bluuebunny/crossref_metadata_2025 huggingface dataset:
Capsaicin-Induced Impairment of Functional Network Dynamics in Mouse Hippocampus via a TrpV1 Receptor-Independent Pathway: Putative Involvement of Na+/K+-ATPase
Authors: Balleza-Tapia Hugo , Dolz-Gaiton Pablo , Andrade-Talavera Yuniesky , Fisahn André
Published: November 2019

The vanilloid compound capsaicin (Cp) is best known to bind to and activate the transient receptor potential vanilloid receptor-1 (TrpV1). A growing number of studies use capsaicin as a tool to study the role of TrpV1 in the central nervous system (CNS). Although most of capsaicin’s CNS effects have been reported to be mediated by TrpV1 activation, evidence exists that capsaicin can also trigger functional changes in hippocampal activity independently of TrpV1. Recently, we have reported that capsaicin induces impairment in hippocampal gamma oscillations via a TrpV1-independent pathway. Here, we dissect the underlying mechanisms of capsaicin-induced alterations to functional network dynamics. We found that capsaicin induces a reduction in action potential (AP) firing rate and a subsequent loss of synchronicity in pyramidal cell (PC) spiking activity in hippocampus. Moreover, capsaicin induces alterations in PC spike-timing since increased first-spike latency was observed after capsaicin treatment. First-spike latency can be regulated by the voltage-dependent potassium current D (ID) or Na+/K+-ATPase. Selective inhibition of ID via low 4-AP concentration and Na+/K+-ATPase using its blocker ouabain, we found that capsaicin effects on AP spike timing were completely inhibited by ouabain but not with 4-AP. In conclusion, our study shows that capsaicin in a TrpV1-independent manner and possibly involving Na+/K+-ATPase activity can impair cognition-relevant functional network dynamics such as gamma oscillations and provides important data regarding the use of capsaicin as a tool to study TrpV1 function in the CNS.
Neurovascular Unit as a Source of Ischemic Stroke Biomarkers—Limitations of Experimental Studies and Perspectives for Clinical Application
Authors: Steliga Aleksandra , Kowiański Przemysław , Czuba Ewelina , Waśkow Monika , Moryś Janusz , Lietzau Grażyna
Published: November 2019

Cerebral stroke, which is one of the most frequent causes of mortality and leading cause of disability in developed countries, often leads to devastating and irreversible brain damage. Neurological and neuroradiological diagnosis of stroke, especially in its acute phase, is frequently uncertain or inconclusive. This results in difficulties in identification of patients with poor prognosis or being at high risk for complications. It also makes difficult identification of these stroke patients who could benefit from more aggressive therapies. In contrary to the cardiovascular disease, no single biomarker is available for the ischemic stroke, addressing the abovementioned issues. This justifies the need for identifying of effective diagnostic measures characterized by high specificity and sensitivity. One of the promising avenues in this area is studies on the panels of biomarkers characteristic for processes which occur in different types and phases of ischemic stroke and represent all morphological constituents of the brains’ neurovascular unit (NVU). In this review, we present the current state of knowledge concerning already-used or potentially applicable biomarkers of the ischemic stroke. We also discuss the perspectives for identification of biomarkers representative for different types and phases of the ischemic stroke, as well as for different constituents of NVU, which concentration levels correlate with extent of brain damage and patients’ neurological status. Finally, a critical analysis of perspectives on further improvement of the ischemic stroke diagnosis is presented.
JMJD3 in the regulation of human diseases
Authors: Zhang Xiangxian , Liu Li , Yuan Xia , Wei Yuquan , Wei Xiawei
Published: November 2019

In recent years, many studies have shown that histone methylation plays an important role in maintaining the active and silent state of gene expression in human diseases. The Jumonji domain-containing protein D3 (JMJD3), specifically demethylate di- and trimethyl-lysine 27 on histone H3 (H3K27me2/3), has been widely studied in immune diseases, infectious diseases, cancer, developmental diseases, and aging related diseases. We will focus on the recent advances of JMJD3 function in human diseases, and looks ahead to the future of JMJD3 gene research in this review.
Effect of Lysyllysine on non-covalent hybridization of single walled carbon nanotube by single-stranded DNA homodimer: in silico approach
Authors: Bagherolhashemi Fateme , Bozorgmehr Mohammad Reza , Momen-Heravi Mohammad
Published: November 2019

In this work, the interactions between adenine–adenine di-nucleotide (DA2N) and carbon nanotube (CNT) in the presence of Lysyllysine (LL) was studied by the molecular dynamics simulation. Different carbon nanotubes including (5.5), (6.6) and (7.7) were used to investigate the effect of CNT type. The binding energies were calculated using the molecular mechanics-Poisson Bolzmann surface area method. The results showed that the contribution of the van der Waals interactions between DA2N and CNT was greater than that of the electrostatic interactions. The LL significantly enhanced the electrostatic interactions between the DA2N and CNT (6.6). The quantum calculations revealed that the sensor properties of the DA2N were not significantly affected by the CNT and LL. However, the five-membered ring of adenine played a more important role in the sensing properties of the DA2N. The obtained results are consistent with the previous experimental observations that can help to understand the molecular mechanism of the interaction of DA2N with CNT.

Graphic abstract
Use of local anesthetic for the resolution of benign anorectal pathology in the Social Security Institute of Guatemala (IGSS)
Authors: Maldonado Hernández Pablo , Ramírez Godoy Laura , Méndez Morán Maxi , San José Gómez Jorge , Cordoba Paíz Juan Pablo
Published: November 2019

Introduction The use of regional anesthetic block has increased, along with the reduction of the use of spine anesthetic in this particular field of surgical activity. In the last decade ambulatory surgery and local anesthetic have lower surgical time, complications of the anesthetic itself, and hospital stay.

Objective Presenting the results obteained with the use of local anesthesic and analgesic in the resolution of benign anorectal pathology.

Methods A prospective, longitudinal, study, from January 2017 to December 2017, patients were classified according to surgical procedures performed using analogical visual scale to determine the pain tolerance, during the procedure, 24 h later and in the 5th post operative day.

Results 253 procedures were performed with 116 local analgesia, 116 were male (45.86%) years 137 female (54%), Milligan-Morgan hemorroidectomy with Ligasure and fistulotomy were the most frequently performed procedures 32% each, followed by biopsy 16%, left lateral esfinterotomy 13% and cutaneous appendix 12%. Females presented better pain tolerance than males patients (92 vs. 81), 68% referred good tolerance through the procedure.

Conclusions 68% of all the patients obtained good pain tolerance through anal anesthetic block, females manifested better pain tolerance than males, in non-complicated anorectal pathology local block ha shown to be safe and reproductible for the treatment of benign anorectal pathology in the Guatemalan Institute for Social Security.
Do SNAP Recipients Get the Best Prices?
Authors: March Raymond J. , Carpio Carlos E. , Boonsaeng Tullaya , Lyford Conrad P.
Published: November 2019

We developed an expensiveness index and used the Food Acquisition and Purchase Survey data set to examine empirically whether Supplemental Nutrition Assistance Program (SNAP) participants pay higher prices compared with nonqualifying and qualifying, but nonparticipating, households. Purchasers’ ability to minimize food expenditures has significant effects on the program’s effectiveness and on participants’ food security. Using ordinary least squares and two techniques that control for the endogeneity of SNAP participation, we found no significant effect of SNAP participation on food prices. Moreover, we found that SNAP participants pay, on average, lower prices than do nonparticipants. We conclude by providing suggestions for policy improvements and implications for future research.
Reforming the Constitution; Reforming the Postcolonial State? Indigenous Peoples and Constitutional Reforms in Taiwan
Authors: VAN BEKHOVEN Jeroen
Published: November 2019

When an authoritarian state starts democratic transition reforms, the constitution can facilitate such reforms. However, a little-studied role of the constitution during democratic transition is that it can back indigenous peoples’ demands. Constitutional reform during democratic transition enables indigenous peoples to challenge the state's ‘internal colonialism’. The democratic institutions and democratic rights established and guaranteed by the constitution open possibilities for indigenous peoples to push for constitutional reforms that promote ‘internal decolonization’. This means that indigenous peoples are empowered and that their interests are protected. For indigenous peoples, a ‘double transition’ can thus take place: from authoritarianism to democracy, and from internal colonialism to internal decolonization. A case study of the constitutional reforms in Taiwan confirms that the constitution can guarantee indigenous peoples’ participation in constitutional reform. But in Taiwan, this involvement has not led to meaningful incorporation of indigenous peoples in the constitution, and it has not fully promoted double transition. The case study highlights serious problems for indigenous peoples to realize strong constitutional reforms. This article provides a foundation for additional research on constitutional change and indigenous peoples. This is critical to advance constitutional theory and to ascertain whether and how constitutions can give indigenous peoples a voice.
Shifting focus toward healthcare-associated bloodstream infections: The need for neonatal intensive care unit–specific NHSN definitions
Authors: Advani Sonali D. , Murray Thomas S. , Murdzek Christina M. , Aniskiewicz Michael J. , Bizzarro Matthew J.
Published: November 2019

Objective:

Healthcare-associated bloodstream infections (HABSIs) are a significant cause of mortality and morbidity in the neonatal intensive care unit (NICU) population. Our objectives were to review the epidemiology of HABSIs in our NICU and to examine the applicability of National Healthcare Safety Network (NHSN) definitions to the NICU population.

Methods:

We performed a retrospective review of all neonates admitted to the 54-bed, level IV NICU at Yale-New Haven Children’s Hospital with a HABSI between January 1, 2013, and December 31, 2018. Clinical definitions per NICU team and NHSN site-specific definitions used for source identification were compared using the McNemar χ2 test.

Results:

We identified 86 HABSIs with an incidence rate of 0.80 per 1,000 patient days. Only 13% of these were CLABSIs. Both CLABSIs and non–catheter-related bloodstream infections occurred primarily in preterm neonates, but the latter were associated with a significantly higher incidence of comorbidities and the need for respiratory support. The NHSN definitions were less likely to identify a source compared to the clinical definitions agreed upon by our NICU treating team (P < .001). Furthermore, 50% of patients without an identified source of infection by NHSN definitions were bacteremic with a mucosal barrier injury organism, likely from gut translocation.

Conclusions:

HABSIs occur primarily in premature infants with comorbidities, and CLABSIs account for a small proportion of these infections. With the increasing focus on HABSI prevention, there is a need for better NHSN site-specific definitions for the NICU population to prevent misclassification and direct prevention efforts.
Cognitive emotion regulation and personality: an analysis of individual differences in the neural and behavioral correlates of successful reappraisal
Authors: Scheffel Christoph , Diers Kersten , Schönfeld Sabine , Brocke Burkhard , Strobel Alexander , Dörfel Denise
Published: November 2019

A common and mostly effective emotion regulation strategy is reappraisal. During reappraisal, activity in cognitive control brain regions increases and activity in brain regions associated with emotion responding (e.g., the amygdala) diminishes. Immediately after reappraisal, it has been observed that activity in the amygdala increases again, which might reflect a paradoxical aftereffect. While there is extensive empirical evidence for these neural correlates of emotion regulation, only few studies targeted the association with individual differences in personality traits. The aim of this study is to investigate these associations more thoroughly. Seventy-six healthy participants completed measures of broad personality traits (Big Five, Positive and Negative Affect) as well as of more narrow traits (habitual use of emotion regulation) and performed an experimental fMRI reappraisal task. Participants were instructed to either permit their emotions or to detach themselves from the presented negative and neutral pictures. After each picture, a relaxation period was included. Reappraisal success was determined by arousal ratings and activity in the amygdala. During reappraisal, we found activation in the prefrontal cortex and deactivation in the left amygdala. During the relaxation period, an immediate aftereffect was found in occipital regions and marginally in the amygdala. Neither personality traits nor habitual use of emotion regulation predicted reappraisal success or the magnitude of the aftereffect. We replicated typical activation and deactivation patterns during intentional emotion regulation and partially replicated the immediate aftereffect in the amygdala. However, there was no association between personality traits and emotion regulation success.
U–Pb ages of Miocene near-trench granitic rocks of the Southwest Japan arc: implications for magmatism related to hot subduction
Authors: Shinjoe Hironao , Orihashi Yuji , Anma Ryo
Published: November 2019

We present a new dataset of zircon U–Pb ages that document igneous activity in the SW Japan arc during middle Miocene time and discuss its relationship with the opening of the Japan Sea, Philippine Sea plate migration, and subduction of the young hot lithosphere of the Shikoku Basin. Precursory magmatism, characterized by dike and stock intrusions, startedc. 15.6 Ma in both Kyushu and the Kii Peninsula. Most plutonism occurred between 15.5 and 13.5 Ma in an area 600 km long and 150 km wide. No along-arc trend was recognized in the U–Pb ages of igneous activity near the trench. Our data indicate that all near-trench middle Miocene igneous activity occurred immediately after the opening of the Japan Sea ceased, i.e. after 16 Ma, implying that melt extraction and the emplacement of granites in the near-trench region had some influence on the back-arc opening. Our data also imply that the trench–trench–trench-type triple junction between the Japan arc and the Izu–Bonin–Mariana arc must have reached the east side of the Kii Peninsula by 15.6 Ma. The wide distribution of contemporaneous magmatic activity along the arc requires a trench-parallel heat source, such as the subduction of a trench-parallel ridge or a young and highly segmented ridge–fracture zone system in addition to the hot wedge mantle condition related to the opening of Japan Sea.
Emotional Stop Cues Facilitate Inhibitory Control in Schizophrenia
Authors: Zheng Qi , Yang Tian-Xiao , Ye Zheng
Published: November 2019

Objective:

Inhibitory control is a key deficit in patients with schizophrenia. This study aims to test whether emotions can facilitate inhibition in patients with schizophrenia when they increase attention to inhibitory process.

Method:

A total of 36 patients with schizophrenia and 36 healthy controls completed an emotional stop-signal task. The task involved selective responses to “Go” stimuli and stopped response when emotional or neutral stop cues occurred.

Results:

In all conditions, patients with schizophrenia took longer time to inhibit response compared with healthy controls, indicating an overall impairment in response inhibition. Importantly, patients with schizophrenia and controls acquired similar size of benefit from the negative stop cues, showing as reduced reaction time to negative than neutral stop cues. However, the negative stop cues impaired subsequent Go performance only in patients with schizophrenia, indicating additional cost of the negative stop cues for patients with schizophrenia. In both groups, the positive stop cues did not have any significant influence on response inhibition.

Conclusions:

These findings provide novel evidence for the benefit of emotional stop cues on inhibitory control in patients with schizophrenia and reveal different after-effects of emotional enhancement effect in patients and healthy populations. The findings may help develop effective interventions for improving inhibitory control in patients with schizophrenia and other clinical populations.
Early results of localised, high-risk prostate cancer treated by moderate hypo-fractionation (70 Gy at 2·5 Gy per fraction): 5-year experiences of a moderate hypo-fractionation regimen
Authors: Tharavichitkul Ekkasit , Chakrabandhu Somvilai , Klunklin Pitchayaponne , Onchan Wimrak , Jia-Mahasap Bongkot , Meungwong Pooriwat , Nobnop Wannapha , Tippanya Damrongsak , Sripun Patumrat , Galalae Razvan M. , Chitapanarux Imjai
Published: November 2019

Background:

Radiotherapy is one of the treatments used to treat prostate cancer, and dose escalation to 74–78 Gy in conventional fractionation is the standard regimen. Currently, according to the hypothesis of low alpha/beta ratio in prostate cancer cells, using hypo-fractionation has been reported in many publications with promising results. This retrospective study was designed to evaluate the implementation of a moderate hypo-fractionation regimen in high-risk prostate cancer in our division.

Materials and Methods:

Between 2012 and 2017, 40 patients with high-risk, localised prostate cancer were treated by a moderate hypo-fractionation regimen (70 Gy at 2·5 Gy per fraction) with intensity-modulated radiation therapy. The data related to treatment outcomes and toxicities were evaluated.

Results:

The mean PSA at diagnosis was 86·2 ng/mL (95% CI 49·9–122·4). Thirty-eight patients received long-term hormonal therapy. Fifty-two percent had a Gleason score of 8–10, and 65% had an initial PSA >20 ng/mL. The mean doses (in EQD2) to the D50% of PTV, D2% of organs at risk (bladder, rectum and bowels) were 80, 78·3, 76·4, and 50·2 Gy, respectively. Two patients had biochemical recurrence during the follow-up period.

Conclusion:

A moderate hypo-fractionation regimen (70 Gy at 2·5 Gy per fraction) is feasible. Our experience found that this regimen yields tolerable, acceptable toxicity profiles in high-risk, localised prostate cancer patients.
MOTIVATED PROOFS: WHAT THEY ARE, WHY THEY MATTER AND HOW TO WRITE THEM
Authors: MORRIS REBECCA LEA
Published: November 2019

Mathematicians judge proofs to possess, or lack, a variety of different qualities, including, for example, explanatory power, depth, purity, beauty and fit. Philosophers of mathematical practice have begun to investigate the nature of such qualities. However, mathematicians frequently draw attention to another desirable proof quality: being motivated. Intuitively, motivated proofs contain no “puzzling” steps, but they have received little further analysis. In this article, I begin a philosophical investigation into motivated proofs. I suggest that a proof is motivated if and only if mathematicians can identify (i) the tasks each step is intended to perform; and (ii) where each step could have reasonably come from. I argue that motivated proofs promote understanding, convey new mathematical resources and stimulate new discoveries. They thus have significant epistemic benefits and directly contribute to the efficient dissemination and advancement of mathematical knowledge. Given their benefits, I also discuss the more practical matter of how we can produce motivated proofs. Finally I consider the relationship between motivated proofs and proofs which are explanatory, beautiful and fitting.
Dynamic Accretion Beneath a Slow‐Spreading Ridge Segment: IODP Hole 1473A and the Atlantis Bank Oceanic Core Complex
Authors: Dick H. J. B. , MacLeod C. J. , Blum P. , Abe N. , Blackman D. K. , Bowles J. A. , Cheadle M. J. , Cho K. , Ciazela J. , Deans J. R. , Edgcomb V. P. , Ferrando C. , France L. , Ghosh B. , Ildefonse B. , John B. , Kendrick M. A. , Koepke J. , Leong J. A. M. , Liu C. , Ma Q. , Morishita T. , Morris A. , Natland J. H. , Nozaka T. , Pluemper O. , Sanfilippo A. , Sylvan J. B. , Tivey M. A. , Tribuzio R. , Viegas G.
Published: November 2019

809 deep IODP Hole U1473A at Atlantis Bank, SWIR, is 2.2 km from 1,508‐m Hole 735B and 1.4 from 158‐m Hole 1105A. With mapping, it provides the first 3‐D view of the upper levels of a 660‐km2 lower crustal batholith. It is laterally and vertically zoned, representing a complex interplay of cyclic intrusion, and ongoing deformation, with kilometer‐scale upward and lateral migration of interstial melt. Transform wall dives over the gabbro‐peridotite contact found only evolved gabbro intruded directly into the mantle near the transform. There was no high‐level melt lens, rather the gabbros crystallized at depth, and then emplaced into the zone of diking by diapiric rise of a crystal mush followed by crystal‐plastic deformation and faulting. The residues to mass balance the crust to a parent melt composition lie at depth below the center of the massif—likely near the crust‐mantle boundary. Thus, basalts erupted to the seafloor from >1,550 mbsf. By contrast, the Mid‐Atlantic Ridge lower crust drilled at 23°N and at Atlantis Massif experienced little high‐temperature deformation and limited late‐stage melt transport. They contain primitive cumulates and represent direct intrusion, storage, and crystallization of parental MORB in thinner crust below the dike‐gabbro transition. The strong asymmetric spreading of the SWIR to the south was due to fault capture, with the northern rift valley wall faults cutoff by a detachment fault that extended across most of the zone of intrusion. This caused rapid migration of the plate boundary to the north, while the large majority of the lower crust to spread south unroofing Atlantis Bank and uplifting it into the rift mountains.
Partly Cloudy With a Chance of Lava Flows: Forecasting Volcanic Eruptions in the Twenty‐First Century
Authors: Poland Michael P. , Anderson Kyle R.
Published: November 2019

A primary goal of volcanology is forecasting hazardous eruptive activity. Despite much progress over the last century, however, volcanoes still erupt with no detected precursors, lives and livelihoods are lost to eruptive activity, and forecasting the onsets of eruptions remains fraught with uncertainty. Long‐term forecasts are generally derived from the geological and historical records, from which recurrence intervals and styles of activity can be inferred, while shorter‐term forecasts are derived from patterns in monitoring data. Information from geology and monitoring data can be evaluated and combined using statistical analysis, expert elicitation, and conceptual and or mathematical models. Integrative frameworks, such as event trees, combine this diversity of information to produce probabilistic forecasts that can inform the style and scale of the societal response to a potential future eruption. Several developments show promise to revolutionize the utility and accuracy of these forecasts. These include growth in the quantity and quality of multidisciplinary monitoring data, coupled with increases in computing power; machine learning algorithms, which will allow far better utilization of this growing volume of data; and new physiochemical volcano models and data assimilation algorithms, which take advantage of a wide range of monitoring data and realistic physics to better predict the evolution of a given physical state. Although eruption forecasts may never be as generally reliable as weather forecasts, and great caution must be exercised when attempting to predict highly complex volcanic behavior, these and other innovations—particularly when combined in integrative, fully probabilistic forecasting frameworks—should help volcanologists to better issue warnings of volcanic activity on societally relevant time frames.
Anisotropy of Magnetic Susceptibility (AMS) of Sediments From Holes U1480E and U1480H, IODP Expedition 362: Sedimentary or Artificial Origin and Implications for Paleomagnetic Studies
Authors: Yang Tao , Zhao Xixi , Petronotis Katerina , Dekkers Mark J. , Xu Huiru
Published: November 2019

Recognition of coring‐induced disturbance, which is essential for magnetic fabric and paleomagnetic studies of poorly lithified sediments, is generally not straightforward. Here, we report on anisotropy of magnetic susceptibility (AMS) and paleomagnetic data of the sediments from Holes U1480E and U1480H, IODP Expedition 362, west of the Sumatra subduction zone. AMS is characterized by steep minimum principal axes (Kmin) in undisturbed sediments. However, a considerable portion of the recovered sediments are affected by significant coring‐induced disturbance. In these cases, we observed three AMS patterns: (1) AMS principal axes are randomly distributed for sediments with mingling and distortion of beds, (2) Kmin axes of sediments with upward‐arching beds are deflected out of the splitting face of the working half, and (3) suck‐in sediments are characterized by vertical Kmax axes. These deformation‐dependent AMS patterns can be attributed to the realignment of mineral particles caused by the coring process and subsequent sampling procedures. Besides a low‐coercivity, vertical, drilling‐induced overprint, we observed a high‐coercivity component that is likely a composite of the primary magnetization with a demagnetization‐resistant portion of the drilling overprint. After accounting for the disturbed intervals, several polarity transitions can be identified in the undisturbed sediments which correlate well with the Pleistocene geomagnetic polarity timescale. These observations demonstrate that great caution is required when attributing geological significance to AMS and paleomagnetic data obtained from soft sediment cores, which are highly susceptible to coring‐induced disturbance. In addition, AMS measurements provide a potential tool for identifying core deformation for further paleomagnetic studies.
Magma Flow Rates and Temporal Evolution of the 2012–2014 Post‐Eruptive Intrusions at El Hierro, Canary Islands
Authors: Benito‐Saz Maria Angeles , Sigmundsson Freysteinn , Charco Maria , Hooper Andrew , Parks Michelle
Published: November 2019

The 2011–2014 volcanic activity at El Hierro (Canary Islands) was characterized by a 5‐month long submarine eruption as well as a series of magmatic intrusions occurring between 5 months and 2 years after the eruption, as revealed by seismic swarms and ground deformation. We study the temporal evolution of the six post‐eruptive magmatic intrusions, using Global Navigation Satellite System and Interferometric Synthetic Aperture Radar observations complemented with relocated earthquakes. Magma volumes and magma supply rates are determined from inversion of the geodetic data using a Bayesian approach. The intrusions last between ~3 and 20 days and are inferred to be sill‐like, thin compared with their lateral extent and emplaced in the ~13–16 km depth range. Initial magma flow rates of ~300 m3/s decay exponentially with time. The two largest intrusions occurred in June–July 2012 and March–April 2013. During each of these events, magma migrated laterally, and >120 ×106 m3 of magma was intruded beneath the island. The shortest events, <1 week‐long, intruded ~(24hyphen;44) ×106 m3 of magma beneath the volcano. We suggest that all intrusions originated from an overpressure in a deep magma body located beneath the center of El Hierro. The crust/mantle boundary and the previous intrusion that fed the 2011–2012 submarine eruption may have discouraged the ascent of the post‐eruptive intrusions to the surface and forced them to migrate laterally away from the island as sill‐like sources.
The Political Psychology of Inequality and Why It Matters for Populism
Authors: Oxendine Alina R.
Published: November 2019

Integrating research from political science, psychology, and related fields, this article analyzes the complex web of relationships and pathways connecting economic inequality to populism. What emerges is an original theoretical framework for understanding populist support, which distinguishes between levels of analysis and considers how economic and cultural influences interact (rather than placing them at odds). It also emphasizes the important distinction between reality and perception and its role in understanding how citizens react differently to the same macrolevel trends and environmental threats. Careful analysis of the existing scholarship suggests that economic stratification exerts an indirect influence on populist support. Inequality likely shapes populist beliefs through macrolevel mediators such as economic dysfunction, rising political polarization, and a decline in the quality of government. Also, several potential individual-level influences mediate the relationship, including heightened sense of intergroup threat, political distrust, status anxiety, and perceptions of system unfairness. This article’s theoretical framework also explores how community environment and relevant personality characteristics like right-wing authoritarianism and social dominance orientation may moderate important associations.
Which out-of-office measurement technique should be used for diagnosing hypertension in prehypertensives?
Authors:   on behalf of the Turkish Society of Hypertension and Renal Diseases, Ulusoy Şükrü , Özkan Gülsüm , Arıcı Mustafa , Derici Ülver , Akpolat T. , Şengül Şule , Yılmaz Rahmi , Ertürk Şehsuvar , Erdem Yunus
Published: November 2019

Hypertension (HT) is diagnosed with high office blood pressure (BP), although confirmation with the addition of out-of-office measurements is currently recommended. However, insufficient data are available concerning the use of out-of-office BP measurement techniques for the diagnosis of HT in the prehypertensive population. The aim of the present study was to determine which out-of-office measurements yielded earlier and more frequent detection of development of HT in prehypertensive patients. Two hundred seven prehypertensive patients under monitoring in the Cappadocia cohort were included in the study. Office BP was measured five times at 1-min intervals, followed by 24-h ambulatory BP monitoring (24-h ABPM). Home BP measurement (HBPM) was performed five times, at the same times in the morning and evening, at 1-min intervals for 1 week. The same procedure was carried out at 4–6-month intervals for ~2 years. HT was diagnosed in 25.6% of subjects, masked HT in 11.1%, and white coat HT in 2.9%, while 23.7% remained prehypertensive and 36.7% became normotensive. Briefly, 56.6% of the patients with HT were diagnosed with office plus 24-h ABPM, 13.2% with office plus HBPM, and 30.2% with office plus HBPM and 24-h ABPM. Office with 24-h ABPM yielded statistically significantly more diagnoses (p < 0.001). In conclusion, our prospective observational study evaluated the usefulness of out-of-office BP measurements in confirming diagnosis of HT in prehypertensive patients. The findings show that 24-h ABPM detected HT earlier and more frequently in this high-risk population.
Long-read sequencing reveals the complex splicing profile of the psychiatric risk gene CACNA1C in human brain
Authors: Clark Michael B. , Wrzesinski Tomasz , Garcia Aintzane B. , Hall Nicola A. L. , Kleinman Joel E. , Hyde Thomas , Weinberger Daniel R. , Harrison Paul J. , Haerty Wilfried , Tunbridge Elizabeth M.
Published: November 2019

RNA splicing is a key mechanism linking genetic variation with psychiatric disorders. Splicing profiles are particularly diverse in brain and difficult to accurately identify and quantify. We developed a new approach to address this challenge, combining long-range PCR and nanopore sequencing with a novel bioinformatics pipeline. We identify the full-length coding transcripts ofCACNA1Cin human brain.CACNA1Cis a psychiatric risk gene that encodes the voltage-gated calcium channel CaV1.2. We show thatCACNA1C’s transcript profile is substantially more complex than appreciated, identifying 38 novel exons and 241 novel transcripts. Importantly, many of the novel variants are abundant, and predicted to encode channels with altered function. The splicing profile varies between brain regions, especially in cerebellum. We demonstrate that human transcript diversity (and thereby protein isoform diversity) remains under-characterised, and provide a feasible and cost-effective methodology to address this. A detailed understanding of isoform diversity will be essential for the translation of psychiatric genomic findings into pathophysiological insights and novel psychopharmacological targets.
Paying attention to attention in depression
Authors: Keller Arielle S. , Leikauf John E. , Holt-Gosselin Bailey , Staveland Brooke R. , Williams Leanne M.
Published: November 2019

Attention is the gate through which sensory information enters our conscious experiences. Oftentimes, patients with major depressive disorder (MDD) complain of concentration difficulties that negatively impact their day-to-day function, and these attention problems are not alleviated by current first-line treatments. In spite of attention’s influence on many aspects of cognitive and emotional functioning, and the inclusion of concentration difficulties in the diagnostic criteria for MDD, the focus of depression as a disease is typically on mood features, with attentional features considered less of an imperative for investigation. Here, we summarize the breadth and depth of findings from the cognitive neurosciences regarding the neural mechanisms supporting goal-directed attention in order to better understand how these might go awry in depression. First, we characterize behavioral impairments in selective, sustained, and divided attention in depressed individuals. We then discuss interactions between goal-directed attention and other aspects of cognition (cognitive control, perception, and decision-making) and emotional functioning (negative biases, internally-focused attention, and interactions of mood and attention). We then review evidence for neurobiological mechanisms supporting attention, including the organization of large-scale neural networks and electrophysiological synchrony. Finally, we discuss the failure of current first-line treatments to alleviate attention impairments in MDD and review evidence for more targeted pharmacological, brain stimulation, and behavioral interventions. By synthesizing findings across disciplines and delineating avenues for future research, we aim to provide a clearer outline of how attention impairments may arise in the context of MDD and how, mechanistically, they may negatively impact daily functioning across various domains.
Molecular and cellular mechanisms underlying the antidepressant effects of ketamine enantiomers and its metabolites
Authors: Yang Chun , Yang Jianjun , Luo Ailin , Hashimoto Kenji
Published: November 2019

Although the robust antidepressant effects of the N-methyl-d-aspartate receptor (NMDAR) antagonist ketamine in patients with treatment-resistant depression are beyond doubt, the precise molecular and cellular mechanisms underlying its antidepressant effects remain unknown. NMDAR inhibition and the subsequent α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) activation are suggested to play a role in the antidepressant effects of ketamine. Although (R)-ketamine is a less potent NMDAR antagonist than (S)-ketamine, (R)-ketamine has shown more marked and longer-lasting antidepressant-like effects than (S)-ketamine in several animal models of depression. Furthermore, non-ketamine NMDAR antagonists do not exhibit robust ketamine-like antidepressant effects in patients with depression. These findings suggest that mechanisms other than NMDAR inhibition play a key role in the antidepressant effects of ketamine. Duman’s group demonstrated that the activation of mammalian target of rapamycin complex 1 (mTORC1) in the medial prefrontal cortex is reportedly involved in the antidepressant effects of ketamine. However, we reported that mTORC1 serves a role in the antidepressant effects of (S)-ketamine, but not of (R)-ketamine, and that extracellular signal-regulated kinase possibly underlie the antidepressant effects of (R)-ketamine. Several lines of evidence have demonstrated that brain-derived neurotrophic factor (BDNF) and its receptor, tyrosine kinase receptor B (TrkB), are crucial in the antidepressant effects of ketamine and its two enantiomers, (R)-ketamine and (S)-ketamine, in rodents. In addition, (2R,6R)-hydroxynormetamine [a metabolite of (R)-ketamine] and (S)-norketamine [a metabolite of (S)-ketamine] have been shown to exhibit antidepressant-like effects on rodents through the BDNF–TrkB cascade. In this review, we discuss recent findings on the molecular and cellular mechanisms underlying the antidepressant effects of enantiomers of ketamine and its metabolites. It may be time to reconsider the hypothesis of NMDAR inhibition and the subsequent AMPAR activation in the antidepressant effects of ketamine.
Cannabidiol promotes apoptosis via regulation of XIAP/Smac in gastric cancer
Authors: Jeong Soyeon , Jo Min Jee , Yun Hye Kyeong , Kim Dae Yeong , Kim Bo Ram , Kim Jung Lim , Park Seong Hye , Na Yoo Jin , Jeong Yoon A , Kim Bu Gyeom , Ashktorab Hassan , Smoot Duane T. , Heo Jun Young , Han Jeongsu , Il Lee Sun , Do Kim Han , Kim Dae Hyun , Oh Sang Cheul , Lee Dae-Hee
Published: November 2019

According to recent studies, Cannabidiol (CBD), one of the main components of Cannabis sativa, has anticancer effects in several cancers. However, the exact mechanism of CBD action is not currently understood. Here, CBD promoted cell death in gastric cancer. We suggest that CBD induced apoptosis by suppressing X-linked inhibitor apoptosis (XIAP), a member of the IAP protein family. CBD reduced XIAP protein levels while increasing ubiquitination of XIAP. The expression of Smac, a known inhibitor of XIAP, was found to be elevated during CBD treatment. Moreover, CBD treatment increased the interaction between XIAP and Smac by increasing Smac release from mitochondria to the cytosol. CBD has also been shown to affect mitochondrial dysfunction. Taken together, these results suggest that CBD may have potential as a new therapeutic target in gastric cancer.
p53 mitotic centrosome localization preserves centrosome integrity and works as sensor for the mitotic surveillance pathway
Authors: Contadini Claudia , Monteonofrio Laura , Virdia Ilaria , Prodosmo Andrea , Valente Davide , Chessa Luciana , Musio Antonio , Fava Luca L. , Rinaldo Cinzia , Di Rocco Giuliana , Soddu Silvia
Published: November 2019

Centrosomal p53 has been described for three decades but its role is still unclear. We previously reported that, in proliferating human cells, p53 transiently moves to centrosomes at each mitosis. Such p53 mitotic centrosome localization (p53-MCL) occurs independently from DNA damage but requires ATM-mediated p53Ser15 phosphorylation (p53Ser15P) on discrete cytoplasmic p53 foci that, through MT dynamics, move to centrosomes during the mitotic spindle formation. Here, we show that inhibition of p53-MCL, obtained by p53 depletion or selective impairment of p53 centrosomal localization, induces centrosome fragmentation in human nontransformed cells. In contrast, tumor cells or mouse cells tolerate p53 depletion, as expected, and p53-MCL inhibition. Such tumor- and species-specific behavior of centrosomal p53 resembles that of the recently identified sensor of centrosome-loss, whose activation triggers the mitotic surveillance pathway in human nontransformed cells but not in tumor cells or mouse cells. The mitotic surveillance pathway prevents the growth of human cells with increased chance of making mitotic errors and accumulating numeral chromosome defects. Thus, we evaluated whether p53-MCL could work as a centrosome-loss sensor and contribute to the activation of the mitotic surveillance pathway. We provide evidence that centrosome-loss triggered by PLK4 inhibition makes p53 orphan of its mitotic dock and promotes accumulation of discrete p53Ser15P foci. These p53 foci are required for the recruitment of 53BP1, a key effector of the mitotic surveillance pathway. Consistently, cells from patients with constitutive impairment of p53-MCL, such as ATM- and PCNT-mutant carriers, accumulate numeral chromosome defects. These findings indicate that, in nontransformed human cells, centrosomal p53 contributes to safeguard genome integrity by working as sensor for the mitotic surveillance pathway.
MKK3 sustains cell proliferation and survival through p38DELTA MAPK activation in colorectal cancer
Authors: Stramucci Lorenzo , Pranteda Angelina , Stravato Arianna , Amoreo Carla Azzurra , Pennetti Annarita , Diodoro Maria Grazia , Bartolazzi Armando , Milella Michele , Bossi Gianluca
Published: November 2019

Colorectal cancer (CRC) is one of the most common malignant tumors worldwide and understanding its underlying molecular mechanisms is crucial for the development of therapeutic strategies. The mitogen-activated protein kinase-kinase 3 (MKK3) is a specific activator of p38 MAP kinases (p38 MAPKs), which contributes to the regulation of several cellular functions, such as proliferation, differentiation, apoptosis as well as response to drugs. At present, the exact MKK3/p38 MAPK pathway contribution in cancer is heavily debated because of its pleiotropic function. In this work, we retrospectively explored the prognostic and pathobiologic relevance of MKK3 in a cohort of CRC patients and assessed MKK3 molecular functions in a panel of CRC lines and colonocytes primary cultures. We found increased MKK3 levels in late-stage CRC patients which correlated with shorter overall survival. Herein, we report that the MKK3 targeting by inducible RNA interference univocally exerts antitumor effects in CRC lines but not in primary colonocytes. While MKK3 depletion per se affects growth and survival by induction of sustained autophagy and death in some CRC lines, it potentiates response to chemotherapeutic drug 5-fluorouracil (5-FU) in all of the tested CRC lines in vitro. Here, we demonstrate for the first time that in CRC the MKK3 specifically activates p38delta MAPK isoform to sustain prosurvival signaling and that such effect is exacerbated upon 5-FU challenge. Indeed, p38delta MAPK silencing recapitulates MKK3 depletion effects in CRC cells in vitro and in vivo. Overall, our data identified a molecular mechanism through which MKK3 supports proliferation and survival signaling in CRC, further supporting MKK3 as a novel and extremely attractive therapeutic target for the development of promising strategies for the management of CRC patients.
Hepatocyte-derived exosomal MiR-194 activates PMVECs and promotes angiogenesis in hepatopulmonary syndrome
Authors: Chen Lin , Han Yi , Li Yujie , Chen Bing , Bai Xuehong , Belguise Karine , Wang Xiaobo , Chen Yang , Yi Bin , Lu Kaizhi
Published: November 2019

Hepatopulmonary syndrome (HPS) is a serious vascular complication in the setting of liver disease. Factors produced by the liver are essential to regulate pulmonary angiogenesis in the pathogenesis of HPS; however, the pathogenic mechanisms of pulmonary angiogenesis are not fully understood. We investigated the role of HPS rat serum exosomes (HEs) and sham-operated rat serum exosomes (SEs) in the regulation of angiogenesis. We found that HEs significantly enhance PMVEC proliferation, migration, and tube formation. We further identified miR-194 was the most notably increased miRNA in HEs compared to SEs. Once released, hepatocyte-derived exosomal miR-194 was internalized by PMVECs, leading to the promotion of PMVEC proliferation, migration, and tube formation through direct targeting of THBS1, STAT1, and LIF. Importantly, the pathogenic role of exosomal miR-194 in initiating angiogenesis was reversed by P53 inhibition, exosome secretion inhibition or miR-194 inhibition. Additionally, high levels of miR-194 were found in serum exosomes and were positively correlated with P(A-a)O2 in HPS patients and rats. Thus, our results highlight that the exosome/miR-194 axis plays a critical pathologic role in pulmonary angiogenesis, representing a new therapeutic target for HPS.
Emergence of the Ug99 lineage of the wheat stem rust pathogen through somatic hybridisation
Authors: Li Feng , Upadhyaya Narayana M. , Sperschneider Jana , Matny Oadi , Nguyen-Phuc Hoa , Mago Rohit , Raley Castle , Miller Marisa E. , Silverstein Kevin A. T. , Henningsen Eva , Hirsch Cory D. , Visser Botma , Pretorius Zacharias A. , Steffenson Brian J. , Schwessinger Benjamin , Dodds Peter N. , Figueroa Melania
Published: November 2019

Parasexuality contributes to diversity and adaptive evolution of haploid (monokaryotic) fungi. However, non-sexual genetic exchange mechanisms are not defined in dikaryotic fungi (containing two distinct haploid nuclei). Newly emerged strains of the wheat stem rust pathogen, Puccinia graminis f. sp. tritici (Pgt), such as Ug99, are a major threat to global food security. Here, we provide genomics-based evidence supporting that Ug99 arose by somatic hybridisation and nuclear exchange between dikaryons. Fully haplotype-resolved genome assembly and DNA proximity analysis reveal that Ug99 shares one haploid nucleus genotype with a much older African lineage of Pgt, with no recombination or chromosome reassortment. These findings indicate that nuclear exchange between dikaryotes can generate genetic diversity and facilitate the emergence of new lineages in asexual fungal populations.
Complex I is bypassed during high intensity exercise
Authors: Nilsson Avlant , Björnson Elias , Flockhart Mikael , Larsen Filip J. , Nielsen Jens
Published: November 2019

Human muscles are tailored towards ATP synthesis. When exercising at high work rates muscles convert glucose to lactate, which is less nutrient efficient than respiration. There is hence a trade-off between endurance and power. Metabolic models have been developed to study how limited catalytic capacity of enzymes affects ATP synthesis. Here we integrate an enzyme-constrained metabolic model with proteomics data from muscle fibers. We find that ATP synthesis is constrained by several enzymes. A metabolic bypass of mitochondrial complex I is found to increase the ATP synthesis rate per gram of protein compared to full respiration. To test if this metabolic mode occurs in vivo, we conduct a high resolved incremental exercise tests for five subjects. Their gas exchange at different work rates is accurately reproduced by a whole-body metabolic model incorporating complex I bypass. The study therefore shows how proteome allocation influences metabolism during high intensity exercise.