bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbiomic differences at cancer-prone oral mucosa sites with marijuana usage
Authors: Newman Taylor , Krishnan Laya P. , Lee Jessica , Adami Guy R.
Published: September 2019

Marijuana smoke contains cannabinoids, immunosuppressants, and a mixture of potentially-mutagenic chemicals. In addition to systemic disease, it is thought to contribute to oral disease, such as tooth loss, tissue changes in the gums and throat, and possibly oral pharyngeal cancer. We used a cross-sectional study of 20 marijuana users and 19 control non-users, to determine if chronic inhalation-based exposure to marijuana was associated with a distinct oral microbiota at the two most common sites of head and neck squamous cell carcinoma (HNSCC), the lateral border of the tongue and the oral pharynx. At the tongue site, genera earlier shown to be enriched on HNSCC mucosa, Capnocytophaga, Fusobacterium, and Porphyromonas, were at low levels in marijuana users, while Rothia, which is found at depressed levels on HNSCC mucosa, was high. At the oral pharynx site, differences in bacteria were distinct, with higher levels of Selenomonas and lower levels of Streptococcus which is what is seen in HNSCC. No evidence was seen for a contribution of marijuana product contaminating bacteria to these differences. This study revealed differences in the surface oral mucosal microbiota with frequent smoking of marijuana.
Label-free detection of biotoxins via a photo-induced force infrared spectrum at the single-molecular level
Authors: Ji Bin , Kenaan Ahmad , Gao Shan , Cheng Jin , Cui Daxiang , Yang Hao , Wang Jinglin , Song Jie
Published: September 2019

Schematic illustration of photo-induced force microscopy combine principal component analysis detected and distinguish single molecule particles of biotoxins AT, RT/ETX with label-free.
Enhanced sensitivity of fluorescence-based Fe(ii) detection by freezing
Authors: Lee Yun Hak , Verwilst Peter , Kim Hyeong Seok , Ju Jinjung , Kim Jong Seung , Kim Kitae
Published: September 2019

The first example of combining the fluorescent probe-based freeze concentration effect with N-oxide chemistry is reported for the highly sensitive and selective detection of ferrous ion (Fe(ii)).
A supramolecular sensor array for selective immunoglobulin deficiency analysis
Authors: Liu Yang , Gill Adam D. , Duan Yaokai , Perez Lizeth , Hooley Richard J. , Zhong Wenwan
Published: September 2019

A host–guest based fluorescence sensor array can fully discriminate five structurally similar Ig protein isotypes, and recognize Ig deficiencies in serum.
Photoswitchable de/adsorption of an azobenzene-derived surfactant on a silica surface
Authors: Wu Ziye , Li Xin , Jiang Xiaoming , Xie Tian , Li Huiyong , Zhang Guozhen , Jiang Jun
Published: September 2019

Microscopic mechanism of photo-controllable adsorption/desorption behavior of an azobenzene-based surfactant on a silica surface was investigated.
A roadmap for renewable C2–C3 glycols production: a process engineering approach
Authors: Marchesan Andressa Neves , Oncken Marina Pinho , Maciel Filho Rubens , Wolf Maciel Maria Regina
Published: September 2019

A review of strategies and challenges for chemical and biochemical production and purification of C2–C3 glycols from renewable sources.
Miniaturized sample preparation on a digital microfluidics device for sensitive bottom-up microproteomics of mammalian cells using magnetic beads and mass spectrometry-compatible surfactants
Authors: Leipert Jan , Tholey Andreas
Published: September 2019

The combination of digital microfluidics and magnetic beads for removal of polymer surfactants enables sensitive LC-MS-based microproteomics analyses down to 100 mammalian cells.
Mechanochemically-assisted solvent-free and template-free synthesis of zeolites ZSM-5 and mordenite
Authors: Nada Majid H. , Larsen Sarah C. , Gillan Edward G.
Published: September 2019

Solvent-free and template-free synthesis of crystalline zeolites using mechanochemical pre-reactions between Na2SiO3 and Al2(SO4)3 forming Na2SO4 and well-mixed aluminosilicate intermediates.
A fast-responsive fluorescent probe based on a terpyridine-Zn2+ complex for sensing hypochlorous acid in aqueous solution and its application in real water samples and bioimaging
Authors: Pan Yaping , Yan Yang , Li Yang , Gao Xue-Wang , Chao Duobin
Published: September 2019

A simple terpyridine-Zn2+ complex was developed as a turn-off fluorescent probe for detection of HClO with a rapid response of 10 seconds.
Recent advances in graphene-based platinum and palladium electrocatalysts for the methanol oxidation reaction
Authors: Ali Asad , Shen Pei Kang
Published: September 2019

Graphene-based electrocatalysts have recently attracted considerable research interest because of the abundant choices they present, with tunable and diverse optical, electronic and chemical properties.
Performance evaluation of enzymatic biofuel cells using a new cathodic catalyst containing hemin and poly acrylic acid promoting the oxygen reduction reaction
Authors: Chung Yongjin , Ji Jungyeon , Kwon Yongchai
Published: September 2019

A new cathodic catalyst for EBCs is developed by adoption of a horseradish peroxidase cofactor mimetic supporter and enzyme–polymer conjugate.
Charge transport effect and photovoltaic conversion of two-dimensional CdSeS quantum dot monolayers in inverted polymer solar cells
Authors: Lim Guh-Hwan , Lee Kyu Seung , Park Young Jae , Shim Jaeho , Choi Jin Woo , Kim Minju , Jin Yeonghoon , Lim Byungkwon , Yi Yeonjin , Lee Chang-Lyoul , Hwang Jun Yeon , Son Dong Ick
Published: September 2019

Herein, we demonstrate that two-dimensional (2D) CdSeS quantum dot monolayers (QDM) can strongly influence efficient charge transport and charge separation, improving the performance of inverted polymer solar cells (iPSCs).
Narzissmus in der therapeutischen Beziehung
Authors: Busmann Mareike , Euler Sebastian
Published: September 2019

Für die Gestaltung der psychotherapeutischen Beziehung ist die Berücksichtigung der narzisstischen Verletzung des Patienten entscheidend. Narzissmus stellt
ein auf entwicklungspsychologischen Grundlagen basierendes System der Selbstregulation dar. Vulnerabler und grandioser Narzissmus wirken sich
unterschiedlich auf die psychotherapeutische Beziehung aus.
Schwerpunktprogramm der Deutschen Forschungsgemeinschaft SPP1629 „THYROID TRANS ACT“ – Neue Aspekte in der Schilddrüsenforschung
Authors: Brix Klaudia , Biebermann Heike , Führer Dagmar
Published: September 2019

THYROID TRANS ACT ist ein deutschlandweiter Forschungsverbund, der sich der Frage widmet: „Wie ist die gesunde Schilddrüsenfunktion definiert?“. In THYROID TRANS ACT arbeiten grundlagenwissenschaftlich, translational sowie klinisch orientierte Schilddrüsenforscher aus Deutschland interdisziplinär zusammen. Das langfristige Ziel ist es, neue Therapiekonzepte für Schilddrüsenpathologien und Schilddrüsenhormonabhängige Erkrankungen zu entwickeln.
Neues zur Pathophysiologie der Spondyloarthritis
Authors: Syrbe Uta
Published: September 2019

Die Spondyloarthritiden (SpA) umfassen eine Gruppe von Erkrankungen, die durch ähnliche klinische Manifestationen und gemeinsame genetische Assoziationen gekennzeichnet sind. Die axialen Manifestationen umfassen Entzündungen im Achsenskelett, insbesondere in den Sakroiliakalgelenken und in den Wirbelkörpern; bei den peripheren Gelenkmanifestationen dominieren Enthesitiden und Daktylitiden neben oligoartikulären asymmetrischen Arthritiden. Die Pathogenese und Krankheitsentwicklung wird stark durch genetische Anlagen bestimmt. HLA-B27 gilt als wichtigster genetischer Risikofaktor, wobei die pathogenetische Funktion von HLA-B27 nach wie vor ungeklärt ist. Daneben wurden in genomweiten Assoziationsstudien u. a. Risikovarianten in Genen, die den Interleukin (IL)-23-IL-17 Signalweg kontrollieren, identifiziert. Die Bedeutung dieses Signalweges spiegelt sich auch in der klinischen Wirksamkeit von IL-17 Inhibitoren bei Patienten mit SpA wider. Histologische Untersuchungen axialer Krankheitsmanifestationen zeigten ein entzündliches Grauationsgewebe, welches destruierende und reparative Eigenschaften besitzt. So fanden sich neben dem Fibroblasten-reichen Granulationsgewebe randständige Osteoklasten, die die Destruktion der Knochenendplatte vorantreiben und Osteoblasten, die Knochenneubildung vermitteln. In Analysen der IL-23- und IL-17-Expression in Wirbelkörperproben von Patienten mit ankylosierender Spondylitis fand sich die Expression dieser Zytokine v. a. in myeloiden Zellen. Im Tiermodell wurden IL-23 Rezeptor-exprimierende Zellen in Sehnenansätzen identifiziert. Auf IL-23 Exposition reagierten diese Zellen mit der Expression von IL-17 und IL-22, was zur lokalen Entzündung gefolgt von Knochenneubildung führte. Neben der genetischen Assoziation besteht bei der SpA eine große Überlappung mit dem Bestehen einer Psoriasis oder einer chronisch-entzündlichen Darmerkrankung (CED). Darüber hinaus fand sich bei einem Großteil der SpA-Patienten, die keine klinischen Zeichen einer CED zeigen, ebenfalls eine mikroskopische Darmentzündung. Es wird angenommen, dass die entzündlichen Reaktionen an Grenzflächen im Kontext von HLA-B27 zur Entwicklung der axialen und peripheren Gelenkentzündung beitragen, wobei unklar ist, ob Translokation bakterieller Antigene oder die Immunaktivierung im Darm über die Freisetzung löslicher Faktoren oder eine Kreuzreaktivität zwischen mikrobiellen und Gelenkantigenen zu den typischen SpA-Gelenkentzündungen führt.
The Trouble with Five: New Synthetic Strategies toward C5
-Symmetric Pillar[5]arenes and Beyond
Authors: Du Ke , Sue Andrew C.-H.
Published: September 2019

Rim-differentiated pillar[5]arenes (P[5]s) are intriguing macrocyclic molecular platforms with C
5-symmetry, but their conventional statistical syntheses suffer from low yields and laborious separation. Our group recently reported a ‘pre-oriented’ protocol that results in highly selective production of C
5-symmetric P[5]s among four constitutional isomers. Subsequently, we devised a more general divergent synthetic route starting with a common P[5] precursor with rim differentiation, followed by a series of high-yielding reactions that permit successive transformations of both rims freely. As a result, a variety of rim-differentiated P[5]s can be made to order in gram-scale quantities. This total solution not only populates the list of C
5-symmetric P[5]s, but also enables further design and synthesis of assorted five-fold organic building blocks towards complex supramolecular architectures.
Large Vertex Epidural Hematoma: Case Report and Review of Surgical Approaches
Authors: Silva Neto Angelo R. , Medeiros Luana , Silva Fábio B. , Velloso Renata N.
Published: September 2019

Vertex epidural hematomas (VEHs) are a special clinical entity due to their clinical presentation, vascular etiology and options of surgical approach. The clinical suspicion involves recognizing the mechanism of the injury and the correct visualization of the hematoma in computed tomography (CT) coronal sequences. In the present article, we describe a case of a very large (146 mL) VEH with central brain herniation, and provide a technical note on the surgical planning and treatment. A 34-year-old male patient was admitted to the hospital after an injury on the left superior parietal region. The Glasgow coma scale score was 6, and the left pupil of the patient was dilated. The CT scan showed a large epidural hematoma on the vertex between the coronal e lambdoid sutures, and a fracture over the sagittal suture. During the surgery, multiple burr holes were made laterally to the sagittal suture, and after inspection and no visualization of bleeding in the superior sagittal sinus (SSS), we performed a standard biparietal craniotomy. The patient was discharged three days after the surgery without any deficits. Currently, with the improvement in imaging modalities, more cases of VEH are being identified. Identifying the etiology prior to the craniotomy is challenging in severe cases. Tears in the SSS can bleed profusely, and they demand strategies during the craniotomy. With multiple burr holes parallel to the sagittal suture, we can visualize whether there is bleeding in the SSS and design a craniotomy with or without a central osseous bridge to anchor the dura. Neurosurgeons must be prepared to plan a surgical strategy in cases of large VEHs. Due to its rare frequency and bleeding risks, VEHs are considered challenging.
‘Work Conquers All’: psychiatry, agricultural labor, and the Juliano Moreira Colony in Rio de Janeiro, Brazil (1890–1958)
Authors: Meyer Manuella
Published: September 2019

This article explores the varied forms of labor used at the Juliano Moreira Colony in Rio de Janeiro during the first half of the twentieth century. It investigates the ideological justification psychiatrists made about the therapeutic value of work, and in particular, agricultural work, as a dominant medical regimen in the Colony. It is suggested that the Colony’s elision with labor resonated with a state that placed work and the worker as socio-political and cultural national centerpieces. Its appeal to the state was most likely the reason why the colony model became the predominant hospital structure when a muscular public health structure reorganized mental health services throughout the nation. The labor of the mentally ill in the Colony had no great generative use-value since their efforts were not sufficient to make the Colony sustainable. Moreover, labor therapy was not able to fully rehabilitate the majority of patients so that they could leave the institution and enter the labor force. Indeed, the presidency of Getúlio Vargas (1930–1945, 1951–1954), with its championing of the working classes, inflected the idea of labor with new significance. Therefore, the performance of labor in the Colony, in and of itself, had potent symbolic value. The work of the mentally ill in agricultural fields or carpentry workshops, although non-productive, can be understood as repertoires of social and political claim-making.
Mie resonator method for reliable permittivity measurement of loss-less ceramics in microwave frequency at high temperature
Authors: Ma Ho Jin , Jung Joonkyo , Kong Jung Hoon , Park Jin Woo , Lee Seung Jun , Shin Jonghwa , Kim Do Kyung
Published: September 2019

This paper describes a new approach, based on the Mie theory, to measure the dielectric properties of lossless materials at temperatures greater than 1500 °C. For the reliable operation of microwave transmitting materials in harsh environments, it is crucial to correctly characterize the permittivity under various temperature conditions. Heating and measurement systems using a propane torch and a single horn antenna were designed to estimate such dielectric properties. The reflection spectrum of Al2O3 ceramics at room temperature was determined using the Mie theory to derive the permittivity and validate the approach. High-temperature dielectric constants are derived from simulated values, which are reliable and have only a slight slope as a function of temperature. These results indicate that the permittivity measurement technique can provide powerful information for the optimal design and accurate evaluation of the dielectric properties of various lossless materials at high temperatures.
Radiometric calibration of thermal emission data from the Asteroid and Lunar Environment Chamber (ALEC)
Authors: Bramble Michael S. , Yang Yazhou , Patterson William R. , Milliken Ralph E. , Mustard John F. , Donaldson Hanna Kerri L.
Published: September 2019

The vacuum and thermal environment of airless planetary surfaces, particularly those dominated by a particulate regolith such as the Moon and asteroids, produces intense near-surface thermal gradients that can substantially alter their thermal emissivity spectra when compared with spectra collected at ambient terrestrial conditions. Therefore, spectroscopic measurements acquired under conditions designed to simulate the radiation environment in which remote measurements of airless bodies are made should be used as the basis for interpreting those data. As a foundation for this goal, we report the radiometric calibration of thermal infrared emission data collected with a Fourier transform infrared spectrometer integrated with the custom Asteroid and Lunar Environment Chamber (ALEC) at Brown University. This chamber is designed to simulate the environment of airless planetary bodies by evacuating the atmospheric gasses to vacuum (<10–4 mbar), cooling the chamber with a flow of liquid nitrogen, heating the base and sides of samples with temperature-controlled sample cups, and heating the top of samples with an external light source. We present a new method for deriving sample emissivity based on the absolute radiometry properties of our system, focusing on the 400–2000 cm−1 wavenumber range. This method produces calibrated radiance spectra from calibration targets, and particulate samples and those spectra are used to derive emissivity spectra. We demonstrate that the ALEC system and data reduction methods successfully replicate independently determined spectral properties of particulate samples under both ambient and cold, vacuum conditions. The ALEC system is shown to be capable of supporting ongoing and future planetary exploration of airless surfaces by facilitating careful investigation of meteorites, lunar samples, and planetary materials at an array of environmental conditions.
Nanofluidic chromatography using a vibrating atomic force microscope tip
Authors: Anderson Mark S.
Published: September 2019

The separation of liquid mixtures is demonstrated using the vibrating tip of an Atomic Force Microscope (AFM). Fluid is collected onto the tip from a liquid surface while under tapping mode operation. This suppresses bulk capillary flow and enhances partitioning based on molecular affinity to the tip. AFM tapping mode separation was tested on liquid films consisting of binary and complex mixtures. The separated components were analyzed using tip enhanced infrared spectroscopy and direct analysis in real time mass spectrometry. The results demonstrate nanometer scale chemical separation for ultratrace analysis and nanofluidic applications.
Visualizing carrier transitions between localization states in a InGaN yellow–green light-emitting-diode structure
Authors: Li Yangfeng , Deng Zhen , Ma Ziguang , Wang Lu , Jia Haiqiang , Wang Wenxin , Jiang Yang , Chen Hong
Published: September 2019

InGaN-based light-emitting diodes (LEDs) have higher luminescence efficiency than other materials used for the blue and green LEDs in spite of their relatively high dislocation density. Localization theory has been used to explain this phenomenon, but the direct observation of localization states in the InGaN active region has been rarely reported. In this paper, we propose an LED structure to obtain higher luminescence efficiency in the yellow-green LEDs and directly observe the transition of carriers between different localization states. The localization states were investigated and confirmed by temperature-dependent photoluminescence and excitation power-dependent photoluminescence. The value of the external quantum efficiency also exhibited a higher radiative efficiency of the quantum well with a higher degree of localization states. These results offer a promising means of realizing high-luminescence LEDs.
Mechanisms of surface charge dissipation of silicone rubber enhanced by dielectric barrier discharge plasma treatments
Authors: Guan Honglu , Chen Xiangrong , Du Hao , Paramane Ashish , Zhou Hao
Published: September 2019

This paper investigates mechanisms of the surface charge dissipation of silicone rubber (SiR) after dielectric barrier discharge (DBD) plasma treatments in an open air. Electrical and physicochemical properties of the untreated and plasma treated samples were evaluated by surface and volume conductivity, surface potential decay (SPD) measurements, Fourier transform infrared (FT-IR), and water contact angle tests. Results show that the surface conductivity of the plasma treated samples evidently increases with the treatment time. The samples with a longer DBD plasma treatment time enhance the SPD rate after the positive and negative corona charging. However, an abnormal surface potential variation is observed at the beginning of the SPD after the negative corona charging. It is found that the top-bottom surface plasma treatment can further accelerate the SPD of the samples compared with the untreated and single surface plasma treated samples. The physicochemical analysis shows that the concentration of polar groups is increased after the plasma treatment, and the water contact angle is consistently declined with the increase of the plasma treatment time. The calculated trap distribution illustrates that the hole trap energy and the electron trap density of the sample are decreased after the plasma treatments. This investigation attributes the measured SPD of the untreated sample and single surface treated samples to the electrical conduction along the sample surface, but the SPD of the top-bottom surfaces plasma treated samples is enhanced by the charge neutralization and transportation through the material bulk as well as the sample top surface conduction.
Convolution identities for Dunkl orthogonal polynomials from the osp(1|2) Lie superalgebra
Authors: Koelink Erik , Lemay Jean-Michel , Vinet Luc
Published: September 2019

New convolution identities for orthogonal polynomials belonging to the q = −1 analog of the Askey-scheme are obtained. Specialization of the Chihara polynomials will play a central role as the eigenfunctions of a special element of the Lie superalgebra osp(1|2) in the positive discrete series representation. Using the Clebsch-Gordan coefficients, a convolution identity for the specialized Chihara, the dual -1 Hahn and the Big -1 Jacobi polynomials are found. Using the Racah coefficients, a convolution identity for the Big -1 Jacobi and the Bannai-Ito polynomials is found. Finally, these results are applied to construct a bilinear generating function for the Big -1 Jacobi polynomials.
Deliberate enhancement of rainfall using desert plantations
Authors: Branch Oliver , Wulfmeyer Volker
Published: September 2019

Significance

Our desert plantation concept aligns closely with research into biological carbon sequestration solutions but uniquely extends into the purview of deliberate rainfall enhancement. With this synergy of carbon sequestration and regional weather modification, we can counteract water scarcity and desertification while minimizing conflicts with food croplands. We have demonstrated that large plantations do enhance rainfall in arid regions and identified the underlying process chain. By using this knowledge we have developed a global index to assess which deserts are most favorable for weather modification and discuss how rainfall impacts can be intensified using agricultural methods. This potential for rainfall enhancement and carbon sequestration makes the research extremely interesting for the scientific community and for society.
Cross-national evidence of a negativity bias in psychophysiological reactions to news
Authors: Soroka Stuart , Fournier Patrick , Nir Lilach
Published: September 2019

What accounts for the prevalence of negative news content? One answer may lie in the tendency for humans to react more strongly to negative than positive information. “Negativity biases” in human cognition and behavior are well documented, but existing research is based on small Anglo-American samples and stimuli that are only tangentially related to our political world. This work accordingly reports results from a 17-country, 6-continent experimental study examining psychophysiological reactions to real video news content. Results offer the most comprehensive cross-national demonstration of negativity biases to date, but they also serve to highlight considerable individual-level variation in responsiveness to news content. Insofar as our results make clear the pervasiveness of negativity biases on average, they help account for the tendency for audience-seeking news around the world to be predominantly negative. Insofar as our results highlight individual-level variation, however, they highlight the potential for more positive content, and suggest that there may be reason to reconsider the conventional journalistic wisdom that “if it bleeds, it leads.”
In Defense of the Requirement of Total Evidence
Authors: Draper Paul
Published: September 2019

According to the Requirement of Total Evidence, when assessing the credibility of hypotheses, we should endeavor to take into account all of the relevant evidence at our disposal instead of just some proper part of that evidence. In “The Fine-Tuning Argument and the Requirement of Total Evidence,” Peter Fisher Epstein offers two alleged counterexamples to this requirement. I show that, on at least one very natural interpretation of the requirement, his alleged counterexamples are not genuine. I close by explaining why this conclusion is important.
3D particle tracking velocimetry for the determination of temporally resolved particle trajectories within laser powder bed fusion of metals
Authors: Eschner Eric , Staudt Tobias , Schmidt Michael
Published: September 2019

Within this work, we present a system for the measurement of the three-dimensional (3D) trajectories of spatters and entrained particles during laser powder bed fusion (L-PBF) of metals. It is comprised of two ultrahigh-speed cameras and a reconstruction task specific processing reconstruction algorithm. The system enables an automated determination of 3D measures from the trajectories of a large number of tracked particles. Ambiguity evolving from an underdetermined geometrical situation induced by a two-camera setup is resolved within the tracking using a priori knowledge of L-PBF of metals. All processing steps were optimized to run on a graphics processing unit to allow the processing of large amounts of data within an appropriate time frame. The overall approach was validated by a comparison of the measurement results to synthetic images with a known 3D ground truth.
Patients’ knowledge about pharmacists, technicians, and physicians
Authors: Perrault Evan K , Newlon Jenny L
Published: September 2019

Purpose

Including pharmacists within care teams can lead to positive health benefits, yet pharmacists remain underused. Misperceptions about pharmacists’ duties and expertise compared to physicians’ may contribute. This study sought to determine how well patients know the differences between pharmacists, technicians, and physicians regarding their duties and levels of education about medications. It also investigated how patients’ perceptions affect their likelihood to initiate interactions with pharmacists, as well as reasons why they choose not to speak with pharmacists.

Methods

An online survey of 477 U.S. adults was administered via Amazon’s Mechanical Turk. Participants’ knowledge of pharmacists’, pharmacy technicians’, and medical doctors’ education and expertise were measured. Logistic regression determined whether patients’ attitudes toward pharmacists predicted patient–pharmacist interactions. Participants’ reasons for choosing to not talk to pharmacists about their medications were assessed via an open-ended response.

Results

Patients generally know the duties pharmacists can perform compared to duties of technicians, but they incorrectly believe that physicians have more years of drug education than do pharmacists. Patients who have more positive attitudes toward pharmacists versus doctors are more likely to initiate interactions with pharmacists. Not seeing a need to interact, believing their doctors told them everything, or their ability to find information elsewhere (e.g., the Internet) were the 3 most cited reasons for not interacting with a pharmacist.

Conclusion

Reaching across disciplinary lines to colleagues in health communication may assist the pharmacy profession in finding ways to increase patients’ knowledge and perceptions about the important role pharmacists can play, thereby increasing the likelihood of patients wanting to interact with pharmacists.
Distinct cellular mediators drive the Janus Faces of Toll-like Receptor 4 regulation of network excitability which impacts working memory performance after brain Injury
Authors: Korgaonkar Akshata A. , Li Ying , Nguyen Susan , Guevarra Jenieve , Pang Kevin C H , Santhakumar Vijayalakshmi
Published: September 2019

The mechanisms by which the neurophysiological and inflammatory responses to brain injury contribute to memory impairments are not fully understood. Recently, we reported that the innate immune receptor, toll-like receptor 4 (TLR4) enhances AMPA receptor (AMPAR) currents and excitability in the dentate gyrus after fluid percussion brain injury (FPI) while limiting excitability in controls. Here we examine the cellular mediators underlying TLR4 regulation of dentate excitability and its impact on memory performance. In ex vivo slices, astrocytic and microglial metabolic inhibitors selectively abolished TLR4 antagonist modulation of excitability in controls, without impacting FPI rats, demonstrating that glial signaling contributes to TLR4 regulation of excitability in controls. In glia-depleted neuronal cultures from naïve mice, TLR4 ligands bidirectionally modulated AMPAR charge transfer demonstrating the ability of neuronal TLR4 to regulate excitability, as observed after brain injury. In vivo TLR4 antagonism reduced early post-injury increases in mediators of MyD88-dependent and independent TLR4 signaling without altering expression in controls. Blocking TNFα, a downstream effector of TLT4, mimicked effects of TLR4 antagonist and occluded TLR4 agonist modulation of excitability in slices from both control and FPI rats. Functionally, transiently blocking TLR4 in vivo improved impairments in working memory observed one week and one month after FPI, while the same treatment impaired memory function in uninjured controls. Together these data identify that distinct cellular signaling mechanisms converge on TNFα to mediate TLR4 modulation of network excitability in the uninjured and injured brain and demonstrate a role for TLR4 in regulation of working memory function.

Highlights

TLR4 suppresses dentate excitability in controls through signaling involving glia

Neuronal TLR4 signaling underlies enhanced dentate excitability after brain injury

TNFα contributes to TLR4 regulation of excitability in the injured brain

Altering TLR4 signaling impacts working memory performance

TLR4 signaling is a potential target to improve working memory after brain trauma
GDNF/RET signaling pathway activation eliminates Lewy Body pathology in midbrain dopamine neurons
Authors: Chmielarz Piotr , Er Şafak , Konovalova Julia , Bandrés Laura , Hlushchuk Irena , Albert Katrina , Panhelainen Anne , Luk Kelvin , Airavaara Mikko , Domanskyi Andrii
Published: September 2019

Neurodegenerative diseases are associated with proteostasis disturbances and accumulation of fibrillar proteins into insoluble aggregates. Progressive age-related degeneration of dopamine neurons is a primary cause of motor dysfunctions in Parkinson’s disease (PD) and substantial evidence supports critical involvement of α-synuclein (α-syn) in the etiology of PD. α-syn is a cytosolic protein present in high concentrations in pre-synaptic neuronal terminals and a primary constituent of intracellular protein aggregates known as Lewy Neurites or Lewy Bodies. Progression of Lewy pathology is a characteristic feature in the PD brains caused by the prion-like self-templating properties of misfolded α-syn. Modelling Lewy pathology progression with application of exogenously prepared α-syn preformed fibrils, we discovered that glial cell line-derived neurotrophic factor (GDNF) prevented formation of α-syn aggregates in dopamine neurons in culture andin vivoafter viral vector expression of GDNF. These effects were abolished by CRISPR/Cas9-mediated deletion of receptor tyrosine kinaseRet, the major GDNF signaling pathway. Similar to GDNF, expression of mutated constitutively active RET (RET_MEN2B) was able to protect dopamine neurons. GDNF protection against α-syn pathology progression was abolished by Src and attenuated by Akt pathway inhibitors. For the first time, we have shown the neurotrophic factor-mediated protection against the misfolded α-syn propagation in dopamine neurons, uncovered underlying receptor and intracellular signaling pathways. These results for the first time demonstrate that activation of GDNF/RET signaling can be an effective therapeutic approach to prevent Lewy pathology spread at early stages of PD.
Why is the explicit component of motor adaptation limited in elderly adults?
Authors: Vandevoorde Koenraad , Orban de Xivry Jean-Jacques
Published: September 2019

The cognitive component of motor adaptation declines with aging. Yet, in other motor tasks, older adults appear to rely on cognition to improve their motor performance. It is unknown why older adults are not able to do so in motor adaptation. In order to solve this apparent contradiction, we tested the possibility that older adults require more cognitive resources in unperturbed reaching compared to younger adults, which leaves fewer resources available for the cognitive aspect of motor adaptation. Two cognitive-motor dual-task experiments were designed to test this. The cognitive load of unperturbed reaching was assessed via dual-task costs during the baseline period of visuomotor rotation experiments, which provided us with an estimation of the amount of cognitive resources used during unperturbed reaching. However, since we did not observe a link between dual-task costs and explicit adaptation in both experiments, we failed to confirm this hypothesis. Instead, we observed that explicit adaptation was mainly associated with visuospatial working memory capacity. This suggests that visuospatial working memory of an individual might be linked to the extent of explicit adaptation for young and older adults.
Transcriptomic Profiling of Developing Melanocortin Neurons Reveals a Role for Prdm12 in Energy Balance
Authors: Chen Xiameng , Wyler Steven C. , Li Li , Arnold Amanda G. , Wan Rong , Xu Pin , Liu Chen
Published: September 2019

The hypothalamus is a critical regulator of many physiological processes essential for life. In the adult brain, each anatomically-defined hypothalamic nucleus consists of functionally heterogeneous neuronal subpopulations that dictate distinct survival behaviors. Nevertheless, how rich neuronal identities are established in the developing hypothalamus remains poorly understood.

Despite their opposing actions on food intake, POMC and NPY/AgRP neurons in the arcuate nucleus of the hypothalamus (ARH) are derived from the same progenitors that give rise to ARH neurons. However, the mechanism whereby common neuronal precursors subsequently adopt either the anorexigenic (POMC) or the orexigenic (NPY/AgRP) identity remains elusive.

We hypothesize that POMC and NPY/AgRP cell fates are specified and maintained by distinct intrinsic factors. In search of them, we profiled the transcriptomes of developing POMC and NPY/AgRP neurons with whole-genome RNA sequencing (RNA-seq). Moreover, cell-type-specific transcriptomic analyses revealed transcription regulators that are selectively enriched in either population, but whose developmental functions are unknown in these neurons.

Among them, we found the expression of the PR domain-containing factor 12 (Prdm12) was enriched in POMC neurons but was absent in NPY/AgRP neurons. Selective ablation of Prdm12 in postmitotic POMC neurons led to early-onset obesity, accelerated linear growth, as well as impaired glucose tolerance, which recapitulates symptoms of POMC/MC4R deficiency in humans. These findings, therefore, establish a previously-unrecognized role for Prdm12 in energy balance. Furthermore, the combination of cell-type-specific genomic and genetic analyses provides a means to dissect cellular and functional diversity in the developing hypothalamus as well as the developmental origins of diverse survival behaviors.
Quantifying topography-guided actin dynamics across scales using optical flow
Authors: Lee Rachel M. , Campanello Leonard , Hourwitz Matt J. , Omidvar Ava , Alvarez Phillip , Fourkas John T. , Losert Wolfgang
Published: September 2019

Periodic surface topographies with feature sizes comparable to those ofin vivocollagen fibers are used to measure and compare actin dynamics for two representative cell types that have markedly different migratory modes and physiological purposes: slowly migrating epithelial MCF10A cells and polarizing, fast migrating, neutrophil-like HL60 cells. Both cell types exhibit reproducible guidance of actin waves (esotaxis) on these topographies, enabling quantitative comparisons of actin dynamics. We adapt a computer-vision algorithm, optical flow, to measure the directions of actin waves at the submicron scale. Clustering the optical flow into regions that move in similar directions enables micron-scale measurements of actin-wave speed and direction. Although the speed and morphology of actin waves differ between MCF10A and HL60 cells, the underlying actin guidance by nanotopography is similar in both cell types at the micron and sub-micron scales.
Brainstem Neurons that Command Left/Right Locomotor Asymmetries
Authors: Cregg Jared M. , Leiras Roberto , Montalant Alexia , Wickersham Ian R. , Kiehn Ole
Published: September 2019

Descending command neurons instruct spinal networks to execute basic locomotor functions, such as which gait and what speed. The command functions for gait and speed are symmetric, implying that a separate unknown system directs asymmetric movements—the ability to move left or right. Here we report the discovery that Chx10-lineage reticulospinal neurons act to control the direction of locomotor movements in mammals. Chx10 neurons exhibit ipsilateral projection, and can decrease spinal limb-based locomotor activity ipsilaterally. This circuit mechanism acts as the basis for left or right locomotor movements in freely moving animals: selective unilateral activation of Chx10 neurons causes ipsilateral movements whereas inhibition causes contralateral movements. Spontaneous forward locomotion is thus transformed into an ipsilateral movement by braking locomotion on the ipsilateral side. We identify sensorimotor brain regions that project onto Chx10 reticulospinal neurons, and demonstrate that their unilateral activation can impart left/right directional commands. Together these data identify the descending motor system which commands left/right locomotor asymmetries in mammals.
Lotus japonicus karrikin receptors display divergent ligand-binding specificities and organ-dependent redundancy
Authors: Carbonnel Samy , Torabi Salar , Griesmann Maximilian , Bleek Elias , Tang Yuhong , Buchka Stefan , Basso Veronica , Shindo Mitsuru , Boyer François-Didier , Wang Trevor L. , Udvardi Michael , Waters Mark , Gutjahr Caroline
Published: September 2019

Karrikins (KARs), smoke-derived butenolides, are perceived by the α/β-fold hydrolase KARRIKIN INSENSITIVE2 (KAI2) and are thought to mimic endogenous, yet elusive plant hormones tentatively called KAI2-ligands (KLs). The sensitivity to different karrikin types as well as the number of KAI2 paralogs varies among plant species, suggesting diversification and co-evolution of ligand-receptor relationships. In legumes, which comprise a number of important crops with protein-rich, nutritious seed, KAI2 has duplicated. We report sub-functionalization of KAI2a and KAI2b in the model legume Lotus japonicus and demonstrate that their ability to bind the synthetic ligand GR24ent-5DS differs in vitro as well as in genetic assays in Lotus japonicus and in the heterologous Arabidopsis thaliana background. These differences can be explained by the exchange of a widely conserved phenylalanine in the binding pocket of KAI2a with a tryptophan in KAI2b, which occured independently in KAI2 proteins of several unrelated angiosperms. Furthermore, two polymorphic residues in the binding pocket are conserved across a number of legumes and may contribute to ligand binding preferences. Unexpectedly, L. japonicus responds to diverse synthetic KAI2-ligands in an organ-specific manner. Hypocotyl development responds to KAR1, KAR2 and rac-GR24, while root system development responds only to KAR1. This organ-specificity cannot be explained by receptor-ligand preferences alone, because LjKAI2a is sufficient for karrikin responses in the hypocotyl, while LjKAI2a and LjKAI2b operate redundantly in roots. Our findings open novel research avenues into the evolution and diversity of butenolide ligand-receptor relationships, their ecological significance and the mechanisms controlling diverse developmental responses to different KAI2 ligands.
Protein network structure enables switching between liquid and gel states
Authors: Schmit Jeremy D. , Bouchard Jill J. , Martin Erik W. , Mittag Tanja
Published: September 2019

Biomolecular condensates are emerging as an important organizational principle within living cells. These condensed states are formed by phase separation, yet little is known about how material properties are encoded within the constituent molecules and how the specificity for being in different phases is established. Here we use analytic theory to explain the phase behavior of the cancer-related protein SPOP and its substrate DAXX. Binary mixtures of these molecules have a phase diagram that contains dilute liquid, dense liquid, and gel states. We show that these discrete phases appear due to a competition between SPOP-DAXX and DAXX-DAXX interactions. The stronger SPOP-DAXX interactions dominate at sub-stoichiometric DAXX concentrations leading to the formation of crosslinked gels. The theory shows that the driving force for gel formation is not the binding energy, but rather the entropy of distributing DAXX molecules on the binding sites. At high DAXX concentrations the SPOP-DAXX interactions saturate, which leads to the dissolution of the gel and the appearance of a liquid phase driven by weaker DAXX-DAXX interactions. This competition between interactions allows multiple dense phases to form in a narrow region of parameter space. We propose that the molecular architecture of phase-separating proteins governs the internal structure of dense phases, their material properties and their functions. Analytical theory can reveal these properties on the long length and time scales relevant to biomolecular condensates.
Engineering a functional NifDK polyprotein resistant to mitochondrial degradation
Authors: Allen Rob , Gregg Christina , Okada Shoko , Menon Amratha , Hussain Dawar , Gillespie Vanessa , Johnston Ema , Warden Andrew , Taylor Matthew , Colgrave Michelle , Byrne Keren , Wood Craig
Published: September 2019

To engineer Mo dependent nitrogenase function in plants expression of proteins NifD and NifK will be an absolute requirement. Although mitochondria have been established as a suitable eukaryotic environment for biosynthesis of oxygen-sensitive enzymes such as NifH, expression of NifD in this organelle has proven difficult due to cryptic NifD degradation. Here we describe a solution to this problem. Using molecular and proteomic methods, we found NifD degradation to be a consequence of mitochondrial endoprotease activity at a specific motif within NifD. Focusing on this functionally sensitive region, we designed NifD variants comprising between one and three amino acid substitutions and distinguished several that were resistant to degradation when expressed in both plant and yeast mitochondria. Nitrogenase activity assays of these resistant variants in E. coli identified a subset that retained function, including a single amino acid (Y100Q) variant. The Y100Q variant also enabled expression of a NifD(Y100Q)-linker-NifK translational polyprotein in plant mitochondria, confirmed by identification of the polyprotein in the soluble fraction of plant extracts. The NifD(Y100Q)-linker-NifK retained function in E. coli based nitrogenase assays, demonstrating this polyprotein permits expression of NifD and NifK in a defined stoichiometry supportive of activity. Our results exemplify how protein design can overcome impediments encountered when expressing synthetic proteins in novel environments. Specifically, these findings outline our progress toward the assembly of the catalytic unit of nitrogenase within mitochondria.
Variation in Soil Properties under Long-Term Irrigated and Non-Irrigated Cropping and Other Land-Use Systems in Dura Catchment, Northern Ethiopia
Authors: Tesfahunegn Gebreyesus Brhane , Gebru Teklebirhan Arefaine
Published: September 2019

There are limited reports about the impacts of long-term irrigated and non-irrigated cropping and land-use systems (CLUS) on soil properties and nutrient stocks under smallholder farmers’ conditions in developing countries. The objective of this research was to examine variation in soil properties and OC and TN stocks across the different CLUS in Dura sub-catchment, northern Ethiopia. Surveys and discussions on field history were used to identify nine CLUS, namely, tef(Eragrostis tef(Zucc) Trot)) mono-cropping (TM), maize(Zea mays L.)mono-cropping (MM), cauliflower (Brassica oleracea var. botrytis)-maize intercropping (IC1), red beet (Beta Vulgaris)-maize intercropping (IC2), cauliflower-tef-maize rotation (R1), onion (Allium cepaL.)-maize-onion rotation (R2), treated gully (TG), untreated gully (UTG), and natural forest system (NF). A total of 27 composite soil samples were collected randomly from the CLUS for laboratory analysis. Data were subjected to one-way analysis of variance and PCA. The lowest and highest bulk density was determined from NF (1.19 Mg m-3) and UTG (1.77 Mg m-3), respectively. Soil pH, EC and CEC varied significantly among the CLUS. The highest CEC (50.3 cmolckg-1) was under TG followed by NF. The highest soil OC stock (113.6 Mg C ha-1) and TN stock (12.2 Mg C ha-1) were found from NF. The PCA chosen soil properties explained 87% of the soil quality variability among the CLUS. Such soil properties and nutrient stocks variability among the CLUS suggested that introduction of suitable management practices are crucial for sustaining the soil system of the other CLUS.
Task sharing clubfoot treatment in Latin America: a cross-sectional survey of expert opinions
Authors: Martinez Roxana , Smythe Tracey , Pettitt-Schieber Christie , Everhart Jennifer , Hyman Joshua
Published: September 2019

While the Ponseti method has quickly become the mainstay of clubfoot treatment in most parts of the world, its dissemination and successful implementation in Latin America has been more limited. The additional shortage of orthopedic surgeons in this region makes task sharing a practical approach to address gaps in service provision. We designed an online survey to assess needs, perceptions, and willingness to task share the delivery of the Ponseti method by Ponseti-method-trained physicians across Latin America. Multiple-response questions were summarized and an applied thematic analysis approach was used to analyze free-response questions. We achieved a 66% response rate (31 of 47 experts responded). Our findings illustrate that most physicians feel the need for disseminating and improving Ponseti training, as well as having additional support for clubfoot treatment. While physicians who treat clubfoot have mixed opinions on the role of nonphysicians treating clubfoot, most report logistical concerns and insufficient training as barriers to their inclusion. Given this and the need for improved, more accessible clubfoot care across Latin America, future clubfoot treatment efforts may benefit from incorporating task sharing between orthopedic surgeons and non-physician personnel.