyear horizons.
Sentiment in Central Banks’ Financial Stability Reports*
Authors: Correa Ricardo , Garud Keshav , Londono Juan M , Mislang Nathan
Published: April 2020

We use the text of financial stability reports (FSRs) published by central banks to analyze the relation between the sentiment they convey and the financial cycle. We construct a dictionary tailored specifically to a financial stability context, which classifies words as positive or negative based on the sentiment they convey in FSRs. With this dictionary, we construct financial stability sentiment (FSS) indexes for thirty countries between 2005 and 2017. We find that central banks’ financial stability communications are mostly driven by developments in the banking sector. Moreover, the sentiment captured by the FSS index explains movements in financial cycle indicators related to credit, asset prices, systemic risk, and monetary policy rates. Finally, our results show that the sentiment in central banks’ communications is a useful predictor of banking crises—a one percentage point increase in FSS is followed by a twenty-nine percentage point increase in the probability of a crisis.
PROCEDURES TO MEASURE MEAN AMBIENT DOSE EQUIVALENT RATES USING ELECTRET ION CHAMBERS
Authors: Leontaris F , Boziari A , Clouvas A , Kolovou M , Guilhot J
Published: April 2020

The capabilities of electret ion chambers (EICs) to measure mean ambient dose equivalent rates were investigated by performing both laboratory and field studies of their properties. First, EICs were ‘calibrated’ to measure ambient gamma dose equivalent in the Ionizing Calibration Laboratory of the Greek Atomic Energy Commission. The EICs were irradiated with different gamma photon energies and from different angles. Calibration factors were deduced (electret’s voltage drop due to irradiation in terms of ambient dose equivalent). In the field studies, EICs were installed at eight locations belonging to the Greek Early Warning System Network (which is based on Reuter-Stokes ionization chambers) for three periods, averaging 5 months each. In the same locations, in situ gamma spectrometry measurements were performed with portable germanium detectors. Gamma ambient dose equivalent rates were deduced by the in situ gamma spectrometry measurements and by soil sample analysis. The mean daily electret potential drop (in Volts) was compared with the mean daily ambient dose equivalent, measured with a portable HPGe detector and Reuter-Stokes high-pressure ionization chambers. From these measurements, ‘field’ calibration factors (electret’s voltage drop due to gamma radiation in terms of ambient dose equivalent) were deduced and found in very good agreement with the values deduced in Laboratory. The influence of cosmic radiation and the intrinsic voltage loss when performing long-term environmental gamma measurements with EICs, was estimated.
Industrial possibilities and false necessity: rethinking production, employment and labor dynamics in the global economy1
Authors: Herrigel Gary
Published: April 2020

Much of contemporary comparative political–economic thinking about global industrial production accepts the following claims (a) that manufacturing is destined to leave rich political economies for lower wage ones; (b) that global industrial production is hierarchically structured with higher value operations concentrated in the rich countries and intermediate component production distributed across increasingly specialized clusters in emerging political economies; (c) that digital technological advance, automation and massive platform firms are ushering in a new historical regime of capitalism that is generating high rates of inequality and threatens to thoroughly degrade work for less educated and less skilled workers all over the globe. This article argues that these three arguments are deeply flawed because they present only a partial picture of contemporary global industrial dynamics. They exclude from view many concurrent developments that suggest that alternative political and economic practices and trajectories are possible. And they downplay the role that politics and struggle have played and can play in the constitution of the political economy. By deconstructing these three arguments, this article attempts to recover possibility from the constraints of false necessity in thinking about global industrial production dynamics.
Legislated Corporate Social Responsibility (CSR) in India: The Law and Practicalities of its Compliance
Authors: Jumde Akanksha , du Plessis Jean
Published: April 2020

When India enacted the Companies Act, 2013, it became one of the few countries of the world to make Corporate Social Responsibility (CSR), a legal obligation for a large number of Indian companies. Using a comprehensive analysis of companies’ CSR disclosures and the interviews of relevant stakeholders, this article provides a bird’s-eye view on the major issues plaguing the current regulatory framework on CSR in India. In addition, this article highlights the major differences between privately owned and government companies on their motivations, approaches and challenges to the implementation and enforcement of CSR law of India. This article finds that the Indian CSR regulations are excessively broad and provide wide flexibilities that are possibly being misused, and hence, need legislative amendments to make them more concise, and improve accountability and transparency. From a broader corporate law perspective, this article finds that while the current company law in India may have adopted a more stakeholder-centric approach by its construction, the approach of many companies towards the enforcement and implementation of CSR and the law remains essentially shareholder centric. In light of the above observations, the article suggests that the existing regulatory framework needs to be strengthened with several legislative measures such as stricter auditing and monitoring measures for third-party implementing agencies and pre-and post-project impact assessment mechanisms.
Transmission and evolutionary dynamics of human coronavirus OC43 strains in coastal Kenya investigated by partial spike sequence analysis, 2015–16
Authors: Abidha Carol A , Nyiro Joyce , Kamau Everlyn , Abdullahi Osman , Nokes David James , Agoti Charles N
Published: April 2020

Human coronavirus OC43 (HCoV-OC43) is a major contributor to seasonal outbreaks of acute respiratory illness (ARI). The origins of locally circulating HCoV-OC43 strains and characteristics of their genetic diversity are unknown for most settings despite significance to effective HCoV control strategies. Between December 2015 and June 2016, we undertook ARI surveillance in coastal Kenya in nine outpatients and one inpatient health facility (HF). Ninety-two patient samples tested HCoV-OC43 positive and forty (43.5%) were successfully sequenced in spike (S) gene region (2,864 long, ∼70%). Phylogenetic analysis confirmed co-circulation of two distinct HCoV-OC43 clades that closely clustered with genotype G (n = 34, 85%) and genotype H (n = 6, 15%) reference strains. Local viruses within the same clade displayed low genetic diversity yielding identical sequences in multiple HF. Furthermore, the newly sequenced Kenyan viruses showed close phylogenetic relationship to other contemporaneous sampled strains (2015–16) including those originating from distant places (e.g. USA and China). Using a genetic similarity threshold of 99.1 per cent at nucleotide level, the HCoV-OC43 strains sampled globally between 1967 and 2019 fell into nine sequence clusters. Notably, some of these clusters appeared to have become extinct, or occurred only sporadically in a few geographical areas while others persisted globally for multiple years. In conclusion, we found that HCoV-OC43 strains spread rapidly both locally and across the globe with limited genetic evolution in the spike gene. Full-genome sequences that are spatio-temporally representative are required to advance understanding of the transmission pathways of this important human respiratory pathogen.
Multivariate analyses of codon usage of SARS-CoV-2 and other betacoronaviruses
Authors: Gu Haogao , Chu Daniel K W , Peiris Malik , Poon Leo L M
Published: April 2020

Coronavirus disease 2019 (COVID-19) is a global health concern as it continues to spread within China and beyond. The causative agent of this disease, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), belongs to the genus Betacoronavirus, which also includes severe acute respiratory syndrome-related coronavirus (SARSr-CoV) and Middle East respiratory syndrome-related coronavirus (MERSr-CoV). Codon usage of viral genes are believed to be subjected to different selection pressures in different host environments. Previous studies on codon usage of influenza A viruses helped identify viral host origins and evolution trends, however, similar studies on coronaviruses are lacking. In this study, we compared the codon usage bias using global correspondence analysis (CA), within-group CA and between-group CA. We found that the bat RaTG13 virus best matched the overall codon usage pattern of SARS-CoV-2 in orf1ab, spike and nucleocapsid genes, while the pangolin P1E virus had a more similar codon usage in membrane gene. The amino acid usage pattern of SARS-CoV-2 was generally found similar to bat and human SARSr-CoVs. However, we found greater synonymous codon usage differences between SARS-CoV-2 and its phylogenetic relatives on spike and membrane genes, suggesting these two genes of SARS-CoV-2 are subjected to different evolutionary pressures.
Endosomal trafficking in human cortical neurons downstream of RTK signaling is defective in Tuberous Sclerosis
Authors: Onesto Massimo M. , Catlett Timothy S. , Gomez Timothy M.
Published: April 2020

Growth cones at the distal tips of developing axons transduce extracellular chemoattractants and repellents into guided motility throughout developing organisms. Repulsive factors can produce abrupt cytoskeletal contraction in growth cones, coupled with internalization of plasma membrane in a process called “collapse”. Using neurons differentiated from induced pluripotent stem cells (iPSCs), we examine mechanisms that control normal human cortical neuron development and dysregulation of these signals in Tuberous Sclerosis Complex (TSC). TSC is a neurodevelopmental disorder caused by pathological variants of the genes encoding TSC1 or TSC2, resulting in the formation of cortical tubers and improper neuronal connectivity. These defects likely contribute to TSC neuropathology such as cognitive deficits, autism, and epilepsy. Using immunoassays and live cell imaging, our lab has shown that TSC2+/− neurons fail to respond the chemorepellent EphrinA1 in several quantifiable measures. TSC2+/− growth exhibit reduced rapid membrane internalization via macropinocytosis and show less elevated receptor tyrosine kinase signaling, as well as reduced cytoskeletal contraction and F‐actin depolymerization. Studies have shown that endocytosis and trafficking of receptor tyrosine kinase (RTK) signaling endosomes are required to elicit a proper guidance response. Immunoassays and live endosome imaging in TSC2+/− growth cones suggest normal EphrinA1‐EphA4 internalization, but defective endosome trafficking of EphrinA1 from early endosomes to late endosomes. Other experiments implicate defects in growth cone microtubule dynamics, a poorly understood but essential process for proper endosome trafficking and guidance cue responses. This research aims to improve our understanding of RTK endosome trafficking and show how defects in these processes can lead to neurodevelopmental disorders.
Anomalous Muscles and Nerves in the Hand of a 94‐year‐old Cadaver‐A Case Report
Authors: Nation Haley , Jeong Seongwoo , Jeong Shinyeong , Occhialini Annette
Published: April 2020

Introduction

During an anatomical dissection of the distal upper extremities, numerous muscular and nervous anomalies were found in the forearm and hand of a 94‐year‐old cadaver. These anomalies are clinically relevant with regard to medical or surgical interventions.

Presentation of Case

The presence of a “flexor digiti minimi longus” muscle was observed passing through Guyon’s canal; to our knowledge this passageway has never been previously reported. An aberrant first lumbrical with three origins was noted. Additionally, numerous atypical nerves were found innervating the hand; the dorsal branch of the ulnar nerve contributed to cutaneous innervation of the palm of the hand (Kaplan’s anastomosis), the superficial ulnar nerve provided muscular innervation to the flexor digiti minimi brevis muscle, and two connections between the common palmar digital branches of the median and superficial ulnar nerves were observed (Berrettini anastomosis).

Discussion

Here, we describe an extranumerary muscle associated with the hypothenar group of muscles. We also describe unusual origins of the first lumbrical muscle, and atypical cutaneous and muscular innervation to the palm of the hand.

Conclusion

Clinically, understanding the existence of these anatomical variations may influence medical care or surgical procedures.
Repurposing Calsyntenin‐1 as a modulator in FSTL1‐mediated Lung Adenocarcinoma Metastasis: The Crosstalk with extracellular ALDOA
Authors: Chiou Jean , Hsiao Michael
Published: April 2020

Previously, we found that FSTL1 downregulation strongly predicts a poorer prognosis in patients with lung adenocarcinoma, but not squamous‐cell carcinoma, and highly correlates with an increased metastatic potential of lung cancer cells in vitro and in vivo. To examine detail molecular mechanisms, we presented protein‐protein interaction (PPI) assays. Several proteins that belong to extracellular or exosomal members were identified by mass spectrometric analysis from the FSTL1‐interacting protein mixture. In our data, we found that CLSTN1 ranked first. CLSTN1, calsyntenin‐1, is a type‐1 neuronal transmembrane protein, which is in the postsynaptic membrane. CLSTN1 was originally identified as a transmitted protein that modulated synaptic signals with proteolytic cleavage fragment. Recent research showed that CLSTN1 overexpressed in lung adenocarcinoma tissue and released to serum. But the molecular mechanisms of CLSTN1 in lung cancer still need to be confirmed. Extracellular ALDOA was detected in lung cancer cell conditioned medium. The detail functions and mechanism of extracellular ALDOA in lung adenocarcinoma is still unclear. CLSTN1 expression in cultured medium was positive correlation with ALDOA expression in cultured medium. Collectively, we may repurpose CLSTN1 as a modulator to regulate lung adenocarcinoma metastasis and their networking, which can be used in combination with targeted therapies, chemotherapies, or radical therapies in future research.
CREB and ERK Activation by Leptin and Angiotensin in the GT1‐7 Cell Model by Capillary Electrophoresis‐Based Western Blotting
Authors: Balapattabi Kirthikaa , Patil Chetan N. , Deng Guorui , Sigmund Curt D. , Grobe Justin L.
Published: April 2020

Leptin (LEP) increases resting energy expenditure in part by decreasing Agouti‐related peptide (Agrp) within the arcuate nucleus (ARC) of the hypothalamus. Prolonged obesity is associated with hyperleptinemia and development of selective LEP resistance (SLR), referring to the loss of ‘metabolic’ but maintenance of ‘cardiovascular’ sympathetic nervous activity responses to LEP. Previously, we discovered that angiotensin II (ANG) type 1a (Agtr1a) receptors located on Agrp neurons of the ARC are dispensable for blood pressure control but critically required for metabolic responses to LEP. Therefore, we generally hypothesize a role for Agtr1a in Agrp neurons of the ARC in the development of SLR. We used single‐nucleus RNA‐seq followed by Ingenuity Pathway Analysis (IPA) to interrogate the transcriptomes of individual cell types of the ARC from mice after 10 weeks of 45% high fat diet (HFD) or chow. We determined that canonical LEP signaling was strongly under‐represented in Agrp neurons, but not other cell types. Similarly, CREB & ERK pathways, which are implicated in the control of Agrp expression, were significantly under‐represented within Agrp neurons from HFD‐fed mice. To explore changes in the function of these second‐messenger cascades in Agrp neurons, immortalized mouse hypothalamic GT1‐7 cells were examined for expression of relevant genes and activation of signaling cascades in response to various stimuli. First, GT1‐7 cells were confirmed to express Agrp, Lepr, and Agtr1a, but not proopiomelanocortin by qPCR. Second, GT1‐7 cells were treated with LEP (1uM), ANG (200nM), forskolin (30uM), or vehicle for 15 min and lysates were isolated for Western blotting. Capillary electrophoresis methodology (Protein Simple WES; standard matrix (12–230 kDa)/anti‐rabbit detection module) was specifically chosen to enable future studies of ARC Agrp neurons captured after dietary interventions by laser capture microdissection (LCM). Phosphorylated (p) CREB (1:50; CST # 9198), total (t) CREB (1:50; CST #9197), p‐ERK (10ug/ml; R&D Systems # AF1018‐SP), t‐ERK (10ug/ml; R&D Systems # AF1576‐SP) and β‐actin (1:100; Abcam ab8227) protein levels were assessed for all four treatments. Peak signal‐to‐noise (S/N) ratios were well above the threshold value of 10 for all protein samples: p‐CREB (ranging from 560–1500), t‐CREB (25–40), p‐ERK (115–1245) t‐ERK (150–270) and β‐actin (1400–1600). LEP, ANG, and forskolin treatment significantly (p<0.05; n=5–6 each) increased p‐CREB and p‐ERK with no change in t‐CREB or t‐ERK, compared to vehicle. Finally, the viability of protein collection from the ARC was confirmed and optimized by measuring β‐actin from cells isolated by LCM. Ongoing studies are focused on assessing ARC Agrp neuron CREB & ERK responses to acute leptin treatment after prolonged exposure to HFD.

Support or Funding Information

HL134850, HL084207
Regenerative Effect of Adipose‐Derived Mesenchymal Stem Cells on Pain in a Rat Model of Osteochondral Defect
Authors: Hemstapat Ruedee , Sriwatananukulkit Orada , Tawonsawatruk Tulyapruek , Rattanapinyopituk Kasem , Luangwattanawilai Ticomporn , Srikaew Narongrit
Published: April 2020

In recent years, a lot of attention has been focused on using adipose‐derived mesenchymal stem cells obtained from infrapatellar fat pad (IPFP‐ASCs) for the articular cartilage regeneration. IPFP‐ASCs constructs were previously characterized and demonstrated chondrogenic differentiation potential to produce hyaline like‐cartilage in vitro. However, little is known about the relationship of its regeneration potential and pain associated with osteochondral defect. This study aimed to investigate the effect of implantation of the 3‐Dimensional (3D) cartilage construct of IPFP‐ASCs on the restoration of an articular hyaline cartilage as well as attenuation of pain associated with the cartilage defect in an osteochondral defect rat model. The chondrogenic differentiation potential of the 3D cartilage construct derived from IPFP‐ASCs was determined prior to implantation and at 4, 8 and 12 weeks post‐implantation by gene expression and immunochemistry analysis. Pain‐related behavior was examined weekly up to 8 weeks post‐implantation by using weight‐bearing test. A significant pain‐associated with osteochondral defect was observed in this model in all groups post‐induction; however, this pain can spontaneously resolve within three weeks post‐implantation regardless of implantation of IPFP‐ASCs constructs. The existences of mature chondrocytes as well as a significant (p<0.05) positively immunostained for type II collagen and aggrecan were identified in the implanted site for up to 12 weeks compared to untreated group, indicating the hyaline cartilage regeneration. Overall, this study reported the successful outcome of osteochondral regeneration with scaffold‐free IPFP‐ASCs constructs in an osteochondral defect rat model. Although the implantation of the cartilage construct could not attenuate pain associated with the cartilage defect, it provides novel and interesting insights into the current hypothesis that 3D construct IPFP‐ASCs may have potential benefits as an alternative approach to repair bone and cartilage defect.
Through regulating Ubiquitin E3 ligase in achieving degradation of aggregated protein and suppression of cell death in polyglutamine degeneration
Authors: Chan Edwin HY
Published: April 2020

Polyglutamine (polyQ) diseases, including Huntington’s disease and several types of spinocerebellar ataxias, are caused by the genomic expansion of coding CAG trinucleotide sequences. This expansion leads to the production and accumulation of misfolded polyQ domain‐containing disease proteins, which cause cellular dysfunction and neuronal death. As one of the principal cellular protein clearance pathways, the activity of the ubiquitin proteasome system (UPS) is tightly regulated to ensure efficient clearance of damaged and toxic proteins. Emerging evidence demonstrates that the UPS plays a crucial role in the pathogenesis of polyQ diseases. Ubiquitin (Ub) E3 ligases catalyze the transfer of a Ub tag to label proteins destined for proteasomal clearance. We recently identified an E3 ligase Y that modulates expanded polyQ‐induced neurodegeneration in both mammalian and Drosophila disease models. We further showed that Y promotes poly‐ubiquitination and degradation of expanded polyQ protein. Our data further demonstrated the nuclear localization of Y is essential for it to function as a polyQ E3 ligase. Intriguingly, we found that an exocyst complex component X, a Y interacting partner, modulates expanded polyQ protein levels and toxicity in an opposite manner to Y. Our data suggest that X exerts, at least in part, its polyQ‐modifying effect through regulating the E3 ligase function of Y. In summary, this study allows us to better define the role of protein ubiquitination in polyQ pathogenesis and understand how the E3 ligase activity can be regulated in a pathogenic condition.

Support or Funding Information

This work was supported by General Research Fund (14122815) of The Research Grants Council of Hong Kong and CUHK Gerald Choa Neuroscience Centre Grant (7105306).
Immunogenicity of an Adenoviral Vector Vaccine (rAd‐MOMP‐CpG) Against Chlamydia Trachomatis
Authors: Ababneh Mustafa , Ghazal Ehab , khalifeh Mohammad
Published: April 2020

Chlamydia trachomatis (C. trachomatis) infection is categorized as an important causes of sexually transmitted diseases in humans. Currently, there is no approved vaccine against C. trachomatis. This study was conducted to develop and evaluate the immunogenicity of a recombinant adenovirus (rAd‐MOMP‐CpG) vaccine against C. trachomatis in mice. The vaccine was constructed using adenovirus type 5 based on the major outer membrane protein (MOMP) antigen of C. trachomatis. Sixty mice were divided into 4 groups. In group 1, mice received rAd‐MOMP‐CpG (5×108 PFU) intranasal, 3 times at 2‐weeks intervals. Mice in groups 2, 3 and 4 received equivalent volume of adenovirus vector, CpG 1826, and PBS, respectively. Splenic cytokine levels and mRNA expression levels of IFNg and IL‐4 were determined by ELISA and qPCR, respectively. Furthermore, serum specific murine anti‐MOMP IgG levels were determined by quantitative ELISA. The constructed rAd‐MOMP‐CpG vaccine provoked a Chlamydia‐specific T helper type 1 response. There was a significant (P = 0.047) splenic IFNg stimulation in vaccinated group in comparison to the vector‐control group. The splenic IL‐4 expression remained at minimal stimulation levels across time points. In addition, the vaccine induced significant increase (P = 0.006) of delayed humoral anti‐MOMP IgG response compared to control groups. A recombinant adenovirus vaccine against C. trachomatis could provide important clues toward a vaccine development for C. trachomatis serovar protection in humans. However, further in vitro and in vivo studies are warranted to determine the most effective dosage, vaccine efficacy and safety.

Support or Funding Information

Jordan University of Science and Technology, Deanship of Research (grant number: 20140275).
Introduction of Mini‐peer Teaching Sessions (MPTs) During Dental Gross Anatomy Laboratory Sessions
Authors: Nonabur Venkatesh , Rarey Kyle E.
Published: April 2020

Dental Gross Anatomy is an integrated course during the first semester of dental education at the University Of Florida College Of Dentistry. The gross anatomy of the human body is still primarily learned in the anatomy laboratory. The purpose of this study was to assess the effectives of creating mini‐peer teaching sessions within assigned anatomy laboratory times.

Multiple mini‐peer teaching sessions (MPTs) were created and held during the assigned anatomy sessions for first year dental students. During each MPT session, students at assigned tables were clustered into two stations (groups A and B). Each station consisted of students assigned to six tables; there were six to seven students presented per table. One student at each table was assigned as a teacher who was responsible for demonstrating dissected structures that their group had dissected.

Other members at the assigned tables rotated every six to seven minutes intervals to learn about the anatomy at the other tables. After first round was concluded in groups A and B, the students were switched between A and B stations and a new teacher was designated to demonstrate the assigned anatomy. The MPTs allowed each student to observe the assigned cadaveric anatomy at all 12 tables during a given MPT.

Students’ perspective of the value of the dental MPT, sessions were extremely positive. An online survey taken during 2018 Fall semester from the First‐Year Dental students identified that the MPTs were extremely effective. Ninety eight percent of the students strongly agreed that their class mates, serving as peer teachers, were beneficial to their learning. Ninety five percent believed rotating to different stations, with different peer teachers, facilitated their learning of the assigned anatomy. Qualitative data further confirmed the positive impact students placed on the MPTs. Although setting up individual MPTs is time‐intensive, the teaching faculty view the MPTs experiences as a means to further enrich student’s knowledge‐base of anatomy.

Support or Funding Information

University of Florida, College of Medicine
Factors Affecting Histone Deacetylase 1 Activity and Selectivity
Authors: Diffley Kelsey , Fierke Carol
Published: April 2020

Acetylation is an important post‐translational modification (PTM). Aberrant acetylation, or deacetylation, has been linked to cancer, diabetes, neurodegeneration and auto‐immune disorders. Lysine acetylation is a reversible PTM, where deacetylation is catalyzed by histone deacetylases. Histone deacetylase function is crucial for a properly functioning cell, yet information about the specific biological pathways regulated by each isozyme is limited. HDAC1 is especially intriguing due to its known involvement in multiple stable nuclear complexes. However, the role of these complexes in regulating the deacetylase activity of HDAC1 is unclear. We have measured changes in activity and selectivity of HDAC1 upon addition of the following known protein binding partners; retinoblastoma protein 1 (Rb1), DNA methyltransferase 1 (DNMT1), rest corepressor 1 (CoREST), and lysine demethylase 1 (LSD1). We have reconstituted the HDAC1‐containing complexes with these proteins in vitro, as indicated by immunoprecipitation and size‐exclusion chromatography. Using substrate peptide analogs, we have measured the effect of binding partners on HDAC1 activity, demonstrating that these binding partners activate and increase HDAC1 activity to varying extents. Measurement of the reactivity of HDAC1 and HDAC1‐containing complexes with acetylated peptide substrates and full‐length protein substrates (i.e. histones) will provide insight into the role of binding partners in determining HDAC1 substrate selectivity.

Support or Funding Information

National Institutes of Health R01‐GM‐040602